Home¶

This is the online home of the Vanderbilt Internal Medicine Residency Handbook.

Dedication¶

The authors and editors dedicate the fourth edition of the Housestaff Handbook to the memory of Dr. Michael Fowler, whose compassion, sincerity, and commitment to education continue to guide and inspire us.

Michael J. Fowler, MD, Associate Professor of Medicine and Associate Professor, Office of Teaching and Learning in Medicine in the Vanderbilt University School of Medicine, was an inspiring teacher and educator, an outstanding physician, and a wonderful colleague who passed away on February 20, 2022. As a Master Clinical Teacher at Vanderbilt, Mike was the Course Director for Physical Diagnosis and taught physical diagnosis to more than 1500 Vanderbilt medical students. As Co-director of the Shade Tree Clinic, he touched the lives of many patients and inspired Vanderbilt medical students to understand how to be a physician who cared for the entire patient. He was a wonderful, passionate teacher and advocate for all students in the clinical setting, in the classroom and in life, and touched many, many people with his kindness, humor, intellect, humility, and medical and teaching skills.

– Alvin C. Powers, MD, Nashville, TN, May 2022

QR code for vimbook.org — QR code link for this online VIMBook

Introduction ↵

Acknowledgements¶

The Vanderbilt University Medical Center (VUMC) Internal Medicine Housestaff Handbook began with an Internal Medicine Resident Quality Improvement Project which was led by Michael J. Neuss, MD, PhD, under the guidance of Jennifer K. Green, MD, MPH in 2019.

We would like to thank the following individuals for their contributions to the 4^th edition of the Housestaff Handbook:

The many VUMC residents (past and present) who have meticulously authored each section of this handbook.
The VUMC faculty who carefully reviewed each topic for its accuracy.
Leah Brown, MD and Joseph Quintana, MD, the 3^rd edition's co-editors-in-chief, whose guidance was instrumental in the transition between editions.
Chase Webber, DO, who was a sounding board for our new ideas throughout the year as the Handbook’s faculty advisor.
C. Beau Hilton, MD for his work in updating and improving the online version of this handbook.
John McPherson, MD, Kim Rathmell, MD PhD, Kristy Braden and Maria Kasel, for their unwavering support.

Editors, Authors, and Reviewers¶

Editors-in-Chief¶

Lauren Chan, MD & Jacqueline Visina, MD

Resident Editors¶

Cardiology: Brittany Saldivar, MD 

Critical Care:  Raymond Dieter, MD

Endocrinology: Kinsley Ojukwu, MD 

Gastroenterology: Taylor Riggs, MD 

Geriatrics: Thomas Horton, MD 

Hematology/Oncology: Michael LaPelusa, MD

Hepatology: Julie Cui, MD 

Hospital Medicine: Soibhan Kelley, MD

Infectious Diseases: Kaitlyn Reasoner, MD

Nephrology: Trey Richardson, MD

Neurology: Hunter Hewitt, MD

Ophthalmology: Jonathan Barnett, MD

Outpatient Medicine: Christina Snider, MD

Palliative Care: Eli Cohen, MD

Physical Medicine & Rehabilitation: Jakob Dovgan, MD, Douglas Bryant, MD, William Galbraith, DO, and Nicholas Abramson, MD

Procedures: Katherine Heckman, MD 

Psychiatry: Soibhan Kelley, MD

Pulmonary: Taryn Boyle, MD

Radiology: Janesh Lakhoo, MD, MS

Rheumatology: Raeann Whitney, MD  

Toxicology: Jennifer Marvin-Peek, MD

Faculty Reviewers¶

Cardiology:  Lisa Mendes, MD and Jared O’Leary, MD 

Critical Care: Todd Rice, MD

Endocrinology: Laura Heller, MD

Gastroenterology: Patrick Yachimski, MD 

Geriatrics: Mariu Duggan, MD, MPH

Hematology/Oncology: Rajiv Agarwal, MD and Benjamin Tillman, MD

Hepatology: Manhal J. Izzy, MD

Hospital Medicine: Chase J. Webber, DO

Infectious Diseases: Milner Staub, MD, MPH and Sean Kelly, MD

Nephrology: JP Arroyo, MD, PhD,

Edward Gould, MD, and Beatrice Concepcion, MD

Neurology: Christopher Lee, MD

Ophthalmology: John Bond, MD

Outpatient: Jennifer K. Green, MD, MPH

Palliative Care: Mohana Karlekar, MD

Physical Medicine & Rehabilitation: C. J. Plummer, MD

Procedures: Garren Montgomery, MD

Psychiatry: Jonathan Smith, MD and Jose Arriola Vigo MD, MPH

Pulmonary: Meredith Pugh, MD

Radiology: Virginia Planz, MD

Rheumatology: Kevin Byram, MD

Toxicology:  Rebecca E. Bruccoleri, MD and Saralyn R. Williams, MD

Disclaimers¶

The handbook is not a substitute for clinical judgment and is intended as an educational guide. Content reflects current national guidelines, as well as practice at VUMC and the Nashville VA. The handbook is not intended to replace more comprehensive references or guides.

Images are used sparingly, but when used are created by the authors themselves, available by public domain, or reproduced under fair use.

Rationale¶

The aim of this handbook is to provide specific, systems-based guidance on practice at VUMC and the VA. We hope to provide readers with direct and actionable guidance, consolidating the combined wisdom of generations of residents and faculty experts.

The Handbook represents a coordinated effort to disseminate details of our practice in a standardized, peer-reviewed format. The guidance provided by the handbook makes legible evidence-based practice as well as the oral tradition of a resident guiding an intern, or an attending a resident. We hope that this handbook will inspire confidence and learning, whether the reader is an intern on July 1 or a senior resident who wishes to refresh their memory of a topic.

Web App Setup¶

This site is optimized for use on mobile devices. It is possible to set up a link from your device's home screen that gives it the look and feel of a web app.

iOS users: Go to VIMBook.org . At the bottom of the screen, hit the "Share" icon (box with upward facing arrow). Hit "Add to Home Screen." Rename it to your liking. The gold Vanderbilt icon will appear on your home screen, and you can click this icon to be taken directly to the website.
Android users: Go to VIMBook.org . Press Menu, then select "Bookmarks." Hold it down until "Add Shortcut to Home Screen" appears, and click it. This will place an icon on your home screen, and you can click this icon to be taken directly to the website.

Ended: Introduction

Cardiology ↵

Acute Coronary Syndromes¶

Anna Berry

Background¶

Completely or partially occluding thrombus on a disrupted atherothrombotic coronary plaque leading to myocardial ischemia/infarction
STEMI: Elevated troponin & elevation in ST segment or new LBBB with symptoms
- > 0.1 mV in at least 2 contiguous leads
- Exception, in V2-V3:
- > 0.2 mV in men older than 40 y/o
- > 0.25 in men younger than 40 y/o
- > 0.15 mV in women
NSTEMI: Evidence of myocardial necrosis (elevated troponin) w/o ST segment elevation
Unstable Angina: Angina without evidence of myocardial necrosis (normal troponin)
Other causes of myocardial injury: coronary spasm, embolism, imbalance of oxygen demand and supply 2/2 fever, tachycardia, hypo-/hypertension

Presentation¶

Classic Angina: dyspnea on exertion, substernal, pressure or vice-like quality, improved with rest. Note that response nitroglycerin is no longer in the guidelines.
Anginal Equivalents: nausea, weakness, epigastric pain (esp. in age > 65 y/o, women, diabetics)
Change in patient’s baseline angina, especially onset at rest
Physical Exam: sinus tachycardia, diaphoresis
If large infarct, can present with symptoms of acute heart failure

Evaluation¶

EKG: Compare to prior EKG and assess for
- New ST elevations or ST depressions
- T wave inversions: not specific but more concerning if deep (> 0.3mV)
- Biphasic T waves and deep T wave inversions in leads V2 & V3 (Wellens' sign [LAD])
Cardiac biomarkers: troponin I is most sensitive for myocardial injury
ACC/AHA guidelines recommend both EKG and trop q2-6 hours
- Consider this if high suspicion for ACS despite normal initial markers
- If negative x2, OK to stop trending
Other labs: lipid panel, TSH, A1C

Management¶

STEMI¶

STAT page Cardiology on call via Synergy (whether in VA or Vanderbilt)
ASAP: aspirin 325mg, heparin drip (high nomogram, with bolus)
Hold P2Y12 receptor blocker until discussed with cards fellow

NSTEMI¶

Medical management followed by left-heart catheterization within 48 hours
General: bedrest, telemetry, repeat EKG with recurrent chest pain, NPO at midnight
Place cath case request (see “pre-catheterization” management below)

Anti-thrombotic therapy¶

Antiplatelet agents

ASA 325 mg loading dose then 81 mg daily after
Do not give P2Y12 receptor blocker until discussed with cardiology fellow
Clopidogrel: prodrug that is metabolized to active form (can have undermetabolizers), irreversible inhibition
Ticagrelor: reversible inhibitor
Prasugrel: prodrug but more rapidly metabolized than clopidogrel with less variation, irreversible inhibition, do not use w/ age > 75 or weight \< 60 kg
Prasugrel and ticagrelor are superior to clopidogrel but have higher bleeding risk
Cangrelor: IV, rarely used

Anti-coagulants

Unfractionated heparin drip
Type this in Epic and select “nursing managed” protocol for “ACS”
VA: it can be found under the “Orders” tab along the left-hand column.
Enoxaparin (LMWH) can be used but requires preserved renal function (CrCl > 30) and most interventionalists prefer heparin prior to LHC

Pre-Catheterization Care¶

Ensure pt. is NPO at MN for planned cath
Continue anticoagulation with heparin gtt
Place cardiac catheterization request (must be in cardiology context). Can also call cath lab to ensure pt. is scheduled appropriately

Post-Catheterization Care Catheterization Documentation¶

The most appropriate guidance for post-cath care is in the cardiac catheterization report
VUMC: Epic Cardiac tab Cardiac Catheterization/Intervention Report
VA: Note tab Post-Procedure note and Cardiac Catheterization note
If there is a delay in filing the final report at VUMC: Review the Cardiac Catheterization Nursing Documentation which shows if stents were deployed

Post-Catheterization Heparin¶

Medical management w/o intervention: stop heparin unless directed in report
If indication for CABG (ex: Left main, proximal LAD), continue heparin gtt until surgery
PCI placed: stop heparin and continue/start DAPT as directed by cardiology
Other medical indication for anticoagulation (DVT/PE, atrial fibrillation): restart ~ six hours after catheterization

Cath Site Checks¶

6 - 8 hours post catheterization (typically can be signed out as 0000 cath check), only needed for femoral arterial access
Look, listen, feel: evaluate for hematoma & pseudoaneurysm; call fellow if concerned
Small amount of bruising and mild tenderness at the site is normal
Listen above and below the site for a bruit; the area should be soft
Hypotension after femoral access is concerning for RP bleed
- STAT CBC, CT A/P & call the cardiology fellow
Femoral oozing: Cardiology fellow, will need to hold pressure
Radial oozing: instruct nurse to re-inflate the TR band and restart the clock on deflation

Post ACS Care¶

Echo prior to discharge
DAPT: Aspirin 81 mg daily and P2Y12 agent
Beta blocker in all patients within 24 hours
Metoprolol, carvedilol & bisoprolol have proven mortality benefit with reduced EF
High intensity statin (ex: rosuvastatin 40 or atorvastatin 80). See outpatient lipids section
ACEi/ARB if anterior STEMI
Lifestyle Modification: weight loss, smoking cessation, diabetes control
See heart failure section for management of HFrEF

ACS Complications¶

VT/VF, sinus bradycardia, third-degree heart block, new VSD, LV perforation, acute mitral regurgitation, pericarditis and cardiogenic shock; More common with STEMI CCU post-cath

Additional Information¶

Initiate treatment if there is true concern for ACS and bleeding risk acceptable, medications can always be discontinued
TIMI score: >2 correlates with ↑ mortality, indicating a need for aggressive treatment
ACC Guideline Clinical App is a useful resource with summaries of guideline-based recs

Arrhythmias¶

Kunal Patel, Madeline Rukavina

Acute management of arrhythmias¶

12-lead EKG if possible and have defib pads on patient
Is the patient unstable (hypotensive, signs/symptoms of hypoperfusion)?
Is the information real?
Review tele strips if stable: VUMC Web Resources -> VUH PIICiX Philips Web -> patient selection -> alarm review (vuhphilipsweb.app.vumc.org)
Review past EKGs to determine if patient has had this rhythm before
Ensure pt has good IV access
Labs: BMP, Mg, TSH, and ± troponin, tox screen

Bradyarrhythmias¶

Kunal Patel

Background¶

Broadly classified as sinus node dysfunction (pacing defect) or atrioventricular block (conduction defect)
Clinical presentation varies widely based on underlying cause, timing, degree of block/dysfunction
Unlikely to cause symptoms if HR >50
Symptoms include syncope/presyncope, dyspnea, angina

Etiologies¶

Infection/sepsis
Ischemia
Rheumatologic/Inflammatory
Post-cardiac surgery
Hypothyroidism
Sleep apnea
Infiltration (amyloid, hemochromatosis)
High vagal tone (pain, nausea)
Medications: Antihypertensives, antiarrhythmics, psychoactive meds, anesthetics, cannabis, muscle relaxants, etc.

Sinus node dysfunction

Symptomatic sinus bradycardia, tachy-brady syndrome, chronotropic incompetence, sinus pause, SA exit block
Asymptomatic sinus bradycardia (esp in young/healthy patient) is unlikely to be true bradyarrhythmia

AV Block

AV block

Evaluation¶

TTE if structural disease suspected
Ambulatory cardiac monitoring if frequently symptomatic

Management¶

Avoid nodal blocking agents – Adenosine, Beta-blockers, CCBs, Digoxin
Observation if asymptomatic
Treat identified underlying causes
If symptomatic or high-grade block (Mobitz II or complete heart block), EP consult for pacemaker evaluation
If unstable:
Atropine (0.5 mg every 3 to 5 minutes; maximum total dose: 3 mg)
- Do NOT use in heart transplant
- Call CCU Fellow
- Dopamine (5 to 20 mcg/kg/minute) OR Epi (2 to 10 mcg/min)
- Transvenous pacing (Pacer pads on the defib device are capable of pacing, but don’t forget to sedate!)

Tachyarrhythmias - Narrow complex¶

Kunal Patel

Background¶

Three causes of tachyarrhythmias
- Re-entry: patient with structural heart disease (ex post-infarction scar)
- Abnormal Automaticity: electrolyte abnormalities or acute ischemia (Purkinje fibers)
- Triggered Activity: early and late after depolarizations. Ex: Hypokalemia, ischemia, infracts, excess calcium and drug toxicity

Tachyarrhythmia differential

tachyarrhythmia

Evaluation¶

Unstable tachyarrhythmia
Start with treatment, determine type later
Synchronized cardioversion: place defibrillator pads, consider 0.5-2mg IV midazolam for sedation, prepare for synchronized cardioversion at 200J (can ↑ to 300-360 J)

Management¶

Sinus tachycardia
- Almost always secondary
- Address underlying causes: fever/sepsis, hypo/hypervolemia, anxiety, anemia, PE, ACS, hypoxia, pain, urinary retention, withdrawal
Atrial Fibrillation/Flutter – See Atrial fibrillation section
AVNRT/Orthodromic AVRT
- Look for p buried in QRS, rate 150-250, AVRT will have delta waves when NSR
- Vagal maneuvers (1^st line): Sit patient upright have them blow into tip of 10cc syringe for 10-15 seconds rapidly lay supine and raise legs
- Adenosine (2^nd line): therapeutic (break AVRT/AVNRT) and diagnostic (allows visualization of underlying rhythm)
  - Do NOT give in heart transplant, severe COPD, pre-excitation causing wide complex tachycardia (WPW antidromic AVRT)
  - Peripheral line at AC or above w/ arm elevated: 6mg x1, 6mg x1 (if not effective after 1-2 min), 12mg x1 (if refractory to 6mg)
  - Central line: cut dose in half to 3mg x1, 3mg x1, 6mg x1
Multifocal atrial tachycardia
- 3 or more p wave morphologies. Seen in cardiac and pulmonary disease
- Usually does not cause hemodynamic instability
- BBs and non-DHP CCBs can be effective, need to address underlying issue

Drug	Dosing	Benefits	Side Effects
Metoprolol	5mg IV q5m x3 PO metoprolol tartrate 12.5mg q6 hours ↑ every 6 hr to target	Good 1st line agent Less BP effect than dilt	Hypotension, Negative inotropy
Diltiazem	10-20 mg IV over 2m q15m x2 drip = 5-15 mg/hr	Good 1st line w/ normal EF with drip needed	Hypotension Avoid in HFrEF
Esmolol	500 mcg/kg bolus drip = 50-200 mcg/kg/min	Rapid onset/offset RBC metabolism	Hypotension
Amiodarone	150 IV over 10-30m, then 1 mg/m for 6h, then 0.5mg/m for 18h	Minimal BP effects Long lasting; Relatively fast onset (acute effect is mostly beta blockade)	Pulmonary and thyroid toxicity Cardioversion
Digoxin	500mcg IV x1, then 250mcg IV q6h x2-3	Great for reduced EF, positive inotropy	Slow onset Depends on vagal tone – poor in hyper- adrenergic states
Procainamide	20-50 mg/min loading, 1-4 mg/min maintenance	Use in pre-excitation syndromes (i.e. WPW), does not inhibit AV nodal conduction	Lupus-like syndrome Hypotension

Tachyarrhythmias - Wide Complex¶

Madeline Rukavina

Definitions¶

Ventricular tachycardia (VT): a run of 3+ PVCs

Sustained VT: VT for 30 seconds or shorter if it requires intervention
Nonsustained VT (NSVT): VT for \< 30 seconds
VT storm: 3+ separate episodes of sustained VT within 24 hrs.

VT Morphologies

Monomorphic VT: similar QRS configuration from beat to beat
- Usually 2/2 scar-mediated VT from prior infarction
Polymorphic VT: a continuously changing QRS configuration from beat to beat
- Ischemia until proven otherwise
Torsades de Pointes (TdP): a form of polymorphic VT with a continually varying QRS that appears to spiral around the baseline of the ECG in a sinusoidal pattern
Ventricular fibrillation (VF): chaotic rhythm characterized by undulations that are irregular in timing and morphology, without discrete QRS complexes

Ventricular Tachycardia vs. SVT with aberrancy

VT: The action potential originated in the ventricles (ex: VT)
Supraventricular tachycardia with aberrancy: the action potential originates from a focus above the ventricles & conducts through the AV node with a delay or block resulting in a wide QRS (mimics VT)
Ex: sinus tachycardia w/ bundle branch block (block may be rate dependent), AF w/ LBBB

Many ways to differentiate VT vs. SVT w/ aberrancy

Consult cardiology for assistance
Look for ECG features suggestive of VT
Very broad complexes >160 ms
RsR’ complex with a taller left rabbit ear In V½
AV dissociation (P/QRS dissociation)
Capture Beats: native QRS complexes making a cameo during the VT
Fusion Beats: QRS which appears like a signal average of VT and native complex

capture beat fusion beat

There are more advanced criteria to help distinguish. The aVR (Vereckie) criteria is one example that is fast and accurate

Management¶

Unstable

Sedate with midazolam 1-2mg
Cardioversion for monomorphic VT. Synchronized shock at 100-200J
Defibrillation if VF/polyVT

Stable

Medications (as below)

Amiodarone

150mg IV over 10 min, then 1mg/min for 6 hours; repeat bolus if VT recurs

Class III

-K+ channel blocker; has class Ia, II, & IV effects

Bradycardia, hypotension (acutely)

Lidocaine

1-1.5 mg/kg (usually 75-100 mg) at a rate of 25-50mg/min; lower doses of .5-.75mg/kg can be repeated every 5-10 min as needed

Class IB

-fast Na+ channel blocker-> slows conduction

Slurred speech, AMS, seizures, bradycardia

Procainamide

20-50mg/min until arrhythmia terminates or max dose 17mg/kg is reached

Class IA

-fast Na+ channel blocker -> slows conduction

-K+ channel blocker-> prolongs repolarization

Bradycardia, hypotension, torsades, drug-induced lupus

Avoid in HF pts, prolonged QT

Cardioversion If refractory to medical management
Treatment of underlying cause if identifiable
- Ischemia, electrolyte disturbances, heart failure, drugs

Premature Ventricular Complexes (PVCs)¶

Madeline Rukavina

Background¶

Premature Ventricular Complex (PVC): early ventricular depolarization ± mechanical contraction
PVC burden: % of beats of ventricular origin / total beats over a 24h period
PVCs are common: Up to 80% of apparently healthy people have PVCs
Normal number of PVCs in an adult is \<500 in 24h

Etiologies¶

HTN with LVH, prior MI/scar, HF, myocarditis, ARVC, HCM, idiopathic VT, OSA, pHTN, COPD, thyroid disease, substance use (EtOH, nicotine, stimulants, caffeine)

Inpatient Evaluation & Management¶

12 lead EKG: conduction disease, long QT syndrome, Brugada syndrome, ARVC
Labs: K, Mg, TSH, drug screen
Evaluate for QT prolonging agents (risk of Torsades)
Evaluate tele for PVC burden
Inpt consult to EP for PVCs rarely warranted unless significant PVC burden (>5 PVC/min, consistently) in setting of reduced LVEF.
For pts with >5 PVC/min or pts with symptoms, discharge with Ziopatch (VA) or mobile cardiac telemetry (VU) and obtain TTE if none recent.

Atrial Fibrillation & Flutter¶

Brittany Saldivar

Background¶

AF: 12-lead EKG with absence of p-waves and irregularly irregular QRS complexes
Flutter: sawtooth atrial F waves (300 BPM) with regular or regularly irregular QRS complexes
Ventricular rate ratio of F waves: V waves ~150 (2:1), ~100 (3:1), or ~75 (4:1)
3 classifications
- Paroxysmal (terminates within 7 days)
- Persistent (persisting beyond 7 days)
- Permanent (normal rhythm cannot be restored)
Rapid ventricular response (RVR) is HR > 100 (ie AF/Flutter w/ tachycardia)
AF/RVR is far more often a consequence of hypotension than the cause of it

Evaluation¶

Causes: Mnemonic “H PIRATES”
- Hypertension
- Pneumonia, Pericarditis, Post-op
- Ischemia (rare)
- Rheumatic Valve
- Atrial Myxoma or Accessory Pathway
- Thyrotoxicosis
- Ethanol or Excess Volume
- Sick sinus, Sepsis

Management¶

Treatment goals
- Rate control, Goal HR \< 110 (RACE II)
- Rhythm control (if indicated)
- Stroke prevention

Rate control (inpatient)

RVR ~ sinus tach of AF; Always work to address the underlying cause (infection, volume overload, etc). Rate control is rarely an emergency unless the patient is unstable
If stable with RVR (SBP >90)
- IV if HR > 130 or symptomatic (metop 5 mg IV or dilt 15-20 mg IV), otherwise do PO
- AV nodal blocking agents
  - B-blockers: Start with metop tartrate (titratable) consolidate to succinate. Avoid in decompensated or borderline HF
  - Calcium channel blockers (diltiazem): avoid in HFrEF
Peri stable (SBPs 80s-90 with preserved perfusion)
- Amiodarone: Consider if decompensated HF, accessory pathway, anti-coagulated. Caution that you may cardiovert pt (stroke risk)
Unstable (SBPs \<80)
- Cardioversion

Rate control (outpatient)

typically achieved with beta blocker therapy, metoprolol is most frequently used

Rhythm control (inpatient)

New onset a-fib (first time diagnosis): most pts will be a candidate for trial of cardioversion
If onset clearly within 48 hours, can proceed without TEE. Often TEE is done anyway (pt may have had intermittent asymp AF)
If onset >48 hours or unclear, will need TEE to rule out LAA thrombus
Pharmacologic options include class 1C: flecainide, propafenone (avoid in structural heart disease) and class 3: Amiodarone, dronedarone, sotalol, ibutilide, dofetilide (some require loading inpt)
- Caution using antiarrhythmics in any pt you wouldn't electrically cardiovert without TEE

Rhythm control (outpatient)

Consider EP consult for ablation in symptomatic paroxysmal or persistent AF refractory to anti-arrhythmic drugs, AF in HFrEF, or flutter
Stroke Prevention (for AF and flutter)
- CHA2DS2-VASc risk score >2 in M or >3 in F should prompt long term AC in AF persisting >48 hours
- NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) are preferred to warfarin except in moderate to severe MS or mechanical valve
If cardioversion planned for new onset AF, start AC as soon as possible
- Post-cardioversion, anticoagulate for at least 4 weeks due to atrial stunning and stroke risk
If no contraindications or procedures, continue anticoagulation while inpatient
Typically do not need to bridge AC for AF in the setting of procedures unless mechanical valve is present. Decide on a case by-case basis
Left atrial appendage closure can be considered in those with increased risk of bleeding

Autonomics and Orthostatic Hypotension¶

Leonard Chiu

Background¶

Orthostatic Hypotension: SBP ↓ > 20 mmHg, DBP ↓ > 10 mmHg), or HR Increase > 30 within 3 min of standing up or head-up tilt to 60% on a tilt table
Etiologies: Neurogenic OH (nOH) vs non-neurogenic OH
nOH associated with autonomic failure
- Blunted tachycardia during hypotension characteristic of autonomic failure
- nOH: If HR rise is \<15
- nOH also associated with periods of high BP (supine hypertension)
- Ex: Neurodegenerative disease, neuropathy (diabetes, amyloid, paraneoplastic, etc)
Other causes: volume depletion (most common), medications (diuretics, alpha-1 blockers, BB, etc), pump failure (severe AS, arrhythmia)

Evaluation¶

Orthostatic vitals signs (checking supine, sitting, and standing with 5-minute wait in each position)
Volume status exam
Labs: CBC, CMP, EKG, TSH, B12, , LFTs,
Consider SPEP/UPEP, paraneoplastic panel, autonomic function testing depending on clinical context
Autonomic Function Testing: Available at 4:15pm Tues, Wed, Thurs NPO 4 hours prior
Hold oral pressors and antihypertensives 12 hours prior

Management¶

Conservative:
TED hose and abdominal binder for ambulation
Drink 16oz of fluid 15 min prior to standing
If they have supine HTN, keep HOB 30-45 degrees at all times
Add 2.3-4.6g of salt per day to diet (if no contraindications)
Avoid high temperatures (which cause peripheral vasodilation)
Supine HTN therapies: transdermal nitroglycerin (preferred); minoxidil, hydralazine, or clonidine in select patients

Orthostatic hypotension pharmacologic therapies

Drug	Dose	Mechanism	Side effects
Fludocortisone (Florinef)	0.1mg QD ↑ by 0.1 mg Max: 0.3 mg QD	Mineralocorticoid increase blood volume. Enhances sensitivity to circulating catecholamines	Edema HTN HypoK Do not use in CHF
Midodrine	2.5mg TID ↑ by 2.5mg Up to 10mg TID	Peripheral-selective α1 agonist → constricts both aa & vv	Supine HTN Pilomotor reactions Pruritus GI upset Avoid in uncontrolled HTN, urinary retention, heart disease
Droxidopa	100mg ↑ by 100mg Up to 600mg TID	NE precursor → carboxylated to NE. Can cross BBB.	Supine HTN, less than midodrine
Atomoxetine	10mg or 18mg	SNRI	Do not use w/ glaucoma or MAOI

Bedside Echocardiography¶

Jamie Pfaff

Finding an Ultrasound¶

MICU: radiology room behind charge nurse's desk in middle hallway
VA ICU: In front of resident workspace
8N: Behind nursing station before entering cleaning supply room
8S: In supply closet to left as you walk toward nursing station - (door code is 1-3-5)
6MCE: COVID restricted (ask nurses)
CCU/5N only: supply room on left as entering CCU
Round wing: 5^th floor, ask nurses

TTE Standard Views¶

Parasternal long¶

Probe position: Rotate probe 180 degrees with right edge of probe/probe marker pointing toward pt’s left shoulder
Make sure probe is centered over mitral valve (In right spot if you can see MV and AV)
E Point Septal Separation (EPSS)
- Distance separating the anterior MV leaflet from the septal wall as measure of LV systolic function (easy evaluation of systolic function)
- Place M mode spike at tip of mitral leaflet and hit M mode (perpendicular to septum)
- Identify E point (passive filling of LV) and determine distance from interventricular septum (IVS)
  - <7mm = Normal
  - >10mm = HF
- Confounders that elevate EPSS: AR, MS

Parasternal short¶

Probe position: Rotate probe 180 degrees with right edge of probe/probe marker pointing toward patient’s left shoulder
Good position to assess EF by visualizing wall thickening

Apical four chamber¶

Probe position: Slide down and look near patient’s left nipple (or in the intermammary fold after lifting up breast tissue if needed - at PMI if able to palpate)
Good to assess EF by visualizing cardiac shortening

Subxiphoid¶

Probe position: Push probe head into pt’s abdomen just below xiphoid and flatten probe to make nearly parallel to pt’s position, marker to pt’s left
Troubleshooting: shift probe slightly left of midline (toward pt’s right) and angle toward heart/right to use liver as acoustic window or ask pt to take big breath (moves heart closer to probe)
Best window to visualize pericardial effusion

IVC¶

Probe position: subxiphoid area with probe marker facing toward pt’s head tilted slightly left of midline, trace IVC into RA to verify correct vessel (vs aorta)
IVC size and collapsibility used as a surrogate for CVP and RAP
- <2.1 cm and >50% collapse: RAP ~3mmHg
- <2.1 cm and < 50% collapse or >2.1cm and >50% collapse: RAP ~8mmHg
- >2.1cm, <50% collapse: RAP ~ >15mmHg

Resources¶

https://www.coreultrasound.com/basic-cardiac-function/
http://pie.med.utoronto.ca/tte
https://www.echocardiographer.org/TTE.html
App: FATE CARD (Focus Assessed Transthoracic Echocardiography)

Cardiac Devices¶

Marcus Threadcraft

Types of Cardiac Implantable Electronic Devices (CIED)¶

For Controlling Arrhythmias: Implantable Pulse Generators
Pacemakers: Anti-bradycardia pacing
ICDs: Anti-tachycardia pacing and defibrillation
Biventricular Pacemakers: CRT for ventricular dyssynchrony (LBBB & Heart Failure)
Loop Recorders: implantable devices for monitoring arrhythmias (most often Afib)
LVADs: augment cardiac output for end-stage heart failure (not covered here)

Pacemakers¶

Provide anti-bradycardia pacing by stimulating myocardium
Peripheral permanent pacemakers (PPMs)
SubQ generator, transvenous leads
- Single chamber RV lead
- Dual chamber RV and RA leads
- BiV: RV, RA, and LV (coronary sinus) leads
Leadless pacemaker
- Implanted generator in RV

Indications

Symptomatic Bradycardia
Heart Block: 2^nd Degree Type II w/ sx or 3^rd Degree
Sick Sinus Syndrome
Carotid Sinus Syndrome
After catheter ablation of AV node for AF
CRT

Implantable Cardioverter/Defibrillators (ICDs)¶

Pacing lead + defibrillation coil
Detect and treat VT/VF v
- Anti-tachycardia pacing (ATP)- attempts to entrain and terminate VT
- Defibrillation If ATP unsuccessful

Indications

Primary prevention
- HFrEF
  - EF \<35% and NYHA II-III or EF \<30% and NYHA I
  - Must be >90d from revasc, >40d from MI, and on GDMT
- Arrhythmogenic syndromes
  - Arrhythmogenic RV cardiomyopathy, Brugada syndrome, HCM and cardiac sarcoid with specific risk factors
Secondary prevention
- Hx VF arrest or VT
- Inducible VT on EP study with history of syncope

Cardiac Resynchronization Therapy (CRT)¶

BiV pacer that coordinates LV/RV contraction through synchronized activation of each ventricle following atrial contraction.
-P: CRT pacing only
-D: ICD function

Indications

Class I: LBBB and QRS≥150 with EF\<35%, NYHA II- IV, on GDMT, NSR
Class IIa: EF\<35%, NYHA II- IV, on GDMT, NSR AND
- LBBB & QRS 120-149, non-LBBB & QRS≥150, or EF\<35% and expected to require >40% ventricular pacing

Interpreting Pacemaker Codes¶

	1^st Letter	2^nd Letter	3^rd Letter	4^th Letter
A: atrial, V: ventricular, D: dual, O: none, I: inhibition, R: rate-adaptive	Chamber Paced	Chamber Sensed	Response to Sensed Beat	Program Features

Examples of Common Pacing Modes¶

VVI: Single RV lead that delivers a beat if no beat sensed. Often used with chronic AF with bradycardia
DDDR: Senses and paces both the atria and ventricle. If beat not sensed within a predefined interval, beat delivered. R indicates rate responsivity (changes rate based on changes in patient activity)
Magnet: Paces at a fixed rate without respect to native electrical activity (AOO,VOO,DOO). Deactivates ICD shock. Often used in surgery or at end of life to avoid ICD shocks

Additional Configurations¶

Epicardial Leads- pacemaker/defibrillator leads attached to outside of the heart (requires OR) vs traditional transvenous lead placement, which are inserted in the Cath Lab
- Epicardial Leads generally placed in smaller children or during cardiac surgery with expected need for pacing/defibrillation
Abandoned leads
- Absolute contraindication to MRI (ungrounded, produces heat and thermal Injury In setting of magnetic field)

Placement Complications¶

Acute: pocket hematoma, pneumothorax, myocardial perforation, cardiac tamponade, infection, lead displacement or disconnection
Long-term: secondary device infection, lead fracture (lead lifetime 10-15 years), insulation failure

Chest Pain¶

Nicholas King

Chest Pain / Angina Framework¶

Determining likelihood that chest pain has a cardiac etiology depends on symptoms and lies on a spectrum
Cardiac > possible cardiac > noncardiac is more useful than typical vs atypical angina

Diagnoses Not to Miss: “The Serious Six”¶

Acute Coronary Syndrome
Mediastinitis (e.g, esophageal perforation)
Aortic Dissection/Aneurysm
Cardiac Tamponade
Pulmonary Embolus
Pneumothorax

Other Differential Diagnoses¶

Skin: Laceration, herpes zoster
Subcutaneous: cellulitis, abscess
Musculoskeletal: Costochondritis, fracture, myositis, sprain/strain
Pleural space (no pain receptors in the lung): PNA, tumor, pleuritis
Pericardium: Pericarditis
Heart: Myocarditis, spontaneous coronary artery dissection (SCAD), coronary vasospasm, aortic stenosis, stress-induced cardiomyopathy (Takotsubo), decompensated heart failure
Esophagus: GERD, esophagitis
Trachea: Tracheitis, tracheal tear

Physical Exam¶

Vitals: BP in both arms (do while interviewing - quick, easy, inexpensive)
Hemodynamic profile (warm/dry, warm/wet, cold/dry, cold/wet)
Palpate chest: evaluate costochondral junction, subcutaneous emphysema, examine skin
Cardiac: murmurs, rub for pericarditis, JVD for heart failure or PE with RV strain
Pulm: absent breath sounds for PTX, crackles for left heart failure, PNA
Abdomen: abdominal pain mistaken or referred as chest pain
Extremities: asymmetric leg swelling (>2 cm difference) for DVT/PE

Diagnostic Studies¶

EKG: ACS (STEMI, new LBBB, ST depressions, T wave Inversions, Wellens' sign), pericarditis, pericardial effusion
Labs: Troponin (ACS, PE, myocarditis), CBC, BNP, lactate
CXR: PTX, PNA, dissection, esophageal rupture
Bedside ultrasound: pericardial effusion, R heart strain for PE, wall motion abnormality for infarct/ischemia or stress-induced CM, valvular disease, lung sliding/PTX
CTA: gold standard for PE. Dissection can be diagnosed w/ CTA, MRA, or TEE

Evaluation for Coronary Disease
Test	Indications	Benefits	Risks	Considerations
EKG Stress	Low to Intermediate risk patients Do not stress active or suspected ACS Serves as screening with high NPV	Functional status w/ Bruce treadmill protocol	Exercise tolerance limits use	Cannot have LBBB, nondiagnostic if 85% target HR not achieved
Dobutamine Echo Stress		More sensitive than EKG	Contraindicated: arrhythmias, LVOT obstruction, HTN, AS	Can be useful to eval low grade low flow AS Hold BB
SPECT stress		More sensitive than echo, Assess viability	Adenosine or Regadenason contraindicated in reactive airway disease	No caffeine or theophylline prior
PET stress		Better PPV than Echo Assess viability	Better for pts with larger abdominal girth (less diaphragmatic attenuation)
Cardiac MRI		Assesses viability	Can assess nonischemic vs ischemic cardiomyopathy; HR must be < 70, gold standard for structure and function
Coronary CT		Very high NPV for stenosis	Contrast media reactions CIN lower risk than cath	Might have poor lumen visualization if heavy calcium burden HR < 70
Coronary Angiogram	STEMI High risk NSTEMI: Refractory angina, new arrhythmia, cardiogenic shock (HF) Suspected true ACS Diagnostic and Therapeutic	Direct visualization of lumen Therapeutic PCI	CIN with contrast Cath site complications Rare: SCAD, cholesterol emboli	Positive Screen (above) necessitates LHC Case request cath lab NPO MN prior Groin check if femoral access

Heart Failure¶

Brittany Saldivar

Background¶

ACC/AHA Stages of HF

Stage A: At risk but without structural heart disease or symptoms
Stage B: + structural HD, - symptoms
Stage C: + structural HD, + prior or current symptoms
Stage D: refractory HF requiring specialized intervention

NY Heart Association (NYHA) Functional Classes of HF

Class I: Normal physical activity is not limited
Class II: Comfortable at rest; normal physical activity results in HF symptoms
Class III: Comfortable at rest; less than normal activity leads to HF symptoms
Class IV: Inability to perform any physical activity without symptoms

Etiologies¶

HFrEF (Clinical diagnosis + LVEF \< 40%)
- Ischemic: Obstructive CAD, previous/current myocardial infarction
- Non-ischemic:
  - Load: HTN, valvulopathy
  - Arrhythmia: tachyarrhythmia, pacemaker induced
  - Myocardium
- Toxins (EtOH, drugs, chemo, radiation),
- Inflammatory (infections, AI),
- Metabolic (thyroid, thiamine deficiency),
- Infiltrative (amyloid, sarcoid, hemochromatosis)
- Stress induced/takotsubo CM
  - Genetic
  - Idiopathic
HFpEF: HTN, CAD, obesity, DM, infiltrative, hypertrophic cardiomyopathy

Causes of Heart Failure Exacerbations (FAILURES)

Forgetting medications or taking drugs that can worsen HF (e.g. BB, CCB, NSAIDs, TZDs), chemo (anthracyclines, trastuzumab)
Arrhythmia/Anemia: AF, VT, PVCs; Increased arrhythmia burden on device check?
Ischemia/Infarction/Infection: myocarditis; Acute vascular dysfunction (e.g. endocarditis), especially mitral or aortic regurgitation.
Lifestyle choices: Dietary indiscretions - high salt, EtOH, excessive fluid intake. Obesity.
Upregulation (of CO): pregnancy and hyperthyroidism
Renal failure: acute, progression of CKD, or insufficient dialysis (Increased preload)
Embolus (pulmonary) or COPD (leads to increase right-sided afterload)
Stenosis (worsening AS, RAS) leading to hypertensive crisis high left-sided afterload

Presentation¶

Volume overload: shortness of breath, dyspnea on exertion, Orthopnea, PND
Nausea/poor po intake (hepatic and gut congestion)
Confusion (decreased CO)
Exam: Edema (legs, sacrum), rales, S3, S4, murmur (AS, MR), elevated JVD, + hepatojugular reflex, ascites

Evaluation¶

CBC, CMP, Magnesium, Lactate, TSH, iron studies
Troponin, ECG
BNP (Pro-BNP if on Entresto) – high negative predictive value for HF (false negative can occur in obese patients)
CXR – differentiate other causes of dyspnea
TTE
Determine hemodynamic and volume profile
- Cold vs warm
- Dry vs wet

Low

Warm Extremities

Adequate UOP

Normal PPP

Warm and Dry

Forrester Class I

Tx: GDMT as tolerated

Warm and Wet

Forrester Class II

Tx: Diuresis, Vasodilators

Normal

Cardiogenic Shock

Cool Extremities

Renal Failure

Narrow PP

Cold and Dry

Forrester Class III

Tx: Inotropes

Cold and Wet

Forrester Class IV

Tx: Diuresis +Tailored therapy (+/- vasodilators, inotropes)

Management¶

Telemetry, Daily STANDING weights, 2 L fluid restriction, 2g sodium diet, strict I/Os
Diuresis: Place on 2.5 x home dose of IV diuretic, dose BID-TID (DOSE Trial)
Goal is to be net negative (generally 1-2 L per day but patient dependent)
Check BMP BID and Mg QD, keep K>4 and Mg>2
Low threshold for substantial increase (double) in loop vs transition to drip if not diuresing adequately
Can also augment with sequential nephron blockade (thiazides, acetazolamide)
Continuation/optimization of GDMT (below)

Guideline-Directed Medical Therapy for HFrEF¶

Brittany Saldivar

General Principles¶

Starting patients on low dose of multiple agents preferred to max dose of single agent
D/C summary should have discharge weight, diuretic regimen, and renal function
Daily weights at home with rescue diuretic plan (pm dose for 3 lbs in 1 day, 5 lbs in 3 days

Drug	Indication	Mechanism/ Benefits	Precautions
Beta Blockers
Carvedilol Metoprolol succinate Bisoprolol	HFrEF <40 % Stage C HF (NYHA class I – IV)	Reduces catecholamine stimulation. Decreased HR, myocardial energy demand, less adverse remodeling.	Avoid if pt is decompensated (cold); “start low and go slow” Can continue during exacerbation if patient compensated
ARNIs
Sacubitril/ valsartan	HFrEF < 40% NYHA class II – IV Used in place of ACE/ARB	Prevents vasoactive natriuretic peptide degradation involved in pathogenesis of HF (+ action of ARB)	Need a 36 hr wash-out period if transitioning from ACEi to ARNI Hypotension Risk of angioedema
ACEIs
Lisinopril Enalapril Captopril Ramipril	HFrEF <40 % Stage C HF (NYHA class I – IV)	Blocks harmful effects of RAAS activation and attenuates adverse cardiac and vascular remodeling	Risk of angioedema Monitor renal function and K
ARBs
Losartan Valsartan Candesartan	HFrEF <40 % Stage C HF (NYHA class I – IV)	See ACEIs	See ACEIs Preference for ARB > ACEi if plans to start ARNI
MRAs
Eplerenone Spironolactone	NYHA class II-IV and GFR >30	Diuretic and blood pressure lowering effects and blocks deleterious effects of aldosterone on the heart (including hypertrophy and fibrosis)	Hyperkalemia – avoid if CrCl <30 or K >5
SGLT2i
Dapagliflozin Empagliflozin	HFrEF <40% with and without DM NYHA class II-IV In conjunction with background GDMT	Osmotic diuresis and natriuresis, improve myocardial metabolism, inhibit sodium-hydrogen exchange in myocardium, reduce cardiac fibrosis	UTI/ GU infections Risk of ketoacidosis (both DKA and euglycemic)
Vasodilators
Hydralazine Isosorbide Dinitrate	Persistently symptomatic black patients despite ARNI/ BB/ MRA/ SGLT2i NYHA class III-IV	Reduces cardiac afterload and preload and may also enhance nitric oxide bioavailability Reduction in mortality for African American patients	Hypotension
Ivabradine
Ivabradine	HFrEF <35%, on maximally tolerated BB, sinus rhythm with HR > 70 NYHA class II or III	If current inhibitor involved in SA node activity Decr HR associated with improved outcomes	Need sinus rhythm Caution in sinus node disease and conduction defects
Iron Repletion (IV)
Iron sucrose Ferric carboxymaltose Iron dextran	Ferritin <100 µg/L or ferritin 100-299 µg/L AND transferrin saturation <20%	Decreases HF hospitalizations Improves exercise function and QOL	Risk of anaphylaxis higher in iron dextran

Device therapies (after optimization of medical GDMT)¶

Cardiac resynchronization therapy (CRT)
- Class I indication: NYHA class II to IV, LVEF ≤35% with QRS ≥150 ms and left bundle branch block (LBBB)
- Class II (consider) If EF \< 35% and:
  - QRSd > 150, without LBBB
  - AF that requires ventricular pacing and AVN ablation
  - Undergoing placement of device with anticipation of >40% ventricular pacing
ICD
- Class I indication: NYHA class II – VI with LVEF \<35% (must have >1yr expected survival and 40+ days from MI)
Mitra Clip
- Criteria: moderate to severe mitral regurgitation (3-4+), on maximally tolerated GDMT, an ejection fraction >20%, and a left ventricle end-systolic dimension of less than 7 cm

Approach to the ECG¶

Melis Sahinoz

Method = mastery, approach each EKG the same.

Rate¶

Regular rhythms = “Rule of 300” = 300 ÷ (large boxes between QRS complexes)
1 box = 300 bpm, 2 boxes = 150 bpm, 3 boxes = 100 bpm, 4 boxes = 75 bpm, 5 boxes = 60 bpm, 6 boxes = 50 bpm
Irregular rhythms or severe bradycardia = (total number of QRS complexes on ECG) x 6

Rhythm¶

Determine regular vs irregular: calipers or march out QRS complexes on paper
Criteria for Sinus rhythm: P before every QRS; Upright P in Lead I, II; Negative in aVr

Axis¶

Normal: - 30^o to + 90^o
Quick method: Leads I and II
Normal Axis: Upright in I and II
Left Axis Deviation: Upright in I, down in II
- Causes: LVH, LBBB, Left anterior fascicular block, prior inferior MI
Right Axis Deviation: Down in I, up in II
- Causes: RVH, RBBB, Left posterior fascicular block, prior lateral MI, PE

Intervals¶

PR Interval: normal 120 – 200 ms
- If < 120 ms, consider pre-excitation with accessory pathway (i.e. WPW)
- If > 200 ms, first degree AV block
QRS Complex: 60 – 100 ms (normal)
- If 100-120 ms: Incomplete BBB or non-specific intraventricular conduction delay (IVCD)
- If > 120ms: complete BBB, ventricular tachycardia, hyperkalemia
QT interval: Normal duration < 450ms in men and < 460ms in women
- QT is inversely proportional to HR (QT interval shortens at faster HRs)
- Quick estimate: normal QT is less than half the preceding RR interval
- QTc estimates the QT interval at a HR of 60 bpm (to allow for comparison across HRs)
- A couple formulas exist to calculate QTc:
  - QTcB= most commonly used due to simplicity, most accurate HR of 60
  - QTcF= more accurate when HR is outside the range of 60-100
- Clinically significant when generally QTc > 500 ms
- Causes of Prolonged QTc: hereditary, medication-induced (anti-emetics, ABX, psychiatric meds), hypokalemia, hypomagnesemia, hypocalcemia, ischemia

Morphology¶

P wave: P waves in limb leads should be ≤2.5 small box high and ≤2.5 small box wide
- Right Atrial Enlargement: Peaked P Wave in Lead II that measures >2.5 mm
- Left Atrial Enlargement
  - Lead II: Bifid P Wave (two humps) with total duration > 110 ms
  - Lead V1: Biphasic P wave, terminal deflection > 1mm wide and deep
- If ≥ 3 different P wave morphologies in same lead: wandering atrial pacemaker (HR < 100) or multifocal atrial tachycardia (HR > 100)
QRS complex
- Voltage
  - Low voltage: QRS amplitude < 5mm in limb leads or < 10mm in precordial
    - Causes: pericardial effusion, infiltrative cardiomyopathy, obesity
  - Right Ventricular Hypertrophy: Tall R Waves in V1 (> 7mm) and right axis deviation
  - Left Ventricular Hypertrophy: multiple criteria exist
    - Sokolow-Lyon criteria is a common example: S in V1 + R in V5 or V6 >35mm, R in aVL ≥ 1.1 mV
Conduction delays
- RBBB: Wide QRS and RSR’ in V1 or V2; deep broad S In lateral leads
- LBBB: Wide QRS, large S in V1, broad monophasic R wave in lateral leads (I, aVL, V6)
R wave progression
- R wave normally gets progressively larger from V1 to V6
- If the transition does not occur by V4, this is called "poor R wave progression". This is seen in chronic lung disease, LVH, left anterior fascicular block, and anterior MI.
Q-wave: Small Q waves are normal in most leads
- Never normal in V1-V3
- Pathologic Q waves: > 1 box wide and 2 boxes deep or > 25% height of R wave
ST Segment
- ST Elevation: STEMI, LBBB (ST elevation in leads with deep S waves), LVH, ventricular paced rhythm, pericarditis (associated with PR depression), coronary vasospasm, Brugada syndrome
- ST Depression: ischemia, reciprocal change in STEMI, posterior myocardial infarction (V1-V3), digoxin, hypokalemia
- See ACS section for STEMI criteria, Wellens Syndrome
T wave
- Normal T waves are upright in all leads except aVR and V1
- Inverted T Waves
  - Acute ischemia (if present in contiguous leads), LBBB (in lateral leads), RBBB (V1-V3), LVH (‘strain’ pattern similar to LBBB), RVH (RV ‘strain’ in V1-V3 or inferior leads), PE (right heart strain or part of S1,Q3,T3), intracranial pathology
- Peaked T Waves
  - Hyperkalemia vs ‘hyperacute’ T waves that precede ST elevation and Q waves in STEMI

Inpatient Hypertension¶

Lee Richardson

Background¶

Hypertensive urgency: SBP > 180mmHg/DBP > 120mmHg
Hypertensive emergency: SBP > 180mmHg/DBP > 120mmHg + end organ damage

Evaluation¶

Are there signs/symptoms of end organ damage?
Neurologic symptoms: agitation, delirium, stupor, seizures, visual disturbances
Focal neurologic deficits
Chest pain
Back pain (consider aortic dissection)
Dyspnea (consider pulmonary edema)
BMP, LFTs, Troponin, BNP: Lab findings suggestive of end-organ damage

Management¶

Goal is to lower BP back to normal over 24-48 hours
Initial lowering should be 10-20% in minutes if HTN emergency; goal should be 10-20% in 2-4 hours if HTN urgency
Typically aim for initial goal BP near 160/110
Exceptions to gradual lowering include:
- Acute stroke: call code stroke, lower ONLY if BP > 185/110 in pts under consideration for reperfusion therapy; or BP > 220/120 in pts not candidates for reperfusion therapy
- Aortic dissection: Goal = rapidly lower BP in minutes to target of 100-120 systolic to avoid aortic shearing forces
Pharmacologic therapy
- If pt was previously on anti-HTN meds, ensure their home medicines have been restarted at appropriate doses, formulation (long acting vs. short), and dosing intervals
- If pt has a rapid acting anti-HTN med, can consider giving a dose early or an “extra dose” and then up titrating their overall daily dose
Rescue therapies
- Captopril PO (12.5mg or 25mg dosed Q8H; conversion ratio of captopril:lisinopril = 5:1)
- Hydralazine PO (10-20mg initial dosing Q6H)
- Isosorbide dinitrate PO (5-20mg TID)
- Nifedipine XL PO (dose at 30mg initially, max 90 mg BID; NOT sublingual)
- Labetalol IV (10-40mg initially; dosed up to every 20-30mins)
- Hydralazine IV (10-20mg initially; dosed up to every 30 mins).
- Nitropaste 1” (can add/wipe away for titration; dose Q6H until oral meds can be started for better long-acting control)
Dialysis if missed session

Additional Information¶

Refractory HTN: try additional agents listed above vs. escalation of care for drip (nicardipine, nitroglycerin, nitroprusside, esmolol).
Most drips that can be done for this indication are done in stepdown and usually require no-titration of the infusion and occasionally the MD to be bedside to initiate the infusion.
This includes diltiazem, labetalol, nitroglycerin, and verapamil drips. Nicardipine, esmolol, and nitroprusside drips are not allowed on step down.

Pulmonary Embolism¶

Anna Berry

Background¶

A thrombus originating in a deep vein (LE > UE) embolizing to the pulmonary arterial circulation.

Risk Factors = Virchow’s Triad
- Stasis: immobilization, hospitalization, spinal cord injury, or long travel
- Hypercoagulable state: cancer, prothrombotic genetic conditions such as Factor V Leiden, OCPs, antiphospholipid syndrome, nephrotic syndrome, pregnancy, infection, etc.
- Endothelial Injury: surgery, trauma

Most originate from a DVT in the iliac, femoral, and popliteal veins

Presentation¶

Dyspnea and tachypnea
Respiratory alkalosis on blood gas from hyperventilation
Hypoxemia
Sinus Tachycardia or atrial arrhythmias
Hemoptysis
Lower extremity pain, swelling, and redness – occurs in 50% of pts with DVT
RV Failure (large PE) – elevated JVP, hypotension, syncope, R parasternal heave, accentuated P2, hepatomegaly

Evaluation¶

If hemodynamically unstable and PE suspected, provide hemodynamic support (ie. O2, pressors, etc.) and perform emergent bedside TTE
If no RV strain evident on TTE, low likelihood of hemodynamically significant PE. Consider other causes of shock.
Hemodynamically stable
- EKG
  - Most commonly sinus tachycardia
  - Less commonly and indicative of large PE: RAD, RVH, RBBB, RA enlargement, S1Q3T3 (deep S in lead I, deep Q and inverted T in lead III), TWI in V1-V3
- CXR: Typically normal. May see linear atelectasis, pleural effusion, PA cutoff sign
- Labs: ABG, troponin, BNP
- May consider lower extremity dopplers
- Imaging vs d-dimer based on pre-test probability:
  - Low pre-test probability (use Wells Criteria) d-dimer
  - For moderate to high pre-test probability CTA Chest PE protocol
    - If high pre-test probability or moderate pre-test probability with >4 hour delay in work-up, start empiric anticoagulation if bleeding risk is acceptable while work-up is ongoing
- TTE

Management¶

Definition

Hemodynamically stable

No evidence of right heart strain or myocardial necrosis on labs or TTE

Hemodynamically stable

Evidence of right heart strain or myocardial necrosis: RV strain on TTE (ex: D-sign), BNP >150, trop >0.05

Hemodynamically unstable (ex: SBP<90)

Evidence of RV strain

Management

Start anticoagulation

LWH or heparin gtt (if renal impairment)

Can also use NOAC. Rivaroxaban & apixaban can be used as initial management. Edoxaban & dabigatran can be used after 5-10 days of parenteral therapy

Provide hemodynamic support, monitor for decompensation

Start anticoagulation with unfractionated heparin gtt

STAT consult cardiology for consideration of catheter directed thrombolysis (EKOS) or embolectomy

Provide hemodynamic support.

Start anticoagulation with unfractionated heparin gtt

Page CCU fellow STAT. Consider systemic tPA (this is a fellow/attending level decision).

Discuss with cardiology catheter directed thrombolysis (EKOS) or embolectomy

tPA Considerations¶

Dose is 100mg tPA over 2hrs
Most effective within 24 hours but effective up to 14d
Contraindications:
- Absolute:
  - CNS Pathology: hemorrhagic or ischemic CVA within 3 mo, AVM, CNS neoplasm, recent surgery
  - Trauma: Recent head trauma w/ fx or injury
- Relative
  - Surgery: surgery w/in 3 wks
  - Heme: active bleeding, bleeding diathesis, plt \< 100, oral AC
  - Age: >75 yo, dementia

Long-term management¶

Anticoagulation: see “Venous Thromboembolism” in Hematology/Oncology

Right Heart Catheterization¶

Pakinam Mekki

Background¶

Pulmonary artery catheter (PAC): Multilumen catheter that sits in the right heart to provide invasive measurement of hemodynamic parameters
Indications for PAC placement
- Diagnose undifferentiated shock
- Severe cardiogenic shock
- Diagnose pulmonary hypertension
- Diagnose left -> right shunting
- Diagnose valvular and pericardial disease
- Titrating medications, specifically inotropes, pulmonary vasodilators, diuresis
Contraindications to PAC placement
- RA/RV mass or thrombi
- Tricuspid or pulmonic valve endocarditis
- Mechanical tricuspid or pulmonic valves
- Presence of RV assist device
Complications of PAC placement
- Arrythmias: VT, RBBB, 3^rd degree AV block if preexisting LBBB
- Infection (endocarditis of the pulmonary valve)
- Bleeding
- Pulmonary embolism and pulmonary Infarct
- Pneumothorax
- Air embolism
- Pulmonary artery perforation / rupture
- Endocardial/valvular damage

PAC Pressure Tracings¶

	Definition	Normal "Rule of 5s"	Interpretation
Central Venous Pressure (CVP)	Pressure in superior vena cava, often an indicator of volume status	0 - 5 mmHg	Elevated CVP is indicative of cardiac dysfunction and/or fluid retention Low CVP is indicative of volume depletion or decreased venous tone
Right Atrial Pressure (RAP)	Surrogate for preload, should be same as CVP	0 - 5 mmHg	Elevated with disruption in forward cardiac flow or increase in intravascular volume
Right Ventricle Pressure (	Right ventricular systolic and diastolic pressures; RVSP can be surrogate for PASP	25/5 mmHg	Elevated with diseases that elevate PA pressure and pulmonic valve disorders. Severe RVP elevations are generally chronic while acute conditions typically have RVSP <40-50.
Pulmonary Artery Pressure (PAP)	Measured as systolic, diastolic, and mean pressures. Diagnoses pHTN.	25/10 mmHg Mean: 10 - 19 mmHg	Elevated In acute conditions (PE, hypoxemia induced pulmonary vasoconstriction) or pHTN (mean PAP > 20 mm Hg)
Pulmonary Artery Wedge Pressure (PAWP or wedge)	Pressure measured by wedging the PAC into a small pulmonary arterial branch; surrogate for left atrial pressures and LVEDP	10 mm Hg	Increased with elevated LVEDP: systolic or diastolic heart failure, mitral and aortic valve disorders, hypervolemia, R to L shunts, tamponade, constrictive/restrictive cardiomyopathy
Thermodilution Cardiac Output & Index	Amount of blood pumped in one min. CI is the cardiac output divided by body surface area (to standardize for body size)	CO: 3.4-15 L/min CI: 2.8-4.2 L/min/m^2	Low CI: systolic/diastolic heart failure, severe valvular disorder (MR, AS), RV failure, pHTN, cardiogenic shock. Elevated CI (high-output state): sepsis, anemia, thyrotoxicosis, A-V shunt
Mixed central venous oxyhemoglobin saturation (SvO2)	% of oxygen bound to Hgb in blood returning to the right side of the heart, reflects total body O2 extraction	65-70%	High SvO2 (> 65%) = decreased O2 demand or “high flow” states seen in distributive shock (sepsis) Low SvO2 (< 50%) = decreased O2 delivery seen in cardiogenic or hypovolemic shock. In low SvO2 states, there is less O2 supply to same demand)

Calculating Hemodynamic Parameters from PAC Pressures¶

	Definition	Normal Values	Interpretation
Fick CO and CI	Calculated CO based on Oxygen consumption (VO2), Hbg, and O2 sats of arterial and venous blood	4-7 L/min 2.5-4 L/min/m²	See "Cardiac Index" above.
Systemic Vascular Resistance (SVR)	Measurement of afterload; helpful in delineating the etiology of shock as well as guiding afterload-reduction therapy in HFrEF	700-1200 dynesscm^-5	Elevated SVR is seen in hypovolemic, cardiogenic, and obstructive shock Decreased SVR is seen in distributive shock (sepsis, anaphylaxis, neurogenic)
Transpulmonary gradient (TPG)	Differentiates between pre- and post-capillary pulmonary hypertension.	< 12 mmHg	A TPG value greater than 12 mmHg indicates that a component of the pHTN is secondary to pulmonary vascular disease
Pulmonary Vascular Resistance (PVR)	Gold standard in the estimation of the severity of pre-capillary pHTN Reflects the pressure drop across the pulmonary system only and is independent of the LA, mitral valve and the LV	< 3 Wood Units 30-90 dynesseccm⁵	Elevated PVR (>3 Wood units) suggests pre-capillary pHTN Normal PVR seen in pulmonary venous hypertension (diastolic dysfunction)
Pulmonary artery pulsatility index (PAPi)	Pulmonary pulse pressure relative to preload (RAP), Indicator of RV function	> 0.9	PAPi < 0.9 predicts in-hospital mortality and/or need for RVAD in acute MI. Can be decreased in pure RV failure or biventricular failure
Cardiac Power	Cardiac output relative to afterload, a measure of LV contractile reserve	Normal > 1	CP< 0.6 strongly suggestive of LV failure Found to be a strong independent hemodynamic correlate in pts with cardiogenic shock. Predictor of mortality in CCU

Cardiogenic Shock¶

Ashley Cozart

Definition¶

Impairment of cardiac output due to primary cardiac disorder that results in end-organ hypoperfusion and hypoxia

Etiology¶

Cardiomyopathic: myocardial infarction with LV dysfunction, exacerbation of heart failure, myocarditis, myocardial contusion, drug-induced
Arrhythmic: atrial tachycardias (atrial fibrillation/flutter, AVRT, AVNRT), ventricular tachycardia and fibrillation, complete heart block, second degree heart block
Mechanical: valvular insufficiency, valvular rupture, critical valvular stenosis, ventricular septal wall defect, ruptures ventricular wall aneurysm, atrial myxoma

Presentation¶

Cold (decreased perfusion) due to reduced cardiac output (can be wet- increased PCWP OR dry normal PCWP)
Symptoms of volume overload + end-organ hypoperfusion (altered mental status, nausea, abdominal pain, decreased urine output)
Hypotension; narrow pulse pressure

Evaluation¶

EKG
Labs: CBC, CMP, BNP, troponin, lactate
Evidence of end organ damage: lactic acidosis, acute kidney injury, acute liver injury
Echocardiogram: assess EF and valves
LHC If ischemia (see ACS)
Hemodynamic monitoring via Swan-Ganz or PA catheter:
- No benefit for general shock but does improve in-hospital mortality for those with cardiogenic shock
- PA catheter hemodynamic profile:
  - Cardiac index \< 2.2, cardiac power \<0.6, SVR 800-1600, SVO2 \<60%
  - LV-dominant: RA (CVP) \<15, PCWP >18, PAPi >1.5 (pulmonary artery pulsatility index)
  - RV-dominant: RA >15, PCWP \<18, PAPi >1.5
  - Bi-V-dominant: RA >15, PCWP >18, PAPi >1.5
  - PAPi \< 1 indicates that patient will likely need RV support
  - CP \< 0.5 strongest independent hemodynamic correlate of mortality in CS
  - See right heart cath section for interpreting PA catheter profiles

Management (medical & mechanical circulatory support)¶

Medical management¶

Focus on optimizing preload, afterload, and contractility.

Preload: IV diuresis
Afterload: IV – nitroglycerine, nitroprusside; PO – hydralazine, isosorbide dinitrate; vasoconstricting pressors (phenylephrine, vasopressin) if needing BP support
Contractility - Inodilators (increase contractility, decrease afterload – milrinone, dobutamine) or inoconstrictors (increase contractility and afterload – epinephrine, norepinephrine)

Mechanical circulatory support indications¶

Shock refractory to >1 pressor
Shock 2/2 MI (physiology: unloads LV, increases systemic perfusion, increases myocardial perfusion, and provides hemodynamic support during PCI)

Types of mechanical circulatory support (MCS)

	Intra-aortic Balloon Pump	V-A ECMO	Tandem Heart	Impella
Dynamics	Inflates during diastole, deflates during systole	Blood from femoral vein is oxygenated and pumped to femoral artery	LV: blood aspirated from LA to femoral artery RV: blood aspirate from RA to PA	Impella 2.5, 5.0 & CP: Blood aspirated from LV to aortic root Impella RP: Blood aspirated from IVC and delivered to PA
Flow	1 LMP	4.5 LPM	4-5 LPM	2.5: 2.5 L/min CP: 3.33 L/min 5.0: 5 L/min RP: 4 L/min
Support	LV	BiV	LV, RV, or BiV	LV or RV (RP)
Effects	Reduces afterload Increases stroke volume (SV) Increases coronary perfusion Reduces LV preload and PCWP	Increases afterload Reduces SV Reduces LV preload and PCWP Improves tissue perfusion	Increases afterload Reduces SV Reduces LV preload and PCWP Improves tissue perfusion	Reduces SV Reduces preload and PCWP Improves tissue perfusion
Complications	Thrombocytopenia Thrombosis Arterial obstruction Aortic rupture or dissection Air embolism	Circuit thrombosis LV dilation Hypothermia Gas embolism	Tamponade d/t perforation Thrombosis Embolism (gas or thrombus) Arterial Shunt	Pump migration Hemolysis Aortic regurg LV perf VT/VF

Daily management of MCS devices:

Ensure optimal placement of device with daily CXR
Anticoagulation (based on device)
Hematoma monitoring at device site
Check distal pulses to monitor for limb ischemia

Pearls for MCS

MCS devices are contraindicated in following situations: aortic regurgitation or metallic aortic valve, aortic aneurysm or dissection, severe aortic or peripheral artery disease, left ventricular or left atrial thrombi, bleeding diathesis, uncontrolled sepsis
ECMO is placed by the cardiac surgery team, once a patient is cannulated they will move onto the cardiac surgery team
Impella, tandem heart, and IABPs are placed in the cath lab
MCS is a bridge to recovery/definitive therapy, durable cardiac support (VAD), or transplant

Syncope¶

Sarah Myers

Background¶

Definition: abrupt, transient loss of consciousness with rapid & spontaneous recovery
Presyncope – symptoms occurring before syncope including lightheadedness, tunnel vision/other visual disturbances

Classification¶

Cardiac syncope
Tachyarrhythmias: VT, SVT
Bradyarrhythmias: sinus node dysfunction, AV blocks (high grade)
Structural: Aortic Stenosis, HCM, cardiac tamponade, congenital anomalies, masses/tumors
Vascular: Pulmonary embolism, aortic dissection, severe pHTN
Noncardiac syncope
Reflex mediated
- Vasovagal; most common form of reflex mediated syncope
  - Can occur sitting/standing or with trigger (stress, pain, medical settings)
  - Classically has prodrome of nausea, diaphoresis, tunnel vision followed by hypotension and/or bradycardia
- Situational (micturition/defecation/coughing)
- Carotid sinus sensitivity syndrome
Orthostatic
Medications (diuretics, nitrates/CCB/alpha blockers, TCAs)
Volume depletion (hemorrhage, dehydration)
Autonomic dysfunction

Differential diagnosis¶

Seizure, stroke, metabolic derangements, Intoxication/withdrawal, hypoglycemia, head trauma
With rare exceptions, these do not result In complete LOC with spontaneous recovery

Evaluation¶

History and physical are essential for evaluation of a syncopal event
Characteristics associated with cardiac syncope
Male, >60, known structural/ischemic heart disease, brief/no prodrome, syncope while supine/at rest or during exercise, family hx of SCD/premature death, abnormal exam
Characteristics associated with noncardiac syncope
Younger age, syncope while standing or with positional changes, prodrome (nausea, vomiting, warmth), specific triggers, previous episodes that have been similar

Workup¶

EKG on all patients with syncope, monitor those who are admitted on telemetry
CBC, CMP, troponin, BNP (If cardiac cause suspected), POC glucose, UDS, orthostatic VS
EEG and neuroimaging if concern for seizure activity or focal neuro deficit
TTE and consider stress testing particularly in exertional syncope

Management¶

Cardiac: managed as indicated based on pathology
If arrhythmia is suspected but not captured on admission, consider discharge with event monitor
Noncardiac
Reflex
- Vasovagal- consider tilt table testing If recurrent or diagnosis not clear
- Situational- mainly avoiding triggers
- Carotid sinus syndrome- may require PPM
Orthostatic
- Medication related
  - Appropriate to hold potentially offending medications (diuretics, vasodilators) during evaluation
  - Monitor for worsening supine hypertension, arrhythmias, or heart failure when holding
- Volume depletion; resuscitate as appropriate
- Autonomic dysfunction: see autonomics section
Driving: TN law does not require any MD to inform the state of TLOC
Should still recommend patients not drive while work-up ongoing. Document all conversations about driving with patients

Valvular Heart Disease¶

Jonathan Napper, Marcus Threadcraft

Aortic stenosis¶

Jonathan Napper

Etiology¶

Degenerative calcification of the aortic cusps
Congenital bicuspid aortic valve
Chronic deterioration (calcific)
Prior rheumatic fever/inflammation

Presentation¶

Angina, syncope, exertional dyspnea, heart failure (HF carries worse prognosis)
Typically aged 70 – 80 y/o; if bicuspid aortic valve expect 10-20 yrs earlier
Physical exam: Systolic crescendo-decrescendo murmur that radiates towards the carotids
Late peaking murmur, faint or absent S2, or delayed carotid upstroke suggest severe AS

Evaluation¶

TTE with doppler is test of choice

Severity	Valve Area (cm²)	Mean Gradient (mmHg)	Velocity (m/s)	Indexed Valve Area (cm²/m²)
Mild	>1.5	<20	2.0-2.9	>0.85
Moderate	1.0-1.5	20-39	3.0-3.9	0.60-0.85
Severe	<1.0	>40	>4.0	<0.6
Critical	<0.5	--	--	--

AS stages

A: at risk of AS (those with bicuspid anatomy or calcification
B: Asymptomatic non-severe AS
C: asymptomatic AS
- C1: normal EF
- C2: abnormal EF
  - This stage might benefit from exercise or stress testing to elicit symptoms
D: Symptomatic AS
Some with symptomatic AS might not have enough LV reserve to produce high velocities and gradients (ex EF of 10% w/ critical valve area) = low flow/low gradient AS; consider dobutamine to unmask AS

Management¶

No proven effective medical therapy
Definitive treatment is valve replacement for:
- Stage D
- Stage C with inducible symptoms on stress testing, low EF, or undergoing other cardiac procedure
- Rapid progression (increase in velocity >0.3m/sec per year)
Consult cardiac surgery for determination of SAVR vs TAVR
- In general, high risk surgical patients benefit most from TAVR
- At VUMC: If determined to be intermediate to high operative risk by Cardiac Surgery, they will often recommend contacting the TAVR team for evaluation
Avoid rapid hemodynamic shifts and aggressive changes in preload or afterload
Aim for normotension
- Avoid preferential vasodilators such as hydralazine or nitroglycerin
- Significant vasodilation may ↓ coronary filling pressures -> myocardial ischemia

Monitoring¶

Severe AS: TTE q 6-12 months
Moderate AS: TTE q 1-2 years
Mild AS: TTE q 3-5 years

Post AVR anticoagulation¶

All patients will get 3-6 months of AC s/p AVR
Continued duration based on type of AVR
- Bioprosthetic (TAVR and some SAVRs): antiplatelets alone after Initial AC
- Mechanical: lifelong AC with warfarin only

Aortic Regurgitation¶

Jonathan Napper

Etiology¶

Primary valve disease (rheumatic disease, bicuspid aortic valve, infective endocarditis, syphilis)
Primary aortic root disease (medial degeneration, aortic dissection, Marfan’s syndrome, bicuspid aortic valve, syphilis, non-syndromic familial)

Presentation¶

Acute AR: LV cannot respond to increased volume to maintain stroke volume pulmonary edema and cardiogenic shock
Chronic AR: indolent presentation, often patient will develop symptoms of heart failure including DoE, orthopnea, PND
Physical exam: “Water-hammer” pulses, wide pulse pressure, laterally displaced PMI, high pitched “blowing” decrescendo murmur best heard at third intercostal space at left sternal border, S3

Management¶

Acute severe AR
- Prompt surgical repair
- Vasodilators such as nitroprusside and diuretics can be used to stabilize patient
Chronic severe AR
- Medical management
- Early symptoms of exercise intolerance can be treated with diuretics
- Systolic BP should also be controlled with goal SBP \< 140 in chronic AR
Repeat imaging should be performed 3-6 month to assess for depressed LVEF or LV dilation
Stages of Chronic AR: Ranging from Stage (A): Asymptomatic but “At Risk” AR to Stage (D) Symptomatic Severe AR
- If symptoms are present, automatically Stage D, otherwise Progression through stages is determined by AR Jet Width
Class I indications for Valve Repair:
- Stage D (Symptomatic) or Stage C (Asymptomatic Severe AR) with LVEF \< 55%, or are undergoing other cardiac surgery
- If LVEF > or equal 55%, patients should be considered for surgery if LV is dilated (LVESD > 50 mm (class IIa) or LVEDD > 65 mm (class IIb))
- Any patient with progressive AR, even if they do not meet criteria for severe AR, should consider valve replacement if undergoing cardiac surgery for other reasons
- Note: TAVI for isolated chronic AR is challenging 2/2 dilation of the aortic annulus and root

Mitral Regurgitation¶

Marcus Threadcraft

Etiology¶

Primary MR – caused by direct involvement of the valve apparatus (leaflets or chordae tendineae)
Degenerative/myxomatous mitral valve disease (mitral valve prolapse with flail leaflet, mitral annular calcification, chordal rupture)
Rheumatic fever
Infective endocarditis
Papillary muscle rupture following acute (inferior) MI
Secondary MR- caused by changes of the LV that lead to valvular incompetence
Dilated Cardiomyopathy
HOCM with systolic anterior motion
Coronary Artery Disease or prior MI leading to papillary muscle tethering

Presentation¶

Acute MR- sudden onset reduction in forward cardiac flow and left atrial/pulmonary vein volume overload
Dyspnea with flash pulmonary edema
Left-sided heart failure
Chronic MR- progressive symptoms d/t cardiac remodeling to compensate for mitral flow reversal
Progressively worsening heart failure: dyspnea, orthopnea, PND
LV dilation from volume overload
LA remodeling/dilation leading to afib

Auscultation¶

Holosystolic Murmur
Best heard at Apex
Radiation to the Axilla
Frequently associated with S3
Murmur may be absent in acute MR due to large regurgitant orifice/low velocity regurgitant jet
Increases w/ increased preload or afterload
Pulmonary Rales

Evaluation¶

CXR: assess for pulmonary edema, r/o other causes of acute dyspnea
ECG: often non-specific, LVH
Echocardiography: assess valve apparatus, size, and function of LA/LV, grade severity of MR

Chronic MR stages¶

A: No symptoms
B: >mild MR w/o hemodynamic changes or symptoms
C: Severe MR w/o symptoms
- C1: preserved EF and normal LV size
- C2: reduced EF (\<60%), dilated LV (LVESD > 40mm)
D: Severe/symptomatic

Management¶

Acute hemodynamically significant MR

Urgent surgical repair or replacement
Medical stabilization as a bridge to surgery
- Afterload reduction is key to promote forward flow
- Vasodilators (nitroprusside, nitroglycerin) reduce afterload
- Diuresis to reduce preload and improve pulmonary edema
- IABP placement can be used as mechanical afterload reduction

Chronic severe primary MR

Surgical repair favored over valve replacement
Class I:
- Asymptomatic patients w/ LVEF 30-59% or LVESD > or equal 40mm
- Symptomatic patients w/ EF > 30%
Class II:
- A: asymptomatic patients with progressive EF decline or LV dilation on serial monitoring; or very severe MR
- B: new onset AF
Secondary MR can consider MV repair with persistent class III-IV symptoms while on guideline directed medical therapy
In HFrEF, consider MitraClip after volume optimization (see Heart Failure section)

Mitral Stenosis¶

Marcus Threadcraft

Etiology¶

Characterized by thickened mitral valve leaflets and fused leaflet tips.

Rheumatic Fever (leading cause worldwide)
Calcification of the mitral valve annulus (common in high income countries)
Autoimmune Diseases: SLE, Rheumatoid arthritis

Presentation¶

Progressive symptoms: Asymptomatic Heart Failure
Orthopnea
PND
Hoarseness/Dysphagia (compression of recurrent laryngeal nerve/esophagus by enlarged left atrium from pressure overload)
Symptoms of Right Heart Failure
Acute Symptoms may present in settings of increased cardiac output (pregnancy, sepsis, or exercise) or tachyarrhythmias
Dyspnea
Fatigue
Palpitations

Physical exam¶

Low-pitched rumbling, diastolic Murmur, best heard at apex, low-pitched, rum
- Loud S1, opening snap after S2
- Prominent P2 if pulmonary HTN develops
Pulmonary Rales

Evaluation¶

CXR: LA enlargement, increased pulmonary vasculature
Echocardiography: thickening of mitral valve leaflets, decreased area of valve leaflets, left atrial enlargement

Management¶

Varies between rheumatic MS and calcific MS (in general, intervention of calcific MS is very challenging and high risk)
Severe, symptomatic rheumatic MS:
- Percutaneous mitral balloon commissurotomy (PMBC)
- Surgical repair/replacement if patient failed PMBC or undergoing other cardiac surgery
Calcific MS has a poor prognosis with 5-year survival \<50%, Intervention is higher risk and should be reserved for severely symptomatic patients
No role for commissurotomy with calcific MS
Surgical valve replacement may be considered for severely symptomatic patients (technically challenging)

Anti-Coagulation¶

Anti-coagulation is indicated if:
- Mechanical prosthetic mitral valve
  - Warfarin, goal INR 3-4 lifelong
- Bioprosthetic mitral valve replacement
  - Warfarin, goal INR 2-3 for first 3-6 months
- Atrial Fibrillation regardless of CHADS2VASC score

Ended: Cardiology

Critical care ↵

ABCDEF (A2F) Bundle¶

Kaele Leonard

Background¶

Post-Intensive Care Syndrome (PICS): complex constellation of cognitive, physical, and psychological impairments that impact most survivors of critical illness, leading to disability, frailty, and poor quality of life
Predicted by (1) duration of immobility and (2) delirium
Both are reduced by >80% compliance with ABCDEF (A2F) Bundle concepts
ABCDEF (A2F) Bundle: Interprofessional, evidence-based safety bundle of care principles to help reduce LOS, mortality, bounce-backs, and the duration of ICU delirium and coma
Goal: allow pt to “prove us wrong” about readiness for liberation from devices, sedatives, etc.

**A**ssess, prevent, and manage pain

Tools to assess pain using facial expressions, body movements, muscle tension, compliance with ventilator, or vocalization for extubated pts
Ex: Critical Care Pain Observation Tool (CPOT): scale 0-8, uncontrolled pain 3
Uncontrolled pain increases risk for delirium, limits inspiratory effort & weaning from ventilator, and limits ability to mobilize
Treatment: multi-modal: parenteral opioids, neuropathic meds (e.g., gabapentin, ketamine), adjunctive non-opioids analgesics (e.g., acetaminophen, NSAIDs), nonpharmacologic interventions (repositioning, heat/cold)

**B**oth spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs)

SATs = daily sedative interruptions
RN-driven protocol involving safety checklist: no active seizures, alcohol withdrawal, agitation, paralytics, myocardial infarction, or increased ICP
If pass SAT, then proceed to SBT
If fail SAT (anxiety, agitation, pain, resp distress) restart sedation at ½ doses
SBTs = PS ventilation (Fi02 ≤ 50%, PEEP ≤ 7.5; typically 40% and 5/5) for ≥ 30 minutes
RT or physician/APP-driven protocol with safety screen: passed SAT, O2 sat ≥ 88%, inspiratory efforts, no myocardial ischemia, no/low vasopressor support
If pass SBT, physician/APP judgment on extubation
If fail SBT (RR > 35 or \< 8, O2 sat \< 88%, resp distress, mental status change) restart full ventilatory support
Evidence:
- Liberated pts from mechanical ventilation 3 days sooner, decreased ICU and hospital length of stay by 4 days, and 14% absolute reduction in mortality at 1 year

**C**hoice of analgesia and sedation

Richmond Agitation-Sedation Scale (RASS): sedation & level of arousal assessment tool (Figure 1)
Target light sedation of RASS -1 to 0 with goal of (1) pt following commands without agitation and (2) limiting immobilization
Over-sedation: hold sedatives till target, then restart at ½ prior dose
Analgosedation with focus on treating pain first and then adding sedation meds PRN
Sedatives: dexmedetomidine (dex) or propofol >>> benzodiazepines
Benzodiazepines increase risk of delirium in a dose-dependent fashion

Figure 1: Richmond Agitation-Sedation Scale (RASS) Delirium - assess, prevent, and manage

**D**elirium- assess, prevent, and manage

Screening for delirium: q4hr using CAM-ICU (Figure 2)
Affects 60-80% of ventilated pts and associated with increased morbidity and mortality, longer ICU and hospital length of stay, long-term cognitive dysfunction
Risk factors and treatment: see Delirium section in Psychiatry

**E**arly mobility and exercise

Prolonged immobilization during critical illness leads to ICU-acquired weakness, associated with worse outcomes: ↑ mechanical ventilation, increased hosp length of stay, greater mortality, and greater disability
Consult PT/OT to initiate rehab at the beginning of critical illness
Can be done safely in pts receiving advanced support

**F**amily engagement and empowerment

Especially important when pts are unable to communicate themselves
Incorporate family at the bedside and on rounds to learn pt preferences and values, engage in shared-decision making, and address questions and concerns

Acute Respiratory Distress Syndrome (ARDS)¶

Judd Heideman

Background¶

A syndrome of diffuse inflammation and injury of the alveoli and capillary endothelium leading to fluid and protein accumulation in the interstitium and alveoli, pulmonary edema, and hypoxemic respiratory failure; 30-50% mortality rate
Triggers:
Pulmonary
- Pneumonia (viral and bacterial) • Lung contusion
- Direct inhalation injury • Aspiration
- Primary graft dysfunction of pulmonary transplant
Extra-pulmonary
- Sepsis (most common cause) • HSCT
- Trauma • Burns
- Massive blood transfusions/TRALI • Pancreatitis
- Drugs (amiodarone, chemotherapy, cocaine, opioids)

Evaluation¶

Diagnosis: Berlin Criteria
New or worsening respiratory symptoms beginning within one week of diagnosis
New bilateral opacities present on chest radiograph or CT chest
- Not explained by effusions, collapse of lobe/lung, or nodules
Absence of left heart failure or volume overload
Severity: based on PaO2/FiO2 ratio with a PEEP ≥ 5 cm H2O
PaO2 = arterial partial pressure of O2 (requires ABG)
FiO2 = fraction of inspired oxygen (expressed as a decimal between 0.21 and 1.0)

	PaO2/FiO2 ratio	PEEP
Mild	201-300	≥5
Moderate	101-200	≥5
Severe	\<100	≥5

Management¶

Frequently requires intubation; non-invasive ventilation not a great treatment
Low tidal volume (Vt) ventilation mortality benefit
Goal Vt = 4-8 mL/kg of predicted body weight (obese patients don’t have bigger lungs)
Plateau pressure goal: ≤30 cm H2O
Oxygenation goal: PaO2 55-80 or SpO2 88-95%
pH goal: ≥7.20, “permissive hypercapnia”
Treat the underlying cause (see “Triggers” above)

Brain Death¶

Anna Berry

Background¶

Brain death= complete and permanent loss of brain function. Defined by coma with loss of capacity for consciousness, brainstem reflexes, and the ability to breathe independently

Checklist for Determination of Brain Death (American Academy of Neurology)

Prerequisites (all must be checked)
- Coma, irreversible and cause known
- Neuroimaging explains coma – usually CT or MRI
- Absence of CNS depressing drugs
- No evidence of residual paralytics (electrical stimulation if paralytics used)
- Absence of severe acid-base, electrolyte, endocrine abnormality
- Normothermia or mild hypothermia (core temp >36°C)
- SBP ≥100 mm Hg
- No spontaneous respirations
Examination (all must be checked) – Attending MUST be present for brain death exam

Apnea testing (all must be checked) – Attending MUST be present
- Pt is hemodynamically stable
- Ventilator adjusted to provide normocarbia (PaCO2 35–45 mm Hg)
- Preoxygenate with 100% FiO2 and PEEP of 5 cm water for >10 minutes to PaO2 >200 mmHg
- Provide oxygen via a suction catheter to the level of the carina at 6 L/min or attach T-piece with continuous positive airway pressure (CPAP) at 10 cm H2O
- Disconnect ventilator
- Spontaneous respirations absent
- Arterial blood gas drawn at 8–10 minutes, patient reconnected to ventilator
- PCO2 ≥60 mm Hg, or 20 mm Hg rise from normal baseline value; OR:
- Apnea test aborted due to spontaneous respirations present, hemodynamic instability, or hypoxia
Ancillary testing (Order one test if clinical examination cannot be fully performed due to patient factors or if apnea testing inconclusive/aborted)
- Cerebral angiogram
- HMPAO SPECT (Single photon emission computed tomography)
- EEG & TCD (transcranial Doppler)

Organ donation caveats¶

Discussions about organ donation should take place between Tennessee Donor Services (TDS) and the surrogate. You SHOULD NOT be having conversations with the surrogate about donation. Direct questions to TDS.

Running Codes¶

Jacqueline Visina

Arrival to a Code¶

Questions to answer when you arrive: Is someone running the code? Who is doing compressions? Do we have pads on the patient? What is our IV access?
Take charge: establish if anyone is actively running the code, if someone is running the code, introduce yourself and ask how you may be helpful. If someone is NOT, have someone begin chest compressions IMMEDIATELY and assume responsibility for the running the code
IV access: IV access preferred, if no immediate IV access, place IO
Obtain a brief medical history and events surrounding the code and the patient’s code status
Have someone find the nearest crash cart and get pads on the patient as soon as possible

Running the Code¶

Assess the rhythm
If Vfib/VT- immediately shock
For polymorphic VT, this is ischemia until proven otherwise unless the patient is on a large amount of QTc prolonging medications.
If PEA/Asystole- resume compressions, give Epi 1mg ASAP
Strong ACLS
Q2min- pulse check, rhythm check, shock?
Remember the two interventions with proven mortality benefit are high quality chest compressions and early defibrillation. Do not interrupt these actions for other things
Monitor the quality of chest compressions
Warn resuscitators when shock is being delivered
Consider Advanced Airway
Remember chest compressions save lives. Not intubation. Do not stop compressions for intubation
Stay Calm
Closed Loop communication- continue giving instructions, use names, minimize interruptions
Do not move from foot of bed if you are running the code
Ensure delivery of adequate compressions. Avoid excessive ventilation
If you are running the code, it is helpful to maintain a constant verbal running summary of interventions that have been tried and the course of the code
Have a member of the team locate an ultrasound for line placement and diagnostics
Allow family to be present
H’s and T’s: Treat Reversible Factors
Some of the fellows here will empirically give 2 grams of magnesium, 1 amp of D50, 1 amp of bicarb, and 1g calcium chloride at the onset of the code irrespective of presenting rhythm
Can send Labs – ask for a “loaded gas”. This will usually be a VBG/ABG with lactate, K, Ca, and Hgb. Often information does not result quick enough to change immediate management. Have someone look up most recent labs in Epic (looking for recent hyperK, acidosis)

Terminating a Code¶

Consider initial rhythm, patient comorbidities, cardiac vs non-cardiac arrest, bedside echo findings. ROSC or rhythm changes during code?
Persistent ETCO2\< 10mmHg after 20min CPR has minimal survival
Ask your team if they have any other therapies that they feel would be indicated
Ask if anyone remains in favor of continuing CPR
When unanimous, terminate the code and announce time of death. Thank your team. Take a moment of silence for the deceased patient

Post-Arrest Care¶

Immediately following ROSC is the most dangerous point of ACLS
Airway: Secure airway if not done during code, ensure RT avoids hypoxia or hyperoxia
BP: MAPs>65, IVF and/or pressors if needed
If on floor, prioritize moving patient to a unit for ongoing care once hemodynamically stable enough for transfer. Would not delay for other diagnostics/interventions (lines, CXR, etc)
Cardiac: obtain EKG. Assess if urgent cardiac intervention is required for STEMI vs unstable cardiogenic shock vs VT storm or Vfib
Neuro: if not following commands, consider TTM. TTM is still performed at VUMC with a strict protocol and inclusion criteria. If there is any question about TTM eligibility, page the CCU fellow
Send rainbow labs (CBC, CMP, Mg, coags, trop, lactate, VBG/ABG). Treat rapidly reversible causes
CXR
Propofol/fentanyl infusion if the patient is intubated. Pressor of choice post ROSC is usually levophed
If not done during the code, usually central access will be obtained and an arterial line will be placed

Intern role during codes¶

maintain hand on femoral pulse
place IO if needed
have access to the patient’s chart to answer questions that arise during the code.
If family is not available, looking up primary contact information is invaluable.
In the MICU, your role is to grab the yellow IO kit prior to leaving for the code

Family presence during CPR¶

Studies show that it reduces the frequency of PTSD-related symptoms and does not interfere with medical efforts

Treatable Causes of Cardiac Arrest: The H’s and T’s
H’s	T’s
Hypoxia	Toxins
Hypovolemia	Tamponade
H+	Tension Pneumothorax
Hypo/Hyper K	Thrombosis: Pulmonary
Hypothermia	Thrombosis: Coronary

MICU/CCU Drips¶

Patrick Barney

Most have order sets in Epic. Typically choose “Titration Allowed” in ICU

Vasopressors:
Drug	Dose	Receptors	Indications	Considerations
Norepinephrine (Levophed)	1 – 100 mcg/min	αα1 > β1	1st line septic shock	Peripheral ischemia, skin necrosis
Phenylephrine (Neosynephrine)	Bolus: 0.05 – 0.5 mg q 10-15 min Infusion: 40-360 mcg/min	αα1	Periprocedural hypotension (Neostick), pts w/ tachyarrhythmias, Critical AS or HOCM with severe LVOT obstruction and shock	Reflex bradycardia, Peripheral ischemia, skin necrosis
Epinephrine	1 – 40 mcg/min	αα1=β1=β2	Post PEA arrest, Anaphylaxis, Septic shock (severe), Cardiogenic shock	Tachy-arrhythmias, Peripheral ischemia, skin necrosis
Vasopressin	0.04 U/min (no titration)	V1, V2, V3	2nd line septic shock, Right heart failure	Hyponatremia, Bradycardia
ANG II needs approval from MICU leadership	20 – 40 ng/kg/min	ANG II	Refractory vasodilatory shock	Thrombosis pt MUST have chemical DVT ppx. Contraindicated in heart failure
Dopamine	2 – 20 mcg/kg/min	Dopamine (1-5 mcg) > β1 (5-10 mcg) >α1 (>10mcg)	Hypotension, Cardiogenic shock	Tachy-arrhythmias, peripheral ischemia, skin necrosis
Dobutamine	2.5 – 20 mcg/kg/min	β1 >>> β2	Cardiogenic shock	Vasodilation Hypotension, Tachycardia, Tachyphylaxis
Milrinone	0.375 – 0.75 mcg/kg/min	PDE-3	Cardiogenic shock	Hypotension, renally cleared

Sedatives/Anxiolytics:
Drug	Dose	Class	Side effects
Propofol	Infusion: 5 – 150 mcg/kg/min	General anesthetic (GABA R agonist)	Severe hypotension, bradycardia, hypertriglyceridemia, propofol infusion syndrome (rare) Monitor for toxicity with q4 day TGs and CK
Dexmedetomidine (Precedex)	Infusion: 0.1 – 1.5 mcg/kg/h	Central αα2 agonist	Hypotension, bradycardia
Midazolam (Versed)	Push: 0.5 – 5 mg Infusion: 0.25 – 5 mg/h (no max dose)	Benzodiazepine	Hypotension, risk of BNZ withdrawal if used for long periods with sudden discontinuation
Lorazepam (Ativan)	Push: 0.5 – 10 mg Infusion: 0.5 – 5 mg/h (no max dose)	Benzodiazepine	Hypotension, propylene glycol carrier - AGMA
Ketamine	Push: 1-2mg/kg Infusion: 0.2mg/kg/hr, titrate by 0.1 q15min	NDMA antagonist	Delirium/hallucination – use caution in patients with psychiatric hx, hypertension, tachycardia Pretreat with 0.4mg IV glycopyrrolate to avoid hyper-salivation

Analgesic:
Drug	Dose	Side effects
Fentanyl	Push: 25 – 100 mcg Infusion: 25 – 400 mcg/h	Hypotension, Serotonin syndrome, chest wall rigidity at high doses
Morphine	Push: 1 – 5 mg q1-2h prn Infusion: 1 – 5 mg/h	Hypotension (profound), itching, constipation, HA; avoid in renal failure
Hydromorphone (Dilaudid)	Push: 0.25 – 1 q1-2h prn Infusion: 0.5 – 3 mg/h	Hypotension, respiratory depression, itching

Anti-hypertensives
Drug	Class/MOA	Dose	Indications	Side effects	Comments
Esmolol	Beta blocker	Bolus: 1mg/kg over 30s Infusion: 50-300mcg/kg/min (max 300)	Aortic dissection, HTN emergency	Bradycardia, hypotension	Titrate to desired BP or HR. Caution in HFrEF
Nicardipine	CCB	Infusion: 5-15mg/hr (max 15)	HTN emergency	Bradycardia, hypotension	Titrate to desired BP, avoid in HFrEF
Nitroprusside	Metabolized to NO vasodilatory effect (arterial roughly = venous)	Infusion: 0.3mcg/kg/min; titrate q2min to max 10mcg/kg/min	HTN E, flash pulmonary edema, HFrEF for afterload reduction	Hypotension, cyanide toxicity	Contraindicated in hepatic and renal failure
Nitroglycerin	NO mediated venous > arterial vasodilation	Infusion: start 0.25mcg/kg/min, titrate by 1mcg/kg/min q15min (max 10mcg/kg/min)	Refractory angina, flash pulmonary edema, HTN emergency	Hypotension, headache, palpitations	Contraindicated in severe RHF and concurrent use of PDE-5 inhibitor

Anti-Arrhythmics:
Drug	Dose	Indications	Side effects	Comments
Adenosine	6 – 12 mg IV rapid push and flush; may repeat x2	PSVT conversion	Complete AV nodal blockade	10 second half-life Must have continuous EKG/tele monitor
Amiodarone	ACLS: 300 mg IV push Non-emergent: 150 mg over 10 min then 0.5 mg/min	Vtach/Vfib, Afib	Pulm, ophthalmic and thyroid toxicity w/ chronic use	Less hypotension than other agents, safe in heart failure. May chemically cardiovert patients, caution if off therapeutic AC
Diltiazem	Push: 10 – 20 mg q15 min x 2 if no response Infusion: 5 – 15 mg/h	Afib, Aflutter, PSVT	Bradycardia, hypotension	Avoid use in pts with HFrEF
Lidocaine	ACLS: 1 mg/kg x 1 Infusion: 1 – 4 mg/min	Vtach	Bradycardia, Heart block	Avoid use in liver failure/ Okay for HFrEF. Often 1^st line CCU med for VT/ May need to check levels if using for longer than 24 hours
Procainamide	15 mg/kg over 30 min then 1 – 6 mg/min	Vtach, refractory afib	Bradycardia, hypotension	Drug-induced lupus, cytopenias

Intubation and Extubation¶

Daniel Motta-Calderon

Intubation¶

Background¶

Intubation is the definitive therapy for patients with worsening respiratory failure
Indications for intubation- hypoxic or hypercarbic respiratory failure, airway protection

Intubation checklist¶

Prepare the patient
- IV access: at least two large bore IV access sites.
- Optimize position: Supine sniffing position
- Assess the airway: Assess for difficult intubation predictors (opening mouth \<3cm, Mallampati ≥ III, neck circumference >40cm, thyromental distance \<6cm, head-neck extension \<30 degrees)
- Optimal pre-oxygenation: using FiO2 100% (facemask, high flow nasal cannula)
- Optimize medical status: resuscitation, temporize hyperkalemia, Hb >7
Prepare the equipment
- Monitoring: SpO2, capnography, telemetry, BP
- Equipment: bag valve mask, 2 endotracheal tubes (ETT) with cuffs checked, direct laryngoscope, videolaryngoscope, bougie/stylet, working suction, supraglottic airway, oropharyngeal airway
- Medications: paralytic (ex: rocuronium, succinylcholine), induction sedative (ex: etomidate, ketamine, propofol), analgesics (ex: fentanyl), maintenance sedative, IVF hanging in room, pressors (ex: Neostick)
Prepare the team
- First and second intubators, RT, RN, someone to monitor hemodynamics

Rapid-sequence intubation (RSI)¶

Preferred method of induction, associated with increased first-attempt success and fewer intubation-related complications
Simultaneous IV administration of rapidly acting paralytic and induction agents to achieve sedation and paralysis

Post-intubation¶

Ensure correct placement of ETT with capnography and confirming bilateral breath sounds
Secure ETT with taping, tying or tube holder
Obtain post-placement CXR

Immediate complications of intubation¶

Aspiration: Suction airway, ideally prior to initiation of positive pressure ventilation to prevent distal movement of aspirated contents. Cricoid pressure maneuver historically used to reduce risk but unclear if it works so often not performed
Cardiovascular collapse: May be hypotension or sympathetic surge (hypertension, tachycardia, arrhythmias). Manage with fluids/pressors if need, rule out other causes (ex: hypoxia, PTX)
Hypoxemia: Preoxygenate with 100% FiO2 to minimize risk. Rescue maneuvers with bag mask ventilation if needed
Mechanical injury: Dental, soft tissue, tracheal, laryngeal. Retrieve any dislodged teeth, suction blood

Extubation¶

Is the patient ready to be extubated?¶

Are they oxygenating well? SpO2 ≥90% with FiO2 ≤50% and PEEP ≤8cm H20
Has the underlying cause of their respiratory failure improved?
Did patient pass their SBT?
- See ABCDEF Bundle section for details on SBT
Is patient able to protect their airway?
Is the patient on a stable pressor requirement or no pressors?
Is patient coughing and clearing secretions?
Is patient off sedation, alert and following commands?
Positive cuff leak? (See below for steps)
Consider calculating the rapid shallow breathing index (RSBI): RR/tidal volume (L)
- Set PS at 0cm H2O, and PEEP at 5cm H2O and, measure VT & RR for one minute.
- RSBI ≥ 105 predicts likely failure to wean. The use of a RSBI is attending dependent at Vanderbilt and is not frequently calculated when assessing readiness for extubation

Post-extubation complications¶

Post-extubation stridor: 2/2 laryngeal edema
Positive cuff leak test= high risk methylprednisolone 20 mg IV q4h x 4 prior to extubation to prevent
If after extubation: Methylprednisolone 40 mg IV x1 dose + inhaled racemic epinephrine. If stridor >60minutes, consider reintubation
Cuff leak test:
- Suction secretions and set the ventilator into the AC mode
- Inflate the cuff and record inspiratory and expiratory VT to evaluate for differences between the two volumes
- Deflate the cuff record the expiratory VT over the next six breathing cycles. Average the three lowest expiratory VT values
- The cuff leak volume is the difference between the inspiratory VT (measured before the cuff was deflated) and the averaged expiratory VT. If the difference is \<100cc, this is considered failure but is not an absolute contradiction to extubation
Post-extubation respiratory failure
- Recurrent hypoxic or hypercarbic respiratory failure
- Assess for aggravating factors (volume overload, shock, AMS, etc)
- For hypercarbic respiratory failure, may trial BiPAP. If unsuccessful reintubate
- Preventative post-extubation BiPAP not routinely used in all patients but consider in select populations at high risk for failure: severe COPD with preexisting chronic hypercarbia during SBT, patients intubated for cardiogenic pulmonary edema

Modes of Oxygen Delivery¶

Blake Funke

System	L/min	% O2	Comments
Blow by (ex: Trach collar)		21-100%
Nasal cannula	1-8	25 – 45%
Large bore nasal cannula	Up to 15	Up to 65%	Can be identified by larger bore tubing (often green) and nose piece. Colloquially referred to as HFNC at VUMC, but true HFNC = optiflow
Venturi mask	4 to 15	24 – 50%	Actual FiO2 is dependent on patient effort
Non-rebreather	10 to 15	65-95%	Often used as a bridge to higher level of O2 therapy
HFNC: Optiflow (VUMC), AirVo (NAVA)	Up to 60	30-100%	Delivers 0.5-1 cm/H2O of PEEP per 10L of flow
Use of all of these modes requires a spontaneously breathing patient

Non-invasive positive pressure ventilation¶

CPAP
- Indications: obstructive sleep apnea, tracheomalacia
- Settings: CPAP, FiO2
BiPAP
- Indications: hypercapnic respiratory failure (RF), hypoxic RF, pulmonary edema, obstructive sleep apnea, obesity hypoventilation syndrome, RF 2/2 neuromuscular disease
- Settings: IPAP, EPAP, FiO2, RR (sometimes)

Invasive positive-pressure ventilation
Mode	You set	Not set	Comments
Pressure support (PS)	PEEP PS above PEEP FiO2	TV RR Inspiratory flow	Similar to Bipap. Frequently used for vent weaning / SBT. Requires spontaneously breathing pt
Volume Control (AC/VC)	PEEP RR TV Inspiratory flow FiO2	Inspiratory pressure	Mandates a minute ventilation; limits volutrauma (i.e. can guarantee low tidal volume ventilation) Primary mode used in MICU (mode used in major ARDS trials)
SIMV Synchronized Intermittent Mandatory Ventilation	PEEP RR TV PS above PEEP FiO2		Pt gets VC breath for set rate, but if tries to breath over this will get PS breath; VC and PS breaths are synchronized when able
Pressure Control (AC/PC)	RR Inspiratory Pressure PEEP Inspiratory Time (or I:E ratio) FiO2	TV	Minimizes barotrauma (i.e. sets a max inspiratory pressure) does not guarantee a specific minute ventilation (must monitor PCO2 with blood gases) Does not have natural ventilator alarms for protection – need to increase low minute ventilation alarm threshold
PRVC Pressure Regulated Volume Control	PEEP RR TV Inspiratory flow Pressure max FiO2		Adaptive pressure control (NOT actually a volume control mode); tries to limit both barotrauma and volutrauma but if in conflict, minute ventilation will drop (i.e. need to monitor PCO2 with blood gases like any other PC mode) Con: More the pt works, the less the ventilator does
APRV / Bilevel	PEEP (PLow) Pressure High Time Low Time High FiO2	TV	Long periods of inspiratory holds and very brief expirations (i.e. releases), for refractory hypoxemia. Often difficult to ventilate pts on this mode

Refractory Hypercapnia¶

Amelia Muhs

Background¶

Inadequate clearance of CO2 leading to respiratory acidosis (pH ≤ 7.20) despite maximum RR&TV (i.e. minute ventilation) tolerated without causing barotrauma or autoPEEP
Common causes:
- Obstructive lung disease (COPD, emphysema, asthma)
- Hypoventilation (sleep apnea, obesity, sedative medications (ie opiates), neuromuscular weakness, chest wall trauma, ascites/pleural effusion)
- Increased CO2 load (shock, sepsis, malignant hyperthermia)
Presentation:
- Shortness of breath
- AMS, somnolence
- Hypoxemia
- Tachycardia, hypertension (in some cases)

Evaluation¶

Physical exam, mental status, recent medications
ABG or VBG – if increased PCO2 and normal pH, always treat the pH and not the PCO2 (i.e., may be compensated chronic hypercarbia and blowing off more CO2 may be harmful)

Management Algorithm¶

Special considerations
- If history of OSA, make sure they are on home CPAP/BiPAP
- If opiate related trial narcan
- Bronchodilators for reactive airway diseases
BiPAP
- Contraindicated if pt unable to remove BiPAP mask on their own
- Increase MV by increasing Δ between IPAP/EPAP or increasing RR
Mechanical ventilation
- Allows you to control rate and tidal volume (in Volume Control modes)
- NOTE: some pts have higher minute ventilation on their own compared to mechanical ventilation (e.g., DKA); pt-specific considerations regarding intubation
- To increase minute ventilation and CO2 clearance:
  - Increase RR
    - 30-35 is about as high as you can go
    - Need to keep in mind I/E time to avoid breath stacking/autoPEEP (gas trapped in lungs)
    - Some signs of autoPEEP include worsening hypotension and the expiratory limb on the flow waveform on the vent not returning to zero
  - Increase TV we usually start at 4-6mL/kg IBW. You can consider increasing to 8mL/kg IBW as long as plateau pressures remain \< 30 cm H2O
    - Goal peak pressures ≤ 35 cm H2O / plateau pressures ≤ 30 cm H2O
ARDS permissive hypercapnia (goal pH ≥ 7.2)
V-V ECMO / Extracorporeal carbon dioxide removal (ECCO2R)
Indications for hypercapnia:
- Severe dynamic hyperinflation and/or severe respiratory acidosis
- pH ≤ 7.25 with PaCO2 ≥ 60 for 6 hr with RR at 35/min and TV increased to target maximum MV while keeping plateau pressure ≤ 32 cm H2O
- Similar considerations and contraindications as refractory hypoxemia (see above)
- Benefits: Reduces work of breathing, promotes early ventilator weaning/extubating allows early mobilization and recovery

Refractory Hypoxemia¶

Amelia Muhs

Background¶

Inadequate arterial oxygenation despite high levels of inspired O2 or the development of barotrauma in mechanically ventilated pts
Generally start to consider the interventions below if needing FiO2 >80%
Differential:
- Worsening underlying primary process (e.g. progressive ARDS)
- PE
- Pneumothorax
- Fluid overload
- Ventilator-associated Pneumonia
- New ARDS

Evaluation¶

Always get CXR STAT if pt has new or worsening O2 requirement
ABG is frequently helpful as well
Can use POCUS to check for lung sliding (pneumothorax) or RV enlargement/septal bowing/McConnell’s sign (RV strain in PE)

Initial management¶

Remember – if at any point the pt is rapidly decompensating, you can always disconnect them from the vent and bag them until they recover/while calling for help
Early consideration of ECMO consult in appropriate pts (discuss with MICU fellow)
Optimize fluid status consider diuresis/dialysis if not making urine
Consider higher PEEP strategy
Increased PEEP higher mean airway pressure, generally improves oxygenation especially with diffuse pulmonary pathologies
- Exceptions may include certain focal/shunt pathologies (e.g. dense lobar PNA)
- Worsening oxygenation may occur with overdistension of alveoli increase dead space ventilation; generally determined empirically at the bedside
Titrate up slowly; generally do not exceed PEEP 18
- Limited by high plateau pressures/barotrauma, overdistension/dead space ventilation, decreased preload/venous return
ARDSnet FiO2/PEEP Tables: At VUMC we typically use the Lower PEEP table
Other recruitment maneuvers
- Reposition pt – can try elevating HOB or positioning so “good lung” is down
- If concern for mucus plug, consider need for bronch
- If concern for significant atelectasis can try recruitment maneuvers with the vent including sustained inflation (setting expiratory pressure to ~30 for ~30 seconds) and PEEP titration (setting PEEP to 20-25 and decreasing by 2cm at a time) – call the fellow before attempting

Management Algorithm for Refractory Hypoxemia¶

Inhaled vasodilators: Distribute preferentially to well-ventilated alveoli local vasodilation improved V/Q matching
VUMC formulary preference: inhaled epoprostenol (aka Flolan)
Alternatives: inhaled milrinone, inhaled nitric oxide
Data suggest improved PaO2/FiO2; large RCT without evidence for mortality benefit
Deep sedation (RASS -4 or -5)
- Promotes ventilator synchrony
Neuromuscular blockade (paralysis) – call your fellow before doing this
- Rationale: maximal vent synchrony (eliminates residual chest wall/diaphragm tone)
- Pt MUST be RASS -5 (need analgesia + sedation)
- Trial one time IV push of vecuronium 0.1 mg/kg
- If improved vent synchrony/oxygenation, consider cisatracurium (Nimbex) drip
- Data are mixed ACURASYS 2010 (improved 90-day mortality but underpowered likely overestimating benefit); ROSE 2019 (no difference in 90-day mortality)
Prone positioning (Need attending approval)
- Pts with moderate to severe ARDS (PaO2/FiO2 ratio \< 150)
- At VUMC, we use regular ICU beds and manually flip pts; cycle prone 16 hrs/supine 8 hrs
- When proning or supining a pt, always have a provider who can intubate in the room in case unplanned extubation occurs
- Considerations: need a team of people to reposition, high risk of ET tube malposition, difficult to access lines/perform procedures, high risk of pressure injuries
- Data: PROSEVA 2013 proning improved 28-day mortality; study complicated by imbalances between groups
Alternative ventilator modes (usually Pressure Control or APRV/BiLevel/BiVent)
APRV/BiVent should be avoided in people with bad obstructive lung disease, hemodynamic instability, refractory hypercarbia
Venovenous (V-V) ECMO
- Indications for hypoxemia:
  - PaO2/FiO2 \< 50 with FiO2 >80% for >3 hrs OR
  - PaO2/FiO2 \< 80 with FiO2 >80% for >6 hrs AND
  - Mechanical ventilation ≤ 1 week
- Absolute Contraindications:
  - Poor short-term prognosis (e.g. metastatic cancer)
  - Irreversible, devastating neurologic pathology
  - Chronic respiratory insufficiency without the possibility for transplant
- Can calculate RESP score predicts in-hospital survival with ECMO
- CONSULT EARLY if a pt may be a candidate; allows ECMO team to assist with evaluation
- Data:
  - CESAR 2009: improved 6-month survival without severe disability
  - EOLIA 2018 : no mortality benefit but 28% crossover from control to ECMO arm dilutes potential effects

Sepsis¶

Charlie Oertli

Background¶

Most recent definition (Sepsis-3): organ dysfunction from dysregulated host response to infection

2021 Surviving Sepsis Guidelines: SIRS, MEWS, NEWS superior to qSOFA for screening sepsis
SIRS ≥2 of any of: 1) RR>20, 2) T \<36 or >38, 3) HR >90, 4) WBC \<4 or >12 or >10% bands
Septic Shock = sepsis + vasopressors + lactate >2 meq/dL (Sepsis 3 definition)
Alternate screening systems you may see which are more specific and better at prognosis of in hospital mortality than SIRS:
- Acute change in baseline SOFA score ≥2: P/F ratio, Plts, Tbili, SBP, GCS, Cr
- "Quick" SOFA (qSOFA): ≥2 of AMS (GCS≤13), SBP≤100 mmHg, RR≥22/min

Evaluation¶

Cultures prior to antibiotics if possible (but don’t delay antibiotics just to get cultures)
Consider sputum Cx, paracentesis, thoracentesis, wound Cx, LP, joint aspiration
Lactate (even if not hypotensive)
Imaging: x-ray, CT, or US of potential source

Management¶

Source control: Remove old lines, chest tube for empyema, drain abscesses, etc

Antibiotics

Early antibiotics: within 1 hour if septic shock, within 3 hours if sepsis
Target organisms most likely to cause infection in suspected organ; if source unknown, start empiric broad-spectrum
MRSA coverage - vancomycin/daptomycin/linezolid/ceftaroline
Pseudomonas coverage - zosyn/cefepime/meropenem /cipro/gentamicin
Pneumonia: add atypical coverage (azithromycin/levaquin; 2^nd line doxycycline if prolonged QTC or elderly) if severe or being admitted to the ICU
Fungal coverage for Candida: if neutropenic, TPN, abdominal surgery, prior antibiotics
De-escalation: Once source is controlled, if abx duration is unknown use procalcitonin, culture susceptibilities, and clinical evaluation to help guide de-escalation

Resuscitation

Give 1-3 L (≥30 mL/kg of body weight) of IV balanced crystalloid within first 3 hours
Only give blood if Hb \< 7, unless evidence of bleeding or myocardial ischemia
Monitor HR, BP, mental status, urine output – do NOT give beta-blockers to slow HR in the setting of sepsis unless dangerously high and limiting diastolic filling (discuss with fellow), this is an appropriate stress response
Assess fluid responsiveness by leg raise (if BP improves with leg raise, give more fluids). Other options US IVC (mixed data), pulse pressure

Vasopressors

Start if MAP not responsive to fluid resuscitation
Target MAP > 65mmHg, also monitor mental status, serum lactate, and urine output; may need higher goal for pts with chronic HTN
Start with norepinephrine -- via central line, PICC, or port. Can run through peripheral IV (at least 18g, proximal to wrist) up to 15 mcg/min for up to 48 hours if no central access
- SOAP II trial: norepinephrine > dopamine (less arrhythmias)
- No upper limit of NE but can cause peripheral ischemia with prolonged use
Add vasopressin at fixed dose of 0.04 units/min when NE dose >= 50 mcg/min
- VASST trial: possible benefit for pts on 5-15 of NE; however, this was opposite of hypothesis and vasopressin is expensive
Add epinephrine or dobutamine if low cardiac output
Add phenylephrine for pts with tachyarrhythmias (reflex bradycardia)
Consider Angiotensin II (discuss with fellow, needs MICU leadership approval) contraindicated with CHF and DVT/PE/clots/hypercoagulability
Consider steroids if vasopressors failing or on steroids chronically hydrocortisone 100mg IV q8hr or 50mg IV q6hr for 5 to 7 days

Management of Shock¶

Alex Toporex, Soibhan Kelley

Distributive Shock¶

Background¶

Pathophysiology: severe, peripheral vasodilation
CO/CI increased, SVR decreased, PCWP and RAP normal to low
Etiologies: sepsis (most common), anaphylaxis, neurogenic, adrenal insufficiency, pancreatitis
Signs/symptoms:
- Sepsis: localizing signs of infection; tachycardia, tachypnea, may be hypo/hyperthermic; POCUS with hyperdynamic cardiac function
- Anaphylaxis: history of anaphylaxis; urticaria, edema, diarrhea, wheezing on exam
- Neurogenic: history of CNS trauma; focal neurologic deficits on exam
- Adrenal insufficiency: hx chronic steroid use, may have GI symptoms, hyponatremia (common), hyperkalemia (rare), hypoglycemia, hypo/hyperthermia, NAGMA
- Pancreatitis: abdominal pain, elevated lipase, evidence on CT scan

Management¶

Sepsis: see sepsis section
Anaphylaxis: 0.3mg IM epinephrine ASAP to be repeated q5-15min x 3; after third IM epi, consider IVF and epi gtt if persistent hypotension. Adjuncts: albuterol nebs for bronchospasm, H1 and H2 blockers, ± glucocorticoids (methylprednisolone 1mg/kg). EPINEPHRINE SAVES LIVES.
Neurogenic: caution with IVF resuscitation, can worsen cerebral and spinal cord edema; preferred pressors are norepinephrine and phenylephrine; for neurogenic shock 2/2 spinal cord pathology, consider higher MAP goal 85-90 mmHg
Adrenal insufficiency: stress dose steroids with hydrocortisone 100mg IV q8hr or 50mg q6hr
Pancreatitis: IVF + pressors; trend H/H and Ca; treat complications (necrotizing pancreatitis, abdominal compartment syndrome); address underlying etiology (see GI section)

Cardiogenic Shock¶

Background¶

Pathophysiology: CO/CI decreased, SVR increased, PCWP and RAP elevated (left heart failure) or PCWP low/normal and RAP elevated (right heart failure)
Etiologies: Cardiomyopathy (LHF, RHF or biventricular), arrhythmia, mechanical such as acute AR (ex: dissection) or MR (ex: ruptured papillary muscle)

Presentation¶

Edematous, elevated JVP, “cold and wet”; hypoxia w/crackles and pulm edema; mixed venous sat \< 50-60%; POCUS with plump, non-compressible IVC, reduced EF, and B-lines

Management¶

See cardiogenic shock in cardiology section

Hypovolemic Shock¶

Background¶

Etiologies: Hemorrhagic and non-hemorrhagic
Signs/symptoms:
- Hemorrhagic: Common sources include GI, retroperitoneal (*needs high index of suspicion), traumatic, intraabdominal, thighs, thorax
- Non-hemorrhagic: 2/2 GI losses or decreased PO intake
POCUS with thin, collapsible IVC

Management (Hemorrhagic)¶

Ensure good access with two large-bore (at least 18G) IVs ideally in AC or above; Cordis or MAC CVC (can also use dialysis catheter, if necessary)
Hyperacute bleed:
- 1:1:1 ratio FFP:Plt:RBC (balanced resuscitation), massive transfusion protocol (MTP)
- Monitor iCa and replete (citrated blood products will deplete Ca)
- Minimize crystalloid if possible, w/primary use to prevent immediate hemodynamic collapse (contributes to coagulopathy, hypothermia, acidemia, trauma/surgery)
- Permissive hypotension until source control/transfusions with arterial bleeds (high MAP/SBP -> clot destabilization); trend POC lactate/exam to guide
- Acute traumatic arterial bleed or post-partum hemorrhage consider TXA (1-2 gm bolus)
- Reverse anticoagulation, if applicable
- Vasopressors -> generally poorly effective, would start with norepinephrine
- Source control -> GI, IR, or EGS
Variceal bleed: See GI Bleeding section for specific management

Management (Non-Hemorrhagic)¶

Aggressive IVF resuscitation (balanced crystalloid); target MAP ≥65
Can support BP during resuscitation with pressors (usually norepinephrine)

Obstructive Shock¶

Background¶

Etiologies: Massive pulmonary embolism, tension pneumothorax, and cardiac tamponade
Signs/symptoms:
- Pulmonary embolism: acute hypotension, known DVT, evidence of R heart strain on EKG, POCUS w/enlarged RV, septal bowing, McConnell’s sign, ↑ BNP, PE on CTA
- Tension pneumothorax: history of COPD or fibrotic lung disease, ventilated pts w/ high peak pressures, unilateral decreased BS on auscultation and tympany on percussion, POCUS without lung sliding, CXR w/ PTX and mediastinal shift
- Cardiac tamponade: elevated JVP, muffled heart sounds, pulsus paradoxus, POCUS with diastolic collapse of RV and large pericardial effusion (best in subcostal window)

Management¶

Massive pulmonary embolism: see Pulmonary Embolism Section for specific management
Tension PTX: needle decompression using 14-16G needle into the second intercostal space at the midclavicular line; call trauma surgery or fellow for chest tube ASAP
Cardiac tamponade: STAT page cardiology or cardiothoracic surgery; can temporize hypotension with IVF resuscitation—500-1L IVF boluses (may not work if pt is euvolemic or hypervolemic); no proven benefit from inotropy (e.g., dobutamine)

Temperature Abnormalities¶

Soibhan Kelley

Hypothermia¶

Background¶

Core temperature \<35°C (95°F). Mild 32-35C (90-95F), moderate 28-32C (82-90F), or severe \<28C (82F) ± pulseless
Ensure thermometer is “low-reading,” standard thermometers not accurate
Core temperature can be measured w/ bladder catheter probe or esophageal probe (may be falsely ↑ if heated oxygen being delivered). Rectal temp can be used but is less accurate
Etiologies:
- Heat loss: Environmental, burns, iatrogenic (CRRT, cold IVF, massive transfusion protocol), vasodilatory drugs/toxins
- Decreased heat production: endocrinopathies (hypothyroidism, adrenal insufficiency, hypopituitarism, hypoglycemia), thiamine deficiency
- Impaired regulation: Spinal cord injury, hypothalamic lesions, drugs (classes including antihyperglycemics, beta blockers, sedatives, ETOH, alpha agonists, general anesthetics)
- Multiple mechanisms: sepsis, pancreatitis, DKA

Evaluation¶

Infectious work-up
POC blood glucose, TSH/FT4, cortisol, lipase, UA, UDS, EtOH level, additional tox as appropriate, DKA work-up if relevant
Physical exam + history for exposures and trauma
CBC, CMP, Lactate, ABG, CK, PT/PTT, Fibrinogen
EKG

Management¶

Treat underlying cause [see appropriate sections]
Mild hypothermia:
- Passive external rewarming (PER): blankets, increase ambient temperature
- Note that PER requires sufficient underlying physiologic reserve to generate heat. This is often impaired in elderly pts, malnutrition, sepsis
Moderate hypothermia, refractory mild hypothermia, or cardiovascular instability:
- Active external rewarming (AER): forced warm air (ie Bair Hugger), heated blankets, heat lamps, hot packs (consider burn risk)
Severe hypothermia or refractory moderate hypothermia:
- Active core rewarming: Warmed IV crystalloid (limited rewarming potential unless large volume but will decrease ongoing losses), warmed humidified inspired air, warmed bladder lavage
- More extreme methods such as peritoneal/thoracic lavage more likely to be used in severe environmental cases in ED
Pulseless severe hypothermia (“You aren't dead unless you are warm and dead”)
- Continue CPR until re-warmed as severe hypothermia is neuroprotective and pts can have good neurologic outcomes despite hours of CPR
- ACLS medications and shocks will have poor effectiveness; prioritize circulation (i.e. chest compressions) and rewarming
- Consider ECMO (likely venoarterial if pulseless); would need transfer to CVICU
Identify and manage complications: bradycardia/heart block, arrhythmias, shock, coagulopathy/DIC, rhabdo; rebound hyperkalemia/hypoglycemia with rewarming

Fever and Hyperthermia¶

Background¶

Fever: T >38.0°C (100.4°F) driven by hypothalamus activity in response to systemic triggers (i.e. cytokines); may use lower threshold for immunocompromised pts
Hyperthermia: T >41.0 C (105.8°F) uncontrolled heat production with failure of thermoregulation
Infectious etiologies:
- Considerations in the ICU include central-line associated blood stream infection, catheter-associated UTI, pneumonia (including ventilator-associated), sinusitis (esp in pts with NGT or ETT), clostridium difficile, acalculous cholecystitis
Non-infectious etiologies:
Drug fever
- Difficult to distinguish from other causes; Can begin hrs-wks after starting a drug
- Sources: antibiotics (penicillins, cephalosporins, sulfonamides), anticonvulsants (phenytoin, carbamazepine, phenobarbital), allopurinol, heparin, dexmedetomidine
- Drugs of abuse with sympathomimetic activity (cocaine, meth, ecstasy)
- Anticholinergic or salicylate intoxication
Idiosyncratic drug reactions
- Serotonin syndrome
- Neuroleptic malignant syndrome
- Malignant hyperthermia
Transfusion reactions
PE/DVT
Endocrine: hyperthyroidism/thyroid storm, adrenal insufficiency
CNS pathology (intracranial bleed/stroke, particularly hypothalamic region)
Malignancy
Heat stroke (exertional or non-exertional)
Other inflammatory states: Pancreatitis, gout, pericarditis, pneumonitis

Evaluation¶

Infectious work-up ± LP; may consider pan-scan if unable to identify source
POC glucose, BMP, LFT, Mg/Phos, CBC w/diff
Consider coags + fibrinogen (DIC), CK/UA (rhabdo), UDS, acetaminophen and salicylate levels, TSH/FT4, cortisol, lipase, ABG
Review medication list: antibiotics, serotonergic drugs, anti-psychotics, recent sedation for OR or recently intubated with succinylcholine, dexmedetomidine
Consider CT/MRI head

Management¶

Treat underlying etiology [see appropriate sections]
Serotonin syndrome -> stop serotonergic drugs; add cyproheptadine
Malignant hyperthermia ->activate malignant hyperthermia team; add dantrolene
Cooling
- Target \<38.0°C (100.4°F)
- Surface cooling: Ice (bath, or ice packs more likely in our MICU), evaporative cooling with misted lukewarm water and fan
- Internal cooling: Cold IV fluids (pharmacy keeps ~3L of cold LR on-hand, they will cool more if you call down and ask), dry ventilation (evaporative) with non-humidified nasal cannula or vent circuit
- Avoid shivering -> give opiates (except in serotonin syndrome), precedex, propofol, benzos, ketamine
Antipyretics
- Acetaminophen, NSAIDs
- Block prostaglandin-mediated temperature elevations
- Effective for most causes of fever- infection, pancreatitis, DVT/PE, pneumonitis
- AVOID for true hyperthermia (ineffective and potentially harmful) -> neuroleptic malignant syndrome, malignant hyperthermia, serotonin syndrome, heat stroke
Monitor for complications
- Rhabdo, DIC, arrhythmias
If high suspicion for infection and not improving on antibiotics, consider other infectious etiologies including fungal (ex: candida)

Tracheostomy¶

Jared Freitas

Indications¶

Prolonged mechanical intubation and weaning
Tracheal stenosis
Acute airway obstructions (head and neck cancers)
Trauma
Neuromuscular disease

Benefits of Tracheostomy vs ET tube¶

Improved pt comfort and decreased need for sedation
Reduced laryngeal damage
Increased ability to communicate (i.e. speaking valve)
May decrease risk of developing ventilator associated pneumonia (mixed data)
May reduce time to wean from the vent and decrease time in the hospital (mixed data)

Timing¶

No mortality difference or ↓ in hospital length of stay for early (day 4) vs late (day 10)
Generally performed after 2 weeks of intubation, but not backed by data
Pts that might get tracheostomy earlier: anticipated prolonged mechanical ventilation (i.e. those with acute neurologic injury affecting spinal cord)

Types of Tracheostomy Tubes¶

Different brands: most common in hospital = Shiley
Components:
- Faceplate: keeps tube in place, has the model and size on it
- Inner cannula: can be removed, cleaned and replaced in case of obstruction
- Cuff (may or may not have): allows for pt to be ventilated; may prevent some aspiration
- Fenestration (may or may not have): allow speaking without valve
Common sizes:
- Initial: 8-0; Standard downsizing: 6-0
- Lengths: standard vs larger XLT (P = longer proximal end, D = longer distal end)
Presenting on ICU rounds = size/cuff status/brand (e.g. 8-0 cuffed shiley)

Speaking Valves¶

Passy Muir Valve (PMV): one-way valve placed on the outer portion of the trach; air moves in with inspiration but is blocked and thus funneled up through the vocal cords during exhalation allowing for phonation
Contraindication: severe upper airway obstruction or aspiration risk, copious secretions, decreased cognitive status, severe medical instability, or inability to tolerate cuff deflation
IMPORTANT SAFETY PRINCIPLE: cuff must be deflated, since air needs to be able to travel back up the airway, if the cuff is not deflated and you put the PMV on, then pt cannot exhale

Maintenance of Tracheostomy Tubes¶

Inner cannula should be cleaned 2-3 times per day
Daily stoma care should be initiated to prevent pressure ulcers and stoma infections
As needed suctioning for secretions

Complications and airway emergencies in a tracheostomy pt¶

Hemorrhage (mild bleeding from surface vessels and granulation tissue is common, major bleeding is rare think erosion into brachiocephalic [innominate] artery)
Airway damage subglottic or tracheal stenosis; tracheobronchitis
Fistulas (tracheoarterial, tracheoesophageal)
Unintended tracheostomy tube dislodgement:
- Bag mask (use hand/gauze to occlude stoma) or intubate from above (i.e. through the mouth); if complete laryngectomy then must use stoma
- Fresh trach (≤ 14 days): do NOT replace due to risk of misplacement into the mediastinum and loss of airway; airway management from above
- Older trach: can be replaced at bedside with obturator by trained staff
- All pts with trachs have a yellow sign above bed with date, type, size of trach as well as a replacement trach with obturator in the room

Secretion Management¶

Respiratory hygiene (“pulmonary toilet”): heated vent, guaifenesin, hypertonic saline, duonebs, cough assist device, appropriate suctioning (too much = worsen secretions), acapella, inspiratory spirometer

Ultrasound in Critical Care¶

Audrey White

Volume assessment¶

IVC measurements
Clinical Questions: Will the patient respond to fluid resuscitation? Is CVP low or high?
Protocol: See cardiology POCUS section
Limitations: Non applicable in patients with elevated abdominal pressure or abdominal contractions during measurement
Troubleshooting: Use the liver as a window to the IVC to avoid bowel gas. Start at the right mid-axillary line with the leading edge toward the head of the patient, and fan to view the IVC in longitudinal axis.

Lung Assessment¶

Lung ultrasound relies on recognition of ultrasound artifacts to identify normal and pathologic findings.
Normal findings
- “Bat sign”: Ultrasound cannot penetrate reflective rib surface, casting a vertical shadow
- A- lines: hyperechoic horizontal lines descending from the pleural line at regular intervals. This reverberation artifact occurs in normal aerated lung
Pathologic findings
- B-lines, comet tails: Vertical hyperechoic lines which (1) extend from the pleural line through the depth of the image, (2) move with lung sliding, and (3) obliterate A lines. Multiple B lines indicates excess interstitial fluid
- Lung rockets: >3 B lines indicates interstitial syndrome. Most common cause is acute pulmonary edema, also consider ARDS, PNA, pulmonary fibrosis, & pulmonary contusion. Helps distinguish CHF vs COPD exacerbation in patients with dyspnea
- Loss of lung sliding, barcode sign: The shimmering, twinkling appearance of the dynamic aerated lung is lost. Can confirm in M-mode with barcode sign- smooth homogenous lines indicating no movement of lung tissue. Lung sliding=suspicion for PTX but NOT specific unless can identify lung point
- Lung Point: The precise location where the lung detaches from the pleura can sometimes be identified. Can confirm in M-mode which will show “barcode” and “seashore” patterns adjacent. 100% specific for pneumothorax
- Pleural effusion, jellyfish sign: Anechoic fluid is visualized between the diaphragm and dynamic lung
Probe: linear or phased array
Protocol
- Adjust the depth to ~10cm to start. Position the probe vertically on the midclavicular line. Slide the probe so that the hyperechoic pleural line is visualized between rib shadows. Note presence/absence of A lines, B lines, lung sliding, and alveolar consolidation
- Repeat on the opposite side and lower anterior lung fields
- Repeat on the right and left mid-axillary line, upper and lower lung fields. Look for pleural effusion between the diaphragm and lung
- Repeat on the posterior lung fields if indicated to complete a 12-zone lung examination

Cardiovascular¶

Goal-directed echocardiography for acute shock

Pericardial tamponade
- Apical 4 chamber (A4C): pericardial effusion, may see end diastolic collapse of right atrium
- Parasternal long (PLAX): pericardial effusion will appear anterior to thoracic descending aorta, may see collapsing right ventricle
- False positives: pericardial cyst, pericardial fat pad, pleural effusion (posterior to thoracic descending aorta on PLAX)
Acute cor pulmonale
- PLAX, PSAX: paradoxical septal motion, D shaped left ventricle, dilated RV
- A4C: end-diastolic RV area : LV area > 1
- Subxiphoid (SUX): dilated IVC
LVEF- see cardiology section

Abdominal assessments¶

FAST exam
Clinical questions: Is there fluid in the peritoneal or pericardial spaces?
Probe: curvilinear or phased array
Protocol
- Start on abdominal mode at depth 21-25cm. Assess for pericardial effusion in SUX view
- Reduce depth to 12-16cm and place probe on the right anterior axillary line between ribs 8-12 with the indicator toward the patient’s head. Sweep medially to identify the right kidney. Assess for anechoic fluid in Morrison’s pouch between the kidney and liver, subdiaphragmatic space, and paracolic gutter. Rock the probe to assess for fluid cephalad to the diaphragm. Slide inferiorly to confirm no fluid around the inferior pole of the kidney
- Place probe on the left anterior axillary line between ribs 8-11 with the leading edge toward the patient’s head. Sweep medially to identify the left kidney. Assess for anechoic fluid in the splenorenal interface, subdiaphragmatic space, pleural space, paracolic gutter, and left kidney inferior pole
- Place probe midline just superior to the pubic symphysis. Identify the bladder in longitudinal and transverse view. Assess for fluid outside the bladder wall and in the pouch of Douglas (females) or rectovesicular space (males)
Limitations: Cannot detect retroperitoneal bleed. False positives from ascites, pleural effusion, subcapsular hematoma, ruptured cysts, physiologic fluid in pouch of Douglas, epicardial fat pad. Exam may be indeterminant if significant bowel gas or obesity
Small bowel obstruction assessment
- Overall SBO ultrasound has ~92% sensitivity and ~97% specificity to detect SBO and greater diagnostic accuracy than abdominal XR
- Probe: curvilinear
- Protocol: Have the patient lie supine and relax the abdominal wall. Place the probe vertically on the abdomen and sweep across all four quadrants in sagittal view. Repeat in transverse view. Measure small bowel wall thickness and diameter using the caliper tool
- Signs of SBO:
  - Diameter > 2cm • Decreased peristalsis
  - Wall thickness > 4mm • Back and forth stool movement
  - Tanga sign: In severe SBO, may see triangular pocket hypoechoic free fluid surrounding the small bowel near the obstruction
Renal ultrasound
- Protocol is similar to FAST exam. Fan the probe through each kidney in sagittal and transverse view to assess for dilation of the collecting ducts. To move the kidney inferiorly, ask the patient to take a deep breath
- Bilateral hydronephrosis and full bladder suggests urinary obstruction distal to the ureter
- Unilateral hydronephrosis suggests nephrolithiasis or ureteral obstruction
- Limitations: Renal US has a reported sensitivity of 70% and specificity of 75% to detect nephrolithiasis compared to CT

Introduction to Vent Management¶

Jared Freitas

Ventilator Settings¶

See table in Modes of Oxygen Delivery for variables adjusted in each ventilator mode
Trigger: what initiates a breath; time, flow, or pressure (pt triggers are flow and pressure)

Static Ventilator Readouts¶

Plateau pressure (Pplat): measure with inspiratory hold, assesses static lung compliance
Auto-PEEP: measure with expiratory hold; occurs when volume of previous breath is not entirely expelled before the next breath is initiated

Dynamic Ventilator Readouts¶

Measured RR: in most modes, pt may trigger breaths above set RR; if set and measured RR match consider ↓ respiratory drive (sedation, neurologic injury) or iatrogenic over-ventilation
VTi / VTe: tidal volume of inspiration (VTi) and expiration (VTe)
VTi should approximately equal VTe, if not then concern for air leak (e.g. cuff leak or pneumothorax) or auto-PEEP
Minute ventilation: calculated from VTe x RR; higher MV = more CO2 clearance
Peak pressure: highest pressure reached in the entire ventilator cycle

Critical Non-ventilator hemodynamic readouts¶

SpO2: if poor waveform or discordant with PaO2, may need serial ABG
HR: quickest indicator of emergencies such as pneumothorax, PE, ventilator disconnection
Blood pressure: positive pressure ventilation decreases preload and afterload; depending on the underlying pt physiology, increases in positive pressure may be detrimental or beneficial for BP

High Peak Pressure

Static compliance issue (stretch of the lung - doesn't change with airflow) versus dynamic compliance issue (resistance of the circuit when there is air flowing)

Step 1: Check plateau pressure by performing inspiratory hold. Must be in VC mode.

High Peak and Low Plateau = Dynamic compliance issue High Resistance

Check circuit tubing for excess water condensation or a kink. Ask RT to disconnect and clear circuit
Check if patient is biting ETT bite block, pain control/sedation
Incline suction to clear secretions or proximal mucous plug
Auscultate for wheezing or stridor to indicate bronchospasm or airway obstruction->give bronchodilators

High Peak and High Plateau = Static compliance issue Worsening alveolar process

Emergencies to quickly assess for:

Tension pneumothorax (exam, US for lung sliding, CXR)
Main stem intubation (ask about any tube migration, listen to breath sounds, CXR)

Consider worsening alveolar process leading to decreased lung compliance: worsening pulmonary edema, PNA, DAH, ARDS or other non-alveolar process such as new pleural effusion, obesity, intraabdominal hypertension/compartment syndrome

CXR, US to assess for b-lines, tracheal aspirate, bronch, etc
Treat according to etiology (chest tube, reposition ETT, diuresis, abx, etc)

Low Tidal Volume/Low Minute Ventilation (VE)

Pt is not getting the desired tidal volume/VE that was set in the vent parameters. The alarm reports exhaled VE. May cause inadequate ventilation, CO2 retention, potentially hypoxia

Compare inspiratory tidal volumes (Vti) with expiratory tidal volumes (Vte) on the ventilator. If Vti>Vte, check for a leak in the system

Have RT check all connections
Listen for a cuff leak – can have RT check a cuff pressure and if low then re-inflate->sometimes need to do an ETT exchange

If low tidal volumes and no leak (ie. Vti = Vte) and RR WNL

Pt may need more support, ie switching to a different vent mode (PS to PRVC). Discuss with RT or fellow

If low RR and no leak and Vt at goal

Patient may be oversedated
Ensure pt has a back-up rate in case they aren't triggering the vent->may need to switch vent modes for this (i.e. take off pressure support) or increase set/ventilator respiratory rate

Apnea

No breaths are being triggered by the vent your patient is NOT breathing this is an emergency

***Check that patient hasn't self-extubated, trach hasn't fallen out, or been unhooked from vent***

If self-extubated or tracheostomy decannulated, then immediately start bagging the patient (may need to bag from trach stoma if s/p laryngectomy). Have nurse call staff assist so that patient can be re-intubated if necessary or have trach team called to replace a fresh (<7 days old) trach

Ended: Critical care

Demo ↵

Pleural Effusions¶

Eddie Qian

Background¶

There is a normal influx of fluid into the pleural space due to leaky capillary membranes and the pleural space’s negative pressure. This fluid is constantly reabsorbed by lymphatics. An imbalance in the system will result in accumulation.

Some examples:
- Increased influx: increased filtration from the capillaries from high intravascular hydrostatic pressure (i.e., heart failure, renal failure) or low intravascular oncotic pressure
- Other liquid entry into the pleural space through anatomic deficits: CSF, chyle, urine, blood, ascites (the diaphragm is naturally porous)
- Decreased efflux: obstruction of the parietal pleural stoma (from protein or cellular debris in exudative pleural effusions)
- Increased systemic venous pressure (lymphatic system drains into the systemic venous circulation so high venous pressure prevents lymphatics from draining appropriately)

Evaluation¶

Imaging¶

CXR: lateral decubitus position (if effusion moves with gravity, suggests free flowing)
Ultrasound: assess size, location, loculations (fibrinous septations which may prevent simple drainage)
CT Chest with contrast (not always indicated; helpful to eval septations)

Thoracentesis (see Procedures section)¶

Will it change management?

If septated or empyema, consider pulm consult for chest tube.

Orders:

Always: Pleural LDH, protein, cell count/diff, culture
Don’t forget serum LDH & protein!
Consider: pleural cytology, hematocrit, triglycerides, glucose, amylase

Interpretation:

Lights Criteria	>=1 of the following = exudative
pleural protein : serum protein	> 0.50
pleural LDH : serum LDH	> 0.60
pleural LDH : upper limit of normal of serum LDH	> 0.66

Transudative: CHF exacerbation, hepatic hydrothorax, atelectasis (caused by increased intrapleural negative pressure), hypoalbuminemia, renal failure
Exudative: infections (bacterial, TB, fungal), malignant, rheumatologic, PE

Pearls about initial tests:

Protein: >5 think TB or malignancy, =< 0.5 think urine, CSF, peritoneal dialysate
Glucose: =< 60 think about malignancy, TB, rheumatologic, and less specific hemothorax or parapneumonic
Cell count/differential: polys represent an acute process, monocytes represent a chronic process, lymphocytes think about TB or malignancy, eosinophils think about air/blood, TB, malignancy, asbestos, drugs
Two separate processes may co-occur and a transudate may mask an exudative effusion; if concerned for this and you have clinical stability, trial diuresis prior to thoracentesis.

References

Lights Criteria Original Paper

Ended: Demo

Endocrinology ↵

Adrenal Incidentalomas¶

Matthew Gonzalez

Background¶

Adrenal mass >1cm, discovered by chance on radiographic imaging
Less than 1% are malignant
Supportive of benign: <4 cm in size, smooth borders, homogenous appearance, <10 HU (Hounsfield units), rapid contrast washout (on "adrenal phase" imaging)
Supportive of malignancy: >4 cm in size, irregular borders, > 20 HU on unenhanced CT, delayed contrast washout, tumor calcifications, increase in size over time, presence in young pts and hx cancer

Evaluation¶

All incidentalomas should be screened for pheochromocytoma (~3% incidence) before operative intervention
Cortisol secreting adenoma (~6% incidence) causing Cushing's syndrome: baseline serum DHEAS, low dose (1mg) overnight dexamethasone suppression test
Aldosterone secreting adenoma (<1% incidence) causing hyperaldosteronism: if hypertensive (HTN) or hypokalemic order plasma aldosterone and renin, confirmatory testing with sodium loading (oral vs IV) and 24-hour urine aldosterone, sodium, and creatinine

Management¶

If benign appearing and not hormone producing: interval imaging in ~1 year, and repeat hormone work up
Unilateral adrenal incidentaloma
- If progression free (stable size, and not hormone producing) can consider monitoring cessation after 4 years
Pheochromocytomas should undergo surgical evaluation for removal
- Alpha blockade (phenoxybenzamine) + propranolol prior to resection to avoid HTN crisis
Aldosteronoma: should undergo surgical evaluation for definitive treatment; if unable to undergo surgery can treat with medical management with long term mineralocorticoid antagonist (e.g. spironolactone)
Cortisoloma: if clinically significant should undergo surgical removal, will need perioperative glucocorticoid administration to avoid iatrogenic adrenal insufficiency
Macroadenomas (masses >4 cm) are usually malignant and should be considered for surgical resection due to higher risk of carcinoma

Adrenal Insufficiency¶

Griffin Bullock

Background¶

Differential: Primary (Adrenals) vs Secondary (Pituitary):
- Exogenous steroid use (>10 mg for >3wks) undergoing severe physiologic stress or sudden discontinuation of steroid
- Autoimmune adrenal insufficiency
- Infection/Infiltration: tuberculosis, sarcoidosis, malignancy
- Hemorrhage (Waterhouse-Friderichsen syndrome)
- Pituitary mass/tumor, infarct, infiltration, surgery, trauma

Presentation¶

Generalized weakness, lightheaded, abdominal pain, nausea, weight loss, fatigue
Lab Abnormalities: hyponatremia, hyperkalemia, hypoglycemia

Evaluation¶

Inpatient Setting
- Draw AM cortisol and ACTH (ideally 8am) -> 0.25mg cosyntropin -> cortisol 1 hour after
  - Cortisol level ≥18-20 rules out primary adrenal insufficiency (and most secondary)
Outpatient Setting
- Draw AM cortisol level for screening (>15 rules typically rules out adrenal insufficiency)
- ACTH stimulation for confirmation

Management¶

Consult endocrine if ACTH stimulation test is abnormal
Adrenal crisis (if concerned, treat first, test later)
- BMP, glucose monitoring, ACTH level, serum cortisol
- Fluid resuscitation: NS or D5NS. Do not use hypotonic saline
- Hydrocortisone 100mg x1 followed by 50mg q8h

Inpatient Diabetes Mellitus (DM)¶

Will Bassett

Background¶

Blood glucose (BG) goal
- Wards: <140 mg/dL fasting; <180 mg/dL random; increase for elderly, “sicker” patients
- ICU: 140-180 mg/dL (NICE-SUGAR Trial)
- Avoiding hypoglycemia in critically ill patients is more important than targeting ideal BG

Management¶

Initial orders
- HOLD all home oral diabetes medications (except consider continuing empagliflozin in heart failure pts)
- Typically recommend dose reducing home insulin (usually 50% of home dose for type 2; varies for type 1) for changes in diet. If AKI present, consider reducing by more.
  - Patients with Type 1 DM always need basal insulin, even if NPO or else will lead to DKA
  - If patients with Type 1 DM are eating, they will need prandial insulin as well
- Order set “SUBCUTANEOUS INSULIN ORDER(S)”
  - Hemoglobin A1c. Can consider if none in last 3 months and concern for poor outpatient control. A1c does not routinely affect inpatient management
  - Fingerstick blood glucose: Typically AC/HS (before meals and nightly)
  - Hypoglycemia management: Select all of these
  - Basal insulin:
    - Type 2 DM, consider ↓ home dose (50-60% to home dose) as often inpatients have reduced PO intake and ↓ renal function
    - Type 1 DM, DO NOT hold basal insulin, and avoid ↓ < 80% of home dose
    - Unnecessary if no home basal insulin
  - Insulin lispro meal: ↓ home dose by ½, do not give while NPO
  - Lispro insulin correction scale: Start with Low or Medium sliding scale and ↑ prn
  - Carb-controlled or carb-restricted diet
Insulin adjustments
- If BGs persistently >200
  - Calculate all insulin needs over 24h (basal + mealtime + sliding scale)
    - Give 50% as basal and other 50% as 3 divided mealtime doses
    - E.g. 10 basal + 0 mealtime + 14 sliding scale total = 24 units total daily = 12u basal + 4u TID with meals
    - If new to basal, safe start is 0.2 u/kg daily if normal GFR
- If BGs < 70
  - If overnight/AM, reduce basal insulin dose
  - If daytime/post-prandial hypoglycemia, reduce mealtime and sliding scale
  - Less is more! Blood glucose in the low 200s is better than the 50s
  - If endocrine consulted for inpatient glucose management, please notify >24h prior to discharge if you want recommended discharge regimen

Steroid-induced Hyperglycemia¶

Steroids increase insulin resistance causing elevated postprandial BG
Insulin adjustments
- Double mealtime + correction dose with leaving the basal the same
- Modified basal bolus regimen (30% basal, 70% bolus)
- Add NPH once daily (weight + dose based, per below*) if on daily prednisone
  - Prednisone 10 mg = 0.1 u/kg NPH
  - Prednisone 20 mg = 0.2 u/kg NPH up to 0.4 u/kg daily
  - lower dose if AKI, administer at the same time as prednisone dosing
- On discharge, if steroids will be longstanding, increase home insulin regimen per inpatient requirements. If steroids will be tapered or discontinued soon after, either continue hospital regimen for remainder of steroid course or return to home regimen (hyperglycemia is better than hypoglycemia)

Additional Information¶

Tube feeds
- Dose regular insulin q6h (not TID AC as they don’t have distinct “meals”)
- Consolidate for bolus feedings based on 24-hour insulin needs prior to discharge
Insulin pumps
- If a patient has a pump and supplies, reasonably controlled BG, is willing and able to manage pump then s/he can keep the pump on. This requires a Diabetes Consult.
- Still order POC BG checks AC/HS for nurse to chart and fill out MedEx pump contract

Diabetic Ketoacidosis (DKA)¶

Will Bassett, Matthew Gonzalez

Background¶

Classically in type 1 diabetes but can also occur in insulin-dependent type 2 diabetes
Definition: ↑ blood glucose (typically >350) w/ high anion gap and ketones in blood/urine
If glucose is significantly elevated but little to no ketones/anion gap present, you likely have HHS, which is typically associated with ↑ serum osm and BG > 600

Evaluation¶

Labs: BMP with anion gap (AG), CBC, phos, blood gas, serum osms, UA, consider beta-hydroxybutyrate
Workup aimed at discovering the underlying cause (The "I’s"):
- Infection/ Inflammation: CBC, CXR, UA/UCx, LFTs; consider BCx, lipase (pancreatitis). Note: Leukocytosis will be present in DKA, even if infection isn’t the precipitating factor
- Ischemia (MI, CVA, mesenteric ischemia): EKG, Troponin, CT(A) if clinical suspicion
- Intoxication - Ethanol (can cause ketosis with or without acidosis), cocaine, MDMA
- Impregnation - Beta HCG if appropriate
- Insulin-openia/Iatrogenic: steroids, SGLT2 inhibitors, other meds, insulin delivery failure (pump failure, insulin degraded by heat, etc.)

Remember to correct sodium for hyperglycemia (Na + 2.4 mEq * (BG-100))

Management¶

Initial monitoring: q2-4h BMPs (monitor K closely), q1h BG fingersticks
- Can space less frequently once gap is closed x 2 and patient off insulin infusion
Ensure IV access
Start IV fluids, insulin, and potassium as below
- Start insulin gtt
- Start subcutaneous long-acting insulin as soon as insulin drip/IV insulin is started
  - Either start home long-acting (dose reduce as needed) or if insulin naïve, lantus 0.2-0.3u/kg/day
- Lactated ringers’ preferred fluid if no contraindication
- Dextrose should be added when BG <200 (or clear liquid diet)
- Turn off insulin drip when anion gap is closed on two consecutive BMPs. Make sure your long acting insulin has been given at least four hours prior to drip being turned off
Consult endocrinology early
Management algorithm below (Diabetes Care. 2009 Jul; 32(7): 1335–1343)
Note: pts are usually deficient in total body potassium even if their serum potassium is high

Additional Information¶

Pts on insulin drip can be admitted to stepdown (8MCE) with order set
Pts can be admitted to stepdown on a subcutaneous insulin protocol with mild DKA with endocrinology guiding insulin management
Avoid ordering C-peptide if concern for new type 1 diabetes, beta islet cells can be "stunned" with recent hyperglycemic states and may be falsely low
SGLT2 inhibitors are being prescribed much more often and can cause a euglycemic DKA, where acidosis and ketosis present but no elevated BG. These patients still require an insulin gtt until their acidosis has improved and their gap closed, regardless of BG level

initial management of dka

Hyperthyroidism¶

Griffin Bullock

Background¶

Low TSH and High T4 and/or T3 (primary): Graves’ disease, Toxic goiter, TSH-producing adenoma, hyperemesis gravidarum, subacute granulomatous thyroiditis, amiodarone, radiation, excessive replacement, struma ovarii
Low TSH/Normal T4 and T3: Subclinical hyperthyroidism, central hypothyroidism, non-thyroidal illness, recovery from hyperthyroidism, pregnancy (physiologic)
Subclinical Hyperthyroidism: repeat testing to verify abnormality is not transient

Presentation¶

Anxiety, emotional lability, heat intolerance, tremor, palpitations, increased appetite, unexplained weight loss, new onset atrial fibrillation, myopathy, menstrual disorder, exophthalmos, tachycardia, pretibial myxedema, hyperreflexia, lid lag, changes to hair or skin

Evaluation¶

TSH, free T4, free T3 (only T3 or T4 may be elevated, though both often are)
Biotin affects assay, causes falsely ↓ TSH and falsely ↑ FT4/FT3
CBC: May have a normocytic anemia due to increased plasma volume

Management¶

Thyrotropin antibodies (Graves-specific test, not sensitive)
Radioiodine uptake scan if thyrotropin antibodies negative
- Note: if pt has had a contrasted study wtih radioactive iodine in the past 6 weeks, the RAI update scan will not be helpful
Treatment: methimazole, PTU, beta blockers, radioiodine ablation, surgery
Pts should be referred to endocrinology for treatment plan based on work up

Hypoglycemia¶

Will Bassett

Background¶

Definition: BG <70 mg/dL in a patient on insulin or an oral hypoglycemic; <55 mg/dL for other patients
- Generally worse outcomes than hyperglycemia
Causes: infection, liver failure, iatrogenic (e.g. insulin not adjusted for AKI or being NPO)
Symptoms vary from tremor, palpitations, delirium, dizziness, AMS, coma

Management¶

Give PO carbohydrate load (15-20g oral glucose) if pt is alert and tolerates PO
Give IV D50 if severe (<50), or cannot take PO
Repeat measurements after 15 minutes and treat again as needed
- As a rule of thumb, 15g of carbs should raise BG within 15 minutes
Give glucagon 0.5-1mg SQ/IM if no IV access and impaired consciousness
- Effect is transient and IV access should be obtained ASAP for glucose infusion
Do NOT hold basal insulin for T1DM: treat the low, then reduce dose if needed

Hypothyroidism¶

Griffin Bullock

Background¶

Elevated TSH and low FT4 (primary hypothyroidism)
- Hashimoto’s (autoimmune) thyroiditis, iodine deficiency, drugs (amiodarone, dopamine antagonists), adrenal insufficiency, thyroid hormone resistance (genetic), non-thyroidal illness (recovery phase), post-surgery or ablation for hyperthyroidism
Elevated TSH and normal FT4: subclinical hypothyroidism
Low-Normal TSH, low FT4: central hypothyroidism, sick euthyroid

Presentation¶

Often non-specific and vague: fatigue, cold intolerance, weight gain, constipation, dry skin, myalgia, edema menstrual irregularities, depression, mental dysfunction
Goiter, bradycardia, diastolic hypertension, delayed relaxation following reflex testing
Lab abnormalities: microcytic anemia, hypercholesterolemia, hyponatremia, elevated CK

Evaluation¶

TSH: If elevated repeat TSH and obtain T4
Lipid panel, CBC, BMP

Management¶

Treatment required if ↓ T4, significantly ↑ TSH (>10), or symptoms with any lab abnormality
Titrate therapy to a normal TSH (unless central hypothyroidism, then target free T4 levels)
Observation of asymptomatic pts with subclinical hypothyroidism (normal T4, mild ↑ TSH)
Treatment is with formulation of T4 (full replacement is approximately 1.6 mcg/kg/day)
Initial Dose:
- Young/healthy patients: full anticipated dose
- Older patients or patients with CAD: 25-50 mcg daily
Increased doses required for: pregnancy, estrogen therapy, weight gain, PPI therapy, GI disorders (↓ absorption), ferrous sulfate therapy

Additional information¶

Pts should take Levothyroxine alone, 1 hr prior to eating to ensure appropriate absorption
Of note, missed doses can be taken along with the next dose
Symptoms improve in 2-3 weeks. TSH steady state requires 6 weeks
Dose can be titrated every 6 weeks based on TSH
Pregnancy: Pregnancy causes lab changes due to differing levels thyroid binding globulin. Use tables based on trimester to interpret values
- TPO antibody testing should be conducted if abnormal as this affects risk of complications
Hypothyroid pts are at increased risk for preeclampsia, placental abruption, preterm labor/delivery
Refer to endocrine for close monitoring and adjustment to avoid fetal complications
Inpatients who are pregnant and have abnormal TFTs warrant endocine consult.

Severe Hypertriglyceridemia (HTG)¶

Chloe de Crecy

Background¶

Elevated triglycerides (TG) on a fasting lipid panel
- Normal: <150 mg/dL
- Moderate HTG: 150-499 mg/dL
- Moderate to severe HTG: 500-999 mg/dL
- Severe HTG: >1000 mg/dL
Nearly all patients with severe HTG have a genetic predisposition and an additional factor known to raise serum TGs (e.g. diabetes, alcohol abuse, oral estrogen therapy, hypothyroidism, nephrotic syndrome, propofol, ART, pregnancy)
Risks of hypertriglyceridemia: pancreatitis (can occur if serum TG >500 mg/dL), ASCVD
Signs: xanthomas, hepatosplenomegaly, lipemia retinalis, milky appearance of plasma
Symptoms: short-term memory loss, abdominal pain, flushing with alcohol

Evaluation¶

Order lipid panel for: usual outpatient screening, acute pancreatitis, cutaneous xanthomas, family members with familial HTG, monitoring HTG treatment
Note: Sodium, glucose, amylase, LDL readings can be affected by HTG
Consider sending A1c, Cr, TSH
Assess medication list for secondary causes

Management¶

HTG induced pancreatitis
- If pt has hypocalcemia, lactic acidosis, or multi-organ dysfunction
  - Initiate plasmapheresis and monitor serum TG after each cycle until <500
  - Severe dietary fat restriction (<5%) until TG <1000
- If none of the above and pt is hyperglycemic
  - Start insulin gtt, IVF, monitor q1h BG and q12h TG
  - Discontinue insulin when serum TG <500
  - Severe dietary fat restriction (<5%) until TG <1000
- If none of the above and patient is euglycemic
  - Monitor q12h TG until <500
  - Severe dietary fat restriction (<5%) until TG <1000
  - Consider initiation of insulin gtt as well (regardless of BG level) as insulin will help metabolize TG particles
Long-term Management (once TG <1000, otherwise decreased efficacy)
- Pharmacologic: fibrates (most commonly fenofibrate), statins, niacin, omega-3 fatty acids
- Nonpharmacologic: discontinue alcohol use, dietary fat and sugar restriction (target fat intake at <10% of calorie intake), exercise

Steroid Conversions¶

Neil Phillips

Drug Name	Equivalent doses (mg)	Anti-inflammatory activity relative to hydrocortisone	Duration of action (hrs)
Hydrocortisone (cortisol)	20	1	8 to 12
Cortisone acetate	25	0.8	8 to 12
Prednisone	5	4	12 to 36
Prednisolone	5	4	12 to 36
Methylprednisolone	4	5	12 to 36
Triamcinolone	4	5	12 to 36
Dexamethasone	0.75	30	36 to 72
Betamethasone	0.6	30	36 to 72

Stress Dose Steroids¶

Griffin Bullock

Primary Options¶

Dexamethasone 4 mg IV: does not affect cortisol assays, ideal if diagnosis uncertain
Hydrocortisone 100 mg IV bolus then 50 mg q8h until stable: greater mineralocorticoid activity. Ideal if adrenal insufficiency known/confirmed or if hyperkalemic (K>6.0)

When to Use¶

Concern for adrenal crisis
Patients with known adrenal insufficiency:
- Minor Illness: ↑ dose x3 for 3 d or until clinically improved & acute stress resolved
Surgery: dependent on severity of operation
- Minor (e.g. hernia repair): hydrocortisone 25 mg for 1 day
- Moderate (e.g. cholecystectomy): 50-75 mg day of surgery and post-op day 1
- Major (e.g. CABG): 100-150 mg daily 2-3 days (would consult endocrine in this setting)
- Trauma, critical illness, or unclear give stress dose

Thyroid Nodules¶

Terra Swanson

Background¶

~50% of adults will have a thyroid nodule on ultrasound
Benign: goiter, cyst, inflammatory, Hashimoto’s, follicular adenoma (microadenoma)
Malignant: follicular, papillary, medullary, anaplastic, metastatic, thyroid lymphoma
Risk factors for malignancy: age <30, head or neck radiation, family history of thyroid cancer

Evaluation¶

TSH, Free T4, Thyroid U/S

Management¶

If Low TSH: Likely a hyperfunctioning "hot" nodule (benign in 95% of cases)
- Order Iodine-123 or technetium-99m thyroid scan
  - If hyperfunctioning → measure T3/free T4 if ↑, treat for hyperthyroidism
  - If non-functioning → proceed as if TSH were normal
Normal or elevated TSH:
- FNA indicated based on U/S findings listed below (determined by TI-RADS system)
  - Nodules >1 cm that have high- or intermediate-suspicion pattern
  - Nodules >1.5 cm that have low-suspicion pattern
  - Nodules >2 cm that have very-low-suspicion pattern
FNA cytology determines the plan of action:
- Benign → periodic US monitoring at 12-24 months, then at increasing intervals
- Indeterminate → repeat FNA in 3-12 months
- Malignant → surgical referral
Nodules that do not meet FNA criteria, US findings determine the timing for follow-up imaging:
- High suspicion: 6-12 months
- Low to intermediate suspicion: 12-24 months
- Nodules >1 cm with very ↓ suspicion OR pure cyst: >24 months if at all
Nodules <1 cm with very ↓ suspicion OR pure cyst: no further imaging necessary

Thyroid Storm¶

Gaby Schroeder

Background¶

Diagnosis is based on recognition of exaggerated signs/symptoms of thyrotoxicosis leading to multi-organ dysfunction in the setting of precipitating event
Common Precipitants: Grave’s Disease, surgery, trauma, pregnancy, stress, infection, MI/PE, medication non-compliance, iodine loads
Use Burch-Wartofsky Point Scale (BWPS); available on MD Calc
- > 45: highly suggestive
- 25-44: impending storm
- \< Less than 25: unlikely to represent storm

Management¶

ENDOCRINE EMERGENCY - if suspected consult Endocrine ASAP
Therapies directed towards thyroid gland
- PTU: Preferred because it inhibits peripheral conversion of T4 -> T3 as well as production of T4, 500-1000mg loading dose, followed by 250mg q4 -6 hours (PO, rectal)
- Methimazole: q4-6 hours, dose varies (PO, rectal, IV)
Therapies directed toward decreasing T4 to T3 conversion
- Propranolol (60-80mg PO q4)
- Hydrocortisone (300mg x1, 100mg q8) - treats high incidence of co-existing adrenal insufficiency
Cholestyramine 4g QID can be considered to reduce enteric recirculation
Refractory Storm: plasmapheresis and plasma exchange
Close hemodynamic monitoring, may need vasopressors (consider transfer to ICU)

Ended: Endocrinology

Gastroenterology ↵

Acute Abdominal Pain¶

Alex Mamunes

General Approach¶

Rule out life threatening causes: Obstruction, Perforation, Dissection, AAA rupture, Inferior MI, Ectopic Pregnancy
History: pain quality/timing/location/severity, aggravating and alleviating factors (eating, bowel movements, position), nausea/emesis, bowel changes, flatus & prior episodes
Initial labs: CBC, BMP, LFTs, INR, lactate, lipase, U/A, urine hCG

System	Causes	Common features	Workup
Esophagus	Esophagitis – GERD, EOE, candida, HSV, CMV, pill, functional	Epigastric pain, nocturnal reflux, odynophagia, dysphagia, thrush, immunocompromised	Trial PPI, nystatin swish and swallow, consider EGD
Stomach	Dyspepsia	Epigastric pain, indigestion, bloating	H. pylori testing, Trial PPI, ± EGD
	Peptic ulcer disease	NSAID use, better or worse w/ food, ± melena	CBC, H. pylori testing, EGD
	Gastritis	NSAID use, ETOH abuse, burning epigastric pain
Liver	Hepatitis: Ischemic, Viral, ETOH, trauma, toxins, autoimmune, congestive	RUQ pain ± jaundice EtOH, Tylenol or IVDU	LFTs, INR, ETOH, Tylenol lvl, viral panel, RUQ U/S + dopplers; CT
Spleen	Splenomegaly: increased size, infarct, abscess	LUQ pain	Physical exam, CT
Biliary	Biliary colic	Overweight, ♀, 40’s, lasts hrs, worse with food, RUQ pain scapula	LFTs, RUQ U/S
	Cholecystitis	RUQ pain (Murphy’s sign), nausea, emesis with fever
	Choledocholithiasis	RUQ pain, N/V with jaundice	CBC, LFTs, RUQ U/S, blood cx
	Ascending cholangitis	RUQ pain, N/V, jaundice, fever; hypotension, AMS
Pancreas	Acute or chronic Pancreatitis; Complications (fluid, collection, necrosis, pseudocyst)	ETOH use, gallstones, epigastric pain back, N/V Chronic pancreatitis: calcifications on CT	Lipase, CT A/P (rarely necessary within 24-48 hrs), RUQ U/S for gallstones
Intestines	Gastroenteritis	N/V, sick contact, undercooked food, travel	Supportive care
	Diverticulitis	Older, h/o diverticulosis, LLQ pain with fever	CBC (leukocytosis) CT A/P w contrast
	Constipation	h/o IBS, narcotic use, unable to pass stool, straining	KUB
	Bowel Obstruction/Ileus	Prior hernia, abd surgery or malignancy, pain, nausea, emesis, distention inability to pass stool or flatus	KUB (air fluid levels) CT is more sensitive If concerned, page EGS and consider NGT to suction
	Acute Small Bowel Mesenteric Ischemia	Vascular disease, A-Fib, dissection, thrombosis, rapid onset, severe, periumbilical with N/V, recent hypotensive episode, post-prandial	CBC (leukocytosis) BMP (metabolic acidosis), Lactate CT A/P w contrast (CTA if suspicion)
	Colonic non-occlusive Mesenteric Ischemia: ischemic colitis	Cramping pain, laterally (most often left), urge to defecate + hematochezia	CBC, BMP, Lactate CT A/P w contrast +/- colonoscopy
	Appendicitis	Periumbilical to RLQ with N/V, later fever	CBC, Lactate, CT A/P w/contrast
	IBD Flare	H/o Crohn’s or UC, Abd pain, fever, diarrhea, hematochezia	CBC, Lactate, CTE, ESR, CRP, C-diff, GIPP
	C. diff colitis	Antibiotic exposure, diarrhea, abdominal cramping	C-diff PCR, CBC (leukocytosis) KUB (megacolon)
	Ogilvie’s syndrome	Pseudo-obstruction in elderly pt, signs of obstruction w/o mechanical cause	CBC, lactate, CT A/P w contrast
	Volvulus	Progressive abdominal pain, nausea, distention, constipation, vomiting	CBC, lactate CT A/P w contrast
	Typhlitis	Neutropenia, abdominal pain (often RLQ), fever	CBC with diff, CT A/P w/ contrast, blood cx, C-diff; empiric abx
OBGYN	Ectopic pregnancy	Sexually active, 6-7 wks after LMP, RLQ or LLQ pain + vaginal bleeding	Urine hCG, pelvic US, CBC, T&S
	Pelvic inflammatory disease, endometritis, Tubo-ovarian abscess	Sexually active, h/o STI, purulent discharge, cervical motion tenderness, ± fever	Pelvic exam w/ culture, GC probe, pelvic US
	Ovarian torsion	Young, sudden onset & severe, often with N/V	Pelvic US w/ doppler
Kidney	Nephrolithiasis	h/o kidney stones, Crohn’s disease, sharp flank pain, paroxysms, ± hematuria	U/A, CT A/P without contrast
	UTI	Suprapubic pain, dysuria, cloudy urine, new odor	U/A with culture
	Pyelonephritis	Flank pain, fever/chills, CVA tenderness, usually UTI symptoms	U/A with culture, BMP CT A/P w/contrast
	Urinary Retention	Older pt, male with BPH, anticholinergics	Post-void residual
	Renal infarct	h/o vascular disease or A-fib, acute flank pain with N/V, +/- fever, HTN	CBC, BMP, UA, ECG (r/o a-fib) CT A/P w contrast
Vascular	Myocardial infarction	CAD risk factors, DoE, epigastric, diaphoresis	ECG, troponin
	Aortic Dissection	Vascular Risk factors, sudden onset, tearing pain back	CT dissection rule out
	AAA rupture	Vascular risk factors, sudden onset back, hypotensive, pulsatile abdominal mass	CT A/P w contrast, consult vascular surgery
MSK/skin	Herpes zoster	Immunocompromised, dermatomal rash, burning pain	Physical exam Vesicle PCR for zoster
	Muscle strain	h/o trauma, overuse, heavy exercise, worse with twisting or bending	Physical exam; rest, NSAIDs
	Hernia	Bulge, worse w/valsalva	CT A/P non con
Pulmonary	Pneumonia	Productive cough, fever	CXR, CBC, sputum cx
Pulmonary	Pulmonary embolus	Tachycardia, tachypnea, hypoxemia	ECG, trop, BNP CTA chest
Functional	IBS, depression, dyspepsia, anxiety abdominal migraine, functional	Imaging negative Otherwise negative workup	Above workup
Other	Adrenal crisis	Hypotension, fatigue, lethargy, N/V, weight loss, hyperpigmentation	BMP (↓Na, ↑K, ↓ Glu) Cort. stim
	Intra-abdominal abscess	Prior intra-abdominal disease or surgery, fever	CBC, blood cx CT A/P w/ contrast
	DKA	Nausea, emesis, general abdominal pain	CBC, BMP, U/A β–hydroxy butyrate
	Hypercalcemia	N/V, constipation, ↑ thirst, ↑ urination, bone pain, muscle weakness, confusion, fatigue	BMP, ionized calcium, PTH, Vit D, PTHrp
	Acute intermittent porphyria	Severe, poorly localized with motor/sensory neuropathy, red urine, tachycardia	Urinary PBG

Acute Diverticulitis¶

Michael Koenig

Background¶

Inflammation and/or infection of a diverticulum, a small out-pouching along wall of colon
Presence of colonic flora on urine culture or pneumaturia suggests colovesical fistula
Most pts with uncomplicated diverticulitis have significant improvement 2-3 days after antibiotics

Presentation¶

Lower abdominal pain (85% LLQ), tenderness to palpation on exam, N/V, low-grade fever, change in bowel habits (constipation or diarrhea)

Evaluation¶

CBC w/diff, CMP, Lipase, U/A, β - hCG
Imaging: CT abdomen/pelvis with oral and IV contrast
CT findings: localized bowel wall thickening (>4mm), paracolic fat stranding, presence of colonic diverticula

Management¶

Bowel rest vs. clear liquids (advance diet as tolerated)
PO or IV antibiotics: should cover GNRs and anaerobic organisms
Zosyn, cefepime + metronidazole, or meropenem (if high risk for organisms w/ESBL)
Cipro/flagyl if PO
If low risk and mild disease, may not need antibiotics
Continue IV abx until abdominal pain/tenderness is resolved (usually 3-5 days), then transition to oral: cipro + metronidazole or Augmentin to complete 10-14 d course
Colonoscopy after complete resolution of symptoms (6 – 8 weeks) to definitively rule out presence of underlying colorectal cancer (unless performed in last year)

Complications¶

Pts who fail to improve or deteriorate require repeat imaging
Abscess continue antibiotics & percutaneous drainage (if possible) for abscesses > 4 cm
Surgery if no improvement 2-3 days after drainage
Obstruction: radiographic differentiation between acute diverticulitis and colon cancer is difficult; thus surgical resection of bowel is needed to relieve obstruction and rule out cancer
Fistula: Rarely heal spontaneously, require surgical correction
Perforation:
- Microperforation (contained perforation):
- Presence of small amount of air bubbles, but no oral contrast outside of colon on CT
- Most treated with IV abx and bowel rest like uncomplicated diverticulitis
- Frank perforation:
  - Intraabdominal free air, diffuse peritonitis requires emergency surgery

Acute Pancreatitis¶

Alex Wiles

Background¶

Common causes: Gallstones (40%), EtOH (30%)
Other causes: post-ERCP, pancreatic cancer/obstruction, blunt abdominal trauma, hypertriglyceridemia (TG >1000), hypercalcemia, drugs (thiazides, protease inhibitors, azathioprine, 6MP), mumps, Coxsackie, vasculitis, pregnancy, genetic (PRSS1, SPINK1, CFTR), autoimmune (IgG4), scorpion venom
Several scoring systems:
- BISAP (BUN >25, Impaired mental status, SIRS, Age >60, Pleural effusion)
  - 0–2 Mortality <2%; 3-5 Mortality >15%
- APACHE II (MD Calc, several factors)
  - 0–8 Mortality <4%; > 8 Mortality 11–18%

Presentation¶

Must have 2 out of the three:
- Pain characteristic of pancreatitis (sharp, epigastric, radiating to back)
- Imaging characteristic of pancreatitis (US, CT, MRI)
- Enzymes (lipase or amylase) >3x ULN (use lipase, much more specific)
- *If pain is characteristic and lipase > 3x ULN, no need for CT A/P
Grading Severity:
- Mild: no organ failure or systemic complications
- Moderate: transient organ failure (<48 hours)
- Severe: persistent organ failure (>48 hours)

Evaluation¶

Lipase, CBC, CMP, lipid panel, lactate, direct bilirubin
Obtain RUQ U/S for all pts, evaluates for gallstones
CT A/P w/ IV contrast if indicated
- Reserved for patients not improving at 48-72 hour to assess for complications
- If performed at onset, underestimates severity (necrosis takes 72 hours from onset)

Management¶

Fluids, Fluids, Fluids:
- First 12-24 hrs: IVF at 200 to 500 cc/hr, or 5-10 cc/kg / hr (2.5 –
  
  4 L within first 24 hrs)
- Follow HCT and BUN as markers for successful fluid resuscitation
- Aggressive IVF in first 24 hours reduces both morbidity and mortality
- Persistent hemoconcentration at 24 hr is associated with necrotizing pancreatitis
Pain Control:
- Common starting narcotic regimen is oxycodone 10 mg q6h PRN and hydromorphone 0.5 mg q4h for breakthrough
Nutrition:
- NPO but start PO diet as soon as patient can tolerate (even within 24 hours)
- Clear liquid diet or mechanical soft and advance as tolerated
- Low fat diet (Fatty acids → CCK → trypsinogen to trypsin)
- If NPO > 72 hours, attempt PO and if fail, place Dobhoff for enteral nutrition at latest by day five… outcomes with NG/NJ >>> TPN
Antibiotics:
- Fever, leukocytosis common, not an indication for ABX as the necrosis is sterile
- Infection of the necrosis should be suspected with failure to improve 7 days after onset
- Cefepime + Flagyl or carbapenem
EUS or IR guided drain for aspirate: can be done on immature collections for diagnostic purposes but typically only done if collection is walled-off—at least 4 weeks
Endoscopic Intervention (cystogastrostomy) has emerged as first-line therapy for symptomatic pseudocysts or walled-off pancreatic necrosis , with step-up therapy to video assisted retroperitoneal debridement (VARD) or surgery when needed

Additional Information¶

If choledocholithiasis on Imaging urgent ERCP for patients with cholangitis or obstructive jaundice, otherwise elective ERCP
If Intermediate probability for choledocholithiasis MRCP or EUS or (for patients requiring cholecystectomy Intraoperative cholangiogram
If biliary sludge but no stones on U/S, still consider cholecystectomy (likely microlithiasis)
Complications:
- ARDS, abdominal compartment syndrome, AKI, DIC
- < 4 weeks after pancreatitis: Peripancreatic fluid collection, acute necrotic collection
- 6 weeks after pancreatitis: Pancreatic pseudocyst, walled-off necrosis (WON)
Most fluid collections should be followed over time as acute collections can resolve and are unable to be sampled safely with EUS
Gallstone pancreatitis:
- All pts should have cholecystectomy once recovered (recurrence is 25-30%) with EGS
- Performed during initial admission in cases of mild acute pancreatitis

Biliary Disease¶

Alex Wiles, Anton de Witte

Pearls¶

ERCP is not available at VA: requires fee-basis consult to VUMC, contact GI to arrange
Prior cholecystectomy CBD normally dilates to 10 mm, not pathologic
Pneumobilia generally indicates performance of prior biliary sphincterotomy and/or biliary stent
CBD dilation classically > 6mm, but CBD dilates with age: 70 yo 7mm, 80 yo 8mm; opiates can also cause biliary dilatation

Biliary Colic¶

Transient biliary obstruction typically at the GB neck without GB inflammation (no fever)
Presentation: Constant (not colicky) intense, dull RUQ pain and N/V for 30 minutes to 6 hours, then resolves, provoked by fatty foods (CCK), absent Murphy’s sign
Biliary colic generally consists of discrete episodes separated by weeks to months, and not daily pain
Evaluation: Normal (CBC, LFTs, Lipase, Lactate)
Imaging: RUQ U/S: cholelithiasis (stones in GB)
Management: Elective cholecystectomy as outpatient

Acute Calculous Cholecystitis¶

Inflammation of the GB from an obstructing stone in the GB neck or cystic duct
Ddx: PUD, pancreatitis, choledocholithiasis, ascending cholangitis, IBD, Fitz-Hugh Curtis
Presentation: Severe constant RUQ pain, fever/chills, N/V, + Murphy sign
Evaluation: CBC (leukocytosis), CMP (mild AST/ALT ↑), Lipase, Lactate, BCx x2
Imaging: RUQ U/S: gallstones + GB wall thickening or pericholecystic edema
- If U/S non-diagnostic (no stones or GB inflammation) HIDA Scan (lack of GB filling)
Management
- NPO, IVF, IV Abx until resolved or surgical removal
- Urgent Cholecystectomy (<72H) with EGS;
- If poor surgical candidate: Cholecystostomy with IR; endoscopic drainage options for selected patients (i.e. poor surgical candidates also with ascites)
Complications: gangrenous cholecystitis, perforation, emphysematous cholecystitis, chole-cysto-enteric fistula, gallstone ileus

Acute Acalculous Cholecystitis¶

Inflammation of the GB without obstructing stone (due to stasis and ischemia)
Presentation: Seen in critically ill/ICU pts; similar history as above; may present as unexplained fever or RUQ mass (rarely jaundice)
Ddx: calculous cholecystitis, pancreatitis, hepatic abscess
Evaluation: Same as acute calculous cholecystitis
Imaging: GB wall thickening, pericholecystic edema, intramural gas, GB distention
Management
- Supportive care, antibiotics, GB drainage
- IVF, correct electrolyte abnormalities, NPO
- Broad spectrum antibiotic coverage
- Place CT-guided procedure consult for cholecystostomy placement vs Endoscopic drainage (transpapillary cystic duct stent via ERCP or cholecystoduodenostomy by EUS)
- Consult EGS if necrosis, perforation, or emphysematous changes present

Choledocholithiasis¶

Obstruction of biliary outflow by CBD stone without inflammation (no fever)
Impacted cystic duct stone (cholecystitis) with compression of the CBD (Mirizzi syndrome)
Presentation: RUQ pain (can be painless), N/V and jaundice
Evaluation:
- CMP and D-bili (Bili/ALP/ GGT ↑↑↑, AST/ALT mild ↑), CBC (Leukocytosis suggests cholangitis), Lipase
- Imaging: RUQ U/S: dilated CBD (ULN is 6mm) MRCP/EUS vs ERCP (see below)
  - MRCP preferred given non-invasive but has lower sensitivity for smaller stones (consider EUS if still have suspicion despite negative MRCP or if patient contraindication to/intolerance of MRI)
Management:
- NPO & IVF, pain control PRN
- Stratify risk to determine whether to pursue MRCP (noninvasive, diagnostic) vs ERCP
- If any one of the following, patient is HIGH risk consult GI for
  
  ERCP + EGS to consider cholecystectomy
  - CBD stone on imaging
  - Acute cholangitis
  - Tbili > 4 AND dilated CBD (>6mm with GB, > 8mm without GB)
- If any one of the following, patient is INTERMEDIATE risk consider MRCP (or EUS or cholecystectomy with intraoperative cholangiogram)
  - Abnormal liver enzymes
  - Age > 55
  - Dilated CBD on U/S with Tbili < 4
  - If CBD stone seen on MRCP or EUS ERCP,
  - If no CBD stone but patient has GB sludge or cholelithiasis EGS consult for cholecystectomy + intraoperative cholangiogram

Acute Cholangitis¶

Bacterial infection of biliary tract 2/2 obstruction (typically stones) or prior instrumentation (ERCP)
Pts with malignant obstruction typically do not develop cholangitis
Presentation: Charcot triad (RUQ pain, fever, jaundice); Reynolds’ Pentad (AMS, Hypotension)
Evaluation
- CBC, CMP (D bili, ALP ↑↑↑) Blood Cultures, Lipase, Lactate
- CRP, AST/ALT can be ↑↑ as well
- Imaging: RUQ U/S: dilated CBD (ULN is 6mm), no need for MRCP/EUS
- Consider MRCP overnight if ERCP is not being done emergently
Management
- NPO, IVF
- Consult GI for urgent/emergent ERCP (generally within 24 hr)
- If ERCP not feasible or fails to establish biliary drainage, can consider EUS-guided biliary drainage, percutaneous transhepatic cholangiography, or surgical decompression
- Antibiotics for Biliary Disease (IDSA Guidelines):
  - Mild to moderate acute cholecystitis (stable):
  - Ceftriaxone 2g daily, Cefazolin 1-2g q8H
- Cholangitis or Severe acute cholecystitis (unstable or immunocompromised):
  - Zosyn 3.375g q8H, Meropenem 1g q8H or Cipro 500 q12H and Flagyl 500 q8H
- Healthcare-associated Biliary infections: consider Vancomycin (order w/ PK consult)

Clostridioides Difficile Infections¶

Anton de Witte

Background¶

Clostridioides difficile is the causative bacteria for antibiotic-associated colitis
Always consider C. diff in a hospitalized patient with unexplained leukocytosis
Microbiology: Anaerobic gram-positive, spore-forming, toxin-producing bacillus
Outside colon, exists in spore form – resistant to heat, acid, and antibiotics (why we must wash our hands)
Spores are transferred from environment to person, once in intestine convert to functional vegetative, toxin-producing forms susceptible to antibiotics
To be pathogenic, must release toxin (A+B) to cause colitis and diarrhea
Risk Factors: Antibiotic use (during use or typically up to 1 month after use), age >65, hospitalization, enteral feeding, obesity, stem cell transplant, chemo, IBD, cirrhosis, ± PPI use (no clear causal relationship)

Presentation¶

Spectrum from asymptomatic carrier to fulminant colitis with toxic megacolon
Asymptomatic carrier: 20% of hospitalized patients (50% of adults in long term care facilities)
Non-severe disease: watery diarrhea (>3 unformed stools in 24 hours), lower abdominal pain, nausea, ± fever, leukocytosis (WBC >15,000)
Severe disease: diarrhea, diffuse abdominal pain, abdominal distention, fever, lactic acidosis, AKI (Cr > 1.5), marked leukocytosis (sometimes >40,000)
Fulminant disease: Severe criteria + hypotension/shock, ileus (rare), or megacolon (>7cm colon diameter and/or >12cm cecum diameter)
Recurrent disease (relapse > reinfection): resolution of symptoms on therapy followed by reappearance of symptoms within 2-8 weeks after stopping therapy; (Up to 25% of patients have recurrence)
If symptoms never resolve, consider refractory C. diff or alternative diagnosis

Evaluation¶

Stool PCR for toxigenic strains (very sensitive, can detect asymptomatic carriers w/o toxin production); with reflex EIA (enzyme immunoassay) for toxins A and B (specificity of 99%)
- PCR (+)/Toxin (-) = carrier
- PCR (+)/Toxin (+) = treat
- PCR (-) = no treatment
Imaging
- Nonsevere disease: no imaging necessary
- Severe or fulminant disease: CT a/p with oral and IV contrast
Endoscopy: Typically used when alternative diagnosis is suspected; not warranted for classical symptoms, positive laboratory tests, or clinical response to treatment

Management¶

Contact precautions until at least 48 hours after diarrhea resolves
Classify patient disease severity to guide treatment algorithm
Do not repeat stool testing – 50% remain positive after treatment up to 6 weeks later

Clinical Condition	Treatment
Non-fulminant disease
Initial episode (non-severe or severe)	-First line: PO Vancomycin 125mg QID x 10 days OR PO Fidaxomicin 200mg BID x 10 days -Second line: (only for non-severe disease in low-risk patients): PO Metronidazole 500mg TID x 10-14 days
Recurrent episode	Consult GI First Recurrence: -First line: PO Fidaxomicin 200mg BID x 10 days -Second line: Vancomycin Taper (PO 125mg QID x 14 days PO 125mg BID x 7 days PO 125mg QD x 7 days PO 125mg q72h x 2-8 weeks) -Adjunctive therapy: IV Bezlotoxumab 10mg/kg x1 Second or Further Recurrence: -Same as above -Consider Fecal Microbiota Transplantation (FMT)
Fulminant disease
Fulminant disease	Consult GI and EGS Ileus Absent: -PO Vancomycin 500mg QID + IV Metronidazole 500mg TID Ileus Present -Same as above + consider Vancomycin enemas 500mg q6h Consider colectomy or FMT

Chronic Pancreatitis¶

AJ De Witte

Definition¶

A syndrome characterized by irreversible chronic progressive pancreatic inflammation, fibrosis, and scarring, resulting in damage to and loss of exocrine (acinar), endocrine (islet cells), and ductal cells

Etiology¶

TIGAR-O mnemonic

Toxic Metabolic: EtOH, tobacco use, hyperCa (Ca > 12), HLD (fasting TG > 300, nonfasting > 500), CKD 5, medications, toxins
Idiopathic: early onset (age \< 35), late onset (age > 35)
Genetic: Autosomal dominant (PRSS1 gene), recessive (CFTR, SPINK1, etc.)
Autoimmune: IgG4-related (AIP type 1), AIP type 2
Recurrent, severe acute pancreatitis
Obstructive: pancreas divisum, ampullary stenosis, main duct pancreatic stones or strictures, widespread calcifications, mass causing duct obstruction

Presentation¶

Abdominal pain (most common)
Exocrine insufficiency: diarrhea, steatorrhea, weight loss
- Typically occurs later in disease process
Endocrine insufficiency: diabetes
Occasionally asymptomatic

Evaluation¶

Imaging: CT or MRI (may be negative early in course of disease)
- If CT or MRI negative but suspicion for CP remains high, consider EUS ± biopsy or secretin-enhanced MRCP
Labs:
- BMP, LFTs, lipid panel, PeTH
- Consider genetic testing, especially in younger patients and/or patients without clear etiology
- Pancreatic function testing diagnoses exocrine insufficiency but is not necessary for diagnosis of CP
  - Gold standard = 72-hour fecal fat (> 7g of fat per 100g stool per day) - rarely done
  - More practical = fecal elastase (<100 = diagnostic, 100-200 = indeterminate)
    - Must be performed on formed stool, can be false positive If watery specimen
    - Do not have to stop pancreatic enzymes to measure
- Lipase and amylase levels can be elevated, but are usually normal due to pancreatic scarring and fibrosis

Management¶

Tobacco and EtOH cessation
Pancreatic enzyme replacement therapy if evidence/diagnosis of exocrine insufficiency
- Usual dose: 50,000 units/meal + 25,000 units with snacks
- Should take with first bite of a meal and consider adding extra enzymes or splitting up dose throughout meal if lasting longer than 15 mins
- If lack of response: try increasing dose, confirm compliance, add PPI, split up dose throughout meal, look for concurrent GI disorders
Pain: Tylenol + NSAIDs > Opioids (Tramadol), consider SSRI/SNRI/TCA or gabapentin
- For refractory pain, other options include celiac plexus blockade or total pancreatectomy with islet auto transplant
Vitamin supplementation + Vit D + Ca
Consider antioxidants (selenium, ascorbic acid, β-carotene, and methionine, vitamin E) – mixed evidence but some studies have shown improved pain control
Routine testing for osteoporosis and fat-soluble vitamin deficiencies

Constipation¶

Chelsie Sievers

Background¶

Definition: presence of lumpy/hard stools, straining, use of digital maneuvers, sensation of incomplete evacuation, frequency \<3 BM per week.
Common etiologies: opioid-induced, medications (anti-depressants, iron, anticholinergics) hypothyroidism, hypokalemia, pregnancy, IBS, neurogenic (trauma, MS, Parkinson disease, diabetes, autonomic dysregulation).
Always think about risk of obstruction (prior abdominal surgeries, oncology history or risk for GI/GU malignancies, history of IBD/Crohn’s).

Evaluation¶

Evaluate etiologies plus lifestyle factors (low fiber intake, low fluid intake, reduced mobility, acute illness)
Clinical diagnosis, no need for imaging unless concerned for obstruction → KUB/ CT
BMP + Mg to evaluate electrolytes, consider TSH if chronic
Rectal exam to exclude rectal mass or fecal impaction (constipation + diarrhea doesn’t exclude impaction/obstruction. Overflow around mass = encoparesis)

Management¶

Stop or minimize offending medications if possible
Optimize lifestyle factors: out of bed, walking hallways, increase fluid intake, + cup of coffee if appropriate.
Escalating pathway: ensure meds are scheduled not PRN
- MiraLAX (PEG) 17g BID (can give TID) + Senna nightly (can > increase to BID and/or 2 tabs) → Bisacodyl suppository → enema > (tap water or SMOG) → stronger osmotic laxative (lactulose > 20mg once, Mag-citrate, Golytely) → escalate lactulose dosing > 20 – 30 mg q2hrs
Other considerations:
- Avoid Fleet enemas (sodium-phosphate) in CKD and geriatric > populations
- “The hand that writes for opioids also writes a bowel regimen”
  - Generally, start with scheduled MiraLAX (PEG) 17g daily + senna nightly
  - If severe and unrelieved by escalating therapies, can try methylnaltrexone
- Lactulose can cause severe bloating and cramping
- In patients unable to take PO: place DHT to deliver meds or rectal lactulose (important for patients with cirrhosis with AMS/HE).
- In patients with CF (at risk for distal intestinal obstruction syndrome): ensure have pancreatic enzymes ordered, managed more like constipation than true obstruction: PO/ NGT MiraLAX QID or Golytely.
- Acute colonic pseudo-obstruction (Ogilvie's syndrome): >12cm cecal diameter = severe dilation, risk of perforation. Treated with neostigmine, 2mg IV over 3 to 5 minutes. Monitor for bradycardia, hypotension, and dysrhythmias (relative contraindications: recent MI, asthma, PUD, epilepsy). Decompression with colonoscopy used in some cases.
- Consider pelvic floor dysfunction, pelvic floor PT may be helpful

Laxatives
Mechanism	Examples	Effects
Bulking-agent	Psyllium seed (Metamucil), methylcellulose (Citrucel)	Absorb water and increase fecal bulk
Osmotic Laxatives	Polyethylene glycol (PEG = MiraLAX and Golytely), lactulose, mag-citrate	Hyperosmotic substances, pull fluid into GI tract
Stimulant Laxative	Senna, Bisacodyl (Dulcolax)	Stimulates peristalsis
Stool Softener	Docusate (Colace)	Generally ineffective
Opioid antagonist	Methylnaltrexone (Reslistor)	Peripheral acting opioid antagonist, inhibits opioid-induced decreased gastrointestinal motility
cGMP Agonist	Linaclotide (Linzess), Plecanatide (Trulance)	Stimulates intestinal secretion of Cl-/HCO3-
Prostaglandin derivative	Lubiprostone (Amitiza)	Increases intestinal chloride-rich fluid secretion

Diarrhea¶

Charles Oertli

Background¶

3 BM/day OR abnormally loose stool
Acute (<2 weeks), persistent (2-4 weeks), or chronic (>4 weeks)
95% of acute diarrhea is self-limited & no additional treatment needed
Most cases of acute diarrhea are due to infections
Non-infectious etiologies become more common with increasing duration
Voluminous watery diarrhea more likely disorder of small bowel
Small volume frequent diarrhea more likely disorder of colon
Nocturnal diarrhea suggests an inflammatory or secretory etiology

Acute Diarrhea¶

Etiology¶

Watery diarrhea: viral gastroenteritis (norovirus, rotavirus, enteric adenovirus), C. diff, C. perfringens, S. Aureus, Bacillus cereus, enterotoxigenic E. coli, Cryptosporidium, Listeria, Cyclospora, vibrio cholerae, (Giardia is typically more chronic), Tropheryma whipplei, COVID
Inflammatory diarrhea: Salmonella, Campylobacter, Shigella, EHEC, Yersinia, E histolytica, invasive viruses (CMV, HSV), Non-cholera vibrio. Look for red flag symptoms (see below).
Medications, specifically antibiotics

Presentation¶

Evaluate for red flags (BATS are Vulnerable vampires)
- Bloody stools,
- Antibiotics/Recent hospitalization
  - Any antibiotic can cause C. diff; the longer the treatment, the more likely
  - Most common to cause C. diff: Clindamycin >> Penicillins/Cephalosporins/Fluoroquinolones
- Too many stools: >6 unformed stools/day
- Sepsis (Fever) or Severe abdominal pain
- Vulnerable (Age >70 yr, immunocompromised, IVDU, IBD, pregnant, travel)

Evaluation¶

All patients: CBC w/ diff and BMP to eval for leukocytosis (C.diff), AKI, electrolyte abnormalities, thrombocytopenia/anemia (HUS), eosinophilia (parasites)
If red flag symptoms or diarrhea > 7d: ESR/CRP, C.diff, GIPP
If immunocompromised: consider CMV, MAC, microsporidia
If abdominal pain: consider CT A/P with IV contrast
If concern for IBD or hx of IBD: CT Enterography with PO and IV contrast
Blood Cultures if febrile/septic

Management¶

All patients: supportive care with PO or IVF, electrolyte repletion
If C.diff negative or treatment for C.diff started, ok for symptomatic treatment with Loperamide
- Start with Loperamide 4mg x1 then transition to 2mg QID (AC+HS) (maximum 16mg/day)
- If fever or inflammatory symptoms and C.diff not back, ok for Bismuth subsalicylate (Pepto-Bismol) 30mL or 2 tablets q30min x8
Indications for antibiotics:
- GIPP negative for Shigella, 0157:H7 (can precipitate HUS) and salmonella (can prolong carrier state)
- Empiric antibiotic therapy ONLY if toxic appearance or high concern for progressive illness/decompensation
- Ciprofloxacin 500 mg BID or levofloxacin 500 mg daily x 3-5 days
- Azithromycin 500 mg daily x 3 days
- Ampicillin + gentamicin used for pregnant women to cover for Listeria
- C. diff positive (see section below)

Approach to Chronic Diarrhea¶

Causes of Watery Diarrhea
Secretory	Motility	Osmotic
Microscopic colitis Bile acid malabsorption Carcinoid Crohn’s disease Gastrinoma VIPoma Mastocytosis Addison’s disease	Hyperthyroidism Diabetes Amyloidosis Systemic scleroderma	Lactose intolerance Bile salt diarrhea Sugar alcohols: sorbitol, mannitol, xylitol
Meds: antibiotics, caffeine, colchicine, NSAIDs, antineoplastics, antiarrhythmics (digoxin), metformin, carbamazepine	Meds: macrolides, metoclopramide, bisacodyl, senna, pyridostigmine	Meds: citrates, lactulose, magnesium-containing antacids, mycophenolate, antibiotics, propranolol, hydralazine, procainamide
Functional: IBS

Malabsorption

Inflammatory

Celiac disease

Gastric bypass

Short bowel syndrome

Tropical Sprue

Whipple disease

Small intestinal bacterial overgrowth (SIBO)

Post-infectious malabsorptive diarrhea

Maldigestion

Pancreatic insufficiency

Hepatobiliary disorders

Diverticulitis

Ischemic colitis

Neoplasia

Radiation colitis

Arsenic poisoning

Microscopic colitis

Invasive infections: bacterial (tuberculosis, yersinosis), viral (CMV, HSV),

Parasites (amebiasis, strongyloidiasis)

Inflammatory bowel disease

Evaluation¶

Labs: CBC w/ diff, CMP, ESR/CRP, TSH, celiac serologies if high suspicion (anti-TTG)
Spot fecal elastase Steatorrhea (greasy, malodorous stools that float)
Colonoscopy indicated if alarm symptoms are present ( >45 yrs and hasn’t had one, or \<45 yrs and concern for IBD, CMV, ischemic colitis or microscopic colitis)
If concern for IBS: Rome IV criteria (see section on “IBS” below)

Management¶

IBS: trial elimination diet/low FODMAP, antidiarrheals
Pancreatic insufficiency: enzyme replacement (Creon), consult nutrition for assistance
Celiac: eliminate gluten, will need outpatient nutrition follow-up
Bile acid malabsorption: can try cholestyramine (can affect absorption of other meds)

Esophageal Disorders¶

Caroline Barrett

Dysphagias¶

Oropharyngeal dysphagia = difficulty initiating a swallow
Associated with coughing, choking, nasopharyngeal regurgitation, and aspiration
Causes: Structural (Zenker’s diverticula, malignancy, goiter, stricture, radiation injury, infection), Neuromuscular (stroke, Parkinson disease, dementia, ALS, MS)
Esophageal dysphagia: Difficulty swallowing several seconds after initiation; associated w/sensation of food getting stuck in esophagus
Dysphagia to solids = mechanical obstruction
- Foreign body: Inability to swallow solids and/or liquids, including oral secretions
  - Most common foreign body = food in esophagus
- Progressive: esophageal stricture, peptic stricture, esophageal, cancer
- Intermittent: esophageal ring/web, eosinophilic esophagitis (particularly in young pts)
Dysphagia to solids and liquids = motility disorder
- Causes: achalasia, scleroderma, distal esophageal spasm (DES), hypercontractile (nutcracker) esophagus

Evaluation¶

If oropharyngeal dysphagia: videofluoroscopic modified barium swallow and fiberoptic endoscopic evaluation of swallowing (FEES)
When to order barium esophogram:
- Pre-endoscopy if clinical history suspicious for proximal esophageal lesion (i.e. Zenker’s) or known complex stricture (post-caustic injury or radiation)
  - Don’t order if a food impaction is suspected or if imminent endoscopy
- Post-endoscopy if mechanical obstruction is still suspected (EGD can miss lower esophageal rings or extrinsic esophageal compression)
EGD if concerns for mechanical obstruction
Manometry for motility disorders

Management¶

Food impaction: IV glucagon to relax lower esophageal sphincter to allow food passage
Otherwise, requires urgent upper endoscopy for removal
Additional management is specific to the final diagnosis

Odynophagia¶

Pain with swallowing
Associated with esophagitis

PIECE mnemonic for esophagitis:

Pill-induced: NSAIDs, ART, KCl, doxycycline, bisphosphonates
- Discontinue culprit med or substitute with liquid formulation; prevent by taking culprit meds w/ 8oz water and sit upright for 30 mins after
Infectious: usually in immunosuppressed pts
Candida Esophagitis: most common in HIV or heme malignancies, pts on antibiotics and steroid use
- Can exist without OP thrush
- Diagnosis: white mucosal plaque-like lesions on EGD biopsy and culture
HSV Esophagitis. Occurs most commonly in solid organ, BMT transplant recipients, and immunosuppressed patients
- Diagnosis: well-circumscribed ulcers on EGD, biopsy or brushings of ulcer edge
- Rx: acyclovir 400mg PO five times daily for 14-21 days (immunocompromised) or acyclovir 5mg/kg IV q8h for 7-14 days if unable to tolerate PO; 200mg PO five times daily or 400mg PO three times daily for 7-10 days (immunocompetent)
CMV Esophagitis: suspect in HIV pts w/ CD4\<50
- Diagnosis: linear/longitudinal ulcers on EGD, biopsy
- Rx: ganciclovir 5mg/kg IV q12h for 21-42 days; change to PO once pt able to tolerate; If contraindication to ganciclovir (leukopenia, thrombocytopenia) can use Foscarnet. PO valganciclovir can be used in patients who can tolerate and absorb oral medications. Treatment duration is 3-6 weeks based on expert opinion and response to disease
Eosinophilic Esophagitis (see below)
Caustic: alkali-induced injury, acid-induced injury, acute period (several days) following esophageal radiofrequency ablation for Barrett’s.
GERD (see below)

GERD¶

Background

Condition that develops when reflux of stomach contents causes symptoms and/or complications
Classified base on appearance of esophageal mucosa on EGD
Erosive esophagitis: endoscopically visible breaks in distal esophageal mucosa + GERD
Nonerosive reflux disease: presence of symptoms of GERD without esophageal mucosal injury

Presentation

Esophageal symptoms: heartburn, regurgitation, chest pain, dysphagia, globus sensation, odynophagia
Extra-esophageal symptoms: chronic cough, hoarseness
Complications: Esophageal stricture, Barrett’s esophagus, esophageal adenocarcinoma

Evaluation

Dx can often be made clinically in pts with classic heartburn and/or regurgitation
If dx uncertain, can perform ambulatory pH monitoring + impedance
EGD indicated for the following:
Presence of alarm features (dysphagia, persistent vomiting, GI cancer in 1º relative, odynophagia, GI bleeding, weight loss, iron deficiency anemia, ≥age > 60 y/o with new-onset GERD symptoms)
Risk factors for Barrett’s esophagus (duration of GERD at least 5-10 years [must be present], >50 yo, male, white, hiatal hernia, obesity, nocturnal reflux, tobacco use, first-degree relative w/ Barrett’s and/or adenocarcinoma)
Abnormal UGI tract imaging (i.e. luminal abnormalities).
Continued symptoms despite adequate PPI therapy

Management

Lifestyle and dietary modifications in all pts (weight loss; elevate HOB; avoid precipitants such as fatty foods, caffeine, alcohol, spicy foods, large meals, late night meals)
Mild/intermittent symptoms (\<2 episodes/wk) and no erosive esophagitis step-up therapy q4-8 wks until symptoms are controlled, then continue for at least 8 wks:
Low-dose H2RA prn standard dose H2RA BID (min 2 wks) discontinue H2RA and start daily low dose PPI standard dose PPI
Frequent symptoms (>2 episodes/wk, and/or severe symptoms that impair QOL) step-down therapy in order to optimize symptom relief
Standard-dose PPI daily (8 wks) low-dose PPI daily H2RA (if mild/intermittent symptoms) stop if asymptomatic
- PPIs should be prescribed at lowest dose and for shortest duration appropriate
- Instruct patients on optimal PPI use: most effective at gastric acid suppression when taken 30-60 minutes before a meal
- Taper if taking for >6 months and plan to discontinue
Medications:
- Low dose H2RA: famotidine 10mg BID
- Standard dose H2RA: famotidine 20mg BID
- Low dose PPI: omeprazole 10 mg daily
- Standard dose PPI: omeprazole 20 mg daily

Additional Information

Erosive esophagitis and Barrett’s esophagus:
- Require maintenance acid suppression with a standard dose PPI daily given likelihood of recurrent symptoms and complications if stopped
Recurrent Symptoms (⅔ of pts with nonerosive reflux disease relapse when acid suppression is discontinued):
- If ≥3 months after discontinuing repeat 8-week course
- If <3 months of discontinuing, EGD (if not already performed) to rule out other etiologies or complications

Eosinophilic Esophagitis¶

Background

Pt usually with a history of asthma/allergies/eczema
Dysphagia (most commonly to solid foods), food impaction, central chest pain, GERD/refractory heartburn, upper abdominal pain

Evaluation

Diagnostic criteria
Symptoms related to esophageal dysfunction
EGD with >15 eos/hpf on biopsy and exclusion of other causes
50-60% pts will have elevated serum IgE lvl; peripheral eosinophilia can be seen but is generally mild.

Management

Standard dose PPI for 8 weeks ± elimination diet if still symptomatic after 4 weeks, increase PPI to BID if responsive, continue PPI at lowest dose possible for symptom control
Alternative treatment is swallowed budesonide or fluticasone
Intermittent dilation of strictures to relieve dysphagia, but no effect on underlying inflammation
Should undergo evaluation by allergist, given strong association with allergies

Gastroparesis¶

Hashim Hayat

Background¶

Syndrome of objectively delayed gastric emptying in absence of mechanical obstruction
Etiology: Diabetes (most common), post-surgical (gastric or bariatric surgery), thyroid dysfunction, autoimmune or neurologic disorders, medication-induced (GLP-1 agonists, narcotics, anticholinergic agents

Presentation¶

Nausea, vomiting (may contain food eaten several hours prior), abdominal pain (dull, crampy; rarely a predominant symptom), early satiety, postprandial fullness, bloating, weight loss in severe cases

Evaluation¶

Exclude mechanical obstruction and mucosal disease with CTE and EGD
Scintigraphic gastric emptying study = gold standard for diagnosis (measures gastric retention of solids at 4h)
Stop medications that may affect gastric emptying 48 hrs prior to testing
Must have blood sugar \< 275 (Hyperglycemia delays gastric emptying)

Management¶

Support with IVF and electrolytes – PO intake preferred
Glycemic control in diabetics
Stop offending medications
Nutrition consult for teaching on frequent small volume meals that are low in fat and soluble fiber
If continued symptoms after above, try prokinetics and antiemetics
Prokinetics
- Liquid formulations preferred for better absorption
- Give 15min before meals and at bedtime.
- First line is Reglan. If no response, try Domperidone and subsequently erythromycin (not good for long term, pts develop tachyphylaxis)
Antiemetics: helps symptoms but do not improve gastric emptying
In severe cases patients may require enteral feeding (post pyloric preferred) or venting g-tube
Emerging endoscopic treatment options: G-POEM (gastric peroral endoscopic myotomy)

GI Bleeding¶

Matthew Meyers

Background¶

Intraluminal blood loss anywhere from the nasopharynx/oral cavity to the anus
Don’t forget epistaxis or oropharyngeal bleeding as possible source of melena
IV PPI prior to endoscopy may ↓ need for endoscopic therapy but does not impact transfusion requirement, rebleeding risk, need for surgical intervention, or mortality
Classification: relative location to the Ligament of Treitz (LoT)
Upper = proximal to LoT
- PUD, gastritis (alcohol, stress, NSAIDs, ASA), esophagitis, variceal bleed, Mallory-Weiss tear, AVM, Dieulafoy’s lesion, aorto-enteric fistula, gastric antral vascular ectasias, malignancy
Lower = distal to LoT
- Diverticular bleed, ischemic/infectious/IBD/radiation colitis, malignancy, angiodysplasia, anorectal (hemorrhoids, anal fissure), Meckel’s diverticulum, post-polypectomy bleed

Presentation¶

Hematemesis (very specific for upper GI bleed), hematochezia (usually lower although brisk upper possible), melena (usually upper), coffee-ground emesis, epigastric/abdominal pain, acute or chronic, hx of GI bleed and prior endoscopies, NSAID use, alcohol use, anticoagulant use, hx of cirrhosis
Exam: VITALS – assess stability to determine resuscitation needs, MICU vs. floor; orthostatic vs, rectal exam every time (smear stool on white tissue paper to look for melena), look for signs of cirrhosis (jaundice, palmar erythema, ascites, spider angiomata)

Evaluation¶

CBC, PT/INR, CMP, Lactic Acid, Blood Gas
EGD: usually best
Difficulty localizing GIB: pill-capsule, balloon enteroscopy Meckel’s scan, tagged RBC scan
Massive lower GI bleeds will require arteriography

Management¶

Secure airway (intubation) if comatose, extremely combative, or massive hematemesis
At least 2 large bore IV’s (> 18 gauge) – ask nurses directly to ensure these are placed
Maintain active type and screen
Bolus IVF to maintain MAP >65H/H monitoring q6-q12 hours; transfusions as indicated
IV PPI (pantoprazole) 40 mg BID if thought to be upper/possible ulcer
If cirrhotic, Ceftriaxone 1g daily for empiric SBP prophylaxis
If possibility of variceal bleed: Octreotide IV 50 mcg x1 then 50 mcg/hr drip x 3-5 days
NPO if unstable vs. clear liquids (no reds or purples) until morning for EGD
Never give prep to a patient for colonoscopy (GoLytely) without discussing with GI fellow
Consult gastroenterology to facilitate endoscopy
If endoscopy is unable to stop bleeding IR is next who can embolize
If embolization fails EGS for source removal

GI Manifestations of COVID¶

Taylor Riggs

Background¶

GI manifestations are reported up to 60% of patients with COVID
GI symptoms may be the only symptom or precede other symptoms
GI manifestations are felt to be due to expression of ACE2 receptor throughout the GI tract

Presentation¶

Diarrhea – more common in severe disease
~20% have diarrhea as first symptom of COVID; on average, lasts about 5 days
Nausea and vomiting – associated with more severe disease
Mesenteric ischemia – likely due to intestinal microvascular injury
Elevated liver enzymes – likely due to inflammatory response and direct virus-related toxicity
Hepatocellular pattern of injury most common; elevated bilirubin seen in severe disease
Usually self-limited
Pancreatitis has been reported in several cases, but no causal link has been established

Management¶

Largely supportive care
Monitor LFTs, coags, consider checking lipase if abdominal pain
If LFTs not improving after several days or underlying chronic liver disease, obtain RUQ U/S, consider hepatitis serologies
Consider medications/antiviral medications as culprit and discontinue as indicated

Irritable Bowel Syndrome¶

Hashim Hayat

Background¶

Diagnose by the Rome IV criteria, no longer a diagnosis of exclusion
Recurrent abdominal pain on average at least 1 day/week in the last 3 months with an onset at least 6 months prior, associated with two or more of the following criteria
- Pain related to defecation
- Change in frequency of stool
- Change in form (appearance) of stool
Patient has none of the following warning signs: >50yrs, evidence of GIB, nocturnal pain or BMs, unintentional weight loss, family hx of colorectal cancer or IBD, palpable abdominal mass or LAD, IDA, +FOBT
Classified based on predominant bowel habits
- Diarrhea: >25% BMs with Bristol stool types 6 or 7
- Constipation: >25% BMs with Bristol stool types 1 or 2
- Mixed: both of above

Evaluation¶

Thorough H&P for alarm symptoms as above
Consider limited testing with CBC, CMP, CRP, celiac serology, fecal calprotectin

Management¶

Treatment involves lifestyle and dietary modifications, psychosocial treatment, and pharmacologic treatment
Pain:
- Peppermint oil (smooth muscle relaxant) – IBGuard, Iberogast
- Antispasmodics: Hyosciamine acts faster than Dicyclomine
- TCAs: Amitriptyline or nortriptyline (causes less constipation so better in IBS-C)
Bloating:
- Low FODMAP diet
- Rifaximin as empiric treatment for SIBO
- No evidence for probiotics (can potentially worsen bloating 2/2 SIBO)
Bowel regulation:
- IBS-D: Start with Loperamide (up to 16g daily), consider Lomotil if refractory
- IBS-C: Miralax, fiber supplement (Ispaghula husk orange), Linzess (first line but can be expensive), Trulance, or Amitiza
Other
- Psychotherapy, CBT
- SSRIs, SNRIs for concomitant mood disorders
- Gabapentin, lyrica

Inflammatory Bowel Disease¶

Francesca Raffa

Background¶

Ulcerative colitis (UC): colon only (can have backwash ileitis); contiguous lesions; mucosal inflammation
Crohn’s disease (CD): any part of the GI tract; “skip lesions”; transmural inflammation
Important historical considerations to include in your documentation and presentation:
- Location of disease (CD: LB/SB, LB only, SB only; UC: proctitis, left-sided or pancolitis)
- Complications: Fistulizing, strictures, perianal, prior surgeries, current IBD treatment
- Include last endoscopies and imaging findings; current and prior IBD treatment and reason for transition (SEs, failure), primary IBD provider

Presentation¶

UC: frequent diarrhea (often bloody), tenesmus, urgency, abdominal pain; may have fever, malaise, and weight loss
- Complications: severe bleeding/anemia, fulminant colitis, toxic megacolon
CD: abdominal pain, nausea/vomiting, fever, malaise, weight loss; May also have diarrhea (± bloody depending on CD location)
- Complications: fistulas (entero-enteric, entero-vesicular, entero-cutaneous, rectovaginal, perianal, retroperitoneal), abscesses, strictures, obstruction
Extra-intestinal (EI): arthritis, sacro-iliitis, uveitis, episcleritis, aphthous ulcers, erythema nodosum, pyoderma gangrenosum, PSC (esp. UC), nephrolithiasis, thromboembolism

Evaluation¶

CBC w/diff, CMP, CRP, ESR, ± blood cultures
If diarrhea: GI Pathogen panel and C. diff
If anemic: obtain iron studies and type & screen
If weight loss or concern for malnutrition: albumin, pre-albumin, Vitamin D, B12, folate
Imaging:
- CT Enterography (oral contrast) preferred in CD, for luminal/extra-luminal complications
- How to order CTE: “CT abdomen pelvis enterography”, order barium (Volumen) 0.1% oral suspension x2, 1^st dose to be given by nurse 60 min before study, 2^nd study to be given 30 min before (nurse should be in contact with CT tech)

Management¶

Acute Flare
Pain control: usually a major component of hospital course
- Avoid NSAIDs, oral pain medications are preferred
- If pain is difficult to control, consider Acute Pain Service consult
- Narcotics and Imodium are contraindicated in toxic megacolon
Antibiotics: appropriately treat infections (intra-abdominal or perianal abscess) with antibiotics (consider prior culture data, often use cipro/flagyl)
VTE Prophylaxis: All IBD patients, even if having blood in stool (unless requiring transfusion) as they are at much higher risk of VTE
Nutrition: Nutrition consult for all IBD patients; For severe malnutrition or if prolonged bowel rest is needed, TPN is sometimes initiated
Anemia: Ferritin \<100 or iron sat \<20 with ferritin \<300, consider iron infusions (if no bacteremia) or transfuse for severe anemia
Smoking Cessation (esp. with CD): discuss smoking cessation & consult tobacco cessation
Consult Colorectal Surgery (not EGS): SBO, toxic megacolon, bowel perforation, peritonitis
Immunosuppression: (Infections must be ruled out and/or treated before starting)
Steroids:
- Methylprednisolone (Solumedrol); often 20 mg BID for three days
- Transition to oral (40 mg prednisone daily) once clinically improved/tolerating PO; typically prescribe a prolonged taper on discharge (often down by 5 mg every week)
- If severe proctitis: consider rectal steroids (hydrocortisone enema/foam)
If lack of response to steroids: additional medical therapy (biologics), bowel rest with TPN, or surgical intervention
- Infliximab (Inflectra) is available at VUMC
- If patient fails to respond to steroids, should consider possibility of CMV colitis (usually evaluated by biopsy on flex sig or colonoscopy)
- Prior to initiating a biologic, all patients must have the following negative studies within the last year: Quantiferon Gold and CXR, Hepatitis B serologies, HIV, urine histoplasma Ag (some providers)

Intestinal Ischemia¶

Michael Koenig

Acute Mesenteric Ischemia¶

Sudden onset ↓ or absence of blood flow to the small intestines
Mesenteric Arterial Occlusion:
- Arterial Embolism: Associated with cardiac arrhythmias (atrial fibrillation), valvular disease, endocarditis, ventricular aneurysm, aortic atherosclerosis, and aortic aneurysm
- Arterial thrombosis: Most commonly from atherosclerotic disease; can also be 2/2 abdominal trauma, infection, or dissection
Venous thrombosis:
- Associated w/ hypercoagulable states, malignancy, prior abdominal surgery, abdominal mass venous compression, intra-abdominal inflammatory processes
Non occlusive mesenteric ischemia:
- Intestinal hypoperfusion and vasoconstriction; associated with decreased cardiac output, sepsis, vasopressor use

Presentation¶

Early: Abdominal pain is most common symptom, abdominal distension
Abdominal tenderness is not prominent early (“pain out of proportion to the exam”)
Arterial occlusion: Sudden onset, severe periumbilical pain, nausea, and emesis
Venous thrombosis: More insidious onset abdominal pain, waxing and waning
Nonocclusive mesenteric ischemia: variable location and severity of abdominal pain; often overshadowed by a precipitating disorder
Late: As transmural bowel infarction develops, abdomen becomes distended, bowel sounds become absent, and peritoneal signs develop

Evaluation¶

Type and Screen, Lactic acid, BMP, CBC
Imaging: KUB: Normal in > 25% of cases
Ileus w/ distended bowel loops, bowel wall thickening, ± pneumatosis intestinalis
Free intraperitoneal air immediate abdominal exploration
CT Angiography: no oral contrast, obscures mesenteric vessels, ↓ bowel wall enhancement
Focal or segmental bowel wall thickening, intestinal pneumatosis, portal vein gas, porto-mesenteric thrombosis, mesenteric arterial calcification, mesenteric artery occlusion

Management¶

General: IVFs, NPO, hemodynamic monitoring and support (try to avoid vasoconstricting agents), anticoagulation, broad-spectrum antibiotics, pain control
If develops peritonitis or evidence of perforation on CT EGS consult for surgery
Mesenteric arterial embolism: Embolectomy vs. local infusion of thrombolytic agent
Mesenteric arterial thrombosis: Surgical revascularization vs. thrombolysis with endovascular angioplasty and stenting
Venous thrombosis: Anticoagulation; possible thrombolysis if persistent symptoms
Nonocclusive occlusion: Treat underlying cause, stop vasoconstriction meds, consider intra-arterial vasodilator infusion

Chronic Mesenteric Ischemia¶

Background¶

↓ blood flow to intestines, typically caused by atherosclerosis of mesenteric vessel
High-grade mesenteric vascular stenoses in at least two major vessels (celiac, SMA, or IMA) must be established

Presentation¶

Recurrent dull, crampy, postprandial abdominal pain
Pts develop food aversion and often have associated weight loss

Evaluation¶

CTA abdomen/pelvis is preferred (>90% sensitivity and specificity)
Can also consider duplex U/S and gastric tonometry

Management¶

Conservative management if asymptomatic: smoking cessation and secondary prevention to limit progression of atherosclerotic disease
Nutritional evaluation
Revascularization (open vs. endovascular) is indicated if symptoms are present
Mesenteric angioplasty and stenting is first-line therapy
Goal is to prevent future bowel infarction

Ischemic Colitis¶

Background¶

Sudden, transient reduction in blood flow to colon
Typically at “watershed” areas, such as the splenic flexure and rectosigmoid junction
Most often nonocclusive (95% of cases) and affects older adults
Risk factors: ACS, hemodialysis, shock, aortoiliac instrumentation, cardiopulmonary bypass, extreme exercise (marathon running)

Presentation¶

Rapid onset, mild cramping abdominal pain, associated with urge to defecate, hematochezia
Tenderness present (typically over left side)

Evaluation¶

Lactic acid (nonspecific but elevated), LDH, CPK, CBC (leukocytosis), BMP (metabolic acidosis)
KUB; if peritonitis or signs of severe ischemia → surgery
CT A/P with IV contrast (and oral contrast if patient can tolerate)
Consider CTA A/P if suspicion for vascular occlusion
Colonoscopy confirms diagnosis.
Edematous, friable mucosa; erythema; and interspersed pale areas; bluish hemorrhagic nodules representing submucosal bleeding
Segmental distribution, abrupt transition between injured and non-injured mucosa

Management¶

General: IVFs, bowel rest, antibiotics (Zosyn vs CTX/flagyl)

Ischemic Colitis Management
	Classification	Management
Mild	No risk factors (see below)	Supportive care and observation Antibiotics can be stopped if no ulceration
Moderate	1-3 risk factors	Same as mild ischemia if no vascular occlusion Systemic anticoagulation +/- vascular intervention if mesenteric occlusion
Severe	> 3 risk factors, peritoneal signs, pneumatosis, pneumoperitoneum, gangrene or pancolonic ischemia on colonoscopy	Consult EGS for abdominal exploration and segmental resection
Risk factors: male, SBP <90, HR >100, WBC>15k, Hgb <12, Na <136, BUN >20, LDH >350, isolated right-sided colonic involvement, abdominal pain with rectal bleeding

Nausea & Vomiting¶

Taylor Riggs

Etiology¶

VOMMIIT mnemonic

Vestibular: Labyrinthitis, vestibular neuritis, meniere’s disease, cerebellar stroke
Obstruction: adhesions, hernia, volvulus, constipation, gastric outlet obstruction
Motility: gastroparesis, GERD, autonomic dysfunction
Medications: antibiotics, SSRI, opioids, cannabinoid hyperemesis
Infection: gastroenteritis, hepatitis, pyelonephritis, cholecystitis
Inflammation: PUD, pancreatitis
Toxins: uremia, ketoacidosis, hypercalcemia, chemotherapy

Evaluation¶

All patients: CBC (leukocytosis, Hgb), BMP (AG, Ca, lytes, AKI), LFTs, lipase, lactate, UA
If risk factors: consider TSH, AM cortisol, troponin, β hCG, UDS
EKG to eval for ischemia and baseline QTc
Imaging:
- If concern for obstruction (abd distention, decreased BMs) KUB, consider CT A/P
- If concern for biliary pathology (RUQ pain, abnl LFTs) RUQ U/S
- If vestibular/concern for CNS pathology CTH vs MRI brain

Management¶

Address underlying cause and stop medications as appropriate

Many antiemetics prolong QTc, however in patients without underlying cardiac conduction abnormality, electrolyte abnormality, or organ failure the risk of QTc prolongation leading to significant arrhythmia is low.
Obtain screening EKG in patients with underlying heart disease, electrolyte abnormalities, organ failure or on other QTc prolonging meds (antiarrhythmics, antipsychotics, antibiotics)
4-8 mg of IV Zofran is estimated to prolong QTc by ~6ms
Try to pick a medication that will address the underlying etiology of nausea
If patient does not respond to a medication in a certain class, try a medication from a different class (see below)

Anti-Emetics
Med (by class)	Typical Dose	Side Effects	Prolongs QT?
Serotonin antagonists
Ondansetron (Zofran)	4-8mg PO/IV q6h	Constipation, headache, arrhythmia, serotonin syndrome	Yes
Granisetron (Kytril)1	1 mg PO BID, 2mg pre-chemo, OR 10mcg/kg IV pre-chemo	‘’	Yes
Dopamine Antagonists
Prochlorperazine (Compazine)	5-10 mg PO/IV q6h, 25 mg PR q6h	EPS, less sedation than H-blockers (e.g. Phenergan)	Yes
Haloperidol (Haldol)	0.5-1 mg PO/IV q6h	EPS, arrhythmia	Yes
Zyprexa (Olanzapine)	5 -10mg PO qdaily	EPS, constipation, anticholinergic	Mild ^
Dopamine and Serotonin Antagonists
Metoclopramide (Reglan)	10 mg PO/IV q6h	EPS/dystonia, arrhythmias, drowsiness/dizziness, diarrhea	Yes
GABA-A Agonist
Lorazepam (Ativan)	0.5-1mg PO/IV q6h PRN	Sedation, delirium, amnesia, respiratory depression	No
H1 Antagonists
Promethazine (Phenergan)	12.5 - 25mg PO /PR /IV q6h (avoid IV use if possible)	Sedation, EPS (D2 antagonist also), arrhythmias, blurry vision	Yes
Diphenhydramine (Benadryl)	25-50mg PO/IV q6h	Sedation, delirium, urinary retention, ileus	Yes
Meclizine (Antivert)	12.5-25mg PO q6h	Sedation, dizziness, falls, blurry vision	Yes
Anticholinergics
Scopolamine	1 mg patch q3day	Dry mouth, blurry vision, drowsiness	No
Glucocorticoids
Dexamethasone	4-8mg PO/IV prior to chemo or XRT, typically use with other agents	Hyperglycemia, fluid retention, delirium	No
NK1 Antagonists
Aprepitant	Given prior to/with chemo	Fatigue, neutropenia	No
CBD Agonists
Dronabinol	2.5-5mg BID	Dizziness, increased appetite, Tachycardia, hypotension	No

Peptic Ulcer Disease¶

Michelle Izmaylov

Background¶

Ulceration in the GI tract wall extending through the muscularis mucosa into deeper layers
Most common in the stomach and proximal duodenum
Less common in the lower esophagus, the distal duodenum, or the jejunum
- ↑ suspicion for unopposed hypersecretory states, like Zollinger-Ellison syndrome
Causes: NSAID use and Helicobacter pylori >> steroids, malignancy, and acute stress

Presentation¶

Episodic gnawing or burning epigastric pain, 2 - 5 hr after meals, nausea, vomiting, heartburn, bloating, postprandial belching, and loss of appetite
Nocturnal pain: acid is secreted in absence of a food buffer
Classic teaching for ulcers: Gastric (pain worse w/eating); Duodenal (pain better w/eating)
May be asymptomatic until complications such as hemorrhage or perforation
Alarm features: unintentional weight loss, persistent vomiting, melena, progressive dysphagia, early satiety, recurrent vomiting, palpable abdominal mass, lymphadenopathy, family history of upper gastrointestinal cancer, and iron deficiency anemia

Evaluation¶

CBC and H Pylori testing if no strong NSAID use history
Urea breath or stool antigen (pt needs to stop PPI for 1-2 weeks, to avoid false - for both)
EGD: if alarm features or patient is older than 55

Management¶

General: treat underlying cause (i.e. H. pylori, stop NSAIDs, etc), encourage smoking cessation, and limit alcohol intake to 1 drink/day.
If complicated peptic ulcer (i.e. bleeding, perforation, or gastric outlet obstruction):
- EGD to determine etiology and for possible treatment
- IV PPI (if bleeding IV PPI for 72 hrs after endoscopic treatment oral PPI)
If uncomplicated peptic ulcer (not caused by H. pylori):
- Antisecretory therapy with oral PPI (i.e. omeprazole 20 to 40 mg daily):
  - If caused by NSAIDs: Duration: \<1 cm ulcer 4-6 wks; ≥1 cm ulcer 6-8 wks
- If not caused by NSAIDs, Duration:
  - Duodenal ulcer: 4 weeks
  - Gastric ulcer: 8 weeks
If ulcer caused by H. pylori:
- Treat with PPI BID for 14 days with an appropriate combination antibiotic regimen.
- Confirm H. pylori eradication (via stool antigen test, urease breath test, or EGD >4 weeks after completion of therapy). If not eradicated, retreat

Additional Information¶

Continue maintenance PPI therapy (omeprazole 20 mg daily) for the following:
- Peptic ulcer >2 cm and age >50 or multiple co-morbidities
- Frequently recurrent peptic ulcers (>2 in one year)
- H. pylori-negative, NSAID-negative ulcer disease
- Failure to eradicate H. pylori (including salvage therapy)
- Condition requiring long term aspirin/NSAID use
- Persistent ulcer on repeat EGD (if performed)
Indications for repeat EGD (8-12 weeks):
- Persistent/recurrent symptoms despite medical therapy
- Complicated ulcer (bleeding), with evidence of ongoing bleeding
- Giant gastric ulcer (>2 cm) or features of malignancy at index endoscopy
- Gastric ulcer that was not biopsied or inadequately sampled on initial EGD
- Gastric ulcer in pt w/risk factors for gastric cancer (>50 yo, H. pylori, immigrant from high prevalence area [Japan, Korea, Taiwan, Costa Rica], FHx, presence of gastric atrophy, adenoma, dysplasia, intestinal metaplasia)

Small Bowel Obstruction (SBO)¶

Alex Wiles

Background¶

Risk Factors: prior abdominal surgeries (adhesions), malignancy, hernia, intestinal inflammation (IBD)/stricture, radiation, abscess, foreign bodies
Indicators for bowel ischemia: fever, leukocytosis, tachycardia, peritonitis
Ddx: early appendicitis, large bowel obstruction, Ogilvie’s, DKA, Pancreatitis, IBD, Gastric outlet obstruction

Presentation¶

Nausea, emesis, intermittent colic, bloating, constipation
Obstipation if completely obstructed, loss of flatulence
Exam: classically with “tinkling” bowel sounds, tympanic abdomen, distended abdomen

Evaluation¶

CBC, BMP, lipase, hepatic function panel, lactate (sensitive, not specific for ischemia)
Start with KUB to rule out perforation but typically will require CT (x-ray only ~80% sensitive)
CT abdomen/pelvis with IV contrast is optimal study if adequate renal function
- No oral contrast (American College of Radiology (ACR) Appropriateness Criteria) as it will not aid diagnosis and can lead to aspiration; IV helps evaluate ischemia
Key word: transition point
Non-specific signs of bowel inflammation: bowel wall thickening, submucosal edema

Management¶

Consult EGS: if any concern for SBO, evaluate need for urgent surgery
Surgical indications complete obstruction, CT with ischemia, perforation
Gastric decompression: place NGT (prevent aspiration)
NPO until obstruction relieved and NGT removed
Fluids: two large bore IVs (nursing communication); LR bolus + maintenance while NPO
If no resolution of partial obstruction at 48 hours:
Fluoroscopy Upper GI small bowel ft (follow through)
- In comments, write “Gastrografin contrast” (water-soluble contrast) which osmotically reduces bowel wall edema and aids peristalsis
- If gastrografin reaches the colon within 24 hours, it predicts clinical resolution of SBO without surgery
- Note: this can also be therapeutic for pSBO and get bowels moving

Ended: Gastroenterology

Geriatrics ↵

Dementia¶

Thomas Horton

Background¶

Alzheimer’s Disease (AD): short-term memory deficits prominent
Vascular Dementia: “Stepwise decline” in memory and functional status
Lewy Body Dementia: hallucinations, memory difficulties with atypical Parkinsonism early
Frontotemporal Dementia: behavioral (aggressive or disinhibited), language (primary progressive aphasias) or memory (Alzheimer’s/FTD overlap) variants
Posterior Cortical Atrophy: visual difficulties and ocular apraxia preceding memory problems
Creutzfeldt-Jakob Disease (CJD): manifests with subacute cognitive decline, seizures, vision loss, personality changes. Can develop startle myoclonus
Corticobasal degeneration: focal neurologic changes with parkinsonism
Neurosyphilis: rare, but treatable, present with a range of cognitive changes. Develop meningovascular encephalitis. Pts can develop an arteritis, headache, and hydrocephalus.
Normal Pressure Hydrocephalus (NPH): “wet, wacky and wobbly” meaning incontinence, gait apraxia and cognitive changes (usually frontal symptoms)
Autoimmune Dementias: includes limbic encephalitis (like NMDA) where there are memory and personality changes, autonomic changes, hallucinations, and seizures

Mild decline in working memory

More effort/time needed to recall new info

New learning slowed but well compensated by lists, calendars, etc.

+

No impairment in social & occupation functioning

Subjective complaint of cognitive decline in at least one domain

+

Cognitive decline is noticeable and measurable

+

No impairment in social & occupation functioning

Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains

+

Causes significant impairment in social & occupation functioning

+

Other medical & psychiatric conditions, including delirium, have been excluded

+

Insidious onset and gradual progression of impairment in at least two cognitive domains

Cognitive domains: learning/memory, language, executive function, complex attention, perceptual motor, social cognition

	Alzheimer’s Disease	Vascular Dementia	Lewy Body Dementia	Frontotemporal Dementia
Onset	Gradual	Sudden or stepwise	Gradual	Gradual (age < 60)
Cognitive Domains & Symptoms	Memory, language, visuospatial	Depends on location of ischemia	Memory, visuospatial	Executive dysfunction, personality changes, disinhibition, language, +/- memory
Motor Symptoms	Rare early Apraxia later	Correlates with ischemia	Parkinsonism	None
Progression	Gradual (over 8-10 years)	Gradual or stepwise with further ischemia	Gradual, but faster than Alzheimer’s disease	Gradual, but faster than Alzheimer’s disease
Imaging	Possible global atrophy	Cortical or subcortical on MRI	Possible global atrophy	Atrophy in frontal & temporal lobes

Evaluation¶

MINI-COG: Screening test for cognitive impairment (highly sensitive)
- Ask pt to remember three words (banana, sunrise, chair). Ask pt to repeat immediately
- Ask pt to draw clock. After numbers are on the face, ask pt to “set hands to 10 past 11”
  - Correct is all numbers in right position AND hands pointing to the 11 and the 2
Ask pt to recall the three words

MOCA: Montreal Cognitive Assessment
- Lengthier test of cognition (but highly specific for cognitive impairment)
- Useful for detecting subtle deficits as in Mild Cognitive Impairment (MCI)
- Scores:
  - 18-25: Mild cognitive impairment
  - 10-17: Moderate cognitive impairment
  - <10: Severe cognitive impairment
Rule out reversible causes of dementia-like symptoms: DEMENTIA
- Drugs
- Emotional (depression)
- Metabolic (CHF, COPD, CKD, OSA)
- Endocrine (hypothyroidism, hyperparathyroidism, hyponatremia)
- Nutrition (B12 deficiency)
- Trauma (chronic SDH)
- Infection
- Arterial (vascular)
B12, thyroid studies
RPR, HIV testing in at-risk patient groups
Neuropsych testing can be done for more clear patterns of dysfunction
MRI brain with contrast if concerned for inflammatory or infectious causes
- CJD: cortical ribboning on DWI with T2 hyperintensity in the thalamus and basal ganglia
- Sulcal crowding and bowing of the corpus callosum can be seen in NPH on imaging

Management¶

Targeting Cognitive Impairment
- Cholinesterase Inhibitors: Donepezil, rivastigmine
  - Indicated for any stage (except FTD)
  - SE: GI (nausea, diarrhea), bradycardia, orthostasis
- NMDA antagonists: Memantine
  - Indicated in moderate to severe AD in combination with cholinesterase inhibitors
  - Fewer SE than cholinergic medications
Vitamin supplementation (i.e. Vitamin E)
- Unclear benefit in delaying progression of dementia
Targeting Behaviors
- Non-pharmacologic management has the best evidence of effectiveness
- Depression: Treat with antidepressants (SSRI’s)
- Sleep Disturbance: Mirtazapine (7.5 mg nightly) or Trazodone (25 mg nightly)
- Agitation: Try SSRI (citalopram, sertraline)
  - Consider antipsychotics (black box warning increased risk of death in elderly)

Falls¶

Thomas Horton

Background¶

Screen annually for falls in the past year
History of fall is a strong risk factor for future falls
Recommended History Screening Tool: CDC STEADI Algorithm
Physical Exam Screening Tools:
If potentially unstable injuries (new spine fracture or lower extremity fracture): Ask ortho to clear the patient for mobility
If no potentially unstable injuries, attempt to get the patient out of bed
- If lying down, have them lift each leg off the bed
- If they can do this, ask them to sit up on side of bed
- If they can do this, ask them to stand
- If they can do this without assistance, then observe them walk
The Timed “up and Go” Test (TUG) tool for fall risk
- Have the patient rise from sitting in a chair, walk 10 feet forward, turn around, walk back to chair, and sit down
- Patients who require > 10 seconds are at increased risk for falls
Med Rec:
- Antipsychotics, antidepressants, anticholinergics, anxiolytics, sedatives/hypnotics, anti-hypertensives, antiarrhythmics, steroids, statins all can increase risk of falls

Management¶

Rule out other causes: Cardiac, Neurologic, Infectious
Check Vitamin D levels (goal > 30) and supplement (800-1000 IU daily) if at increased fall risk
Assess visual acuity (e.g. expedite cataract surgery)
Hearing assessment (audiology screen)
Consult Inpatient PT/OT and refer for HH PT/OT for home safety evaluation at discharge
Recommend non-skid shoes with a backing (sneaker)
Modify extrinsic risk factors for falls: removal of fall hazards, placement of handrails
Referral to Exercise programs: At VUMC = Dayani Center “Ambulatory Referral to Medical Fitness” outpatient order

Frailty¶

Thomas Horton

Background¶

Syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes

Evaluation¶

FRAIL Scale Identifies frailty in community dwelling elders (1 -2 = prefrail; > 3 = frail)
- Fatigue: are you Fatigued more often than not?
- Resistance: are you able to climb a flight of stairs?
- Aerobic: are you bale to walk a block?
- Illness: Do you have more than five illnesses?
- Loss: Have you lost more than 5% of weight in 6 months?
Order Vitamin D and B-12 Levels.

Management¶

Adapt interventions to the individual, incorporating patient preferences and stage on the spectrum of frailty
Exercise programs with additional physical and occupational therapy input if indicated.
Optimize nutrition via supplementation (Vit D, B12)
Comprehensive Geriatric Assessment; Outpatient PACE

Functional Status¶

Thomas Horton

Background¶

Functional status: Ability to perform activities necessary in daily life (ADL)

Dressing

Eating

Ambulating/transfer

Toileting/continence

Hygiene (bathing)

Shopping

Housekeeping & laundry

Handling medications

Accounting (finances)

Food preparation

Telephone

Transportation (driving)

Fulfill societal, community and family roles

Participate in recreational tasks

Evaluation¶

Katz ADL scale, Lawton-Brody IADL scale, Get up and Go test, MMSE, Geriatric depression scale.
Vulnerable Elders Scale-13: Identifies community dwelling pts at risk for decline over 5 yrs
Functional decline is not normal with aging and warrants detailed physical, cognitive, and psychosocial evaluations

Malnutrition¶

Thomas Horton

Background¶

Needs to meet two or more of following criteria:
- Insufficient calorie intake
- Weight loss
- Loss of muscle mass
- Loss of subcutaneous fat
- Localized fluid accumulation that may mask weight loss
- Diminished functional status as measured in handgrip strength
Reversible causes of malnutrition:
- Food security (poverty), dental status (dentition, gum health), dietary restrictions, food-related functional status (shop, prepare meals, feed self), depression, dementia, alcoholism, swallowing ability

Evaluation¶

Assess for depression
Screening with Mini Nutritional Assessment (good sensitivity and specificity)
Order: CBC, CMP, TSH
Nutritional deficiencies: B12, folate, vitamin D
Consider CT C/A/P depending on history
Refeeding: K, Phos, Mg BID until stable and no longer having to replete

Management¶

Manage reversible causes of malnutrition as above
Medications: consider Remeron (7.5 mg nightly). Avoid Megace (NNH = 23 for death)
Liberalize dietary restrictions
Nutritional Supplementation: Oral enteral supplements (i.e. nutritional shakes)

Medication Management¶

Thomas Horton

Medication Reconciliation Upon Admission
Evaluating for Polypharmacy – Beer’s Criteria
Pharmacologic changes in the elderly
- Pharmacokinetic (PK): Decreased hepatic and renal clearance. Reduction in first pass metabolism. Drug distribution changes due to decreased TBW and lean body mass resulting in relative increase in fat.
- Pharmacodynamic (PD): Exaggerated responses to pharmacologic therapy (therapeutic and adverse effects).
Avoid Prescribing Defaults:
- NSAIDs can lead to gastritis, which can lead to prescription of PPI
- Diuretics can lead to urinary incontinence, which can lead to prescription of oxybutynin
- HCTZ can lead to hyperuricemia which can lead to prescription of allopurinol
Discharge Tips for med adherence: provide pillboxes & arrange blister packs for meds
Recommended Tools: deprescribing.org (App available); medstopper.com

Geriatrics Overview¶

Thomas Horton

4 M’s of Age-Friendly Care¶

Endorsed by the IHI to provide best evidence-based care to older patients across all settings of care:

What **M**atters Most: Understand each patients specific healthcare goals in the short and long term. Ask “what matters most” and align the care plan with what matters.
**M**edication: Aim to reduce adverse drug events in the elderly by thorough med rec and avoiding potentially inappropriate medications (e.g. Beers Criteria) when possible
**M**entation: Identify, treat, and manage dementia, depression, and delirium across various settings of care.
**M**obility: Assess and optimize mobility

Vanderbilt’s FACETS Inpatient Geriatrics Curriculum: https://sites.google.com/view/facetscourse

Physiological Changes with Aging¶

Cardiovascular: Decreased vascular compliance and increased stiffness (intimal thickening). Decreased cardiac output. Maximum achievable HR decreases. Increase in systolic BP with decrease in diastolic BP (wider PP).
Endocrine/Immune: Impairment of glucose tolerance (insulin resistance). Decreased sympathetic response to stress. Impairment of T-cell immunity and increased susceptibility to infection.
Gastrointestinal: Decreased GI absorption, gastric emptying, motility, acid secretion, and hepatic blood flow. Reduced appetite and alterations of taste and smell.
Musculoskeletal: Decreased bone density, muscle mass and strength. Increased fracture risk.
Neurologic: Reduced cortical volume. Blunted vision, auditory function, and vibrotactile sensation. Decreased autonomic neural response. Slowed cognition and reflexes.
Pulmonary: Increased chest wall rigidity. Decreased respiratory muscle strength. Decreased FEV1; FVC. Diminished ventilatory response to hypercapnia and hypoxia.
Renal: Increased glomerulosclerosis. Decreased GFR and renal clearance of drugs/metabolites (↓ 1mL/min per year after age 40; Cr may stay the same due to reduced muscle mass). Reduced tubular function.

Urinary Incontinence and Foley Catheters¶

Thomas Horton

Background¶

Types of UI	Mechanism	Associated Symptoms
Stress	Incompetent urethral sphincter (post-prostatectomy)	UI with physical exertion (cough, laughter, sneeze)
Urge	↑ bladder contraction from detrusor instability (infection, stone, T2DM, caffeine, meds, BPH	Frequency, nocturia, sudden urge
Overflow	↓ contractility/outlet obstruction (BPH, anticholinergic medications, T2DM, pelvic trauma, spinal cord disease, MS, polio)	Hesitancy, weak stream, sense of incomplete emptying
Functional	Physical, emotional, or cognitive disability	Depression, pain, evidence of physical, sensory, or cognitive impairment

Evaluation¶

Medication Reconciliation:
- Alcohol, α-Adrenergic agonists, α-Adrenergic blockers, ACE inhibitors, Anticholinergics, Antipsychotics, Calcium channel blockers, oral estrogen, GABAergic agents, NSAID’s, narcotics
Order Hemoglobin A1C, Electrolytes (particularly calcium), UA
Rule out retention using PVR
Rectal exam to rule out fecal impaction

Management¶

Skin care for urinary incontinence:
Barrier creams: Venelex, petroleum, zinc oxide
Diapers only when up out of bed
Chucks while in bed (don’t hold moisture up close to the skin like diapers do)
Offer toileting Q1-2hours
Indications for a foley:
- Inability to void
- Need for accurate UOP monitoring when patient unable to comply
- Urinary Incontinence AND open sacral or perineal wound
- Perioperative Use
- Comfort care at end of life

Ended: Geriatrics

Hematology oncology ↵

Anemia¶

Margaret Wheless

Presentation¶

Symptoms:
- Fatigue/malaise, dyspnea on exertion, angina (if history of CAD)
Signs:
- Pallor, tachycardia, orthostatic hypotension, purpura, glossitis, koilonychia (in IDA)
- Jaundice (if hemolysis)
- Splenomegaly: suggests extramedullary hematopoiesis or sequestration
- Neurologic symptoms: suggests B12 deficiency

Evaluation¶

CBC w/diff, reticulocyte count, peripheral blood smear, Iron studies (TIBC, Ferritin)
RI > 2%: blood loss vs hemolysis; see below
- Hemolysis labs: Bilirubin, LDH, haptoglobin
RI < 2%: hypoproliferative stratify based on RBC size
- Microcytic (<80) vs. Normocytic (80-100) vs. Macrocytic (>100)

Reticulocyte Index >2%¶

Background¶

Etiology: Consumption vs Blood loss
Loss: acute bleed vs iatrogenic from labs
Hemolysis: Microangiopathic hemolytic anemia (MAHA), autoimmune hemolytic anemia (AIHA), intrinsic RBC defects

Evaluation¶

LDH, ↑indirect bilirubin, ↓haptoglobin, PT/PTT
Peripheral blood smear: evaluated for schistocytes, bite cells, spur cells, spherocytes, etc.
Direct antiglobulin test (DAT) to evaluate for autoimmune hemolytic anemia

Extrinsic RBC causes¶

If schistocytes ± thrombocytopenia = MAHA: TTP, DIC, HUS, HELLP, mechanical valves, malignant HTN, cocaine, scleroderma renal crisis
If DAT positive = AIHA

Intrinsic RBC causes¶

Sickle cell disease: chronic hemolysis + splenic sequestration crisis where RI is↑ vs aplastic crisis where RI is↓ (see sickle cell section)
Hereditary spherocytosis
Hereditary elliptocytosis
PNH
G6PD: bite cells, Heinz bodies
- Usually precipitated by drugs: nitrofurantoin, dapsone, sulfonamides, rasburicase, primaquine

Management¶

MAHA
DIC: sepsis, malignancy, pregnancy
- Treat underlying cause
- If active bleeding: FFP, cryoprecipitate (to keep fibrinogen >100) and platelets
TTP: Order ADAMTS13 (prior to plasma transfusion or exchange)
- If concern for TTP you should immediately consult Heme and Nephrology
HUS: + shiga toxin, AKI, diarrhea
AIHA:
- Cold (rare): IgM binds at temp <37
  - Caused by lymphoproliferative disorder (Waldenström Macroglobulinemia), mycoplasma, EBV, HIV
  - Consult heme. Treat underlying. Consider rituximab (steroids ineffective)
- Warm: IgG
  - Idiopathic or associated with lymphoma, SLE, drugs, babesiosis, HIV
  - Can use steroids, IVIG, rituximab

Reticulocyte Index <2% (RBC Size Framework)¶

Normocytic Anemia: MCV 80-100¶

Etiologies
- Anemia of inflammation: (may also be microcytic)
- Anemia of CKD: low Erythropoietin (EPO) levels
- Endocrine disease (hypothyroidism, adrenal insufficiency): ↓metabolic demand/O2 requirement
- Mixed macrocytic/microcytic disease may have a normal MCV: look for ↑RDW
- Pure red cell aplasia: associated with destructive Ab (CLL, thymoma, parvovirus, autoimmune)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Bone marrow failure or infiltration (typically will see pancytopenia)
- Bone marrow biopsy may be indicated if no identifiable cause or anemia is associated with other cytopenia’s

Microcytic anemia: MCV <80 (mnemonic: SALTI)¶

Sideroblastic, Anemia of chronic disease, Lead poisoning, Thalassemia and Iron-deficiency

Disease	Etiology	Evaluation	Considerations
Sideroblastic	MDS Idiopathic EtOH, Lead, Isoniazid Cu deficiency	Social hx, TB, consider Lead level Fe: ↑↑ Ferritin: ↑ to nL TIBC: nL Smear: basophilic stippling BMBx: ringed sideroblasts	In clinical practice this is usually acquired; either due to alcohol (can resolved with cessation) or primary bone marrow disorder (e.g. MDS-RARS)
Anemia of Inflammation (formerly chronic disease)	Chronic inflammation, malignancy, HIV, autoimmune dz, heart failure, etc.	Fe/TIBC >18% Fe: ↓↓ Ferritin: ↑↑ TIBC: ↓↓	Treat underlying disease Replete Fe if ferritin <100 or TIBC <20% EPO if Hgb <10 and serum EPO <10
Thalassemia	↓ synthesis of α or β chains leads to ↓ erythropoiesis and ↑ hemolysis Family Hx of anemia	Mentzer’s index: MCV/RBC <13 = thalassemia Normal Fe studies; can mimic microcytic anemia and Fe overload from transfusions Diagnosis: Hb electrophoresis (α will be normal)	α-thal more common in Asian/African descent β thal common in Mediterranean descent Tx: transfusions, folate, Fe chelator depending on severity
Iron (Fe) deficiency	Chronic bleeding: colon cancer, heavy menstrual periods, cirrhosis (portal gastropathy) Supply: malnutrition, Crohn’s dz, Celiac dz, subtotal gastrectomy Demand: pregnancy	Fe/TIBC <18% Fe:↓↓ TIBC:↑ nl to ↑ Ferritin: < 100 Mentzer’s index: >13 Consider celiac testing based on clinical suspicion Investigate for GIB or source of blood loss	Oral Fe: 6wks to correct anemia, 6mo to replete stores; dose every other day (↑ absorption w/ ↓ GI side effects); add Vit C for ↑ absorption If can’t tolerate PO consider IV Fe (Avoid when bacteremic) HFrEF: IV Fe if ferritin <100 OR 100-300 w/ Fe sat <20%

Macrocytic Anemia: MCV >100¶

Non-megaloblastic
- ETOH, liver disease, hypothyroidism, MDS
- Medications that impair DNA synthesis: zidovudine, 5-FU, hydroxyurea, ara-C, AZT, MTX
Megaloblastic
- B12 deficiency
  - Presentation: neurologic changes (subacute combined degeneration), paresthesia, ataxia, dementia (reversible with early treatment)
  - Etiology: malnutrition (alcoholics, vegan), pernicious anemia, gastrectomy, Crohn’s disease, chronic pancreatitis, celiac disease
  - Diagnosis: ↓B12, ↑MMA, ↑homocysteine
  - Treatment: either monthly IM or sublingual B12 (oral not absorbed if no IF)
- Folate deficiency
  - Etiology: malnutrition, decreased absorption (e.g. Celiac disease), impaired metabolism (MTX, TMP), ↑requirement (hemolysis, malignancy, dialysis)
  - Diagnosis: ↓folate, ↑homocysteine, MMA will be normal
  - Treatment: PO folate 1-4 mg daily

Anticoagulation¶

Madeleine Turcotte

Agent	Treatment Dose	Renal Dose	Prophylaxis	Monitoring
Unfractionated heparin	80 U/kg bolus, then 18 U/kg/hr	No change necessary	5000 U q8h	PTT (automatic in order set)
Enoxaparin (Lovenox)	1 mg/kg q12h	1 mg/kg daily	40 mg daily or 30 mg BID	LMWH level (anti-Xa level) Best checked 4 h after 4th dose
Warfarin (Coumadin)	Start 2-5mg daily and monitor INR Can consult Pharmacy	No change necessary	N/A	PT/INR Use Chromogenic Factor X assay if pt has APLS
Dabigatran (Pradaxa)	After 5 days of a parenteral AC, 150 mg BID	Avoid use	N/A	Can test drug level if concerned (Any DOAC)
Rivaroxaban (Xarelto)	15 mg BID x21 d then 20 mg daily	Avoid use in CrCl<30	10mg QD
Apixaban (Eliquis)	10mg BID x7d, then 5mg BID	VTE: No adjustment	2.5 mg BID	A Fib: 2.5mg BID, if 2 of the following: Cr 1.5, Age > 80 Weight < 60kg
Edoxaban (Savaysa)	After 5 days of a parenteral AC, 60 mg daily	30 mg for CrCl 15-50 Avoid if CrCl > 95		Best studied option in renal dysfunction

Additional Information¶

VA is starting to move towards rivaroxaban and apixaban for extended secondary thromboprophylaxis
- Write in your PADR for apixaban citing “patient uses a pillbox and cannot use dabigatran”
Renal dysfunction: favor warfarin, apixaban or edoxaban
Hx of GI bleed: avoid dabigatran, rivaroxaban, edoxaban (may have higher risk of GI bleed)
Pregnancy: UFH/LMWH (other agents may cross the placenta)

Transitioning Between Anticoagulants with DOACs¶

LMWH to Warfarin
- Warfarin and LMWH given simultaneously until INR is therapeutic for 24 hours
Warfarin to DOAC
- Start DOAC when INR < 2.0
DOAC to Warfarin
- High Risk DVT/PE – start LMWH or UFH, then start Warfarin
- Low to Moderate Risk DVT/PE – Start warfarin while patient on DOAC, Stop DOAC on Day 3 of warfarin therapy, Check INR on day 4
LMWH to DOAC
- Stop LMWH and start DOAC when due for next dose of LMWH (within 2 hrs)
DOAC to LMWH
- Stop DOAC and start LMWH when due for next DOAC dose
UFH to DOAC
- Start DOAC when IV stopped (30 min prior to cessation if high risk for thrombosis)
DOAC to UFH
- Start IV heparin with bolus when next DOAC dose is due

Peri-Procedural Management of Anticoagulation¶

Temporary IVC filter indicated in pts with very recent acute VTE (within 3-4 weeks) if the procedure requires AC delay >12 hours
For those at high risk of thromboembolism:
- Consider continuing AC for low-bleeding-risk procedures, i.e. dental procedures, cutaneous biopsy/excision, ICD placement, endovascular procedures.
- Can bridge with LMWH or heparin drip

	Stop before procedure	Restart after procedure
Warfarin	5 days prior, check INR day of	12 to 24 hours after
Dabigatran	48 hours prior (longer if CrCl 30-50 or procedure is high bleeding risk)	1 day after (2 days if high bleeding risk)
Rivaroxaban
Apixaban
Edoxaban
Heparin	Stop infusion 4-5 hours prior	24 hours after
Enoxaparin	12 - 24 hours prior	24 hours after, (48-72 hours if high bleeding risk)

Strategies for Reversal of Anticoagulation¶

Warfarin¶

Vitamin K: onset within a few hours but takes 24-48 hrs for full effect
Life Threatening Bleeding: Give IV Vitamin K 10 mg over 30 minutes
Intracranial bleed, bleed with hemodynamic instability, emergent procedure non-life threatening
- INR <5: Vitamin K not recommended
- INR 5-10: Vitamin K 1-5 mg IV or PO
- INR >10: Vitamin K 5mg PO or 5 mg IV
Prior to surgery
- Rapid reversal INR > 5: 5mg Vit K IV (24 hours prior to procedure)
FFP
- 15 ml/kg (i.e. 4 units/70 kg person) if need reversal <24 hrs, plus give Vitamin K
KCentra ($$$): Contains Factors II, VII, IX, and X with Protein C, Protein S, and heparin
- Given instead of plasma when insufficient time for plasma/Vit K to work (i.e. for life threatening hemorrhage)
- Avoid giving this in HIT
- Administer with Vitamin K

Dabigatran¶

Idarucizumab ($$$) will reverse if prolonged thrombin time (remember to check!) – Consult Hematology

Factor Xa Inhibitors (rivaroxaban, apixaban, edoxaban)¶

FEIBA (Factor VIII inhibitor bypassing activity) – can promote coagulation but is not a reversal agent; limited data to support use
Consult Hematology before using; andexanet alfa (FDA approved) is not on VUMC formulary but is on the VA formulary

Bone Marrow Transplant¶

Chelsie Sievers

Background¶

Donor selection
- Autologous: self, no matching required (no GVHD risk, but also no graft-vs-tumor effect)
- Allogeneic: non-self, matching based on HLA (more matched = less GVHD risk)
  - Matched-related donor (MRD): fully matched sibling
  - Matched-unrelated donor (MUD): From NMDP database
  - Haploidentical: Half matched sibling or parent
Source of stem cells:
- Peripheral blood stem cells (PBSCs) vs bone marrow-derived cells vs umbilical cord
Conditioning regimens:
- Myeloablative vs Reduced-intensity conditioning (RIC)
GVHD prophylaxis (for allo-SCT):
Regimen varies, can include tacrolimus, MMF, MTX, or thymo and alemtuzumab during conditioning

Complications/Adverse Effects¶

Infectious

Neutropenic fever, neutropenic enterocolitis (typhlitis)
Bacterial infections
Viral infections
- CMV: check weekly PCR levels post-allo-SCT
  - All CMV+ recipients are treated with letermovir prophylactically regardless of donor status
- EBV: check weekly PCR levels post allo-SCT. If EBV VL >1000 on two occasions, can treat with pre-emptive rituximab to reduce the risk of PTLD
Invasive fungal infections (e.g. aspergillus, candida)

Non-infectious

Nausea, vomiting, diarrhea, mucositis, cytopenias
Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS)
- Pathophysiology: sinusoidal endothelial cell damage from conditioning chemo post-sinusoidal portal HTN cytokine release multiorgan failure and death
- Diagnosis: T Bili >2, hepatomegaly/RUQ pain, weight gain >2-5%
- Evaluation: RUQ US with doppler
- Treatment: Per heme attending; generally supportive, consider defibrotide
Graft failure:
- Primary (persistent neutropenia without engraftment)
- Secondary (delayed pancytopenia 2/2 immune phenomena or infection after engraftment)
Engraftment syndrome:
- Pathophysiology: PMN recovery cytokine storm vascular leak
- Symptoms: fever, tachycardia, hypotension, SOB, pulmonary edema, rash, weight gain, bone pain, confusion
- Diagnosis: Clinical
- Treatment: high-dose IV steroids
Acute GVHD:
- Only in allogenic; Increased risk with more HLA mismatch
- Pathophysiology: donor T cells attack recipient (Th1-mediated)
- Symptoms: skin rash, cholestatic liver injury, diarrhea
- Treatment: IV steroids (methylprednisolone 1-2mg/kg x 5d)
  - If refractory: mycophenolate, etanercept, ruxolitinib, antithymocyte globulin
Chronic GVHD (typically after T+100)
- Can involve all organs but typically see a scleroderma-like picture (xerophthalmia, xerostomia dysphagia, arthritis, skin changes, malar rash, obliterative bronchiolitis, cholestatic liver injury, cytopenias)
- Treatment: steroids (also photophoresis for skin), consider trials of ruxolitinib, ibrutinib, rituximab if refractory
PTLD (post-transplant lymphoproliferative disorders)
- Pathophysiology: B-cell proliferative disease typically 2/2 latent EBV
- Symptoms: fever, weight loss, fatigue, lymphadenopathy, extra-nodal masses, ↑ EBV PCR

CAR T-cell Therapy¶

Chelsie Sievers

Background¶

Chimeric antigen receptor T cells (CAR-T) are a type of autologous T-cell therapy collected from the patient and genetically modified to contain an extracellular tumor-specific antigen target linked to the internal component of the T-cell receptor.
Goal: patient's own T-cells can specifically target the tumor cell population.
FDA approved therapies: Kymriah (CD19), Abecema (BCMA), Breyanzi (CD19), Tecartus (CD19), Yescarta (CD19)

Complications¶

Cytokine Release Syndrome (CRS)
- Pathophysiology: Supraphysiologic immune cell response with release of inflammatory cytokines.
  - Grade 1: fever ≥100.4, no hypotension, no hypoxia
  - Grade 2: fever ≥100.4, hypotension not requiring vasopressors and/or hypoxia requiring < 6L
  - Grade 3: fever ≥100.4, hypotension requiring a vasopressor, hypoxia requiring >6L or non-rebreather
  - Grade 4: fever ≥100.4, hypotension requiring multiple vasopressors, hypoxia requiring positive pressure
- Work-up: blood and urine cultures (IV abx if needed)
- Treatment: acetaminophen for fever, ICU transfer (grade 1 okay for floor), Tocilizumab 8 mg/kg IV (max 800mg; up to 3 doses in 24 hours, 8 hours apart), Dexamethasone 10 mg IV q 6 hours (grade 3-4).
ICANS: Immune Effector Cell-Associated Neurotoxicity Syndrome
Pathophysiology: high systemic inflammation leaky blood brain barrier encephalopathy ± cerebral edema.
- Based on ICE score: Orientation: orientation to year, month, city, hospital: 4 points; Naming: ability to name 3 objects (eg, point to clock, pen, button): 3 points; Following commands: ability to follow simple commands (eg, “Show me 2 fingers” or “Close your eyes and stick out your tongue”): 1 point; Writing: ability to write a standard sentence (eg, “Our national bird is the bald eagle”): 1 point; Attention: ability to count backwards from 100 by 10: 1 point.
- Grade 1: ICE score: 7-9
- Grade 2: ICE score: 3-6
- Grade 3: ICE score 0-2
- Grade 4: ICE score 0
Work-up: neuro consult, fundoscopic exam for papilledema, consider MRI brain w/&w/o contrast, consider EEG, consider non-con CT head if headache/lethargy.
Treatment: q4hr neuro checks (q1hr if grade >2 → ICU transfer), Keep Na 135-145 with hypertonic saline if necessary (Na 145-150 if grade 4), consider thiamine supplementation 500mg q8hrs, Dexamethasone 10 mg q 6 hours (if seizure give 20mg x 1, then 10mg q6hrs) (grade 2-3), Methylprednisolone 1000 mg IV q 24 x 3 days (grade 4).

Coagulopathies¶

Jason Jones

Overview¶

Step one: determine if platelet vs coagulation disorder
Platelet Disorders: Skin/mucous membrane bleeding; Petechiae; Often mild bleeding following surgery and tends to immediately follow surgery
Coagulation defect: Bleeding deep in soft tissues (muscles/joints); hemarthroses, hematomas; tendency to have delayed bleeding after surgery that can be severe
Coagulopathies can be divided into Hereditary vs Acquired causes

Hereditary¶

Hemophilia A (Factor VIII Deficiency) and Hemophilia B (Factor IX Deficiency)¶

Inherited in X-linked Recessive pattern
Diagnosis: Isolated prolonged PTT with normalization upon mixing study
Management: purified/recombinant Factor VIII or IX. Desmopressin for mild disease
Consult benign hematology every time these patients are admitted

von Willebrand Disease (vWD)¶

Can be hereditary (common) or acquired
Abnormal quantity or function of von Willebrand Factor (vWF) needed for platelet function
Type 1 (most common): Quantitative defect. Low quantity, normal function of vWF
Type 2: Qualitative defect. Normal quantity, abnormal function of vWF.
Type 3 (rare): Complete absence of vWF, phenotypically similar to hemophilia A
Order in Epic: vW Profile = vWF Ag, Factor VIII Activity, Ristocetin Cofactor Activity
Management: Desmopressin (DDAVP) can be useful as prophylaxis or treatment; most patients are treated with factor concentrate replacements

Acquired¶

Coagulation Factor Inhibitors¶

Associated with autoimmune disease (paraneoplastic vs. autoantibody)
Seen in hemophilia due to frequent treatments with recombinant factors (alloantibody)
Diagnosis: Elevated PTT that does not normalize with mixing study
Management: Immunosuppression with steroids; cyclophosphamide ± rituximab
Consult Hematology always (rare disorder with major bleeding complications)

Vitamin K Deficiency¶

Caused by malnutrition, liver disease, or iatrogenic with warfarin
Diagnosis: elevated PT, if severe may have prolonged PTT as well
Management: Replace vitamin K

Disseminated Intravascular Coagulation (DIC)¶

Eric Singhi

Background¶

Concurrent activation of the coagulation pathway and fibrinolytic pathway
Consumption of platelets, fibrin, and coagulation factors fibrinolysis end organ damage and hemolysis
Etiologies:
- Infection/Sepsis, Liver disease, Pancreatitis, Trauma
- Malignancies: mucin-secreting pancreatic/gastric adenocarcinoma, brain tumors, prostate cancer, all acute leukemias, acute promyelocytic leukemia
- Obstetric complications (i.e. preeclampsia/eclampsia, placental abruption)
- Acute hemolytic transfusion reaction (i.e. ABO incompatible transfusion)

Evaluation¶

Exam: petechiae, bleeding (mucosal, IV site, surgical wound site, hematuria), ecchymoses, thrombosis (i.e. cold, pulseless extremities)
CBC, PT/INR, aPTT, Fibrinogen, D-Dimer, Peripheral Blood Smear
“DIC labs” = q6h fibrinogen, PT/INR, aPTT (space out when lower risk)
Findings suggestive of DIC: thrombocytopenia, prolonged aPTT and PT/INR, hypofibrinogenemia, elevated D-dimer, fibrin degradation products, schistocytes

Management¶

Treat the underlying cause!
Vitamin K for INR > 1.7 or bleeding
Hypofibrinogenemia treatment: Cryoprecipitate 5-10 units if fibrinogen < 100
Thrombocytopenia treatment: plt transfusion as normally indicated
DVT ppx if not bleeding and plt > 50
VTE: anticoagulation if plt > 50 and no massive bleeding

Hypercoagulable States¶

Chris Cann

Background¶

Virchow’s triad: 1. Hypercoagulability 2. Stasis 3. Endothelial injury
Diagnostic thrombophilia testing indications:
- Idiopathic or recurrent VTE
- First VTE at <40 years old
- VTE in the setting of strong family history
- VTE in unusual vascular site (cerebral, renal, mesenteric)
- Recurrent pregnancy loss
Must consider if thrombophilia testing will change clinical management
If the unprovoked VTE warrants indefinite anticoagulation then testing may not be helpful
However, if VTE provoked by minor risk factor (OCPs) with an underlying thrombophilia might change the decision, then testing may be informative
Separated into Acquired and Hereditary conditions:
- Hereditary: Factor V Leiden mutation, Prothrombin mutation, Protein C or S deficiency, Antithrombin deficiency
- Acquired:
  - Antiphospholipid Syndrome (APLS)
  - Heparin induced thrombocytopenia (HIT)
  - Major surgery/trauma
  - Nephrotic Syndrome
  - Smoking
  - Pregnancy
  - Oral Contraceptives
  - Immobilization (bedridden, hip/knee replacement)
  - Active malignancy
  - Estrogen replacement therapy
  - Note: Travel (plane, train, automobile) is NOT on this list and this is NOT considered a provoking risk factor
- Testing: all specific testing for hereditary disorders and APS should be performed at least 4-6 weeks after an acute thrombotic event or discontinuation of anticoagulant/thrombolytic therapies to avoid interference

Antiphospholipid antibody syndrome (APLS)¶

Background¶

Most common acquired disorder (anti-phospholipid antibodies present in 3-5% population)
Recurrent pregnancy loss, provoked DVT in young, unprovoked VTE and arterial thrombosis in young, thrombosis unusual sites, thrombosis in autoimmune disease
This is a clinicopathologic diagnosis (need both clinical and laboratory criteria)

Evaluation¶

Positive for at least 1 lab criterion on at least 2 occasions, at least 12 weeks apart:
- Lupus anticoagulant: can occur in relation to drugs or infection; transient are associated with thrombotic risk
- Anticardiolipin antibodies
- B2GP1 (anti-beta2-glycoprotein) antibodies
Must also meet at least 1 of the following clinical criteria:
- Vascular thrombosis: DVT, arterial thrombosis, or small vessel thrombosis of any organ
- Pregnancy loss: there are specific criteria for this – consult UpToDate or other resource

Management¶

Aspirin for primary prevention; warfarin for treatment (INR 2-3)
Do NOT use DOACs for triple positive APLS (see TRAPS trial: rivaroxaban inferior to warfarin)
Rituximab for recurrent thrombosis despite anticoagulation (controversial) – call hematology

Heparin-induced thrombocytopenia (HIT)¶

Type 1: Mild and self-limited (not immune-mediated)

Occurs within the first 2 days of first-time exposure
Platelet count normalizes with continued heparin therapy

Type 2 (what we typically refer to as HIT): Immune mediated

Fall in plt 30% to over 50% (even if plt count >150) and/or thrombotic event has occurred
4-10 days after new exposure to heparin derivative OR≤
1 day after restarting heparin derivative that had been used 30-100 days prior
- If exposed to heparin within 100 days, will have platelet drop within 24 hr
Frequency: unfractionated heparin > LMWH; Surgical wards > medical wards
50% will have thrombotic event in 30 days if HIT is untreated, with 20% mortality
Arterial thrombi are common in HIT
HIT results from antibodies to complexes of platelet factor 4 (PF4) and heparin, further activating platelets (the activated platelets aggregate causing thrombocytopenia)

Evaluation¶

4T score (0-8 points):
- Thrombocytopenia (0-2 pts): degree and nadir of platelet count drop
- Timing (0-2 pts): timing of fall after initial or recurrent heparin exposure
- Thrombosis (0-2 pts): thrombosis, skin necrosis, non-necrotizing lesions, acute systemic reaction to heparin
- Other causes of thrombocytopenia (0-2 pts): more points if no alternate cause
Solid-phase ELISA for heparin-PF4 antibodies:
- 0.2-0.4 is indeterminate
- 0.4 is positive
- 1.4 HIT is likely
- 2 confirms HIT
- The lab at VUMC will perform functional SRA reflexively for all values >0.2

Management¶

0-3 points: Low concern for HIT; can restart heparin
4-5 points: Intermediate probability (~10%) - hold heparin, start non-heparin anticoagulant
6 points: High probability (~50%) - hold heparin, start non-heparin anticoagulant
Argatroban (direct thrombin inhibitor) for prophylaxis and treatment of thrombosis
Avoid platelet transfusions as can increase thrombogenic effect
Avoid warfarin until complete platelet recovery as may cause microthrombosis
Hematology consult for all confirmed HIT

Factor V Leiden mutation¶

Evaluation¶

Activated protein C resistance assay
- APC ratio in patient vs normal
- normal >2.0, heterozygotes 1.5-2.0, homozygotes <1.5
FVL mutation is then determined via PCR
Screen with APC assay rather than PCR initially; cost effective

Management¶

VTE treatment same as general population
VTE 4-8x risk in heterozygotes; 80x risk in homozygotes
Avoid OCPs: increased risk for VTE

Prothrombin gene mutation¶

Evaluation:¶

PCR of G20210A mutation (2-4% prevalence)

Management:¶

VTE treatment same as general population & avoid OCPs

Protein C & S Deficiency¶

Background¶

Autosomal dominant; first event occurs between 10-50 years of age
Synthesized in liver and Vit K dependent, therefore low levels in hepatic dysfunction and warfarin use/vitamin K deficiency
Protein C: low in settings of thrombosis, DIC, nephrotic syndrome, intra/post-op
Protein S: low in infectious (HIV) and autoimmune processes (IBD)
Protein S decreases during pregnancy (decreased free Protein S, normal total Protein S)
Do not misdiagnose a pregnant patient with PS deficiency

Evaluation¶

Functional Protein C & S assays

Management¶

VTE treatment same as general population
Avoid OCPs
High risk patients may require protein C concentrate prior to surgery
Increased risk of warfarin-induced skin necrosis

Antithrombin deficiency¶

Background¶

Autosomal dominant, does not skip generations
VTE in unusual sites (cerebral sinuses, renal veins)
Present < 50 y/o, but rarely in first two decades
Decreased in liver disease, nephrotic syndrome, protein losing enteropathy, burn, trauma, bypass surgery, metastatic tumors, premenopausal, OCP use, pregnancy

Evaluation¶

Functional antithrombin activity (AT-heparin cofactor assay)
Then perform antigen quantity testing

Management¶

Can use Argatroban as does not require antithrombin function
Warfarin preferred in VTE (titrate up based on expression of antithrombin deficiency)

Acute Leukemia¶

Robert Corty

Background¶

Hematological malignancy caused by unchecked proliferation of WBC precursors in the bone marrow
Pt’s with suspected acute leukemia require hospitalization for urgent diagnosis & treatment
Types:
- AML = Acute Myeloid Leukemia
  - APL = Acute Promyelocytic Leukemia defined by translocation (15;17) PML-RARA
- ALL = Acute Lymphocytic Leukemia
Risk Factors:
- radiation, chemical exposures (e.g benzene), chemotherapy (esp alkylating agents)
- HIV, immunosuppression, smoking
- myeloproliferative disorders, aplastic anemia

Presentation¶

Leukocytosis, leukemia cutis, gingival hypertrophy, leukostasis
Functional Leukopenia, often neutropenia: recurrent infections
Anemia: fatigue, pallor, dyspnea
Thrombocytopenia: gingival bleeding, epistaxis, petechiae, ecchymoses, menorrhagia
Extramedullary hematopoiesis: splenomegaly, hepatomegaly, lymphadenopathy

Evaluation¶

Diagnosis of acute leukemia requires one of the following:
- 20% blasts in peripheral blood
- 20% blasts in bone marrow biopsy
- Any pathognomonic cytogenetic abnormality of t(8;21), inv(16), t(15;17)
Check for the presence of these time-sensitive conditions.
- DIC – check fibrinogen, PT, PTT, platelets
- TLS – check uric acid, phosphate, K+
- Neutropenic fever – check temp, neutrophil count
- Leukostasis (see below)
- Presumptive APL – promyelocytes on diff, DIC or Auer rods on smear
Confirm if peripheral flow cytometry ordered/in process
Use hematology admission order set
Set RBC and Plt transfusion thresholds
Order nurse-driven electrolyte repletion
ECG and TTE to establish pre-chemotherapy cardiac function
Daily labs: CBC, TLS, DIC
TLS prophylaxis

Management¶

Consult hematology
Discuss chemo plan and order double lumen PICC for reliable access
If findings suggest APL start ATRA
Subspecialized lab tests: bone marrow biopsy, cytogenetics, FISH
Monitor for Common Complications/Emergencies: (see individual sections)
- TLS, DIC, Febrile Neutropenia, Leukostasis

Additional Information¶

Obtain blood product consent on admission
APL Specific findings: promyelocytes on differential or Auer rods on smear
Differentiation syndrome: promyelocytes differentiate
- Symptoms and signs: fever, SOB, Hypotn, peripheral edema, pleural effusion, AKI
- Diagnosis: No defined criteria. If suspicious, discuss with hematology fellow
- Management: steroids. If critically ill, hold ATRA and ATO and consider hydroxyurea

Leukemia Treatment Overview¶

General strategy is to use “induction” chemo to try to induce clinicopathologic (as opposed to molecular) “remission”
Defined as absence of symptoms, normal CBC, and <5% blasts in bone marrow (on day 28)
Then waiting in hospital until neutrophil count >500 (typically ~3 weeks)
From there, bone marrow transplant (for high-risk disease) or “consolidation” chemo for normal-risk or low-risk disease

AML Treatment¶

Induction
- Typical is “7+3” i.e. idrarubicin on days 1-3 and cytarabine on days 1-7
- If therapy-related AML, MDS-related AML, or AML with cytogenetics similar to MDS, use “Vyxeos” which is liposomal daunorubicin and cytarabine on days 1, 3, and 5
- If low-risk dz (t(8;21) or inv(16)), use cytarabine on days 1-7, and 3 days of low-dose daunorubicin + gemtuzumab-ozogamicin
- There are other induction regimens that can be used depending on specific cytogenetics and patient frailty, which is beyond the scope of the handbook
Consolidation
- Typically “HiDAC”(high-dose Ara-C i.e. cytarabine)
  - Generally too toxic for pts with age > 60, so a dose reduction is used
- In the case of relapse, typical treatment is a different high-dose chemo and BMT if possible

ALL Treatment¶

Typical induction is “HyperCVAD” (hyper-fractionated cyclophosphamide, vincristine, doxorubicin (“A” due to trade name Adriamycin), and dexamethasone
If t(9;22) (known as Philadelphia chromosome), use tyrosine kinase inhibitor (TKI)
If CD20+, use rituximab

Common Chemotherapy Regimens for Leukemia Encountered as Inpatient¶

Regimen	Components	Use
7+3	Cytarabine (Ara-C) x 7 d & Anthracycline (e.g. idarubicin x3 d)	AML induction
Vyxeos	Cytarabine + liposomal daunorubicin	AML-MRC or t-AML
CLAG-M	Cladribine, cytarabine (Ara-C), Filgrastim (G-CSF), mitoxantrone	AML induction (relapsed/refractory)
HIDAC	High-dose cytarabine	AML consolidation
ATRA	All-trans retinoic acid given with arsenic trioxide (ATO)	APL (APML)
HyperCVAD/MA	CVAD = Cyclophosphamide, vincristine, doxorubicin, dexamethasone MA = methotrexate/cytarabine (Given as alternating cycles)	ALL
R-CHOP	Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone	NHL
R-EPOCH	Etoposide plus the drugs above (dosing is different)	NHL
ABVD	Doxorubicin, bleomycin, vinblastine, dacarbazine	HL

Leukocytosis¶

Kenna Koehler

Background¶

Common progenitor cells (stem cells) are located in the bone marrow and give rise to erythrocytes, myeloblasts, megakaryoblasts
Normal WBC can vary by age and pregnancy, for the purpose of this section will assume this is for an average, non-pregnant adult
Chronic mild neutrophilic leukocytosis (10-20k) is common with tobacco use and obesity, both due to mechanisms related to chronic inflammation
Reactive (typically 11k-30k) - surgery, exercise, trauma, burns, emotional stress
Leukemoid reaction (typically 50k-100k) - severe infections (fulminant C difficile), organ rejection
If greater than 100k, think leukemia or myeloproliferative disorder

Evaluation¶

Neutrophilia (neutrophil count >7k)
- Bacterial infection, pregnancy, rheumatologic disease, steroids, beta agonists, lithium, colony-stimulating factors, splenectomy or functional asplenia, congenital (hereditary/chronic idiopathic neutrophilia), Down syndrome, leukocyte adhesion deficiency, malignancy, smoking, obesity
Lymphocytosis (>40% of WBC count or >4,500k/mm³)
- Infections (pertussis, syphilis, CMV, EBV, hepatitis A/B/C, toxo), hypersensitivity reactions, thyrotoxicosis, Addison's disease, hematologic malignancies, “reactive”
Monocytosis (>8% of WBC count or >880/mm³)
- Infections (TB, fungal disease, protozoa, tick-borne), autoimmune disease, malignancy (CMML)
Eosinophilia (>500/mm³)
- Hypersensitivity (asthma, urticaria, atopic dermatitis, eosinophilic esophagitis), drug reactions, malignancies, connective tissue disease, idiopathic hypereosinophilic syndrome, infections (helminths, Scarlet fever, Hansen's disease), sarcoidosis, SLE
- Hypereosinophilia if AEC>1500, typically merits heme evaluation
- Hypereosinophilic syndrome: AEC>1500 and organ dysfunction from eosinophils
Basophilia (>100/mm³)
- CML, thyroid disease, IBC, chronic dermatitis, infections (varicella)

Lymphoma¶

Danielle Fishman

Background¶

Classically characterized by lymphadenopathy & constitutional “B” symptoms: fevers, drenching night sweats and weight loss
Hodgkin:
- 10%
- superficial, nodal disease with orderly spread
- Bimodal Distribution: 15-35 years and >50 years; M>F
- CD15+, CD30+ (Reed Sternberg cells “owl eyes”)
- Associated with EBV in immunocompromised patient
Non-Hodgkin:
- 90%
- diffuse, nodal and extranodal disease with noncontiguous spread
- Average 65 years, M>F, 85-90% B-cell
- Associated with immunodeficiency (HIV, post-transplant), autoimmune disease, infection (EBV, HTLV-1, H pylori, HCV, Borrelia, C psittacosis, Coxiella)

General Evaluation¶

History
- B symptoms; pruritus (10-15% of pt with HL); history of radiation
Physical Exam
- Head & neck, tonsils, axilla, testes, liver, spleen
- Lymphadenopathy: painless, firm, fixed, >1cm
Lab tests:
- CBC, CMP, LDH, Uric Acid, Phosphorus
- Consider HBV, HCV, HIV, EBV, Quant gold, Treponemal Ab, ANA
Imaging:
- CT chest, abdomen, pelvis
- Most will eventually need PET-CT; MRI brain if neuro symptoms
Consider LP for NHL with high risk of CNS involvement or presence of neurological symptoms
- Risk factors: Burkitt, Lymphoblastic, testicular involvement, double/triple hit
- Multiple LPs may be required to diagnose CNS lymphoma
Diagnosis requires tissue
- Excisional Lymph node biopsy (Surg Onc Consult)
- Core biopsy (CT guided procedure consult)
- Of note, steroids may impact value of biopsy results
Lugano Classification: staging of lymphoma
- I. 1 LN region or single extra lymphatic organ/site without nodal involvement
- II. >2 LN regions, same side of diaphragm
- III. LN regions on both sides of diaphragm
- IV. Disseminated disease w/ 1+ extralymphatic organ
Hodgkin:
- IPS negative prognostic calculator: albumin <4, hemoglobin <10.5, male, stage IV disease, age>45, WBC count> 15K, lymphocyte <8% of WBC count
Non-Hodgkin:
- Good prognosis: Follicular, Marginal Zone, Mycosis Fungoides/Sezary Syndrome
- Poor prognosis: DLBCL – can arise from low grade lymphoma Richter transformation), Double/Triple Hit: bcl-2, bcl-6, or myc aberrations, Mantle Cell, Burkitt, Lymphoblastic Lymphoma, and Anaplastic Large Cell Lymphoma

General Management¶

ECG and TTE to establish pre-chemotherapy cardiac function – many chemo regimens with anthracyclines
Daily labs: CBC, TLS, LDH
TLS prophylaxis: mIVF, allopurinol

Common Chemotherapy Regimens for Lymphoma¶

Regimen	Components	Use
R-CHOP	Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone	NHL
R-EPOCH	Etoposide plus the drugs above (dosing is different)	NHL (Double/Triple hit)
Hyper-CVAD	Cyclophosphamide, vincristine, doxorubicin, and dexamethasone	NHL
HD-MTX + R	High Dose methotrexate + Rituxumab	Primary CNS Lymphoma
ABVD	Doxorubicin, bleomycin, vinblastine, dacarbazine	HL

Medical Oncology Resources¶

Eric Lander

Resources¶

NCCN (National Comprehensive Cancer Center Network, https://www.nccn.org/): consensus based treatment guidelines for most hematopoietic and solid tumors. Free for house staff.

https://www.HemOnc.org - comprehensive, expert-curated, wiki-style resource, seeks to catalogue all treatment regimens across all cancers. Born at VUMC.

VUMC Oncology Rotation Tips¶

The inpatient oncology rotation involves complex decisions often resulting from advancing diseases. The question “What do you want?” is too simple. Rather, it should be “Given your current circumstance, and given our choices, which path would you prefer to take?” Patients want advice from their outpatient doctors who have been caring for them for years. Therefore, treatment and goals discussions often must pass through the inpatient attending to the outpatient attending. Be sure to define how communication with this primary oncologist will be handled.

Oncology summary sentence in presentation:

Cancer type and stage (at diagnosis – stage never changes even if progressed)
Pertinent tumor genetic information
Any relevant surgeries (e.g. resections)
Most recent treatment
Trajectory of disease (e.g. progressive, improving, or stable)
Patient’s primary oncologist

Ex: Ms. X is a 64 y/o female w/ stage IIIa adenocarcinoma of the lung post resection now with metastases to the spine (patient of Dr. Y) admitted w/intractable back pain and leg weakness. Full NGS at diagnosis with no actionable mutations, and was 40% positive for PDL1. No previous chemo.

Myelodysplastic Syndromes¶

Peter Hanna

Background¶

MDS is a malignant clonal myeloid disorder resulting in ineffective (dysplastic) hematopoiesis leading to peripheral cytopenia’s and a risk of transformation to acute myeloid leukemia (AML)
Usually idiopathic, a disease of the elderly (median onset at age 70)
The WHO has several classification schemes for MDS
- Most important for classification is the percent of blasts in the bone marrow
- Note >20% blasts in marrow = AML. Thus MDS & AML are on a continuum

Presentation¶

50% asymptomatic; Symptoms can include nonspecific but gradual fatigue, weakness
Dysplastic cells do not work properly infections and bleeding are more likely
Macrocytic anemia is most common finding; followed by bicytopenia or pancytopenia
Isolated neutropenia or thrombocytopenia are unusual but possible
Ask about secondary causes:
- Exposure to chemicals (benzene, crude oil/gasoline industry, cigarette smoke), chemotherapy, radiation
- Medications, alcohol use, chronic infections (HIV)

Evaluation¶

Goal is to rule out reversible causes of dysplasia and cytopenias
CBC w/differential, Peripheral Smear, B12, Folate, HIV
May consider Copper & Zinc (send out labs, are expensive and rare but check when MDS is being considered)
Dysplastic changes on peripheral smear: hypogranulated/hyposegmented neutrophils, hypogranulated platelets and macrocytosis of RBCs
Circulating myeloblasts can be seen
Final diagnosis made by Bone marrow Biopsy

Management¶

Molecular characteristics define the “risk” of the disease and dictates treatments
Prognostic scoring tools: revised international prognostic staging system (R-IPSS)
Management general paradigm:
- Asymptomatic: with low-risk disease = monitoring
- Low-risk disease + symptoms due to anemia only: transfusions, erythrocyte stimulating agents, and treatment with Luspatercept
- MDS with isolated del(5q): treated with lenalidomide
- High-risk patients: treated with hypomethylating agents
- Only curative intervention = hematopoietic stem cell transplant (HSCT)

Myeloproliferative Neoplasms (MPNs)¶

Christina Snider

Background¶

MPNs = chronic myeloid disorders caused by abnormal proliferation of mature bone marrow cell lineages (granulocytes, erythrocytes, or megakaryocytes)
MPNs differ from myelodysplastic syndrome (MDS); cells in MPNs are normally developed (i.e. not dysplastic)
Four “classic” MPNs: polycythemia vera, essential thrombocythemia, primary myelofibrosis and chronic myeloid leukemia (CML)

Polycythemia Vera (PV)¶

Background¶

Polycythemia is a general term: Men = Hb/Hct > 16.5/49%; Women = Hb/Hct > 16/48%
Relative polycythemia = Concentrated H/H due to decreased plasma volume
- Diuretic use, vomiting, diarrhea; H/H should normalize with fluid resuscitation
Absolute polycythemia = Increased RBC mass
Primary polycythemia: 2/2 Inherited/acquired mutation in RBC progenitor
Secondary polycythemia: Increase in RBC mass due to elevated serum EPO
- Hypoxia/cardiopulmonary associated (chronic pulmonary disease, R-to-L cardiac shunts, sleep apnea, obesity hypoventilation syndrome, chronic carbon monoxide poisoning, including heavy smoking)
- Kidney associated causes (following renal transplant, renal artery stenosis, hydronephrosis)
- Autonomous EPO production from an EPO-producing tumors (rare)
- Steroid Use
Epidemiology: Median age of diagnosis is 60 years; 25% cases present at age <50 years.
95% PV pts have JAK2 V617F mutation, but JAK2 V617F mutation is not specific to PV and can be seen in other MPNs

Presentation¶

Incidentally elevated H/H
Splenomegaly, generalized pruritus (post-warm bath/shower), unusual thrombosis
Erythromelalgia: intermittent occurrence of red, hot, painful extremities

Evaluation¶

CBC with differential and peripheral smear
EPO level
Rule out secondary causes: Sleep Study, Carboxyhemoglobin, steroids
Peripheral blood screen for JAK2 V617F mutation

Management¶

PV treatment aims to prevent thrombosis and bleeding events.
Phlebotomy: maintain Hct <45% (One unit 500 mL decreases Hct by 3%)
ASA 81 mg for thrombosis prevention and symptom control
Hydroxyurea: indicated for high-risk patients (>60 years old or with history of thrombosis)
Interferon-alfa, busulfan, or ruxolitinib: indicated in select high-risk patients

Essential thrombocythemia (ET)¶

Background¶

Clonal stem cell disorder w/ increased platelet counts (>450k/uL)
Risks of thrombosis and hemorrhage
Median age of diagnosis: 60 years; Twice as common in females.

Presentation¶

Incidental thrombocytosis on CBC
Splenomegaly, unusual thrombosis, and erythromelalgia

Evaluation¶

Screen for conditions that cause reactive thrombocytosis: Chronic inflammatory diseases, infections, bleeding/hemolysis, iron deficiency, post splenectomy
CBC with smear (platelet anisocytosis) ranging from very small to giant platelets
CMP, LDH, Uric Acid, iron studies
BCR ABL1 testing should be sent to exclude CML
Bone marrow biopsy with staining, cytogenetics, and molecular testing for JAK2, CALR, MPL mutations

Management¶

Avoid ASA 81 in patients with platelet counts >1 million complicated by acquired von Willebrand syndrome due to increased risk of bleeding

Treatment of ET
Risk Score (IPSET-thrombosis)	Features	Treatment
High	Hx of thrombosis and/or >age 60 with JAK2 V617F mutation	Cytoreduction (target plt 100-400k) w/ hydroxyurea, systemic anticoagulation +/-antiplatelet agent
Intermediate	Age >60, no JAK2 V617F mutation, no history of thrombosis
Low	Age =<60 w/ JAK2 V617F mutation and no history of thrombosis	Observation vs. daily ASA 81
Very Low	Age =<60, no JAK2 V617F mutation, no history of thrombosis	Observation vs. daily ASA 81

Primary Myelofibrosis (PMF)¶

Background¶

Clonal proliferation of myeloid cells with variable morphologic maturity resulting in reactive marrow fibrosis and extramedullary hematopoiesis
Least favorable prognosis out of MPN

Presentation¶

Fatigue, weight loss, low grade fever, bone pain, and night sweats
Marked splenomegaly ±hepatomegaly (due to extramedullary hematopoiesis)

Evaluation¶

smear: teardrop shaped RBCs (dacrocytes)
Bone marrow biopsy: “dry tap” due to extensive reticulin and/or collagen fibrosis mutually exclusive mutations in JAK2, MPL, or CALR

Management¶

Low risk patients: Observe if asymptomatic
Cure by allogenic HCT transplantation in young, high-risk patients
Treatment of anemias include transfusion support
Surgical splenectomy if abdominal pain or transfusion dependent anemia (used very infrequently)

Chronic Myelogenous Leukemia (CML)¶

Background¶

Definition: MPN characterized by the overproduction of myeloid stem cells that can differentiate
Chronic phase:
- Fatigue, weight loss, bleeding
- Abdominal fullness and early satiety due to splenomegaly
- WBC on CBC is typically >100k, and smear shows neutrophilic cells in all stages of maturation with <2% blasts
Accelerated phase: Refractory leukocytosis, 10-19% blasts in peripheral blood or bone marrow, worsening peripheral basophilia, thrombocytopenia
Blast phase = acute leukemia. >20% blasts in peripheral blood or bone marrow, extramedullary proliferation of blasts

Evaluation¶

Typical findings in blood and bone marrow and confirmation of Philadelphia chromosome (BCR-ABL1 fusion gene) via conventional cytogenetics, FISH, or rt-PCR

Management¶

Hydroxyurea can be used to reduce WBC while awaiting confirmation
Oral tyrosine kinase inhibitors (TKIS): Imatinib, dasatinib, nilotinib, and ponatinib
Allogenic hematopoietic cell transplantation: Curative option for pts in accelerated and blast phase, as well as young pts w/chronic phase CML who do not respond to TKI therapy

Neutropenia & Neutropenic Fever¶

Jennifer Marvin-Peek

Background¶

Neutropenia: absolute neutrophil count (ANC) < 1500
Severe neutropenia: absolute neutrophil count (ANC) <500 (Use manual count if available)

Mechanism	Causes	Example (s)
Neutrophil production	Drug associated	Cytotoxic or immunosuppressive agents Methimazole, PTU, Colchicine Macrolides, Bactrim, Dapsone, Vancomycin Amphotericin, Acyclovir, Ganciclovir TCAs, Clozapine, Carbamazepine, Valproate ACEI, Digoxin, Propranolol, Procainamide
	Radiation exposure
	Malignancies	Leukemias, MDS
	Infection	Hepatitis, HIV, EBV, CMV Rickettsia, Tularemia, Typhoid, TB
	Nutritional deficiency	Vitamin B12, Folate, Copper
	Other	Aplastic anemia, Benign ethnic neutropenia
Redistribution	Splenomegaly	Margination and sequestration
Congenital	Genetics	Benign ethnic neutropenia, familial neutropenia
Immune destruction	Autoimmune disorders	RA, SLE
Immune destruction	Other	Autoimmune neutropenia

Management¶

If ANC <500
- Check all lines/IVs for erythema and induration daily
- Check mouth for mucositis, mouth care after meals and before bed
- Assess for Neutropenic Fever & Complications – see below
- Evaluate for indications for prophylaxis – see below
- No evidence to support use of neutropenic diet
- No digital rectal exams or enemas/suppositories (risk of bacterial translocation)

Neutropenic Fever¶

ANC <500 and T >100.4 °F or 38.0 °C
Neutropenic pts are unable to mount an adequate immune response and can become critically ill very quickly
Do not wait for a temp re-check, you need to start antibiotics immediately

Evaluation¶

Chest X-ray
Two sets of blood cultures (one from PICC/port if present)
Urinalysis AND urine culture (not the reflex order set)
If diarrhea, get C. diff PCR
If abdominal pain, get CT A/P with IV contrast

Management¶

Empirically treat with Cefepime
Indications for Vancomycin:
Hemodynamically unstable
Severe mucositis
Focal consolidation on CXR
Erythema/induration around line
Concern for skin/soft tissue infection
GPCs in blood
Fever continues >24h on cefepime
Additional Coverage:
- If abdominal pain/diarrhea: Flagyl 500mg q8h
- Concern for C-diff: PO Vancomycin 125mg q6h
- Still fevering on Cefepime at 72 hrs (differs by attending) Meropenem
Fungal coverage: Consider if risk factors (TPN) or persistent fevers (>72hrs)
- Micafungin 100 mg IV daily or Voriconazole 200mg PO BID

Neutropenic Complications¶

Mucositis
- Presentation
  - Can range from mouth soreness to severe erosions preventing eating/drinking
  - Can become secondarily infected with Candida, HSV
- Management
  - Routine oral care with a soft toothbrush to remove plaque
  - Oral rinses with saline and/or sodium bicarbonate
  - Magic mouthwash for symptomatic relief (or viscous lidocaine at the VA)
  - Typically recovers quickly when ANC > 500
Neutropenic enterocolitis (Typhlitis)
- Life-threatening bacterial translocation due to breakdown of gut-mucosal barrier
- Presentation
  - Abdominal pain + fever
  - ± abdominal distension, nausea, vomiting, watery and/or bloody diarrhea
- Diagnosis
  - CT A/P with contrast, consider C. diff PCR if diarrhea
- Treatment
  - Cefepime/Flagyl OR Zosyn
  - If no perforation/abscess on CT scan, typically continue until 14 days after ANC recovers >500 and abdominal pain resolves
  - Can change to cipro/flagyl once ANC >500
  - If perforation/abscess: will need imaging to confirm resolution, and longer duration of abx
Neutropenic Prophylaxis
- Used if ANC is expected to be \< 500 for > 7 days

	Most Common Regimens	Alternatives
Bacterial	Levofloxacin 500mg daily (renally dosed)	Cefdinir 300mg BID
Viral	Valacyclovir 500mg BID	Acyclovir 400mg BID (renally dosed)
Fungal	Fluconazole 400mg daily	Posaconazole 300mg BID x2 days 300mg daily (AML induction for aspergillus) Micafungin 50mg IV daily
PJP (if steroids)	Inhaled pentamidine 300mg qmonthly	Dapsone (check G6PD) Avoid Bactrim (risk of myelosuppression)

Filgrastim (G-CSF – Neupogen/Zarxio/Granix)¶

Induces bone marrow production of neutrophils
Dose: either 300mcg or 480mcg (rounded from 5 mcg/kg/day)
Common side effects: fatigue, nausea
PEG-filgrastim (Neulasta): long-acting version that is only given as an outpatient

Oncologic Emergencies¶

Bradley Christensen, Madeleine Turcotte

Leukostasis¶

Presentation¶

Primarily occurs with acute myeloid leukemia and acute lymphoblastic leukemia. This is not common with CLL or CML with high leukocyte counts in the absence of a significant increased portion of peripheral blasts
Respiratory: dyspnea, hypoxia (note CXR may be normal)
PaO2 by ABG often falsely low from WBC consuming O2 in vitro. Trust SpO2.
CNS: headache, AMS, vision changes, dizziness, tinnitus, gait instability, neuro deficit

Evaluation¶

CBC with diff and peripheral blood smear
Imaging: CT head to evaluate neuro deficit and to check for ICH
Chest X-Ray vs CT chest to evaluate dyspnea and air space abnormalities

Management¶

Call hematology
Emergent cytoreduction
Leukapheresis: page nephrology and place dialysis catheter
Hydroxyurea and chemotherapy per hematology fellow
Transfer/admit to ICU

Tumor Lysis Syndrome¶

Background¶

Lysis of malignant cells either spontaneously or in response to chemotherapy causing release of K, Phos, nucleic acids, and cytokines
Consequences:
- Hyperkalemia: most urgent and immediately life threatening
- Hyperphosphatemia: binds Ca and leads to CaPhos crystal deposition AKI, HypoCa
- Hyperuricemia (from breakdown of DNA) precipitation in renal tubules AKI
- Hypotension, AKI from cytokine release
Laboratory TLS
Uric acid ≥ 8, Ca2+ ≤ 7, K+, or PO43- ≥ 4.5
or > 25% change from baseline in these values

Evaluation¶

Risk Stratification:
- Highest risk after starting chemotherapy, but can occur spontaneously
- Tumor characteristics which confer a higher risk of developing TLS:
  - High (>5% risk): ALL (WBC> 100K or LDH 2x ULN), AML (WBC> 100K), Burkitt’s (III/IV or LDH≥2xULN, DLBCL with bulky disease, intermediate risk + AKI/CKD
  - Intermediate: ALL (WBC<100K, LDH <2x ULN), AML (WBC 25-100K), Burkitt’s LDH<2x ULN), DLBCL (non-bulky, LDH>ULN), CLL (if tx with fludarabine, rituximab, lenalidomide, or venetoclax +LN 5-10 cm or ALC≥25K), plasma cell leukemia, rare chemo-sensitive solid tumors (small cell)
  - Low: all others

Management¶

Prevention:
- High risk: q6-8h TLS labs, IVF (±loop diuretic if volume overload), allopurinol, ± rasburicase
- Intermediate – q8h TLS labs, IVF, allopurinol
- Low – daily TLS labs, IVF
  - Significant hydration: goal to maintain UOP 80-100 mL/hr
  - Allopurinol: 300 mg PO BID for CrCl > 20 mL/min, UpToDate renal dosing if lower
  - Rasburicase ($$$): contraindicated in G6PD (send G6PD if not urgent and AA, Asian or Jewish descent)
    - Given if uric acid > 8 mg/dL: get fellow approval before ordering
Treatment: (Can use as night/cross cover handoff)
- K+ > 5.5: STAT EKG. Kayexalate 30g orally or 60g per rectum (unless contraindicated) x1
  - Give 10 U insulin/1 amp D50
  - If EKG changes, then calcium gluconate and D5W at 100 mL/hr with repeat BG in 1 hr
- Uric acid > 8 with 25% change from baseline: page hematology fellow to discuss rasburicase
- PO4 > 4.5 with 25% change from baseline: start/↑ phos binder (sevelamer)
- Dialysis may be necessary in patients with poor renal function.
- IV calcium: do not administer unless symptomatic AND hyperphosphatemia is corrected
  - With high phos, IV calcium can lead to calcium deposition and renal failure
- Hemodialysis: pt with anuria, refractory hyperkalemia, and symptomatic hypocalcemia

Superior Vena Cava (SVC) Syndrome¶

Background¶

Commonly Associated Malignancies: Lung Cancer, Non-Hodgkin or Hodgkin Lymphoma, Mediastinal Germ Cell Tumors, Thymic Malignancies
Partial or complete obstruction of the SVC impedes blood return from the upper extremities, head, neck, and brain resulting in upstream congestion
Can be 2/2 a mass in the mediastinum or thrombosis (foreign body i.e. catheter)

Presentation¶

Facial or neck swelling without generalized edema
Sense of head fullness, exacerbated by leaning forward or lying down
Pulmonary symptoms including dyspnea, stridor, hoarseness, cough - due to edema narrowing the nasal passages and larynx or mechanical airway obstruction
Physical Exam: facial and neck edema particularly of the eye lids in the morning, distended neck and chest veins; can also sometimes see upper extremity swelling, papilledema, plethora. Look for associated lymph node enlargement anywhere particularly including supraclavicular, cervical, and axillary region

Evaluation¶

CXR: may show mass, perihilar or mediastinal disease
Contrasted CT scan ± CT Venography: Phased to get a view of clot contribution to obstruction guides decision regarding anticoagulation or stenting
Radiology attending can coordinate with techs (requires verbal direct request)
MRI/MRV may provide additional information (often not possible due to pt too sick)

Management¶

Assess airway and prepare for intubation if needed
Keep head of bed elevated
Thrombosis:
- Removal of lines/catheters associated with thrombus
- Consideration of anticoagulation
Tumor compression: the type of tumor guides treatment (tissue biopsy is key)
Stat/urgent consultations:
- Interventional radiology for possible stenting/dilatation
- Radiation oncology- for radiation therapy
- Interventional pulmonology – for help with tissue dx
- Medical oncology – for help with diagnosis and chemotherapy

Spinal Cord Compression¶

Background¶

Malignancies where cord compression is most common:
- Multiple Myeloma, Lymphoma (both Hodgkin and NHL), Lung, Breast, Prostate Cancer
Tumor mass & compressed and often displaced bone impinges thecal sac or nerve roots spinal cord or any spinal nerves including the cauda equina

Presentation¶

Back pain, motor, or sensory deficits
Cauda Equina syndrome bowel or bladder incontinence, ataxia

Evaluation¶

Neurologic exam with sensation testing seeking level below an identified dermatome
Lab testing: If no known malignancy check CBC, CMP, SPEP, and (in males) PSA
Bladder US if suspicion or retention with or without overflow incontinence

Management¶

If suspected, order MRI without and with contrast; if patient unable to have MRI, CT myelography may be considered
Immediate high dose steroids (dosing is controversial with recommendations ranging from 4 to 100 mg of dexamethasone q6h - choice of dexamethasone is to minimize mineralocorticoid effects. Most common dosing is 10mg IV x1 followed by 4mg IV q6h)
Consider stat/urgent consultation with:
- Neurosurgery for diagnostic/therapeutic intervention
- Radiation oncology- for radiation therapy
- Medical oncology – for help with diagnosis and chemotherapy
Ensure regular neuro-vascular checks and close monitoring.

Brain Metastases¶

Background¶

Common malignancies: Lung (NSCLC), breast, kidney, colorectal carcinomas & melanomas
Significantly more common than primary brain tumors
80% of brain metastasis occur in the cerebrum at grey/white matter junction

Presentation¶

Highly variable: consider brain mets in any cancer pt w/ neurologic or behavioral changes
Headache: worse in the mornings, with bending over or with valsalva
Nausea/vomiting
Cognitive dysfunction: changes in memory, mood or personality
Focal neurologic deficits
Signs of elevated ICP: papilledema, vision changes, drowsiness, presyncope
Seizures
Stroke (particularly in melanoma, choriocarcinoma, thyroid & renal carcinomas)

Evaluation¶

STAT CT if concerned for stroke or elevated ICP
MRI with contrast: most sensitive, can differentiate between metastases vs. other lesions
- Suggestive features: multiple lesions, location, circumscribed margins, vasogenic edema
If pt has no known primary tumor: consider CT C/A/P ± PET to identify primary
Biopsy with histopathology & IHC: if diagnosis in doubt or if only a single lesion is present

Management¶

If severe HA, N/V, focal deficits: systemic glucocorticoids
Dexamethasone 10mg IV x1 followed by 4mg IV q6h (can be PO if tolerated)
Stat/urgent consults:
- Neurosurgery – for diagnostic/therapeutic intervention
- Radiation oncology – for radiation therapy
- Medical oncology – for help with diagnosis and chemotherapy
Ensure regular neuro-vascular checks and close monitoring
Do not perform LP without input from neurology

Pancytopenia¶

Thomas Gracie

Background¶

Framework for differential:
- Impaired production (aplastic anemia, marrow infiltration, marrow suppression, vitamin/nutritional deficiencies, sepsis, cirrhosis)
- Peripheral destruction (autoimmune hemolytic, hypersplenism)
- Combined process (PNH, SLE, leukemia, HLH, infections)

Evaluation¶

Medications: NSAIDs, AEDs, steroids, chemotherapy, antivirals, immunosuppression
PMHx: autoimmune disease (SLE, RA), radiation, gastric surgery, malabsorption, liver disease, hematologic malignancy
Social Hx: EtOH use, malnutrition, occupational exposures, exposures to TB or leishmaniasis
Exam: lymphadenopathy, hepatosplenomegaly, neuropathy, petechiae, stigmata of liver disease, cachexia
Diagnostic studies: CBC w/ diff, CMP, reticulocyte count, peripheral smear, viral studies (hepatitis A/B/C, EBV, CMV, HIV, parvovirus B19), vitamin levels (B12, folate, copper, zinc), iron studies, hemolysis labs (LDH, haptoglobin, Coombs), flow cytometry, bone marrow biopsy, cytogenetics and FISH

Management¶

For pancytopenia that is acute (hospital onset) often observation is the best approach
When pancytopenia is slow, progressive over time, or acute without any other precipitating factors then would consult hematology for consideration of a bone marrow syndromes

Paraneoplastic Syndromes¶

Justin Lo

Hypercalcemia of malignancy¶

Background¶

Caused by PTHrP production, osteolytic lesions, and/or rarely exogenous Vit D
PTHrP: Breast cancer, NSCLC (squamous)
Osteolysis: Multiple Myeloma, Breast Cancer
Exogenous Vit D: Lymphoma

Evaluation¶

Correct [Ca+2] for hypoalbuminemia: add 0.8 x (4.0 – albumin)
Send basic hyperCa+2 work-up – PTH, Vit D, etc. (see hypercalcemia section)
PTHrP is called “Parathyroid Hormone-related Peptide-ARUP” in Epic

Management¶

First-line: IVF without calcium such as Normosol; goal urinary output of 150-200 mL/hr
Strict I/Os; Cautious IV fluids if pt w/cardiac or renal dysfunction
Add Furosemide if hypervolemic (do not empirically start)
Second-line: Zoledronic acid 4mg IV (takes 24-48 hours to see effect)
AMS or severe hypercalcemia (>14mg/dL): calcitonin 4 IU/kg (req. attending approval)

SIADH¶

Background¶

Euvolemic hypotonic hyponatremia with urine sodium >20 and typically urine Osm >100
Associated with: SCLC (most common), head/neck cancers, breast cancer
See "Nephrology" for additional information

Management¶

Free water restriction to 800mL/day
Refractory: salt supplementation (e.g. salt tabs) ± loop diuretic

Carcinoid Syndrome¶

Background¶

Episodic flushing, diarrhea, wheezing/SOB due to secretion of histamine & serotonin
Most common: Neuroendocrine tumors – GI (often with mets to liver and lung)

Evaluation¶

Urine: UR 5-HIAA (ARUP)
Imaging to identify tumor(s) (CT chest/abdomen/pelvis)

Management¶

Short-term treatment: subQ or IV octreotide (see UpToDate for dosing)
Antidiarrheals (Imodium, Lomotil, etc.) to slow transit
Long-term treatment: depot (IM) forms of octreotide and lanreotide

Autoimmune encephalitis, encephalomyelitis, and myelitis¶

Background¶

Encephalopathy (limbic or brainstem), ± myelitis (limb ataxia, sensory deficits)
Associated with small cell lung cancer and checkpoint inhibitor therapy

Evaluation¶

LP: make sure to order CSF oligoclonal bands & CSF IgG index
“Paraneoplastic AutoAb Eval-MAYO” (add "CSF" to the front of the order name if for LP)
NMDA-R can be ordered as a standalone test
CT head
EEG if concern for subclinical seizures

Management¶

Consult Neurology, for possible immunosuppressive therapy (steroids, IVIG)

Lambert-Eaton myasthenic syndrome (LEMS)¶

Background¶

Muscle weakness due to autoantibody against calcium channels resulting in ↓ ACh release
Associated with SCLC (most common) & lymphoma

Presentation¶

Proximal muscle weakness, diminished DTRs

Evaluation¶

Nerve conduction studies: EMG w/ NCV
Serum “Paraneoplastic AutoAb Eval-MAYO”

Management¶

Consult Neurology

Plasma Cell Dyscrasias¶

Rahul Shah, Jennifer Marvin-Peek

Background¶

A heterogenous group of benign, premalignant, and malignant conditions characterized by clonal proliferation of plasma cells
Results in over-production of monoclonal immunoglobulins or polypeptides (i.e., M-protein) that can be detected in serum and/or urine
Includes monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), multiple myeloma (MM), Waldenström Macroglobulinemia (WM), extra-medullary plasmacytoma, AL amyloidosis, POEMS syndrome
Spectrum of MGUS, SMM, and MM represents natural progression of same disease process
Complications: Increased infectious risk, cytopenias, renal failure, hyperviscosity syndrome, malignant hypercalcemia, pain crisis from bony disease
Elevated gamma/protein gap (serum total protein minus albumin >4) often prompts work-up for an underlying plasma cell dyscrasia (high specificity but low sensitivity)

Fatigue, weakness, weight loss

Bone pain

Paresthesias, neuropathy, radiculopathy

Visual disturbances

(if hyperviscosity present)

Lymphadenopathy (uncommon)

Fever (uncommon)

Anemia (Hgb <10)

Renal insufficiency (Cr > 2)

Hypercalcemia (Ca > 11.5)

Elevated protein gap (Total protein - Alb > 4)

Osteolytic bone lesions (typically central)

Unexplained heavy proteinuria

Rouleaux formation on blood smear

Evaluation¶

CBC w/ diff, peripheral blood smear, CMP (for Ca, Cr, albumin), LDH, CRP, urinalysis
SPEP with immunofixation, UPEP (24-hour urine) with immunofixation, serum free light chains (FLC)
Quantitative immunoglobulins (IgA, IgM, IgG, IgD, IgE)
If Hgb <10, Cr >2, Ca >11.5, M-protein >1.5, non-IgG M-spike, abnormal FLC ratio:
Bone marrow biopsy + cytogenetics
β2-microglobulin, serum viscosity (in WM)
Skeletal imaging to identify bone lesions: skeletal survey (x-ray) often done initially, then more sensitive CT/PET-CT/MRI if biopsy shows SMM/MM
If considering amyloidosis: abdominal wall fat pad biopsy with Congo red staining typically sufficient (call pathology to arrange, can typically be done same-day or next-day) vs direct biopsy of amyloid-involved tissue

SPEP/UPEP

Free light chains (FLC)

Urinalysis

Initial screening test to look and quantify M-protein

Serum immunofixation determines clonality

(e.g. mono or polyclonal)

Monoclonal spike >1.5 is indicative of underlying dyscrasia

Polyclonal spike suggests infectious, inflammatory, or reactive etiology

Ratio of kappa/lambda >3 highly suggestive of plasma cell dyscrasia or amyloidosis

Ratio 1.65 to 3 can be due to infectious process or renal insufficiency

Helpful in pts that only produce Bence-Jones protein (FLC w/o heavy chain) which isn't seen on SPEP

Detects albumin, not light chains

In myeloma cast nephropathy, dipstick will be negative since proteinuria is from FLC (i.e. Bence-Jones proteinuria)

In AL amyloid, dipstick will be positive 2/2 albumin loss from nephrotic syndrome

	Monoclonal Gammopathy of Unknown Significance (MGUS)	Smoldering Multiple Myeloma (SMM)	Multiple Myeloma (MM)
% Plasma Cells in BM	<10%	10-60%	≥ 10% (typically >30%)
Monoclonal Protein	IgG, IgA, IgM: 1.5 -3	IgG or IgA >3	IgG or IgA >3
Laboratory studies	Normal Hgb, Ca, Cr	Normal Hgb, Ca, Cr	↓Hgb, ↑Ca, ↑Cr
Symptoms	None	None	Lytic bone lesions, fatigue
Prognosis	1% / year progression to MM	10% / year progression to MM	R-ISS staging (see below)
Monitoring and/or Treatment	Monitoring only Yearly: Symptom check SPEP, FLC, CBC, BMP	Monitoring only In 2-3 months, repeat SPEP, FLC, CBC, BMP Yearly skeletal survey	Chemotherapy, plus SCT for eligible patients

Multiple Myeloma¶

Evaluation¶

Diagnosis requires clonal bone marrow plasma cells ≥10% or bony/extramedullary plasmacytoma AND one or more end-organ event (CRAB criteria) or biomarker of myeloma
CRAB criteria
- Hypercalcemia, renal impairment, anemia, bone osteolytic lesions
Biomarkers of multiple myeloma
- Clonal bone marrow plasma cells ≥ 60%
- Serum FLC ratio ≥ 100 or ≤ 0.01
- 1 focal lesion ≥ 5mm on MRI
Skeletal imaging: Whole-body PET-CT or CT preferred, MRI, bone survey (x-ray)

Management¶

First-line induction therapy typically is RVd: immunomodulatory agent (lenalidomide [Revlimid]), proteasome inhibitor (bortezomib [Velcade]) and dexamethasone
Consolidation therapy includes autologous SCT for transplant eligible patients
Maintenance therapy is often given indefinitely, typically lenalidomide or bortezomib
Relapsed disease is often treated with anti-CD38 monoclonal Ab (daratumumab) with a steroid and either immunomodulatory drug or proteosome inhibitor; CAR-T also recently approved for relapsed MM
Supportive Care
- VTE prophylaxis with DOAC or LMWH if on an immunomodulatory agent with 2 VTE risk factors; if only 0-1 VTE risk factors, aspirin
- EPO and G-CSF for treatment-related anemia and neutropenia
- Bisphosphonate (ideally zoledronic acid) to reduce risk of fractures; analgesia ± radiotherapy for bone pain and palliation
- (Val)acyclovir if on bortezomib for VZV prophylaxis

Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (IgM)¶

Presentation¶

Hyperviscosity syndrome: blurred vision, dizziness, diplopia, hypoxia, ataxia, vertigo, stroke, coma
Peripheral neuropathy
Retinal changes: dilated veins, hemorrhages, papilledema
Cryoglobulinemia: large IgM complexes precipitate out in the cold, causing Raynaud's, urticaria, purpura, acral cyanosis, tissue necrosis

Evaluation¶

Requires: IgM monoclonal gammopathy on SPEP, BM biopsy w/≥10% lymphocytes with plasmacytoid differentiation (late stage B-cell differentiation), and MYD88 mutation detected
CBC, coagulation studies, cryoglobulins, IgM, β2-microglobulin
Serum viscosity (If <4 symptoms are rare, If >6 typically symptomatic)

Management¶

Asymptomatic patients managed with close observation
Symptomatic hyperviscosity is treated with plasmapheresis
Induction: may include bendamustine ± rituximab if IgM level is <4000 (Rituximab can temporarily ↑ IgM and ↑ risk of hyperviscosity syndrome)
Monitor response with: IgM levels, monoclonal IgM on SPEP

Other Plasma Cell Dyscrasias¶

Light Chain (AL) Amyloidosis¶

Extracellular deposition of misfolded light chains (most commonly kidney & heart)
Features: nephrotic syndrome, restrictive CM, peripheral neuropathy, HSM, macroglossia, easy bruising/bleeding, dysautonomia/orthostasis
Diagnosis:
- Need ALL 4: amyloid related systemic syndrome, positive congo red staining on any tissue, evidence that amyloid is light chain related, evidence of monoclonal plasma cell disorder

POEMS Syndrome¶

Cause unknown, possibly chronic overproduction of pro-inflammatory cytokines such as VEGF
Features: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (usually λ light chain), Skin changes
Diagnosis:
- Mandatory Criteria: peripheral neuropathy, monoclonal plasma cell disorder
- Major Criteria (need ⅓): osteosclerotic lesions, VEGF, Castleman disease
- Minor Criteria (need ⅙): organomegaly, volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis or polycythemia

Castleman Disease¶

Angiofollicular lymph node hyperplasia
Antibodies to HHV-8 implicated in >50% of cases
Features: Lymphadenopathy, fever, night sweats, fatigue, fluid accumulation, violaceous lymph node biopsy w/ characteristic hematopathology papules

Sickle Cell Crisis¶

Michael J. Neuss

Background¶

Present with severe pain in bone, joints, chest, abdomen
Causes: (HIDISC) Hypoxia, Ischemia, Dehydration, Infection, Stress, Cold
Can’t Miss:
- Acute chest: hypoxia + fever + chest pain + new infiltrate on CXR (consult benign hematology immediately, do not wait until the next day)
- PE (ACS less likely in these patients); avascular necrosis of hip, priapism, stroke

Evaluation¶

Labs: LDH (high), Hgb/Hct (low; check vs baseline), retic, smear, WBC
If febrile: UA + Blood cultures
Send Hgb S level, and compare to baseline w/ other hospital admissions
Imaging: CXR, MRI for hip pain, Abdominal U/S or CT abdomen
Maintain active type and cross given probability of antibodies

Management¶

General:
- Look for a care coordination yellow note in the Summary Tab
  - Heme clinic will have specific management preferences for individual patients
- Maintain hydration, IVF at 150-200 cc/hr (if no contraindication)
- Oxygen: goal sat ~95% (higher O2 goal will help to prevent further sickling!)
- Continue folic acid 1 mg qDay
- Continue hydroxyurea if uncomplicated pain crisis
  - Hold if counts suppressed or concern for infection
- If in the MICU: consider discussion for plasma exchange (if Hgb SS or SC or S-Thal)
- Transfuse: Simple transfusion if Hgb lower than baseline and/or complications
  - Avoid transfusions when able, given risk of antibody formation
Pain:
- Will generally require opiates, likely initiation of PCA
- All SS patients should have pain plans; inpatient pain plans are in the problem list under sickle cell disease or in the care coordination section of Epic
- Outpatient plans (to which you will transition pts back prior to discharge) are not standardized in location, but can be under Media (with a pain contract) or found in notes
Acute chest:
- Consult Hematology at time of admission
- D5 ½ NS @ 150-250 cc/hr
- Transfuse hgb to >10
- PCA w/ dilaudid
- Abx for CAP (vs HAP if risk factors) ± bronchodilators

Therapy Toxicities¶

Rahul Shah

Immune Checkpoint Inhibitor Toxicities¶

Immune checkpoint inhibitors augment the endogenous immune response against tumors, which may lead to autoimmune-like toxicities, known as immune-related adverse events (irAEs)
Treatment: low-dose glucocorticoids (prednisone, 0.5 mg/kg) for mild adverse events, high dose glucocorticoids (prednisone, 1-2 mg/kg) for severe adverse events

Adverse Event Type	Incidence with anti-CTLA-4 (e.g. ipilimumab)	Incidence with anti‐PD1/PD‐L1 (e.g. nivolumab, pembrolizumab)
Skin (rash, pruritus, TEN)	30%	30%
Colitis	25%	5%
Hypothyroidism	20%	20%
Hepatitis	10%	1%
Hypophysitis	10%	rare
Pneumonitis	2-5%	2-5%
Myocarditis	<1%	<1%
Neurotoxicity (GBS, myasthenia gravis, encephalitis)	<1%	<1%

Cytotoxic Agent Toxicities¶

Class	Agent	Side Effect
Alkylating Agents	Busulfan	Pulmonary fibrosis or diffuse alveolar hemorrhage
	Cyclophosphamide	Myopericarditis, hemorrhagic cystitis (prevention: hydration; monitoring: daily UA, tx: mesna)
	Ifosfamide	Encephalopathy (tx: methylene blue), nephrotoxicity, hemorrhagic cystitis
Antimetabolites	5- Fluorouracil (5-FU)/ Capecitabine (metabolized to FU)	Myelosuppression, coronary vasospasm, palmar-plantar erythrodysesthesia, mucositis
	Cladribine, pentostatin	Dose reduced for CrCl
	Cytarabine (Ara-C)	Irreversible cerebellar ataxia (if high dose, neuro checks required), conjunctivitis (prevent with prophylactic steroid eye drops)
	Gemcitabine	Transient transaminitis, peripheral edema, rash, rarely: pulmonary toxicity, hemolytic uremic syndrome, capillary leak syndrome
	Methotrexate	Stomatitis, hepatotoxicity, renal failure, high dose requires leucovorin
Antitumor antibiotics	Anthracyclines (doxorubicin, daunorubicin, idarubicin)	HFrEF (need TTE prior). Most notable with doxorubicin.
	Bleomycin	Pulmonary fibrosis. Potentiated with G-CSF
Monoclonal Antibodies	Alemtuzumab	Severe and prolonged cytopenias
	Bevacizumab	HFrEF, HTN, hyperglycemia, hypomag, DVT, pulm hemorrhage, GI bleeding/fistulas/perforation, wound healing complications
	Rituximab	Hypophos, hepatotoxicity, HBV reactivation (screen all patients), peripheral neuropathy; transfusion reaction during 1^st time infusion
Platinum Agents	Cisplatin, oxaliplatin, carboplatin	Nephrotoxicity, worst with cisplatin. Rental tubular acidosis. Neurotoxicity (parasthesias, cold sensitivity, cramps, peripheral neuropathy), ototoxicity (high frequency hearing loss), constipation, hypomag
Taxanes	Docetaxel, paclitaxel	Hypersensitivity reaction (often require premedication with steroids and H1/H2 blockers); peripheral neuropathy
Topoisomerase Inhibitors	Irinotecan, topotecan, etoposide	Irinotecan- acute diarrhea can be treated with atropine; delayed with atropine
Tyrosine Kinase Inhibitors	Imatinib, Dasatinib, Nilotinib, Bosutinib	QTc prolongation, pulmonary effusion, hepatotoxicity
Vinca alkaloid	Vincristine	Peripheral neuropathy and ototoxicity (vestibular system lost first)

Thrombocytopenia¶

Robert Dunn

Background¶

Platelet count <150k (mild), 50-100k (moderate), <50k (severe)
Framework for differential: consumption, sequestration, destruction, production
Causes to consider:
- Can’t Miss Diagnoses: TTP, HUS, HELLP, DIC, HIT
- Platelet clumping (lab artifact - pseudothrombocytopenia)
- Splenomegaly can represent: Plt sequestration, cirrhosis, portal hypertension
- Drug-induced: (Antibiotics, heparin, chemo, GpIIb/IIIa antagonists, H2-antagonists)
- Rheumatologic cause – SLE, sarcoidosis, scleroderma renal crisis
- Sepsis, independent of DIC
- Immune thrombocytopenia (ITP) is a diagnosis of exclusion
- Massive physiologic consumption: large hematoma, active hemorrhage
- Cirrhosis – results in low thrombopoietin (TPO) and increased clearance
- Chronic alcohol use – direct marrow suppression
- Infections: HIV, HCV, EBV, Parvovirus, Rickettsia, H. pylori, CMV
- Bone marrow failure: aplastic anemia, MDS, leukemia, chemotherapy
- Dilutional: fluid resuscitation and massive transfusion

Presentation¶

Petechiae – typically begins distally on lower legs (in mouth = wet purpura), seen when \<10-20k
Overt bleeding, mucosal bleeding, epistaxis (seen when \<20k)

Evaluation¶

CMP, CBC w/diff, peripheral smear, citrated platelet count, immature platelet fraction (IPF)
LDH, Fibrinogen, d-dimer, PT/aPTT
Determine timing of decline as well as prior values
Look at other cell lines - never normal to have two cytopenia’s
Review recent initiation of drugs: (heparin, antibiotics, and chemotherapy)
Consider abdominal ultrasound to look for splenomegaly and liver pathology
Infectious work up (HIV, HCV)
Calculate 4T Score and consider your pretest probability for HIT testing
HIT Ab: ELISA is first test – only run once/day at VUMC so order early if considering
Reflex Serotonin release assay (SRA) for confirmation (VUMC performs reflexive testing)

Management¶

Plt <50k
- Discontinue pharmacologic DVT prophylaxis (unless HIT)
- If on anticoagulation: consider risk/benefits of continued anticoagulation
  - Can transfuse plt’s if AC is mandatory
Plt <10k
- Transfuse platelets given risk of spontaneous intracranial hemorrhage
- In pt’s with HIT or TTP, there is theoretical concern that transfusing plt can “fuel the fire” and lead to more thrombosis, but if there is active bleeding then consider platelets
  - Therefore, bleeding with HIT or TTP, discuss with Hematology before transfusion
HIT
- If pretest probability is high or HIT is confirmed
- Stop Unfractionated and low molecular weight heparin products
- Start Argatroban gtt
If schistocytes present on peripheral smear = concern for TTP
- Draw ADAMTS13
- Contact Nephrology and Hematology for PLEX

Additional Information¶

Clumping on lab draws:
- Obtain Citrated platelet (“blue top” tube – CPRS refers to it as a blue top platelet count)
- If no resolution, obtain a "Gold top" LAB 301 in Epic (Named: Plt count) (ACD tube)

Transfusion Medicine¶

R. Dixon Dorand

Overview¶

For emergent transfusions:

Call the blood bank (VUMC: 615-322-2233; VA: 67025, supervisor at 67029).

For non-emergent transfusions:

VUMC:

RNs on 10T and 11N can follow transfusion protocols for pRBCs and Plts – enter as a Nursing Communication or as part of the Hematology/Oncology Admission Order set.
At VUMC, all special processing of blood products (such as irradiation) will be decided by blood bank based on special considerations listed in order set. Examples include: stem cell transplant, hematologic malignancy, or thalassemia
Patients with frequent transfusions (e.g. sickle cell hemoglobinopathy) should have an RBC Extended Phenotype ordered (once) for minor RBC antigens to avoid immunization and antibody development to these proteins
You may ask the VUMC hematology lab to email you pictures of the peripheral smear

VA:

Orders Tab – Blood Bank Orders – follow prompts to select appropriate product. Must order both the blood product AND the transfusion order (“Transfuse blood”)

You need to specify all special processing such as irradiation
To order a Type & Screen as a lab, you must go to Blood Bank Orders
Type & Screen and Transfusion results are under the Blood tab in Results

Red Blood Cell Transfusion¶

Volume 200-300 mL per unit prbc
In general, 1 unit of packed RBCs increases Hgb by 1g/dL and HCT by ~3%
Assessment of the post-transfusion Hgb can be performed 15 min following transfusion, but ideally 1 hour after completion

Indications:

Hgb <9-10 g/dL – Acute coronary syndrome
Hgb <8 g/dL or Hct <25 – Bone marrow failure or receiving antineoplastic therapy
Also sometimes used in pts with pre-existing CAD
Hgb <7 g/dL or Hct <21 – ICU, GI Bleeding, Oncology patient on treatment

Platelet Transfusion¶

Indications:

<11 k/µL – all patients, reduce risk of spontaneous hemorrhage (use on BMT, Brittingham)
<50 k/µL – active bleeding, scheduled to undergo select invasive procedure
<100 k/µL – CNS hemorrhage, intrathecal catheter
- This is also the threshold used for most Neurosurgical procedures

Fresh Frozen Plasma (FFP) & Cryoprecipitate (Cryo)¶

Cryoprecipitate

FFP enriched for von Willebrand factor, factor VIII, factor XIII, and fibrinogen

FFP

Once thawed, must be used in 24 hrs (due to decline in labile coagulation factors)
Must be ABO compatible but not crossmatched or Rh typing
Only administer FFP if INR ≥1.7 (the INR of FFP is ~1.7, so FFP will not fix an INR < 1.7)

Indications:

Bleeding:
- FFP If INR >1.7
- Cryoprecipitate if fibrinogen <100.
DIC:
- Fibrinogen <100: Transfuse 5 – 10 units cryoprecipitate and repeat fibrinogen. If bleeding, consider raising transfusion threshold of cryoprecipitate to fibrinogen <150
- For elevated INR, consider FFP transfusion. Thresholds for doing this vary by attending
Cirrhosis:
General concept: PT/INR, aPTT are unreliable markers for bleeding. Fibrinogen ≤100 – 120 or thromboelastography are better surrogates for bleeding risk
Transfuse fibrinogen ≤100 – 120 if the patient is actively bleeding or about to undergo a procedure or surgery other than paracentesis
Transfuse FFP based on hepatology team preference (generally few indications for FFP)

Transfusion Premedication & Reactions¶

If you are concerned about a serious transfusion reaction, pause the transfusion and contact the blood bank asap
Order the transfusion reaction blood testing in Epic. You will send a CBC, the bag of blood products, and the completed form to the blood bank for analysis

Premedication:

Only if history of severe reaction
Diphenhydramine 25-50mg IV
Acetaminophen 650 mg PO
Meperidine 25-50 mg IV (optional for chills)
Hydrocortisone 50 mg IV (optional, for severe reactions or reactions despite acetaminophen and diphenhydramine)

Reaction	Signs & Symptoms	Etiology	Clinical Action
Allergic (mild)	Pruritus, hives limited to small area	Antibodies to transfused plasma proteins	Pause transfusion. Administer antihistamines. Resume transfusion if improved; NO samples necessary. If no improvement in 30 min treat as moderate to severe.
Allergic (moderate to severe)	Generalized hives (>2/3 body surface), bronchospasm & dyspnea, abdominal pain, hypotension, nausea, anaphylaxis	Antibodies to transfused plasma proteins usually IgE but can also be IgA, Possible allergen in blood product	Administer antihistamines, epinephrine, vasopressors and corticosteroids as needed. Send product to blood bank.
Febrile Non-Hemolytic	Rise of temp >1°C, chills, rigors, anxiety.	Cytokines released from residual white blood cells in the blood product	Mild: administer antipyretics as needed
Acute Hemolytic	Hemoglobinemia / uria, fever, chills, anxiety, shock, flank pain, chest pain, unexplained bleeding, cardiac arrest	Intravascular hemolysis usually due to ABO incompatibility; Recheck for patient ID or clinical error. This is an emergency.	Treat shock w/vasopressors; maintain airway; administer fluids and maintain brisk diuresis; monitor for AKI.. Administer blood products as needed after etiology is clear.
Septic	Rise of temp > 2°C, sudden hypotension or hypertension, shock	Micro-organism (i.e. bacteria) in donor bag (Greater risk in apheresis vs. RBC)	Send bag/tubing to transfusion medicine. Order BCx. Broad spectrum abx Pressor support if necessary.
TRALI – Transfusion Related Acute Lung Injury	Acute respiratory distress usually within 1-2 hours of transfusion. Non-cardiogenic pulmonary edema unresponsive to diuretics; Dx of exclusion.	Usually donor HLA antibodies from transfused plasma. Recipient has corresponding antigens; causes neutrophil activation that results in extravasation of fluid into air spaces	Respiratory support! Most will resolve within 24-96 hours. Steroids, diuretics: no known benefit.

Venous Thromboembolism¶

Kenna Koehler

Background¶

Includes both deep vein thrombosis (DVTs) and pulmonary embolism (PE). See “Pulmonary Embolism” section in cardiology for more information on PEs
Risk Factors for Provoked DVT/PE
- Major risk factors: major surgery >30 minutes, hospitalization > 3 days, C-section
- Minor Risk Factors: Surgery <30 minutes, Hospitalization <3 days, pregnancy, estrogen therapy, reduced mobility >3 days
- Non-transient risk factors: Malignancy (active), IBD, liver disease, hereditary thrombophilia

Evaluation¶

Asymmetric calf swelling of >2cm sensitivity and specificity for DVT of 60-70%
Wells’ Criteria for DVT can help guide diagnostic testing
If a patient has a low pre-test probability, a negative D-dimer can rule out DVT
In a high pre-test probability patient a negative D-dimer is less helpful
Whole-leg ultrasounds with doppler

Management¶

Prophylaxis: Padua score
Score > 4 high risk, recommend pharmacologic prophylaxis
- Subcutaneous Low Molecular Weight Heparin (LMWH) or Subcutaneous Heparin
Score <4 is low risk; recommend ambulation and SCDs
Treatment (see anticoagulation section)
- Subcutaneous low molecular weight heparin (LMWH)
- Oral factor Xa inhibitors (rivaroxaban, apixaban)
- Intravenous unfractionated heparin
- Warfarin (with bridge therapy)
Duration of treatment
- Provoked: 3 months or until provoking factor (trauma, surgery, malignancy) is removed
- Unprovoked: Typically requires life-long anticoagulation along with assistance from hematology
Anticoagulation in malignancy:
- LMWH or DOAC (most evidence for apixaban and rivaroxaban) while malignancy still active
- Avoid rivaroxaban and edoxaban in GI malignancies (increased rates of bleeding)

Additional Information¶

Should we get a follow up ultrasound?
- A follow up ultrasound at the CONCLUSION of anticoagulation can help establish a post-treatment baseline and provide a baseline study for future comparison that can be critical for the diagnosis of recurrent/new DVT (which is very difficult to determine radiographically without a comparison imaging study)
What about IVC filters?
- Select circumstances for these: In patients with acute DVT or PE and in whom anti-coagulation is absolutely contraindicated (thrombocytopenia, recent intra-cranial bleed, recent GI bleed) placement of a retrievable IVC filter should be discussed with Hematology and IR

Ended: Hematology oncology

Hepatology ↵

Acute Liver Injury and Failure¶

Hannah Lomzenski, and Lauren Chan

Background¶

Acute liver injury (ALI): elevated liver enzymes + INR ≥1.5 but NO encephalopathy
Acute liver failure (ALF): elevated liver enzymes + encephalopathy/AMS in the absence of pre-existing liver disease*
- *Chronic autoimmune hepatitis, HBV, Wilson disease, and Budd-Chiari syndrome can have ALF if they develop new AMS, despite the presence of a pre-existing liver disease
Alcohol-associated hepatitis (AH) is not ALF (see above)

Etiology¶

R-factor (if history, exam, and diagnostic data are inconclusive i.e. R-factor is not a replacement to clinical judgement) = (ALT/uln ALT) / (ALP/uln ALP); See chart below
- R > 5 = hepatocellular injury; R<2 = cholestatic injury; R 2-5 = mixed injury
Isolated hyperbilirubinemia: Differentiate direct versus indirect
- Direct: Refer to cholestatic pattern
- Indirect: Gilbert vs hemolysis
Drugs Associated with liver injury
- Hepatocellular pattern: acarbose, Acetaminophen, Allopurinol, Amiodarone, Baclofen, Bupropion, Fluoxetine, HAART (Nevirapine), Kava kava, Isoniazid, Ketoconazole, Lisinopril, Losartan, Methotrexate, NSAIDs, Omeprazole, Oxacillin/Nafcillin, Paroxetine, Pyrazinamide, Propylthiouracil, Rifampin, Risperidone, Sertraline, Statins, Tetracycline, Trazodone, Valproic Acid
- Mixed pattern: Amitriptyline, Azathioprine, Captopril, Carbamazepine, Clindamycin, Cyproheptadine, Enalapril, Flutemide, Nitrofurantoin, Phenobarbital, Phenytoin, Sulfonamides, Trazodone, Verapamil
- Cholestatic pattern: Amoxicillin-clavulanic acid, Anabolic steroids, Chlorpromazine, Clopidogrel, Oral contraceptives, Erythromycins, Estrogens, Irbesartan, Mirtazapine, Phenothiazines, Terbinafine, Tricyclics

Hepatocellular Injury: R factor > 5 (Primary elevation of AST/ALT)
Acetaminophen intoxication^$		Acetaminophen lvl Aspirin lvl
Acute Viral Hepatitis	Hep A^$, B^$, C, D, E EBV, CMV, HSV, VZV	Viral serologies (see below), hx of tattoos, IVDU, piercings, blood transfusion prior to 1990s, intranasal cocaine use and mass vaccinations (in 3rd world countries)
Autoimmune hepatitis\*	Autoantibodies and high serum globulins	Anti-smooth muscle (f-actin), ANA, ANCA, anti-liver kidney microsome (anti-LKM-1), anti-soluble liver antigen/liver-pancreas IgG
Budd-Chiari Syndrome\*	Hepatic vein obstruction	Ultrasound of abdomen w/ doppler, CT w/ contrast
DILI – Drug Induced Liver Injury\*^$	Many drugs	See above \*Query NIH Liver Tox database: https://www.livertox.nih.gov
HELLP Syndrome, Acute Fatty Liver of Pregnancy	Pregnancy	Requires urgent delivery regardless of gestational age
Ischemic Liver Injury (Shock Liver)^$	Shock (can be of any variety)	AST and ALT can be in the thousands, high LDH, history of hypotension
Toxins	Ethanol, cocaine, mushroom (Amanita phalloides)	UDS, ethanol level, PEth lvl
Wilson’s Disease\*	Copper overload	Ceruloplasmin level (screening), 24h urine copper (confirmation), quantitative copper on liver biopsy
\May present with chronic liver injury as well; $May present with AST/ALT >100*

Cholestatic Injury: R Factor \< 2 (Primarily elevated Alkaline phosphatase)
Acute biliary obstruction	Gallstones	Abdominal ultrasound, MRCP, ERCP
DILI – Drug-induced liver injury*^$	Many drugs, consult livertox website	Common: Augmentin, Bactrim, amiodarone, Imuran
Malignancy*	Pancreas, cholangiocarcinoma	CT abdomen, ERCP
Primary Biliary Cirrhosis*	Autoimmune	Anti-mitochondrial antibody
Primary Sclerosing Cholangitis*	Autoimmune, associated with IBD	MRCP, ERCP
Critical illness or COVID cholangiopathy	Hypotension, COVID	MRCP with biliary stenosis, appropriate history
*May present with chronic liver injury as well; $May present with AST/ALT >100

Evaluation¶

Consult hepatology early! (to assist with workup AND for transplant evaluation)
Labs:
- CBC w/diff, CMP, Dbili, Mg, Phos, T&S, BCx, UCx, PT/INR, aPTT, fibrinogen
- Amylase, lipase
- Beta-hCG for females of reproductive age
- ABG with arterial lactate, ammonia (arterial >124 predicts mortality and CNS complications e.g. need for intubation, seizures, cerebral edema, <75 very unlikely to develop ICH)
- Viral etiologies: Virtal hepatitis serologies (HAV panel, HBV panel, HCV IgG ± PCR quant, HDV if known HBV (with low or undetectable HBV load as Misc Reference Test, Hepatitis E PCR ent as miscellaneous if pregnant or travel to southeast Asia), HIV p24 Ag and HIV Ab, EBV Qt, CMV Qt, HSV ½ Qt, VZV IgM/IgG
- Toxins: UDS, ethanol level ± Peth, acetaminophen level (drawn > 4 hours after last known ingestion), Salicylate level
- Autoimmune / genetic: ANA, ASMA, IgG, AMA (if predominantly elevated ALP), ceruloplasmin
Imaging:
- RUQ abdominal ultrasound with doppler (important to assess vasculature!)
- Consider CT with contrast in patients with normal renal function and high suspicion of Budd-Chiari syndrome or malignancy with negative ultrasound (better for assessing the hepatic veins) and helps with transplant evaluation
- Consider TTE to rule out cardiac dysfunction; helpful for transplant consideration

Criteria for Transplantation:¶

King’s College criteria: helps identify patients needing transplant referral/consideration
- ALF due to acetaminophen:
  - Arterial pH \<7.3 after resuscitation and >24 hr since ingestion, OR
  - Arterial Lactate >3 after adequate fluid resuscitation, OR
  - Grade III-IV HE, SCr >3.4, and INR >6.5 all within 24h period
ALF not due to acetaminophen: INR > 6.5 OR 3 of the 5 following criteria:
- Indeterminate etiology, drug-induced hepatitis
- Age \<10 or >40
- Interval of jaundice to encephalopathy >7 days
- Bilirubin > 17.5 mg/dl (300 micromol/L)
- INR >3.5

Management¶

Any pt with concern for ALF should be cared for in MICU (even if mild change in mental status)
Pts with ALF die acutely from hypoglycemia, cerebral edema, and infection
ABC’s:
- Intubate for GCS \<8, Grade 3 or 4 HE
- IVF resuscitation with isotonic crystalloid (most pts are volume deplete; avoid hypotonic fluids due to risk of cerebral edema)
- Vasopressive agents for persistent hypotension (norepinephrine preferred)
Monitoring:
- Q1-2h neuro checks, Q1-2h glucose checks
- Closely monitor CMP, INR q6-8 hrs
Treatment of Primary Injury
- IV N-acetylcysteine - improves transplant-free survival even in patients WITHOUT acetaminophen induced acute liver failure
  - Initial loading dose = 150mg/kg over 1 hour, then 50mg/kg/hr for 4 hours, then 100mg/kg/hr for 16 hours
  - Patients with early stage hepatic encephalopathy (grade I/II) have increased transplant free survival, while those with grade III/IV do not
- See below for etiology-specific treatment; hepatology consult for LT eval
- Early toxicology consultation if suspected ingestion/overdose
  - For acute management contact Poison Control 800-222-1222
Treatment of Secondary Complications
- Infection: abx only if progressing HE, signs of infection, or development of SIRS; ppx abx do not reduce mortality
- Cerebral edema/increased ICP: elevated HOB to 30 degrees, quiet and dimly lit room, minimize IVF, goal Na 145-155, hyperventilation if concern for impending herniation. Consider 3% saline (500mL) and/or mannitol (1g/kg, 20%) for pt at highest risk (serum ammonia >150, grade III/IV HE, ARF, vasopressor support
- Seizures: phenytoin (no evidence to support seizure ppx)
- Renal Failure: early CRRT if persistent Metabolic Acidosis, Volume Overload, Hyperammonemia, falling UOP
- Coagulopathy: IV Vit K; products for invasive procedures or active bleeding only
Additional Supportive Care
- PPI for bleeding ppx
- Enteral nutrition within 2-3 days; avoid TPN if possible; avoid NG feeds if progressive HE; NG should only be placed w/ intubation as gagging increases ICP
- Prefer propofol for sedation for better neuro exams and may reduce cerebral blood flow

Specific Management by Etiology:¶

Acetaminophen
- Early toxicology consultation if suspected ingestion/overdose
- For acute management contact Poison Control 800-222-1222
- Activated charcoal within 4 hours of ingestion, most effective within 1 hour
- IV N-acetylcysteine per protocol, look up Rumack-Matthew Nomogram and consult with toxicology
  - In Epic: search “N-acetylcysteine” and select order set “Acetaminophen overdose”
AFLP/HELLP – delivery
Amanita phalloides – IV fluid resuscitation, PO charcoal, IV penicillin, IV acetylcysteine
Autoimmune – IV steroids following approval by hepatology (and typically post biopsy). Azathioprine generally deferred until cholestasis resolved (Mycophenolate can be used instead)
Budd-Chiari – anticoagulation, IR-guided endovascular therapy, transplant (must rule out underlying malignancy and evaluate for thrombotic disorders)
HAV/HEV – supportive care, consider ribavirin for ALF due to HEV
HBV – nucleos(t)ide analogue; orthotopic liver transplant
HSV – acyclovir

Alcoholic Hepatitis¶

Julie Cui, Alex Wiles

Background¶

Acute onset of rapidly progressive jaundice in pt with heavy EtOH intake (>40g in females or >60g in males EtOH/day for >6 mos, or within <60 days of abstinence)
- May present after they have quit drinking due to immunosuppressive effects of alcohol

Evaluation¶

AST >60, AST/ALT >1.5, both values <400 IU/L; TBili >3.0 mg/dL, documentation of heavy EtOH use until 8 weeks prior to presentation
Prognostication with Maddrey’s Discriminant Function: 4.6 * (PTpt – PTctrl) + Tbili
- Maddrey > 32 = poor 30d prognosis & may benefit from steroids (see below)
RUQ U/S to rule out obstructive cause of jaundice
Biopsy is not typically required but will show neutrophilic lobular inflammation, hepatocyte ballooning, steatosis, and pericellular fibrosis.
Phosphatidylethanol (PEth) level is a biomarker of ethanol consumption over ~ 4wks; >20 ng/mL can indicate chronic moderate/heavy alcohol intake
- A single episode consumption can result in detectable Peth for up to 12 days. Can be elevated for months with regular heavy alcohol intake
- EtOH levels may be negative unless acutely intoxicated

Management¶

Supportive Care is essential! Consult nutrition, start high protein, high calorie diet, high dose Thiamine x 3d, Folate, MVI
Full infection workup (CXR, UA, BCx, paracentesis) regardless of symptoms
Steroids: STOP-AH Trial (NEJM 2015) showed improved mortality at 28 days but not at 90 days in patients with Maddrey > 32 who received steroids; the decision to treat is very nuanced and should be discussed with hepatology attending.
- Prednisolone 40mg daily for pts who meet above criteria
- Contraindications to steroids include: presence of infection (must rule out first including TB, uncontrolled GI bleeding, AKI w/ Cr >2.5 mg/dL)
- The Lille score can be used to guide continuation of steroids after 7 d of therapy
- NAC can be considered as adjunctive therapy to steroids and may decrease 30-day mortality, though has not demonstrated longer mortality benefit at 3 or 6 months
Monitor on CIWA
- Psychiatry consultation as appropriate, consideration of medical therapy (see “Substance Use Disorders” section in psychiatry)

Ascites and Hepatic Hydrothorax¶

Lauren Evers Carlini, Thomas Strobel

Ascites¶

Background¶

Associated with a reduction in 5 year survival from 80% to 30%.
Most often due to portal hypertension. Less common causes include peritoneal or metastatic cancer, heart failure, tuberculosis, nephrotic syndrome, Budd-Chiari, sinusoidal obstructive syndrome (S.O.S), or complications from procedures and pancreatitis


Grade	Definition	Treatment
Grade 1 Ascites	Only seen on imaging	2g Na restriction
Grade 2 Ascites	Moderate, symmetric abdominal distension	2g Na restriction, diuretics
Grade 3 Ascites	Marked, tense abdominal distension	LVP + Na restriction, diuretics (unless refractory)

Evaluation¶

Bedside ultrasound on admission to confirm presence of ascites
Diagnostic paracentesis in all pts with ascites on admission mainly to rule out occult SBP
- Initial paracentesis or when cause of ascites is uncertain: Total Protein, serum and BF Albumin, cell count w/diff, culture
- Subsequent/Serial paracenteses: cell count w/diff, culture, protein
- Always inoculate culture bottles at bedside (VA does not allow bedside innoculation)
See Procedure section for guidance on paracentesis.
Serum-ascites albumin gradient (SAAG) = serum albumin - ascites albumin.

0	1	2
Total Protein Ascites (not serum)	SAAG > 1.1 g/dL (Portal HTN )	SAAG \< 1.1 g/dL (Non-portal HTN )
\< 2.5 g/dL	Cirrhosis	Nephrotic Syndrome Myxedema
> 2.5 g/dL	Post-hepatic portal HTN: Cardiac Ascites Budd-Chiari	Malignant Ascites Pancreatic Ascites TB

Calculate PMNs from fluid (see SBP below)
Other tests:
- Triglycerides: if fluid is milky
- Cytology: if very concerned for peritoneal carcinomatosis. May need up to 3 separate samples (50ml or more) to be able to detect malignant cells
- ADA: if concern for peritoneal TB
- Hematocrit: For bloody appearing fluid (not just serosanguinous) to rule out hemoperitoneum. There needs to be a recent serum HCT for comparison.
- Amylase: If concerned for pancreatic ascites
- Glucose, LDH if concern about secondary peritonitis (see below)

Management¶

2000mg sodium restriction per day for all ascites (Grade 1-3)
Diuretics (spironolactone and typically furosemide)
- Start at 100mg of spironolactone with up titration to 400mg
- Furosemide is added if insufficient diuresis or if limited by hyperkalemia. Use more loop diuretics in patients with CKD
- If Urine Na:K ratio <1, indicates insufficient natriuresis. Can ↑ doses to a max of 400:160
- If poor response can change to torsemide 10mg and ↑ to 40mg max (per single dose)
- Fluid restriction usually not necessary unless serum sodium <125 mmol/L
Large volume paracentesis should be performed for tense ascites or refractory ascites (grade 3), regardless of serum Cr. Pts should be tapped dry with each paracentesis
Give 6-8g of albumin per liter of ascites removed, even if < 5L
Target weight loss of 0.5 kg/day when diuresing to avoid renal injury
Discontinue NSAIDs and ACEI/ARB

Refractory Ascites:¶

Two distinctions:
- Diuretic-resistant: lack of response to diuretics (max spironolactone 400mg/lasix 160mg), Na restriction and rapid recurrence following paracentesis
- Diuretic-intractable: unable to tolerate diuretic therapy 2/2 adverse drug effects (unexplained HE, AKI, K abnormalities, hypoNa, intractable muscle cramps)
Management aside from liver transplant:
- Discontinue diuretics once refractory ascites has been established
- Consider oral midodrine; can be especially helpful if pt is also hypotensive
- Serial paracenteses, generally arranged OP with IR
- Consider TIPS (trans jugular intrahepatic portosystemic shunt; has survival benefit). Following TIPS, cessation or decrease in ascites should occur in 4-6 weeks
- Consider discontinuing beta blockers in patients with refractory ascites if sBP <90, SCr >1.5, or Na <130

Hepatic Hydrothorax¶

Background¶

Transudative effusion, typically unilateral (75% right sided); reflects ascitic fluid that passes through defects in the diaphragm. 10% can develop without clinical ascites.
Present in 4-12% of cirrhotics and portends a poor prognosis (75% mortality within 90 days)

Evaluation¶

Often suspected clinically, though must exclude pleural/cardiopulmonary process
Thoracentesis will demonstrate a transudative effusion and should be evaluated with standard pleural fluid lab tests: cell count, protein, albumin, LDH, culture
- Other considerations: triglycerides, amylase, hematocrit, cytology
Rule out SBE which is diagnosed the same as SBP (PMN>250)

Management¶

Similar management of ascites as noted above
AVOID chest-tube placement. associated with increased morbidity and mortality due to extensive loss of fluid, electrolytes and protein as well as increased infection risk
- PleurX catheters can be considered for palliation (e.g., hospice patients)
Refractory Hydrothorax is defined similarly and managed similarly with serial thoracentesis or TIPS.
Management of spontaneous bacterial empyema is the same as in SBP (see below)

Cirrhosis Overview¶

Hannah Angle, Lee Richardson

Background¶

Standard 1-liner for any patient with cirrhosis:

cirrhosis one-liner

Example 1-liner: 65yo M with cirrhosis due to HCV decompensated by ascites and HE (MELD 25) who is listed for transplant and followed by Dr. Izzy
Etiology of cirrhosis: HCV>HBV, EtOH, NASH, Wilson’s, hemochromatosis, A1AT deficiency, autoimmune hepatitis, PSC, PBC, congestive hepatopathy (right heart failure), medication-induced
Complications that cause decompensation: overt ascites (or hepatic hydrothorax), overt hepatic encephalopathy (HE), esophageal variceal hemorrhage (EVH)
Always calculate daily MELD-Na scores (predicts 3 mo survival based on Tbili, Cr, INR, Na)

Evaluation¶

Goals: establish cause of cirrhosis, evaluate for complications and treat accordingly, determine prognosis, and consider transplant evaluation
History:
- Symptoms suggesting decompensation: confusion, sleep disturbances, abdominal swelling, lower extremity edema, scleral icterus/jaundice, pruritus, easy bruising/bleeding (skin, mouth, GI tract), dyspnea
- Social history: EtOH and drug use hx, date of last drink, average # of drinks/day, duration of EtOH use, prior rehab, hx of DUI, if there has been continued EtOH use despite knowledge of liver disease; these factors all impact transplant candidacy
- Ascites: compliance with diuretics, compliance with salt restriction, frequency of paracentesis (volume removed, date of last para), h/o SBP
- HE: compliance with lactulose, # of BMs per day, any potential triggers (see HE section)
- GIB/EVH: hematemesis, coffee ground emesis, melena, hematochezia (duration, volume, # of bleeding episodes), last EGD (varices, banding) and colonoscopy, compliance with non-selective BBs
Physical exam: asterixis, ascites, edema/anasarca, splenomegaly, muscle wasting, gynecomastia, testicular atrophy, palmar erythema, spider angiomata, scleral icterus/jaundice, petechiae/ecchymoses, caput medusa, Terry’s nails
Labs
- Initial Workup: CMP, CBC, coags, UA, HCV/HBV, Fe studies, PEth
- Unless requested by hepatology, defer to outpatient: AFP, ANA, IgG, A1AT, ceruloplasmin, AMA (PBC), ASMA (AIH), anti-SLA (AIH), anti-LKM (AIH)
Imaging:
- Abdominal US with duplex
- For transplant eval, needs triple phase CT A/P (contrasted study, arterial and venous phases) or MRI abdomen with contrast
Liver biopsy: gold standard for cirrhosis diagnosis but is not always needed if clinical presentation, labs, and imaging consistent with cirrhosis

Lab abnormalities¶

Hyponatremia (see hyponatremia section below)
Cirrhotic coagulopathy (increased INR): due to ↓ coagulation factor production
Thrombocytopenia: due to splenic sequestration, ↓ TPO production
Hypoalbuminemia: indications for 25% albumin transfusion – SBP (1.5g/kg on day 1, 1g/kg on day 3), LVP (6-8g/L of ascites), HRS (albumin challenge: 1g/kg/day with max 100 g/day x 2 days), hypoNa <125 and refractory to fluid restriction

Management¶

Nutrition: high protein diet, 2g Na restriction (if ascites present)
- Mediterranean diet for NASH
- Fluid restriction if hyponatremic
Immunizations: ensure up-to-date with HBV/HAV, PPSV23, Prevnar, Flu, COVID-19 vaccines
Consider consulting Addiction Psych and Social Work for pts with EtOH use disorder - can assist with arranging Intensive Outpatient Program (IOP), Alcoholics Anonymous (AA)
General screenings include: HCC screening (q6 months), EVH screening (see section below), monitor for other decompensations and treat accordingly, monitor MELD and consider transplant evaluation when >15

Medication Tips:¶

Pain: 2g limit Tylenol, No NSAIDs, limit sedating medications especially with HE.
- Tramadol 25-50mg generally safe to use
Pruritus: Sarna lotion, can spot dose antihistamines. Can discuss with pharmacist/attending about starting sertraline, cholestyramine (interacts with many medications), or rifampin.
Anxiety/insomnia: hydroxyzine, avoid benzodiazepines
If needed for EtOH withdrawal, use lorazepam (Ativan) instead of chlordiazepoxide (Librium) or diazepam (Valium) due to its shorter half life

Coagulopathy in Cirrhosis¶

Garren Montgomery, John Laurenzano

Background¶

The liver is responsible for production of both pro- (factor II, V, VII, IV, X, and XI) and anti-coagulants (protein C, S) in hemostasis. Factor VIII is the only one not made by the liver.
Thrombocytopenia is caused by splenic sequestration from portal HTN, failure to produce thrombopoietin (TPO), and bone marrow failure

Evaluation¶

INR/PT, and PTT are poorly reflective of bleeding risk
TEG screens and other measures of comprehensive coagulation in cirrhotics

Management¶

Even in bleeding, there is no need to intervene on an INR or platelet value
Pre-procedural FFP is not recommended, even in the presence of bleeding, but is frequently requested by different proceduralists
Low risk procedures (i.e., paracentesis) do not require pre-procedural blood products
In bleeding pts, the following are recommended per AASLD and AGA guidelines
- IV Vitamin K 10mg x 3 days
- FFP: Not recommended, unless as part of a balanced transfusion effort to avoid transfusion related coagulopathy, or if a TEG screen suggests potential benefit
- Cryoprecipitate: if fibrinogen < 120
- Platelets: No specific targets regardless of bleeding. Pre-procedurally, recommend >50
Appropriate DVT ppx should be given with few exceptions (plts <50k, active hemorrhage)
For TEG transfusion recommendations are as follows:
- 10 mg/kg FFP if R-time >10 minutes
- 1u Plts if maximum amplitude <55 mm
- 5u cryo if alpha angle <45

Hepatic Encephalopathy (HE)¶

Evaluation¶

Asterixis: inability to maintain stable posture; many ways to assess
- Check for clonus
- Have pt “hold out hands like you are stopping traffic” (if following commands)
- Shine light in pupil (look up video of hippus)

0	1	2	3
Grade	Behavior change	Asterixis	Cerebral Edema in Acute Liver Failure:
I	Mild confusion, changes in behavior, increased sleep	No Asterixis	No cerebral edema
II	Moderate confusion, lethargic	Asterixis	Rare cerebral edema
III	Marked confusion, arousable but falls asleep, incoherent speech	Asterixis	~30% cerebral edema
IV	Coma	No Asterixis	~75% cerebral edema

Identify precipitants
- Infection (rule out SBP in addition to CXR, BCx, UA/Cx regardless of sxs),
- Medication non-adherence (lactulose)
- GI bleed (perform rectal exam and observe hgb trend)
- Over-diuresis resulting in dehydration, lyte abnormalities (especially hypoK)
- Sedatives/benzo/opiate administration (UDS)
- Post-TIPS, other large but spontaneous shunt (imaging can be useful to determine if there is a shunt, and if an intervention is feasible on such a shunt).
Ammonia (NH ₃ ) levels do not play a role in the acute management of hepatic encephalopathy; if pt has AMS or HE, you will treat the HE regardless
Arterial NH ₃ is used in acute liver failure for prognostication (not for management)

Management¶

Always determine precipitant and treat underlying condition
Lactulose 30mL TID initially
- Titrate dose to at least 4 BMs daily, avoid excessive stool output which may exacerbate HE due to dehydration and electrolyte abnormalities
- Consider lactulose enemas vs DHT placement if pt unable to tolerate PO
  - DHT are not contraindicated in patients with esophageal varices, but should be avoided in patients with recent hemorrhage or banding
- Add Rifaximin after the second episode of HE, or if failure to respond to lactulose
  - Frequently requires prior auth for OP approval and is expensive
Lactulose is generally continued indefinitely after first episode of HE, though discontinuation can be considered if predisposing factors (recurrent infection, EVH, EtOH use) have resolved

Hepatocellular Carcinoma (HCC)¶

Julie Cui, Lee Richardson

Background¶

Pts with HCV cirrhosis are at greatest risk (incidence 2-4% per year)
In chronic HBV and NASH, pts can develop HCC without having cirrhosis

Evaluation¶

Regular screening in pts with cirrhosis (or chronic HBV without cirrhosis) for HCC
- RUQ U/S q6mo (with or without AFP)
- Routine screening with CT or MRI is not recommended
Options If U/S not satisfactory:
- CT A/P w/contrast, in comments specify triple phase for HCC screening
- MRI, specify Gadovist (preferred contrast agent)
- Contrast-enhanced ultrasound
AFP trend is more useful than one value in time, though AFP >20 should prompt multiphase CT or MRI for further evaluation
Diagnosis can be made either by imaging (most common) or biopsy (rare)
Triple phase CT demonstrates strong early uptake in arterial phase, with subsequent wash-out in portal-venous phase
If diagnosis remains unclear: can surveillance imaging or biopsy
LI-RADS system notes risk of malignancy based on imaging characteristics

0	1	2
LI-RADS	What does it mean?	What do we do?
LR-1 to LR-2	Definitely/Probably benign	Routine surveillance, consider diagnostic imaging within 6 mos
LR-3 to LR-4	Indeterminate/Probably HCC	Repeat or alternative diagnostic imaging in 3-6 mos. Consider Bx for LI-RADS 4
LR-5	Definitely HCC	Plan treatment as noted below
LR-M	Cancer but may not be HCC	NaN

Management¶

Lesions that meet Milan criteria can qualify for MELD exception points and are considered transplant candidates
- This accounts for pts with minimal synthetic dysfunction (and therefore low MELD)
Milan criteria:
- Single tumor with diameter >2cm but <5 cm, no more than 3 tumors, each <3 cm
- No signs of extra-hepatic involvement or vascular invasion
Liver transplant is definitive treatment, although resection can also be curative (favored in pts with early cirrhosis i.e. Child Pugh A)
Locoregional therapies: Pts with unresectable disease, or who are not surgical candidates

0	1
Therapy	Details
Radiofrequency ablation	If in a favorable location and size, IR can percutaneously ablate with a large needle that emits microwave frequencies
Trans-arterial chemoembolization (TACE)	Chemotherapeutic agents injected into the tumor to occlude the feeding blood supply to the area.
Trans-arterial radioembolization (TARE)	Like TACE, though radioactive compound (i.e. Y-90) used to occlude the feeding blood supply.
Stereotactic body Radiation Therapy (SBRT)	Radiation therapy: can be used as an alternative to ablation and is generally performed in those meeting Milan criteria
Systemic Chemotherapy	For metastatic disease

Hepatorenal Syndrome¶

Garren Montgomery

Background¶

Portal HTN causes shear stress on portal vessels -> endothelium release of vasodilators -> splanchnic vasodilation and reduced effective blood volume (decreased MAP) -> RAAS activation -> sodium and water retention and severe renal vasoconstriction
Bacterial translocation (as seen in SBP) -> increased circulating pro-inflammatory cytokines -> splanchnic vasodilation
Definitions:
- HRS-AKI (formerly type I HRS): Rise in Cr ≥0.3 within 48h, rise in Cr ≥50% within 7 days, OR UOP <0.5 mL/kg/hr for 6 hours
- HRS-NAKI (“non-AKI”) (formerly type II HRS):
- HRS-AKD: eGFR<60 for <3 months in absence of other structural causes OR % rise in Cr ≤50% using last available Cr over last 3 months as baseline
- HRS-CKD: eGFR<60 for ≥3 months in absence of other structural causes
Diagnostic Criteria
- Diagnosis of AKI (see above) without other cause (see below
- No response or inadequate response at 48 hrs after volume expansion with albumin and withdrawal of diuretics
- Absence of proteinuria (<500 mg/d), absence of hematuria (<50 RBCs per HPF), normal renal ultrasound (exclude if patient has known CKD
- Suggestion of renal vasoconstriction with FeNa <0.2, FeUrea <20 (most sensitive diagnostic measure). UNa <20 is suggestive but not diagnostic given baseline sodium avidity in cirrhosis and inability to calculate FeNa
- Cut off for ATN in cirrhosis is a FeNa >0.5, rather than 1 in the general population

Evaluation¶

Step 1: Exclude other obvious causes of renal injury such as hypovolemia or ATN
- Common precipitants of AKI: infection, overdiuresis, GI bleeding, recent LVP without subsequent volume expansion, nephrotoxic drugs/NSAIDs
- Workup: BMP, UA with microscopy, urine electrolytes (FeNa, FeUrea), urine protein/Cr ratio, renal ultrasound (to assess for chronicity), diagnostic para to rule out SBP
Step 2: Diuretic cessation/albumin challenge
- STOP all diuretics, beta blockers, NSAIDs, ACE/ARBs, anti-hypertensives, vasodilators, nephrotoxins
- START volume expansion with albumin 1g/kg/day (up to a max of 100 g/day) x2 days
Step 3: Diagnosis of HRS
- If no other clear cause of AKI is identified and SCr has not improved after 48 hours of diuretic cessation and volume expansion, proceed promptly to vasopressor treatment

Management¶

Pharmacologic therapies (in order of preference):
- Terlipressin + albumin. Most effective combo based on clinical trials, NOW AVAILABLE (ongoing clinical trial at VUMC)
- Norepinephrine + albumin (25-50 g/day)
  - Most likely to be used at VUMC, requires central access (PICC vs triple lumen) but can be administered on stepdown unit
  - Guidelines recommend NE to be dosed at 0.5-3 mg/hr. Would ask fellow, attending or pharmacist for baseline. VUMC protocol for ICU and stepdown:
    - Start NE gtt at 3mcg/min. If UOP is <200 or MAP <10mm Hg from baseline, increase by 3 mcg/min every 4 hours
Continue to hold diuretics. LVP is still generally considered safe even in HRS if indicated by tense ascites (account for albumin repletion from LVP and HRS protocol). This can be attending specific and would confirm prior to performing
Therapy is generally continued until HRS is reversed or the hepatology attending deems it refractory to medical treatment
Patients with HRS-NAKI (formerly type II HRS) may respond to the above therapies, but recurrence of renal dysfunction after withdrawal of vasoconstrictors is the norm and thus current guidelines do not recommend them for this scenario
RRT: Dialysis can be considered for those who fail to respond to pharmacologic therapy, particularly ONLY as a bridge to liver transplant. Decision to initiate should be individualized
Liver transplant: The best and most definitive treatment regardless of response to pharmacologic therapy

Simultaneous liver-kidney transplant:¶

HRS often resolves with LT alone. Indications for kidney transplant are usually for patients with severe chronic renal dysfunction or on RRT. Must consult transplant nephrology.
Criteria for SLKT:
- eGFR <60 for >30 days AND latest eGFR <30
- eGFR <25 for >6 consecutive weeks with a documented eGFR q7 days
- Metabolic syndromes and polycystic disease
Can qualify for safety net kidney transplant after liver transplant if eGFR <20 2-12 months post-operatively (would be at higher priority than the rest of the kidney transplant list)

Hyponatremia in Cirrhosis¶

John Laurenzano

Background¶

Most commonly is hypervolemic hyponatremia, driven by release of ADH from decreased effective arterial blood volume (EABV) in the setting of portal hypertension
Hyponatremia in cirrhosis is a marker of advanced disease and is associated with higher rates of SBP, HE, HRS, and mortality.

Evaluation¶

Standard evaluation of hyponatremia, including Uosm, Sosm, UNa to rule out competing processes (e.g. beer potomania)

Management¶

Discontinue anti-hypertensives (including beta blockers) in patients with ascites and hyponatremia. Hold diuretics when Na <125
Fluid restriction is recommended only in patients with Na <125. Restriction is generally effective at 1-1.5L and must be less than daily urine output to increase free water excretion
Replete potassium to 4.0, as potassium is as osmotically active and results in shifts in extra and intracellular fluids which lead to a net increase in serum sodium.
25% albumin infusion (1g/kg split into BID dosing), has been shown to increase serum sodium and have higher rates of hyponatremia resolution at 30 days
Other treatment considerations include vasopressors, vaptans, urea tabs
Salt tabs should not be used to raise serum Na due to worsening hypervolemia
Nephrology should be consulted if not improved after 48 hours

Liver Transplant (LT) Workup¶

Lauren Evers Carlini

Background¶

Model for End-stage Liver Disease (MELD-Na) score: initially developed to predict survival following TIPS placement, though is now used to objectively rank patients in terms of priority for liver transplant (LT)
- Factors in total bilirubin, creatinine, and INR. An updated version, the MELD-Na score, factors in the serum Na as well.
- Exception points given for complications like HCC and hepatopulmonary syndrome (HPS), leading to score in mid to high 20’s even if biologic MELD is low
Listing a patient for LT is determined by a multidisciplinary transplant committee
- Acute liver failure pts take precedence over decompensated cirrhosis pts for LT


Indications	Contraindications*
Cirrhosis with MELD ≥ 15 or evidence of decompensation (ascites, variceal bleed, HE, HPS, portopulmonary HTN)	Ongoing substance abuse (must have documented abstinence ≥ 3 mos); some special considerations for pts who did not know of EtOH hepatitis or EtOH use d/o but highly variable
Acute Liver Failure	Untreated or recurrent malignancy
HCC that meets Milan criteria	Active Infection, AIDS
Pts with early hilar cholangio-carcinoma that meets specific criteria	Documented history of medical noncompliance
Other rare dz (e.g., familial amyloid polyneuropathy or hyperoxaluria)	Lack of Adequate social support
	Anatomic Contraindications; Chronic cardiac/pulmonary conditions that significantly increase perioperative risk (e.g., severe pulm HTN)
* Advanced age (>70) is not in itself a contraindication but candidates > 70 should be almost free of comorbidities to be considered for LT*

Evaluation¶

Abdominal CT (triple phase) or MRI (multiphase with contrast) to evaluate for hepatic malignancy and vascular anatomy
Infectious workup: TB testing, HIV, RPR, VZV, CMV, EBV, and Hepatitis A, B, and C.
Cardiac evaluation: EKG and TTE with bubble are required. Functional testing: CT coronaries with fractional flow, invasive angiography and intervention may be necessary depending on pre-test probability.
PFT’s, carotid ultrasound, panorex, etc.
Appropriate cancer screenings (colonoscopy, pap smear, mammogram, and PSA if applicable)
DEXA scan
Certification of completion of intensive outpatient program (IOP) for substance abuse
Evaluation by hepatobiliary surgical team after obtaining cross sectional imaging
Psychosocial evaluation (consult Psychiatry, social work)
Current VUMC policy: pts should be abstinent from alcohol no less than 3-6 months, although exceptions may be m ade for early liver transplant based on a very strict protocol. Discuss exception criteria iwth attending if suspect patient unlikely to survive hospitalization without transplant
Both living and deceased donor transplant are offered at VUMC. Donor evaluation, however, cannot be started before the potential recipient is deemed a candidate

NASH and NAFLD¶

John Laurenzano

Background¶

Non-alcoholic fatty liver disease (NAFLD): presence of hepatic steatosis in the absence of secondary causes (e.g, EtOH)
Non-alcoholic steatohepatitis (NASH): evidence of active inflammation in conjunction with steatosis (elevated liver enzymes or evidence on bx)
Strong association with metabolic syndrome, T2DM, HTN, obesity, prior cholecystectomy
Generally asymptomatic
Considered to be a common cause of cryptogenic cirrhosis

Evaluation¶

NASH manifests with elevated liver enzymes, typically 2-5x the ULN, in a roughly 1:1 ratio (as opposed to alcoholic steatohepatitis), though ALT may be higher than AST
NAFLD is asymptomatic and frequently found incidentally via imaging
Exclusion of alternative causes and comorbid liver conditions: HCV, HBV, EtOH
Note: Ferritin is frequently elevated, though not to the extent of hemochromatosis. Low level auto-antibodies are also frequently present
Can be diagnosed based on imaging alone (and frequently is)
- Ultrasound is used most frequently, though MRI and CT also are acceptable; use risk scores to determine the risk of advanced fibrosis and identify those who would benefit from biopsy
  - Fibrosis-4 (FIB 4) score
  - NAFLD fibrosis score
- More accurate, non-invasive fibrosis assessments can be done using elastography which can be vibration based (fibroscan), ultrasound based (sheer-wave), or MR-based
  - Available at VUMC and can be ordered by anyone. Insurance will not cover MRE if BMI <35

Management¶

Aggressive risk factor modification and management of comorbidities (HLD, HTN, T2DM)
Weight loss: Mediterranean diet>low fat diet (dose dependent improvement)
No specific medications are FDA approved currently
- Pioglitazone has shown benefit in pts with T2DM and NASH
- Vitamin E has shown benefit in pts without T2DM and proven NASH
- Ongoing studies for SGLT-2i and GLP-1ra; some promise indicated for the latter
While bariatric surgery is not a specific indication for NASH/NAFLD, increasing evidence demonstrates resolution of NASH and fibrosis in pts with clinically significant weight loss
Referral to the surgical weight loss clinic should be considered in any patient who meets obesity guidelines for bariatric surgery (BMI >40, or >35 with metabolic comorbidities)

Additional Information¶

Statins: should be used for HLD in pts with NASH, NAFLD and NASH cirrhosis
Statin use in decompensated NASH cirrhosis is controversial, and they are less likely to derive benefit given overall poor prognosis. There is an increased risk of rhabdomyolysis in pts with acute on chronic liver failure and are considered contraindicated
Metformin is safe and may have a survival benefit in patients with diabetes and cirrhosis. Discontinue only in those who have increased risk for lactic acidosis (renal impairment and significant EtOH). Sulfonylureas are generally avoided.

Portal Vein Thrombosis (PVT)¶

John Laurenzano

Background¶

Portal Vein Thrombosis (PVT) can worsen decompensation (i.e. variceal hemorrhage), however, worsening portal HTN -> more sluggish flow -> increased risk PVT

Presentation¶

Often identified asymptomatically on U/S, but can be identified by new or worsening decompensation of portal HTN
Variceal hemorrhage is the most common decompensating event associated with PVT
Intestinal ischemia (abdominal pain, hematochezia) from PVT is exceedingly rare but associated with significant morbidity and mortality

Evaluation¶

RUQ U/S with doppler
- Once identified, should be further assessed with triple phase CT or MRI with Gadovist contrast to exclude HCC with tumor thrombus
Pts with newly identified PVT should undergo EGD to evaluate for high-risk varices, both for diagnostic and therapeutic considerations
PVT in pts without cirrhosis should prompt evaluation for hypercoagulable disorders

Management¶

Start anticoagulation if acute thrombus occludes >50% of main portal vein, <50% but extends into SMV, thrombus is symptomatic, or patient is a transplant candidate (irrespective of size). Requires discussion with attending/transplant team.
- Anticoagulation options: warfarin, LMWH, or DOAC
- DOAC’s are safe in Childs Class A, can be used with caution in Childs B, and are contraindicated in Childs C
Pts with chronic occlusive PVT (>6 mos) or with cavernous transformation with collaterals do not generally benefit from anticoagulation
Pts with high-risk varices should undergo endoscopic management or be on NSBB for prophylaxis for variceal hemorrhage, as noted above
TIPS with portal vein recanalization has recently emerged as a therapeutic modality for PVT
Pts should undergo follow up intermittently with ultrasound to assess for recanalization. AC may be stopped if there is failure to recanalize.
If pts are not candidates for AC, they'll simply be treated for complications of portal HTN

Spontaneous Bacterial Peritonitis (SBP)¶

Patricia Checinski

Background¶

Infection of ascitic fluid without evidence of a surgical intra-abdominal source
Presentation: fever, abdominal pain, encephalopathy, renal failure, acidosis, and/or leukocytosis

Evaluation¶

Any pt with cirrhosis and ascites who is admitted should have diagnostic paracentesis to rule out SBP. Delaying paracentesis > 12 hours is associated with a 2.7-fold increase in mortality.
Obtain cell count with diff.
- Calculate the PMNs: total nucleated cells x % neutrophils.
- PMNs > 250 cells is diagnostic of SBP. If there are greater than 100k RBCs, you should correct for them: for every 250 RBCs, subtract 1 PMN
A positive ascitic bacterial culture with PMN <250 is called bacterascites and asymptomatic patients should NOT receive antibiotics. You will also frequently see culture-negative SBP (neutrocytic ascites) which SHOULD be treated (see below).

Management¶

Immediately start empiric antibiotics
Guidelines recommend cefotaxime IV 2gm q8 hours x 5 days, but we commonly use ceftriaxone IV 2g q24h for 5-7 days at VUMC and Nashville VA.
- Most common culprits (E. coli, Klebsiella, streptococcal species, staphylococcal species)
- If SBP developed with recent hospital admission (90 days), recent exposure to BSA, diagnosed >48 hours of admission, or with sepsis, consider zosyn or meropenem to cover MDROs
IV albumin 1.5 g/kg on day 1 and 1g/kg on day 3
Discontinue beta-blockers once SBP develops and do not restart until SBP is completely treated, Na >130, and no AKI
PPI’s ↑ risk for SBP in pts with cirrhosis, and should be reviewed for appropriateness
Repeat diagnostic paracentesis two days after antibiotics initiated
- If <25% decrease in PMNs, antibiotics should be broadened and consider secondary bacterial peritonitis

Prophylaxis¶

GI bleed: ceftriaxone 1g daily ciprofloxacin 500mg BID (preferred) or Bactrim one DS tablet BID x 5-7 days
Outpatient lifelong ppx, indications:
- Prior SBP
- Ascitic protein <1.5 AND
  - Child Pugh >9 and bilirubin >3 OR
  - Renal dysfunction (Cr >1.2, Na <130, or BUN >25)
- Preferred: Bactrim DS tab daily or ciprofloxacin 500mg daily
- Alternatives: cefdinir 300mg daily, Augmentin 875/125 daily

If suspicion is high for secondary bacterial peritonitis:¶

Examine serum-ascites albumin gradient (SAAG). SBP develops in pts with portal hypertension, defined by SAAG > 1.1 g/dL. SBP is unlikely if SAAG is < 1.1 g/dL.
While not particularly sensitive, an ascitic leukocyte count of 5-10k should prompt consideration of secondary peritonitis
Amylase from fluid can also be helpful to point towards pancreatic ascites, while bilirubin can indicate gallbladder perforation. Peritoneal fluid CEA and alkaline phosphatase can additionally help identify hollow viscus injury.
Evaluate with cross-sectional imaging and surgical consultation as appropriate
Runyon’s Criteria to distinguish, requires ⅔ criteria below (protein, glucose, LDH)

	Spontaneous	Secondary
Protein (g/dL)	<1	>1
Glucose (mg/dL)	≥50	<50
LDH (U)	Elevated, but < 225	>225
Organisms	0-1	Polymicrobial

Transjugular Intrahepatic Portosystemic Shunt (TIPS)¶

Pakinam Mekki

Background¶

A Transjugular Intrahepatic Portosystemic Shunt or TIPS procedure is done by interventional radiology to manage sequelae of portal hypertension (specifically variceal bleeding and ascites)
A low-resistance shunt is created between an intrahepatic branch of the portal vein and the hepatic vein, allowing blood to bypass the high-resistance vessels within the fibrotic liver

Evaluation¶

Indications for TIPS
- Variceal hemorrhage (esophageal, gastric, etc.)
- Early “preemptive” TIPS is an urgent TIPS placement within 72 hrs (preferably within 24 hours) of initial endoscopic hemostasis in pts at high risk for rebleeding (Child-Pugh Class B with active bleeding upon insertion of endoscope or Child-Pugh Class C with recent bleeding
- “Rescue” TIPS is placed in pts with active, uncontrolled variceal bleeding or if bleeding recurs despite maximal endoscopic and pharmacologic therapy
- Refractory ascites (prolongs survival)
- Other: portal hypertensive gastropathy, PVT recanalization, Budd-Chiari syndrome, hepatic hydrothorax
Contraindications to TIPS
- Absolute contraindications
  - Primary prevention of variceal bleeding, congestive heart failure, severe tricuspid regurgitation, severe pulmonary hypertension, multiple hepatic cysts or masses, Sepsis, unrelieved biliary obstruction
- Relative contraindications
  - Hepatic encephalopathy, hepatic tumors (especially if centrally located), thrombocytopenia, moderate pulmonary hypertension
Pre-procedure preparation
- Labs: CBC, CMP, INR
- Liver imaging to assess portal system patency and exclude liver masses
  - Ideally triple phase CT with contrast
  - In pts with renal impairment or active variceal bleeding, RUQ U/S with doppler is acceptable
- TTE to evaluate for evidence of congestive heart failure, pulmonary hypertension, or valvular disease.
- Antibiotic ppx with ceftriaxone 1g IV once at the time of TIPS insertion as enteric bacteria within the static portal system can enter systemic circulation
- Patients with HE should receive rifaximin prophylaxis starting 2 weeks before procedure

Management Post-TIPS¶

Immediately following TIPS, pts are observed in the hospital overnight for complications
- Monitor CBC and vitals closely. If hemodynamically unstable, STAT CBC and low threshold to obtain CTA A/P to evaluate for a bleeding source
TIPS causes a substantial increase in venous return to the heart, which can unmask cardiac dysfunction that was previously compensated for
Obtain RUQ U/S with Doppler to assess shunt patency 1 month of TIPS placement, or if ascites and/or variceal hemorrhage reoccur
If patient with a TIPS develops refractory HE, can consider TIPS revision to lessen HE symptoms

Gastroesophageal Varices and Hemorrhage¶

Patricia Checinski

Background¶

Varices form due to portosystemic collaterals in the setting of portal HTN
The risk of mortality with each episode of esophageal variceal hemorrhage (EVH) is 15-25%
Recurrence occurs in 60% of patients within 1-2 years of the index event

Variceal Screening¶

Not all pts with cirrhosis require screening. Can be omitted without clinically significant portal hypertension (e.g. low liver stiffness (on elastography) and platelets >150) or if pt already on non-selective beta blocker (NSBB) with HR 55-60
Compensated cirrhosis without varices: EGD q3yr, unless active liver injury (obesity, EtOH use, ongoing viral infxn), then q2yr
Compensated cirrhosis with small varices: EGD q2yr unless active liver injury, then q1yr
Decompensated cirrhosis with no or small nonbleeding varices: EGD q1yr, and at initial time of decompensation

Management (Non-Bleeding Varices)¶

Primary ppx with either NSBB (preferred) or endoscopic band ligation (EBL)
- Nadolol (given nightly as portal pressures are highest at night) or propranolol (BID)
- Carvedilol has greater portal pressures and may be preferred if tolerated (goal 6.25mg BID)
- For 2 º ppx, initiate ~72hr after acute bleed has resolved and octreotide discontinued
- Discontinue if: hypotension (sBP <90), AKI, SBP or hyponatremia with refractory ascites
Secondary ppx with both NSBB and EBL.
NSBB are associated with reduced mortality, while EBL is not

Management (Bleeding Varices)¶

Place two large-bore IVs (18G or larger), resuscitate with blood products and albumin. Activate massive transfusion protocol if needed.
Consider intubation if need for emergent EGD, change in mental status, ongoing hematemesis, concern of ability to protect airway
Start octreotide 50 mcg IV bolus followed by continuous infusion of 50 mcg/h, to be continued for at least 2 days should EVH be confirmed on endoscopy
Ceftriaxone 1g IV q24h for SBP prophylaxis (reduced mortality), then transition to PO ciprofloxacin for total 7-day course
Consult GI for upper endoscopy. Endoscopic therapies performed include variceal band ligation and sclerotherapy.
Consider balloon tamponade with Blakemore as temporizing measure before definitive management. Patient must be intubated before placement, and preferably GI should be made aware prior to placement.
No role for the correction of INR, even in the presence of bleeding as excessive blood products and FFP can increase portal pressures and cause worsening bleeding
- Vitamin K can be given w/ ↑ INR, though is unlikely to help in the acute setting
- Check TEG and fibrinogen and transfuse based on results
- AASLD does not recommend specific platelet targets during variceal hemorrhage
- Administer blood products in balanced ratio to avoid transfusion related coagulopathy (VUMC MTP is 6:4:1 of RBC:FFP:PLT)

Ended: Hepatology

Hospital medicine ↵

Enteral Nutrition¶

Soibhan Kelley

Indications for enteral feeding¶

Patients with high nutritional risk who are unable to maintain their own intake
- Guidelines recommend calculating nutritional risk based on validated scoring tool (ex: Malnutrition Screening Tool). This is usually completed by the nutrition team
- Recognize who would benefit from nutrition consult to assist with risk determination
  - Patients with >5% weight loss in past 1-3 months or decreased oral intake coupled with increased metabolic demands due to medical illness or surgery
Patients with low nutritional risk may not need enteral feeding if it is anticipated they will resume intake in 5-7 days
Critically ill patients: goal is early initiation of tube feeding (within 48 hours)

Contraindications to enteral nutrition¶

Bowel obstruction or severe ileus
Ischemic bowel
Acute peritonitis
Major gastrointestinal bleeding
Intractable vomiting
Significant hemodynamic instability
- Patients who are not adequately volume resuscitated and have significant hemodynamic instability (i.e., have high pressor requirements) are thought to be at increased risk for bowel ischemia
  - Pressors in general are not a contraindication to tube feeds. Ok to start once pressors are down-trending or at a stable level

Initiating tube feeds¶

Enteral access
- Nasogastric or orogastric feeding tube in acute setting. See procedures section for tips on placement
- For most patients, enteral feeding is safe with gastric tube placement
  - Consider post-pyloric placement for patients with high aspiration risk, impaired gastric motility, or patients who have demonstrated intolerance with gastric feeding
- Consider percutaneous endoscopic gastrostomy (PEG) tube placement if anticipate enteral nutrition >4 weeks
Choice of formula and rate
- Place nutrition consult. RD will calculation caloric and protein needs to determine goal rate and formulation
- OK to start tube feeds prior to recommendations and adjust later, especially if recommendations will be delayed. It only takes a simple calculation to make a reasonable tube feeding plan
  - Use weight-based dosing for calorie requirements
    - Use 25-30 cal/kg (use ideal body weight for most patients, use actual weight for underweight patient) to estimate daily needs
  - Most common formula used at VUMC is Nutren 1.5 (1.5 cal/ml) or Novasource renal if significant renal impairment (2 cal/ml)
  - Patients may need additional free water (most tube feed formulas are comprised of 80-85% water but varies with type). Typically dose as bolus of free water every 4-6 hours.
    - May empirically try 250cc free water every 4 hours and monitor Na trends. May need more if already with a large fluid deficit (ex: hypernatremia) or if high volume losses
    - May use clinical calculators as below
- Calculate hourly rate based on daily calorie need and formula calorie density
  - Ex: Patient with IBW of 70Kg will need estimated 1,750 calories per day (70 x 25 cal/kg)
  - If using Nutren 1.5, this will equal 1,167 ml per day (1,750 divided by 1.5 calories per ml). This would equal a goal rate of about 50ml per hour (rounded up) of Nutren 1.5
  - Resources for quick calculations:
    - Search for “tube feed cheat sheet” on google and will find reference tables on EMCrit.org that gives you rate per hour for different weights and formula types
    - Clincalc.com also has a useful enteral nutrition calculator
- Start initially at a low rate (such as 10 mL/hr) to assess tolerability and advance to goal
  - Advance quickly if no concern for refeeding syndrome (ex: increase by 10cc/hr q6h)
  - If risk for refeeding syndrome or other issues with tolerability, typically advance more slowly over several days

Potential Complications¶

Aspiration
- Recommendation to keep head of bed elevated at 30 to 45 degrees (low quality, mixed evidence). Consider risks of this positioning (ex: formation of pressure ulcers)
- Consider post-pyloric placement if issues with aspiration (low quality, mixed evidence)
Diarrhea or constipation
- Consider wheat dextrin fiber supplement (low quality evidence) but discontinue if not associated with clinical improvement. Avoid less soluble fibers such as psyllium due to risk of clogging tube. Avoid in patients with reduced GI motility due to rare risk of bezoar formation
Hyperglycemia
- See endocrine section for management
Refeeding syndrome
- Monitor q8 hour Mg, phos, K in high-risk patients (underweight, recent weight loss, prolonged poor intake) and advance to goal slowly

Guidelines for Pregnant Patients¶

Ahmad Dbouk and Samuel Lazaroff

Acute Cystitis:¶

Significantly increased prevalence in pregnancy
Symptoms: dysuria (urgency/frequency common in pregnancy)
Diagnosis: evidence of pyuria and >103 cfu/ml (note, if neg would test for g/c)
Treatment: Empiric with cephalexin, cefpodoxime, amoxicillin-clavulanate, fosfomycin. Nitrofurantoin ok in second or third trimester. Avoid Bactrim in first trimester and near term. Tailor based on culture results.
Note that asymptomatic bacteriuria is treated in pregnancy (in contrast with general public). Same antibiotic choices as above

Pyelonephritis:¶

Symptoms: fever, flank pain, and nausea/vomiting, dysuria
Diagnosis: clinical suspicion + pyuria and bacteriuria
Treatment: IV antibiotics for 1 ^st 24-48hrs; beta-lactams preferred
Mild to moderate: ceftriaxone or cefepime
Moderate to severe: piperacillin-tazobactam or meropenem

Hyperemesis Gravidarum:¶

Presentation: Hormone mediated nausea/vomiting typically starting before 9wks GA
Differential: gastroenteritis, hepatitis, biliary tract disease, obstruction, pancreatitis, pyelonephritis, nephrolithiasis, ovarian torsion, DKA, hyperparathyroidism, migraines, preeclampsia
Workup: BMP, mg, phos, LFTs, lipase (may be mildly elevated in HG), UA,
Treatment:
- - First Line: Ginger, doxylamine (25mg PO q6), pyridoxine (20mg PO q6)
  - Second Line: metoclopramide (10mg q6), Promethazine (12.5mg q6)
  - Third Line: ondansetron (8mg q12hrs, after 1^st trimester)
  - Hydration: 1L LR on admission + banana bag q24hrs

Hypertension:¶

Both gestational HTN and preeclampsia/HELLP are typically diagnosed >20w GA
Tx options: nifedipine, labetalol, methyldopa, hydral (2 ^nd line), clonidine (2 ^nd line)
Avoid: ACEs, ARBs, MRAs, Nitroprusside

Diabetes:¶

Due to hormonal changes associated with pregnancy, pregnant patients are at higher risk for poor control and DKA
Oral regimens are generally transitioned to insulin-based regimens.

GERD:¶

1^st Line: Can use antacids; avoid sodium bicarbonate and magnesium trisilicate
2^nd Line: Sucralfate 1g PO TID
3^rd Line: Cimetidine 200mg (30min prior to eating)

Asthma:¶

Similar rescue and controller medications as in non-pregnant patient
Would favor using LABA over leukotriene receptor antagonists or theophylline for additional therapy

Lines and Catheters¶

Ahman Dbouk and Samuel Lazaroff

Foley Catheter¶

Indications: urinary retention, close urine output monitoring in critical illness or renal failure, need for strict I&Os (ex: diuresis) and unable to be achieved without catheter, surgery, open sacral/perineal wounds with incontinence, patient comfort at end of life
- Urinary incontinence alone is not an indication for foley catheter
Duration of use is biggest risk factor for CAUTI
- Best way to prevent CAUTI is to avoid inappropriate placement
- Assess daily whether foley can be removed
Chronic Foleys generally should be exchanged at time of admission
Any concern for catheter obstruction (particularly with blood clots) should prompt urgent urology consult for irrigation/intervention (typically after RN has attempted)
Difficult foley placement
- Make sure an attempt has been made with a Coudé catheter. This catheter has a curved tip that can be useful in patients with BPH

PICC¶

Single lumen: long term Abx, stable IV access with intermittent draws
Double lumen: special populations (ICU or chemo), TPN w/ lipids (incompatible with many IV medications)
Risk factors for CLABSI/VTE: ↑↑duration, ↑↑number of lumens, left arm, lower extremity
A note on midlines:
- A midline is just a long PIV inserted into the deep veins in the arm, typically 6-15cm
  - For reference, when you place an US-guided IV, the “long” 18G needles at VUMC are 2.5 inches (~6.4cm)
  - Not much benefit compared to US-guided IV. Useful for stable IV access for meds and fluids. Not a stable route for blood draws

G-Tube¶

Troubleshooting: EGS consult for malposition/not functioning, wound consult for skin breakdown
G-tube study: 30mL Gastrograffin via tube [resident often must push], and order KUB

Telemetry¶

Ahmad Dbouk and Samuel Lazaroff

Background¶

Many monitored pts do not have a true indication
- Leads to alarm fatigue, unnecessary workups, and is expensive
Telemetry is not a substitute for more frequent vital signs
Discuss frequently on rounds: always reassess need and indication
Stable patients without troponin elevation or new arrythmias are typically appropriate for transfers without telemetry

0	1
Clinical Scenario	Duration
Cardiac	Cardiac
ACS Post-MI	24-48h 48h after revascularization
Vasospastic angina	Until symptoms resolve
Any event requiring ICD shocks	Remainder of hospitalization
New/unstable atrial tachyarrhythmias	Until stable on medical therapies
Chronic AF w/ recurrence of RVR	Clinical judgement
Ventricular tachyarrhythmias	Until definitive therapy
Symptomatic bradycardia	Until definitive therapy
Decompensated CHF	Until underlying cause treated
Procedural	Procedural
Ablation (regardless of co-morbidities)	12-24h after procedure
Cardiac surgery	48-72h, or until discharge if high risk for decompensation
Non-cardiac major surgery in patient with AF risk factors	Until discharge from step-down or ICU
Conscious sedation	Until patient awake, alert, HDS
Miscellaneous	Miscellaneous
Endocarditis	Until clinically stable
CVA	24-48h
Electrolyte derangement (K, Mg)	Until normalization
Hemodialysis	Clinical judgement
Drug overdose	Until free of influence of substance

Notable non-indications:

PCI for non-ACS indication (i.e. pre-transplant), non-cardiac chest pain, Pt with AICD admitted for non-cardiac cause, non-cardiac surgery, chronic AF and clinically stable
Contraindicated in hospice/comfort care
Nearly all noncardiac conditions (i.e., undifferentiated sepsis, stable GI bleed, alcohol withdrawal) upon transfer out of ICU

Transitions of Care: Tips for Safe Discharges¶

Soibhan Kelley

Discharge from hospital represents a period of vulnerability for patients. Medical errors (especially medication errors) following discharge are exceedingly common and can lead to adverse events
At VUMC we are fortunate to have the Discharge Care Center
- Multidisciplinary team including nurses, social workers, care coordinators, and pharmacists
- Phone number is included on discharge paperwork and patients can contact them 24/7. The DCC also reaches out to patients through an automated system
How residents can promote safe discharges:
- Communicate with patient’s outpatient team (i.e. PCP)
  - Typically achieved through the discharge summary
    - Include a list of specific, actionable follow-up tasks and assign a responsible party.
    - Place in easy-to-view spot at the top of the summary
      - Ex: Instead of writing “follow-up BMP after initiation of furosemide,” write “PCP to check BMP in 2 weeks after initiation of furosemide”
      - Include any pending studies and appointments from hospital admission
    - All relevant parties should receive a copy of the discharge summary (see appendices section for mechanics of discharge process)
      - It is useful to send patient with a printed copy of the discharge summary if they will follow-up outside VUMC
      - For high-risk discharges (patients with poor health literacy, hx of being lost to follow-up, patients following up outside VUMC) consider calling PCP’s office to set follow-up
Complete an accurate and thorough medication reconciliation
- An accurate discharge medication list depends on having a complete admission medication reconciliation (utilize pharmacy consult!)
  - Three steps to medication reconciliation:
    - Verification: Performing a Best Possible Medication History
    - Clarification: Checking that medications and doses are appropriate
    - Reconciliation: Record all medication changes
  - Seek to use at least two sources of information
  - Keep a list of any held or changed medications in your hospital course. Medication changes can be lost when not communicated during team transitions
  - Review medication changes on rounds and with pharmacist on day of discharge (bonus points for day prior to discharge)
- Highlight any significant medication changes on discharge summary
  - Can include as follow-up tasks if pertinent (ex: PCP to follow-up BP in 2 weeks. Losartan held on d/c due to AKI but anticipate need to reinitiate once Cr normalizes)
- Be sure to communicate any changes with the patient and/or caregiver
Ensure that appropriate resources and follow-up appointments have been requested (PT/OT, skilled or non-skilled nursing HH, PCP follow-up, etc.)
Effectively communicate discharge plan to patient
- Discuss medication changes, tasks for patient to complete, follow-up appointments
  - Key points should also be written in the patient instructions box
  - Useful to include educational sheets in the AVS (searchable in discharge navigator)
  - Utilize the teach-back method to ensure your instructions were effectively communicated

Wounds − Adapted from Dr. Duggan’s Geriatrics Guide¶

To do when admitting a patient with wounds:
- Document ALL wounds that are present on admission. This affects reimbursement
Use the Haiku app on your cell phone to document images of wounds in chart
Wound Service hours are Monday through Friday, 6 AM - 2 PM
- If there is an urgent/emergent wound need (i.e. needs surgical eval or management), consult the appropriate surgical service
- While awaiting consultation, initiate topical wound care orders (detailed below)
Consider contributing factors: nutritional, pressure-offloading equipment, wound supplies, PT/OT, home health nursing

Types of wounds¶

Arterial wound - Calciphylaxis
Venous leg wound - Fistula
Diabetic foot wound - Abscess
Vasculitis - Skin tear
Pyoderma gangrenosum - Pressure injury
Fungating lesion - Ischemic ulcers / gangrene

Vascular Wound Etiologies¶

Arterial: located on distal ends of digits, shallow, well-defined borders, pale/necrotic wound bed, minimal exudate due to poor blood flow, cramping pain or a constant deep ache
Diabetic: plantar surface of foot, callused wound margins; usually painless due to neuropathy
Venous: located on medial malleolus or gravity dependent areas, irregular edges, ruddy red with yellow slough and copious exudate

Pressure Injury Staging¶

stages of pressure sores

Skin Consistency

Boggy

Variable

N/A

Skin color/nature of lesion

Non-blanching purple or maroon, may appear as blood-filled blister

Non-blanching erythema

Abrasion, blister, or shallow crater

Variable

Variable.

If eschar, must be removed in order to stage, or is unstageable

Depth

Epidermis intact

Through surface of epidermis and outer dermis

SQ tissue to, but not through, fascia

Full-thickness loss w/ destruction, necrosis, or damage to muscle, bone, supporting structures

Non-Acute Wound Consult Guidelines¶

Order “Inpatient Consult to Adult Wound" for these wound types: diabetic foot wounds*, venous, arterial, pressure injuries (consult required for DTI, stage 3, 4, and unstageable), IV infiltrate, skin tears, moisture-associated dermatitis, calciphylaxis, vasculitis, pyoderma gangrenosum, fungating lesion, abscess*, surgical wounds*, or wound VAC
*Diabetic foot wounds: if pt being followed by podiatry, order "Inpatient Consult to Podiatry"
*Abscess: if chronic due to IBD, consult colorectal surgery
*Surgical wounds: if pt has VUMC surgeon, consult the respective surgical service
Order "Inpatient Consult to Adult Ostomy / Fistula / Tube" for ostomy, trach, PEG, associated needs or complications (etc)

Acute Wound Consult Guidelines¶

Abscess, hematoma, or osteomyelitis with overlying wound – whom to consult for drainage/debridement:
- Face – Face
- Chest/Sternum – CT surgery
- Breast – General surgery
- Spine – Spine
- Arm (hand to elbow) – Hand
- Lower leg (foot to knee) – Ortho
- Labial – OB/GYN
- Scrotal – Urology
- Buttock, thigh (knee to hip), arm (elbow to shoulder) – EGS consult
- Perirectal/Rectal acute abscess – EGS; (chronic due to IBD – Colorectal Surgery)
Necrotizing Fasciitis – whom to consult for URGENT/EMERGENT surgical eval:
- Genitalia – Urology
- Buttocks, perineum, abdomen – EGS
- Upper extremity (shoulder to hand) – Hand
- Lower extremity (hip to toes) – Ortho

Wound Care (order while awaiting consultant recs)¶

Superficial wounds
- Stage 1 or 2 pressure injuries, moisture-associated skin damage, or skin tears
  - Order “Adult Skin Care Guidelines” and use the order set to guide you
Shallow Stage 3 pressure injuries (i.e., <1cm deep) or diabetic foot ulcers
- Order “Wound Care”: Frequency 2x weekly and prn; Cleanse with NS; protect periwound with Mepilex foam (type in comments)
Painful superficial wounds with no infection (i.e. vasculitis, PG, calciphylaxis)
- Order “Wound Care”: Frequency 2 times daily; Cleanse with NS; Apply Vaseline; Protect periwound with Xeroform and dry gauze (type in comments)
  - If wound is on the hand, arm, foot, or lower leg consider wrapping in Kerlix
  - If wound is on the trunk (i.e., abdomen or buttocks), consider covering with an ABD pad and secure with medipore tape
Infected superficial wounds
- Odor alone does NOT indicate infection; wounds with necrotic tissue may have odor
- Order “Wound Care”: Frequency 2 times daily; Cleanse with NS, Apply Silvadene; Protect periwound with Xeroform and dry gauze (type in comments)
  - If wound is on hand, arm, foot, or lower leg consider wrapping in a Kerlix
  - If wound is on the trunk (i.e., abdomen or buttocks), consider covering with an ABD pad and secure with medipore tape
Medication order required: Silvadene q12h; in Admin Inst put “per wound care orders”
Deep wounds (i.e., stage 3, 4, or deep diabetic foot wound (all >1cm deep))
- Order “Wound Care”: Frequency 2 times daily; Cleanse with NS, pack with Dakin’s 0.025% (1/20 strength) soaked continuous Kerlix roll; Protect periwound with ABD pad & medipore tape (type in comments)
- If wound care is painful, consider changing to daily dressing changes
- Medication order required: Dakin’s 0.025% solution q12h; in Admin Inst put “per wound care orders”
Deep tissue injury
- Medication order required: Venelex (balsam peru-castor oil) ointment q4h; in admin instructions put location to apply ointment and put “no dressing”
Fungating mass
- Order “Wound Care”: Frequency 2 times daily; Cleanse with baby shampoo and water, NS, Metrogel (type in comments); Protect with Xeroform, ABD pad, medipore tape
- Medication order required: metrogel q12h; in Admin Inst put “per wound care orders”
Wound VAC
- Vanderbilt surgeon – consult Vanderbilt provider to provide care
  - Ensure connected to VUMC wound VAC. Pt shouldn't use home unit while admitted
  - Order “nursing communication” to “Obtain wound VAC hospital machine and canister from service center to connect pt to hospital machine.”
  - Wound VAC should not be left without suction for more than 2 hours
  - Settings: 125 mmHg continuous
Non VUMC surgeon (i.e., gets wound care at outside hospital/wound care center)
- Discontinue wound VAC as soon as possible
- Remove all of the clear plastic drape just like you would remove tape
- Remove all of the sponge just like you would remove gauze packing
- Examine the wound to ensure no residual sponge by gently probing site
- Rinse with saline, initiate care based wound type as above
Leg wrap
- Ex: Unna's boot, ACE and 2, 3, or 4 layer compression
- Remove by cutting the wrap off
- Assess the wound and order dressing based on type of wound as above
- Order ACE bandage wrapped toe-to-knee. Remove q12h to assess skin

Ended: Hospital medicine

Infectious diseases ↵

Overview of Antiretroviral Therapy¶

Kathryn Snyder and Quinton Taylor

Fixed Dose Combination regimens		Renal Dosing	Specific Considerations
Biktarvy®	Bictegravir/ Emtricitabine/ Tenofovir (Alafenamide)	Discontinue if CrCl < 30; ok w/HD	↑ Metformin levels Contraindicated with: rifampin, dofetilide, rifabutin Avoid close admin. with: laxatives, sucralfate, polyvalent cations (iron, calcium, etc.)
Dovato®	Doltegravir/ Lamivudine	CrCl 30-50: monitor for hematologic toxicities with lamivudine CrCl<30: do not use combo pill; dose-adjust individual components	↑ Metformin levels Dose adjustment needed with rifampin use Contraindicated w/dofetilide and multiple antiepileptic drugs Avoid close admin. with polyvalent cations (iron, calcium, etc.) Test all patients for HBV prior to initiation
Symtuza®	Tenofavir alafenamide/ Emtricitabin/ Darunavir/ Cobistat	Discontinue if CrCl<30; ok w/HD but dose after HD on dialysis days	Contraindicated w/rifampin, rifabutin, simvastatin, multiple antiepileptic drugs Note that cobistat can increase serum creatinine without affecting glomerular filtration so cautiously interpret serum creatinine levels
Triumeq®	Abacavir/ Dolutegravir/ Lamivudine	CrCL 30-50: monitor for hematologic toxicities with lamivudine CrCl< 30; do not use combo pill; dose-adjust individual components	↑ Metformin levels Dose adjustment needed with rifampin use Contraindicated w/dofetilide and multiple antiepileptic drugs Avoid close admin. with polyvalent cations (iron, calcium, etc.) Test all patients for HBV prior to initiation
Genvoya®	Elvitegravir/ Cobicistat/ Emtricitabin/ Tenofovir (Alafenamide)	Discontinue if CrCl < 30; ok w/HD	Many drug-drug interactions due to CYP 3A4 inhibition with cobicistat

Nucleoside RTI	Dose adj	Specific Side Effects	Major DDI	Special Points
Abacavir (ABC)	Hepatic dysfunction	↑ LDL/TG ↑ risk MI	Tenofovir	Requires testing for HLA B5701
Emtricitabine (FTC)	Renal	Rash, insomnia, rhabdomyolysis, hyperpigmentation in palms/soles	Lamivudine	Active against HBV
Lamivudine (3TC)	Renal	Nausea, HA, peripheral neuropathy, neutropenia, rash	Emtricitabine	Active against HBV
Tenofovir Alafenamide (TAF)	Discontinue if CrCl < 15	↑ lipids	AED’s may ↑ levels	Tx of choice for HBV
Tenofovir Disoproxil (TDF)	Renal	N/V, ↑ LFTs, asymptomatic ↑CK, renal dysfunction, bone mineral density loss	--	Active against HBV

NRTI Additional Information

Tenofovir alone is indicated for HBV, in which case you should be mindful of renal clearance when dosing. In HIV, it is only used in combination with emtricitabine and third agent. Contraindicated if CrCl\<30
Class-wide side effect: Lactic acidosis, steatosis and lipoatrophy (though very rare with contemporary NRTIs)
Resistance: M184V confers high resistance to emtricitabine and lamivudine, mid-level resistance to abacavir, hypersusceptibility to tenofovir

Integrase Inhibitor

Dose Adj.

Specific Side Effects

Major DDI

Special Points

Raltegravir (RAL)

--

Rifampin, AED’s

--

Dolutegravir (DTG)

*see special points*

Hyperglycemia

Weight gain

Rifampin, Efavirenz

↑Metformin

Avoid close admin with laxatives, sucralfate, iron, calcium

May ↑Cr, without effect on renal function

NNRTIs	Hepatic Adj	Specific Side Effects	Major DDI	Special Points
Efavirenz	Stop if Child Pugh B/C	Psychosis, vivid dreams, SI, mania, seizures; ↑ Lipids & glucose	Azoles, antifungals, clopidogrel, some statins, clarithromycin, Buprenorphine	Give before meals; discontinue if rash develops
Etravirine (ETR)		Hypersensitivity ↑ Lipids & glucose	Clopidogrel, clarithromycin
Nevirapine (NVP)	Stop if Child Pugh B/C	Steven Johnson Syndrome	Azoles, OCP’s, statins, clarithromycin	Don’t start if CD4 >250 in women, CD4 >400 in men; Don’t admin with antacids
Rilpivirine (RPV)		None	AED’s, PPI’s, dexamethasone	Must be taken with full meal; Don’t use if HIV RNA >100k + CD4 < 200; Don’t admin with antacids

NNRTI Additional Information

Class-wide side effect: hepatitis, rashes
Resistance: K103N resistance to efavirenz and nevirapine

Protease inhibitors	Hepatic Dose adj	Specific Side Effects	Major DDI	Special Points
Atazanavir (ATV)	Based on Childs Pugh	Jaundice, Kidney stones, AV block, Pancreatitis, Rhabdomyolysis	CYP3A4 Inhibitors PPI and H2 blockers	Admin with meals
Darunavir (DRV)		Rashes Pancreatitis	CYP3A4 Inhibitors Azoles can be used cautiously with drug level monitoring	Must stop if rash
Lopinavir (LPV)		AV block, QT changes Pancreatitis Hepatitis	CYP3A4 Inhibitors	Admin with meals

Protease Inhibitor Additional Information

All protease inhibitors must be boosted:

Ritonavir: can cause MSK pain, rhabdomyolysis, although not expected at usual doses
Cobicistat: may increase Cr without effect on renal function

Class-wide side effects: hepatitis, hypersensitivity reactions, increased cholesterol/TG, hyperglycemia, GI upset, lipodystrophy

Sexually Transmitted Infections¶

Ashley Zeoli

Gonorrhea¶

Background¶

Cause: gram-negative coccus Neisseria gonorrhoeae
Gonorrhea causes a spectrum of disease including urethritis, cervicitis, epididymitis, proctitis, pharyngeal infections, conjunctivitis, PID, and disseminated gonococcal infection

Evaluation¶

Microbial diagnosis is required to diagnose gonorrhea, rather than clinical diagnosis alone
Test of choice: NAAT of the first-catch urine in men; NAAT of vaginal swab in women
- Also perform co-testing for chlamydia
NAAT of pharyngeal or rectal swab should also be performed in patients with reported symptoms and recent sexual exposure. Note this is also routine testing in patients on PREP.
Routine screening should be offered to sexually active patients, as many are asymptomatic

Management¶

Ceftriaxone is the only current antibiotic that meets the strict treatment efficacy goals with single-dose therapy. CTX also has a low rate of drug resistance, which is becoming an increasing issue in the treatment of gonorrhea.
- High dose IM ceftriaxone (<150kg 500mg IM; >150mg 1g IM)
  - Same for pharyngitis or conjunctivitis
- CTX allergies: Azithromycin (2g PO x1) + Gentamicin (240mg IM x1) or Gemifloxacin
Treatment of chlamydia must also be accompanied with gonorrhea treatment when it has not been excluded with molecular testing.
- Doxycycline 100mg BID for 7 days
Patients who have persistent symptoms despite treatment should be suspected of having resistant gonorrhea. Test with culture and antimicrobial susceptibility testing (with or without NAAT).
Patients with recurrent symptoms after period of resolution should be re-evaluated for gonorrhea and other STIs

Chlamydia¶

Background¶

Cause: gram negative bacteria Chlamydia trachomatis
Most individuals are asymptomatic though causes a wide array of infections: urethritis, cervicitis -> PID, conjunctivitis, perihepatitis (Fitz-Hugh-Curtis syndrome), pneumonia, proctitis, epididymitis, reactive arthritis, pharyngitis, lymphogranuloma venereum (LGV), endemic trachoma
Differential diagnosis: Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium

Evaluation¶

Test of choice: NAAT of vaginal swab in females (first catch urine also adequate); NAAT of first catch urine in males.
NAATs can detect both LGV and non-LGV chlamydia trachomatis, but cannot distinguish between them
Any patient with signs and symptoms concerning for chlamydia should be tested. Testing should also routinely be offered to sexually active individuals since most patients are asymptomatic. Note this is also routine testing in patients on PREP.

Management¶

Doxycycline 100mg BID x 7 days is the preferred treatment in non-pregnant patients (azithromycin is NOT preferred) Alternative treatment options (for allergies/severe contraindications): azithromycin (1g PO x 1), levofloxacin (500mg PO daily x7 days), and ofloxacin (300mg BID PO x7 days) Patients with recent potential or confirmed exposure within the last 1-2 weeks should be treated empirically
Patients with persistent symptoms, confirmed infection, and who already underwent appropriate treatment, likely have a re-infection, rather than treatment failure. Test again.
Patients with recurrent symptoms after resolution should be re-tested for chlamydia with a NAAT and other STIs (gonorrhea, BV, etc).
Empiric therapy for gonorrhea should be given to patients unless NAAT is negative

Syphilis¶

Background¶

Caused by the spirochete, Treponema pallidum, which is visualized by dark field microscopy
High rate of HIV co-infection among MSM with syphilis (~42%)
Transmitted by direct contact with an infectious lesion during sex. Infection can occur anywhere inoculation occurs (i.e. contact with infected secretions can result in a lesion on any tissue site)
Can readily cross the placenta -> fetal infection
Patients can present with a variety of symptoms, depending on their place in the disease course

Evaluation¶

Test all patients with signs and symptoms, as well as patients who are at increased risk for acquiring infection (patients with sexual partner with early syphilis, MSM, people living with HIV, high risk sexual behaviors, and history of commercial sex work or incarceration)
HIV testing should be offered to all patients who test positive
Pregnant patients should be screened for syphilis
There are two types of serologic tests: treponemal-specific tests (FTA-ABS, MHA-TP, TPPA, TP-EIA, CIA) and nontreponemal tests (RPR, VDRL, TRUST). Either can be used as initial screening, but confirmatory testing with the other is needed due to false positives.
- Treponemal specific are usually used as confirmatory tests when nontreponemal tests are reactive. They are reported as reactive or non-reactive. Once positive, usually positive for life.
- Nontreponemal quantifies amount of antibody present and can be used to detect titers to assess for treatment. Titers should decline after a patient has been treated. A rise in titers in a previously treated patient should be concerning for new infection.
  - Requires a humoral response, so can be false negatives if immunocompromised
  - False positives: autoimmune diseases, pregnancy, other infections
At VUMC, a positive treponemal IgG reflexes to a RPR titer.
Neurosyphilis can occur at any time after infection. All newly diagnosed patients with syphilis should have a full neurologic exam and if any abnormalities should have an LP sent for CSF-VDRL.
Any patients with syphilis and vision changes should undergo ophthalmology evaluation.

	+ Treponemal	- Treponemal
+ Non-treponemal	Diagnostic of syphilis (completely new, or potentially re-infected)	Likely false positive
- Non-treponemal	Likely history of successfully treated syphilis	Likely not syphilis, or false negative (due to prozone\* effect)
\Prozone effect:* when there is an overabundance of antibodies and they interfere with clumping/formation of antigen-antibody complex so agglutination cannot be visualized

Management

To assess treatment efficacy, we want to see a fourfold decrease in titer after treatment

	Symptoms	Treatment	Treatment Alternatives
Primary	Painless chancre at inoculation site with regional lymphadenopathy	PCN G benzathine 2.4 million units IM x1	Doxycycline 100mg PO BID x 14 days OR Ceftriaxone 1-2g daily IM or IV x 10-14 days OR Tetracycline 500mg PO QID x 14 days OR Amoxicillin 3g BID and probenecid 500mg BID x 14 days
Secondary	Systemic illness with rash (palms, soles), fever, malaise, alopecia, hepatitis, mucous patches, condyloma, pharyngitis
Early Latent	Infected, but no symptoms. Occurs within one year of initial infection.
Tertiary	Symptomatic late syphilis (CV system, gummatous disease)	PCN G benzathine 2.4 million units IM weekly x3 weeks	Doxycycline 100mg PO BID x 4 weeks OR Ceftriaxone 2g daily IM or IV x 10-14 days
Late Latent	Infected, but no symptoms. Occurs >1 year after initial infection. Assume late latent with date of infection unknown	PCN G benzathine 2.4 million units IM weekly x3 weeks
Neuro syphilis	Can occur at any time. Early: asymptomatic or symptomatic meningitis, vision loss, hearing loss Late: brain and spinal cord manifestations (dementia, tabes dorsalis) Treat ocular syphilis like neurosyphilis	Aqueous PCN G 3-4 million units IV q4h x 10-14 days OR PCN G procaine 2.4 million units IM daily and probenecid 500mg PO QID x 10-14 days	If PCN allergic, desensitize Ceftriaxone 2g daily IM or IV x 10-14 days

AIDS Defining Clinical Conditions¶

Rebecca Choudhury

AIDS is defined by HIV infection with concurrent absolute CD4 count \<200, CD4 percentage \<14%, or one of the following conditions (predominately opportunistic infections and HIV associated malignancies):

Neurologic/Ophthalmologic¶

CNS toxoplasmosis¶

Presentation: Variable, depending on disease burden/location, may include AMS, headache, seizure, ataxia, and focal neurologic deficits, ± fever and flu-like symptoms
Evaluation: MRI w/ring-enhancing lesions on brain imaging, serum Toxoplasma IgG/IgM and (ideally) CSF Toxoplasma PCR (though CSF Toxoplasma PCR has a low sensitivity). Response to empiric therapy (~90% will have radiographic improvement after 14 days) can also be diagnostic. Brain biopsy may be indicated if diagnostic uncertainty.
Management: Pyrimethamine, sulfadiazine, and leucovorin is the preferred regimen, discuss dosing with pharmacy. Alternative regimens: clindamycin, Bactrim, atovaquone

Progressive multifocal leukoencephalopathy (PML)¶

Presentation: chronic (weeks to months), progressive neurologic dysfunction, particularly incoordination and other motor dysfunction, aphasia, sometimes cognitive impairment and personality changes
Evaluation: MRI brain w/patchy areas of demyelination in the subcortical white matter; location is variable, but parietal, occipital, and cerebellar involvement are common. JC virus PCR from CSF. Brain biopsy.
Management: Initiation of ART (there is no specific JC virus-directed therapy), IRIS may occur in which case clinical worsening before improvement may be seen. Fatal if HIV goes untreated.

Presentation: Similar to other progressive dementias, with short term memory loss followed by worsening global cognitive dysfunction, motor deficits, sometimes seizures in late stages
Evaluation: MRI w/diffuse cerebral atrophy and/or demyelinating lesions similar to PML. CSF w/elevated protein ± lymphocytic pleocytosis, with no alternative cause. Send HIV RNA from the CSF, usually + in HIV encephalopathy

Cryptococcal meningitis¶

Presentation: Subacute to chronically worsening HA and fevers; meningismus and photophobia may be present but are often absent; rarely, focal neurologic deficits
Evaluation: LP to check opening pressure and can send serum and CSF Cryptococcus Ag. Brain imaging may be non-diagnostic
Treatment: Induction therapy with amphotericin and flucytosine x14 days (at least), with repeat LP close to end of induction to confirm CSF inflammation is improving and fungal culture is negative. Consolidation therapy consists of high dose fluconazole for at least 8 weeks, followed by maintenance therapy with fluconazole for one year. Pts may require serial LP or VP shunt to manage ICP.
- Delay ART for several weeks after start of treatment to avoid risk of IRIS.

CMV retinitis (with vision loss)¶

Presentation: Blurry vision, focal blind spots, visual field deficits, or scotomas and floaters. Typically begins unilateral, though often progresses to bilateral involvement.
Evaluation: Always consult ophtho if you suspect it! May cause complete retinal detachment. Check serum CMV PCR (or vitreous if able)
Management: PO valgancyclovir (+intravitreous ganciclovir or foscarnet in severe disease). If not on ART, must delay ART for at least 2 weeks after start of CMV retinitis treatment to prevent immune recovery uveitis

Pulmonary¶

Pneumocystis jirovecii pneumonia (PJP)¶

Presentation: fever, shortness of breath, cough (usually non-productive), sometimes night sweats and weight loss. Hypoxia out of proportion to exam.
Evaluation: CT chest appearance usually bilateral and diffuse with GGOs and cystic lesions of varying size. Large cysts can rupture, causing pneumothorax.
- Transbronchial biopsy, BAL, or induced sputum with cytology and GMS stain.
- Sputum Pneumocystis PCR can be done, but this is a send-out with long turn-around-time
- Consider serum LDH and 1,3-BD-glucan: should be elevated, but are nonspecific.
Management: Bactrim is the preferred treatment; PO is preferable as Bactrim is 100% bioavailable. Check ABG on ROOM AIR to consider of adding adjunctive steroids (If A-a gradient >/=35mmHg and/or PaO2 \<70mmHg). Alternative regimens may include primaquine + clindamycin or IV (NOT inhaled) pentamidine.

Pulmonary tuberculosis¶

Presentation: With low CD4, can have upper lobe cavities but also atypical radiographic pattern, including a normal-appearing CXR. Have a high degree of suspicion in any patient with advanced HIV and respiratory complaints.
Evaluation: TB skin tests and IGRAs have a high false negative rate in advanced HIV. At VUMC, any pt with HIV and respiratory complaints must be placed on airborne until TB ruleout- 3 sputum mycobacterial cultures collected at least 8 hours apart. If concentrated smear is negative x3, TB is unlikely (though have to follow up final culture to be sure).
Management: RIPE therapy is the standard initial treatment, with adjustment if needed for drug resistance or contraindications

Herpes simplex tracheobronchitis and/or pneumonitis/pneumonia¶

Evaluation: bronchoscopy with positive HSV PCR from BAL ± lung biopsy. (Usually associated with HSV-1)
Management: agent and duration not well defined for bronchopulmonary disease; depending on severity of presentation, likely IV acyclovir to start followed by transition to PO antiviral once evidence of clinical improvement, for a total of 10-14 days.

Gastrointestinal¶

Esophageal candidiasis¶

Presentation: Dysphagia, odynophagia or both. Concurrent oropharyngeal candidiasis (“thrush’) is common but not universal.
Evaluation: Typically presumptive. Treatment is the test; start fluconazole and consider EGD if symptoms do not improve after several days (in which case candidiasis may be severe, or it might not be the cause)
Management: Fluconazole; nystatin is ineffective, especially in the severely immunocompromised

Herpes simplex esophagitis¶

Evaluation: EGD shows diffuse ulcerations throughout the esophagus; in severe disease ulcers may coalesce into dark patches, “black esophagus.” Esophageal biopsy is definitive, but can infer based on EGD appearance and serum studies.
Management: Similar to other mucocutaneous infections, consider IV acyclovir at first and transition to PO once clinically improved

CMV esophagitis/enteritis/colitis¶

Presentation: GI bleeding (colitis) or dysphagia and odynophagia (esophagitis)
Evaluation: serum CMV PCR, consult GI for consideration of EGD/colonoscopy
Management: (val)ganciclovir, foscarnet if ganciclovir resistance or contraindication

Chronic (>1 mo) intestinal isosporiasis¶

Evaluation: Stool ova/parasite can capture Iospora belli (new name Cystoisospora belli), may need serial analysis due to intermittent shedding. Oocysts may also be seen on duodenal biopsy.
Management: Bactrim; pyrimethamine + leucovorin if Bactrim is contraindicated

Chronic intestinal cryptosporidiosis¶

Presentation: Diarrhea; may infect respiratory tract, causing nonproductive cough
Evaluation: on GiPP or Cryptosporidium Ag
Management: Early initiation or optimization of ART; Monotherapy with nitazoxanide is preferred; raising CD4 count >100 is necessary to cure infection

Recurrent Salmonella septicemia¶

Generally sensitive to fluoroquinolones, but if not clinically improving as expected you can request sensitivities from the microbiology lab.

Neoplastic¶

Non-Hodgkin’s lymphoma

DLBCL, Burkitt’s, immunoblastic (subset of DLBCL), primary effusion lymphoma, and 1º CNS

Kaposi’s sarcoma¶

Presentation: Distinctive mucocutaneous lesions, usually raised, papular, violaceous or darkly colored, non-tender and non-pruritic. Can also involve the visceral organs (esp lungs and GI tract) and deep lymphatic system.
Evaluation: clinical, tissue biopsy for staging, HHV-8 serum PCR.
Management: Limited mucocutaneous disease may resolve with initiation/optimization of ART, but widespread or resistant disease may require additional local therapies (eg: radiation) or systemic chemo
Bacillary angiomatosis (caused by Bartonella) may present similarly, but can be distinguished from KS on biopsy. It is neither a cancer nor an AIDS defining clinical condition, and is usually treated with doxycycline.

Cervical cancer¶

Presentation, diagnosis, and treatment are essentially the same as in HIV-negative patients, but incidence is higher and disease progression is often more rapid

Multisystem/Miscellaneous¶

Extrapulmonary or disseminated Mycobacterial infection (TB and non-TB)¶

TB can go everywhere; some notable extrapulmonary sites include lymph nodes (e.g., scrofula), bones and joints (e.g., Pott’s disease of the spine), pleura and pericardium, GU tract, and CNS. Dx can come from tissue culture and sometimes MTB PCR for more rapid detection (needs ID approval).
TB-IRIS may be severe (esp with high infection burden) and hard to distinguish from TB treatment failure; can also be seen in adequately treated TB (provoked by the presence of dead bacteria) and undiagnosed latent TB.
Disseminated MAC is usually diagnosed with AFB blood culture (only 1 positive needed). Think about it in patients with uncontrolled HIV and severe immunosuppression (esp CD4 \<50), with unintentional weight loss, chronic diarrhea and/or dyspnea, and evidence of GI malabsorption or with bone marrow suppression

Extrapulmonary or disseminated Histoplasmosis, Cryptococcocosis, and Coccidiodomycosis¶

Can be difficult to distinguish based on clinical presentation and imaging alone. Diagnosed by culture and/or antigen testing depending on the organism and site of infection, and diagnosis may be supported by serologic studies.
Initial treatment of choice: liposomal amphotericin B in almost all cases

Chronic mucocutaneous HSV¶

Defined as mucocutaneous lesions present for >1 month, can be present at any site

Multicentric Castleman’s Disease¶

See “Plasma Cell Dyscrasias” section in Hematology/Oncology for more details

Antimicrobial Prophylaxis per CD4 Counts¶

Rachel Pellegrino

0	1	2	3	4
CD4 counts	Opportunistic Infection	Indication for Prophylaxis	Medication	Special Notes
<200 cells/mm3	Pneumocystis Pneumonia (PJP)	CD4 < 200, or CD4 < 14%, or CD4 200-250 w/ delayed init. ART & poor f/u	TMP-SMX: 1 DS daily (qd), or TMP-SMX: 1SS qd TMP-SMX: 1 DS TIW	If intolerant of TMP-SMX: dapsone*, or pentamidine, or atovaquone
<200 cells/mm3	Toxoplasma gondii encephalitis	Toxoplasma IgG + and CD4 < 100	TMP-SMX 1 DS tab daily	Alternative regimens: Dapsone, or Atovaquone (all regimens effect. for PJP )
<200 cells/mm3	Mycobacterium avium- intracellulare (MAC, MAI)	Only if not on fully suppressive ART and active disseminated MAC is ruled out	- Azithromycin 1200 mg weekly, or -Clarithromycin 500 mg BID, or - Rifabutin 300 mg daily	NOT indicated for those initiating ART

Infection	Screening Indication	Intervention
Hepatitis A Virus (HAV)	Non-immune w/ ↑ risk for HAV infection (MSM, IVDU) or chronic liver disease	HAV vaccine
Hepatitis B Virus (HBV)	Pts w/o chronic HBV or non-immune	HBV vaccine. Ideally admin. before CD4 < 350
Human Papilloma virus (HPV)	Age 13-45	HPV vaccine series
Influenza A and B Virus	All patients	Yearly inactivated influenza vaccine
Latent Mycobacterium tuberculosis infection (LTBI)	-Pts with positive screening test for LTBI w/ no evidence of active disease. -Pts w/ known exposure	(INH 300mg + pyridoxine 25-50mg) PO daily for 9 months
Streptococcus pneumoniae	All patients	PCV13 and PPV23 (order and timing depends on previous vaccination history and CD4)
Syphilis	All pts exposed to sex partner with syphilis diagnosis	Screening for syphilis and gonorrhea/chlamydia with treatment if indicated.
Varicella Zoster Virus (VZV)	Pre-exposure: CD4 >200, no previous vaccine.Shingrix (recombinant vaccine) is not live virus, only Zostavax (live virus) is contraindicated for CD4 <200). Post-exposure: Close contact, particularly if CD4 <200	Pre-exposure: Consider vaccination Post-exposure: Varicella-zoster immune globulin

Bacteremia: Interpreting GenMark ePlex® Results – VASP¶

Background¶

When BCx turn positive, the lab reports Gram stain and GenMark ePlex® results to help guide empiric therapy, while awaiting further species identification and susceptibilities.

Management¶

Start empiric antibiotic therapy (based on clinical picture and table below)
Consider ordering repeat BCx x2 based on organism to document clearance
- Repeat for: Staph (MRSA or MSSA), Strep lugdunensis
- If source control & no endovascular infxn, no need to repeat (most other strep and GNR’s)
VUMC antibiograms can be used to reference typical resistance patterns and most common organisms in blood cultures.
Candida in a blood culture is NEVER considered a contaminant

GRAM POSITIVE COCCI

Organism	Resistance Marker	Preliminary Recommendation
Staphylococcus aureus or Staphylococcus lugdunensis ID Consult REQUIRED	mecA detected	Start vancomycin IV
	No mecA detected	Start nafcillin or cefazolin Stop empiric vancomycin IV
Staphylococcus epidermidis -Often skin contaminant -Repeat cultures, start therapy if uncertain	mecA detected	Start vancomycin IV
	No mecA detected	Start nafcillin or cefazolin Stop empiric vancomycin IV
Other coagulase negative Staph -Often skin contaminant -Repeat cultures, start abx if uncertain		Start vancomycin IV
Streptococcus: agalactiae, pyogenes, anginosus		Start penicillin IV or CTX IV Stop empiric vancomycin
Streptococcus pneumoniae		Start ceftriaxone Stop empiric vancomycin Await PCN sensitivity data
Other Streptococcus -May be contaminant		Start ceftriaxone Stop empiric vancomycin Await PCN sensitivity data
Enterococcus faecalis ID Consult REQUIRED	vanA or vanB detected	Start daptomycin 8-10mg/kg/day IV Don’t treat w vancomycin IV Contact precautions
Enterococcus faecalis ID Consult REQUIRED	No vanA or vanB	Start ampicillin Stop empiric vancomycin IV
Enterococcus faecium ID Consult REQUIRED	vanA or vanB detected	Start daptomycin 8-10mg/kg/day IV Don’t treat w vancomycin IV Contact precautions
Enterococcus faecium ID Consult REQUIRED	No vanA or vanB	Start vancomycin IV Follow-up ampicillin sensitivities
Micrococcus -Often if in a single blood culture is skin contaminant		Repeat BCx Start vancomycin IV if uncertain

GRAM POSITIVE RODS

Listeria monocytogenes

Start ampicillin

Stop empiric vancomycin IV

Other Gram positive rod (e.g. Bacillus cereus, Corynebacterium, Cutibacterium acnes, Lactobacillus)

-Often skin contaminant

-Repeat cultures, start therapy if uncertain

Start vancomycin IV

Follow-up sensitivities; some GPRs are resistant to vancomycin

GRAM NEGATIVE RODS *Consult ID if carbapenem resistance detected*

Organism	Preliminary Recommendation
Acinetobacter baumannii	Start ampicillin/sulbactam
Bacteroides fragilis	Start metronidazole If polymicrobial infection, piperacillin/tazobactam, ampicillin/sulbactam, or meropenem based on other organisms Do NOT double cover anaerobes
Citrobacter spp.	Start/continue cefepime
Cronobacter sakazakii	Start/continue cefepime
Enterobacter (non-cloacae complex)	Start/continue cefepime
Enterobacter cloacae complex	Start/continue cefepime
Escherichia coli	Continue empiric coverage and await susceptibilities
Fusobacterium nucleatum Fusobacterium necrophorum	Start ampicillin/sulbactam or start/continue metronidazole
Haemophilus influenzae	Start/continue ceftriaxone
Klebsiella oxytoca	Continue empiric coverage and await susceptibilities
Klebsiella pneumoniae group	Continue empiric coverage and await susceptibilities
Morganella morganii	Start/continue cefepime
Neisseria meningitidis	Continue empiric coverage and await susceptibilities
Proteus spp. Proteus mirabilis	Continue empiric coverage and await susceptibilities
Pseudomonas aeruginosa	Start/continue cefepime or piperacillin-tazobactam
Salmonella spp	Start/continue ceftriaxone
Serratia spp. Serratia marcescens	Start/continue cefepime
Stenotrophomonas maltophilia	Start trimethoprim-sulfamethoxazole (15-20mg/kg/day divided q8h for normal renal function)
Gram-Negative Resistance Genes
CTX-M Positive (ESBL)	Start meropenem Consider an Infectious Diseases consult Contact precautions (see Infection Prevention website)
IMP Positive KPC Positive NDM Positive OXA (OXA-23 and OXA-48) Positive VIM Positive	Carbapenemase-producing organism Obtain Infectious Disease consultation Contact precautions (see Infection Prevention website)

Central Nervous System Infection – VASP¶

Bacterial Meningitis¶

Evaluation¶

Blood cultures prior to antibiotics if possible
Head CT pre-LP, only if: Immunocompromised, hx of CNS diseases (shunts, trauma, tumors), papilledema on exam or FND, AMS, or new onset seizure.
If there is a delay in obtaining head CT or LP, DO NOT delay antibiotics.
Lumbar puncture (See Procedures Section):
- Obtain: Opening pressure, cell count + differential, glucose, protein, bacterial culture
- Send an extra tube or two of CSF to the lab, if possible, to be frozen in case extra testing is needed (Order ‘Miscellaneous test’ and for test name put “Please freeze CSF in virology;” reference lab: VUMC, specimen type: CSF)
- Additional studies to consider in select pts: HSV 1, 2 PCR (NOT antibodies), VZV PCR, VDRL, Crypto Ag, fungal and/or AFB cultures, MTB PCR, West Nile Virus Ab, Enterovirus PCR, Histoplasma Ag, or Biofire Meningitis/Encephalitis Panel. These should not be performed routinely on all patients and consult ID where management questions exist.
- If Biofire Meningitis/Encephalitis Panel is performed, double check what is included to avoid sending duplicate individual tests (ie HSV, VZV, enterovirus, etc.) A negative cryptococcus on Biofire does not exclude disease (CSF Crypto Ag is more sensitive)

Management¶

ANTIBIOTICS AS SOON AS POSSIBLE:
- Ceftriaxone 2g IV q12h + Vancomycin, adjusted for renal function
- Piperacillin-tazobactam cannot be used due to poor CNS penetration
- IV ampicillin 2g q4h for optional coverage of Listeria for immunocompromised patients, pregnant women, or age >50 (adjust based on renal function)
- IV acyclovir 10 mg/kg (based on adjusted body weight) q8h, if suspected HSV or VZV meningitis, make sure to run with adequate pre-hydration with NS
- Consider empiric PO/IV doxycycline 100mg BID if tick-borne illness is suspected
Steroids: Based on IDSA guidelines, steroids (dexamethasone 0.15 mg/kg q6h) should be given about 10-20 minutes before the first dose of antibiotics, or at the same time, in patients with suspected bacterial meningitis. IF pneumococcus is isolated, continue IV steroids for 2-4 days; otherwise, can discontinue
ID consultation: Duration should be guided by ID and varies based on organism recovered

Encephalitis¶

Background¶

The presence or absence of normal brain function/cognition is the important distinguishing clinical feature between encephalitis and meningitis

Evaluation¶

MRI more sensitive that CT, although imaging may or may not demonstrate abnormal radiographic findings in patients with encephalitis
LP – similar studies as for meningitis (see above) + BioFire MEP for ALL pts

Management¶

Acyclovir 10mg/kg IV q8hr, consideration of antibacterial therapy if unable to conclusively exclude a bacterial meningitis, consideration of doxycycline if tick-borne infection is on the differential, and further treatment as guided by ID
ID consult is strongly encouraged for all patients with suspected encephalitis

Brain Abscess¶

Evaluation/Management¶

Consult: Neurosurgery and ID
Blood Cultures, HIV testing in any patient with a brain lesion
Empiric antibiotics:
- IV Vancomycin (target trough 15 - 20 mcg/mL) + ceftriaxone 2g IV q12h + metronidazole 500mg IV/PO q6h
- If concern for extension from otitis externa, use an antipseudomonal cephalosporin (cefepime 2g IV Q8h) instead of ceftriaxone
- Brain abscesses generally polymicrobial, thus broad-spectrum antibiotics indicated
Aminoglycosides, macrolides, tetracyclines (e.g. doxycycline), clindamycin, beta-lactam/beta-lactamase combinations (e.g., Zosyn) and 1^st-generation cephalosporins (e.g., cefazolin) should NOT be used as they do not cross BBB at high concentration.
Antibiotic Duration: Based on surgical drainage and Infectious Diseases guidance

Epidural Abscess¶

Management¶

If spinal lesion, consult ‘Spine surgery’ and it will be directed to Ortho-Spine or Neurosurgery, depending on who is on call.
Antibiotics should be started as soon as the diagnosis of epidural abscess is suspected, immediately following the collection of two sets of blood cultures
- Vancomycin 15-20mg/kg IV q8-12h (adjusted for renal function) + ceftriaxone 2g IV q24h (or q12hr if there is secondary meningitis)
- Use cefepime 2g IV q8h instead of ceftriaxone if concern for Pseudomonas
ID consult is strongly encouraged and they will guide duration

Diabetic Foot Infection – VASP¶

Evaluation¶

Plain radiograph for all pts; MRI w/contrast if abscess/osteo suspected
BCx (prior to antibiotics) if systemic signs of infection, or severe infection
- Do not culture swabs of lesions, as these generally only grow colonizing organisms.
Consult podiatry if osteomyelitis present for bone specimen culture and pathology (either from debridement specimen or bone biopsy) prior to starting antibiotics.
Consult surgery if concern for abscess, gas in tissue, joint involvement
Assess peripheral vasculature, consider arterial flow studies/vascular surgery consult

Management¶

Assess Severity:
- Mild: Local infxn, skin/subQ tissue only, erythema >0.5 cm but ≤2cm from ulcer
- Moderate: Local infxn w/erythema > 2 cm from ulcer or deeper structures included without SIRS
- Severe: Local infxn with systemic inflammation as evidenced by >2 SIRS criteria
  - Consider anti-pseudomonal coverage if at risk for Pseudomonas infection (e.g. wet; failure of prior antibiotic therapy; chronic wound).
  - Consider anaerobic coverage with metronidazole if foul-smelling and/or necrotic.

Mild

Cephalexin 500 QID OR

Amoxicillin-clavulanate 875/125 BID

TMP-SMX DS 1-2 tabs BID OR

Doxycycline 100 BID

Moderate

Amoxicillin-clavulanate 875/125 BID OR

Ampicillin-sulbactam 3g q6h OR

Piperacillin-tazobactam 3.375g q8h ext infusion OR

Levofloxacin 500 daily

TMP-SMX DS 1-2 tabs BID + cephalexin 500 QID OR Amoxicillin-clavulanate 875/125 BID

Vancomycin 15-20mg/kg q8-12h + ampicillin-sulbactam 3g q6h (anaerobic, but NO Pseudomonas cvg) OR cefepime 2g q8h (Pseudomonas cvg) + metronidazole 500 q8h (anaerobic cvg)

Severe

Vancomycin 15-20 mg/kg q8-12h + cefepime 2g q8h + metronidazole 500 q8h

Additional Information¶

If pt HDS, hold abx until deep tissue/operative cultures obtained.
Most diabetic foot infections are polymicrobial in nature.
Culture results may guide therapy, but all pathogens identified may not require treatment.

Endocarditis¶

Justin Smith

Background¶

Multiple etiologies of endocarditis:
- Typical Bacterial
  - S. aureus, Enterococcus spp (E. faecalis most commonly), viridans group streptococci, Strep gallolyticus (formerly S. bovis)
  - HACEK : Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella
- Other infectious
  - Culture negative: often recent antimicrobial exposure, slow growing organism
  - Coxiella, Brucella, Bartonella, Chlamydia, Legionella, Mycoplasma, Tropheryma whipplei, Propionibacterium acnes
  - Fungal: Candida and aspergillus most common
- Non-infectious: a.k.a., marantic endocarditis, Libbman-Sacks Endocarditis
  - Rare, most common in advanced malignancy, SLE, inflammatory conditions
  - Higher risk for embolization compared to IE
  - Risk factors: IV drug use, congenital heart disease, valve abnormalities, intracardiac devices, recent cardiac surgery

Presentation¶

Fever (90%), Murmur (85%), Other: splenomegaly, splinter hemorrhages, Janeway lesions, Osler Nodes, Roth Spots
Persistent bacteremia despite appropriate treatment, new onset cardiac dysfunction, new onset valve abnormalities, stroke, other thromboembolic events, metastatic infections/abscesses, splenic abscess, septic pulmonary emboli

Duke Criteria:¶

Pathologic Criteria
- Microorganisms: culture or histology proven: vegetation, embolus, or intracardiac abscess
- Pathologic vegetations: vegetation of abscess with histology proven endocarditis
Clinical Criteria
- Major:
  - 2x positive blood cultures from a typical organism
  - Evidence of endocardial involvement
Minor
- Predisposing heart condition/IVDU
- Fever
- Vascular phenomena (Glomerulonephritis)
- Immunologic phenomena (Osler Nodes, Roth Spots, +Rheumatoid factor, GN)
- Micro (Cultures that don’t fit the above, or serologic evidence of acute infection)
  - - - -
Definite: 2 Major, 1 major and 3 minor, or 5 minor
Possible: 1 major and 1 minor, or 3 minor
Rejected: firm alternate diagnosis, resolution of evidence with \<4 days of antibiotics, or absence of pathologic evidence with \<4days of antibiotics

Evaluation¶

Physical exam: murmur, decreased peripheral perfusion, evidence of heart failure, petechiae, splinter hemorrhages, Janeway lesions/Osler nodes, organomegaly
Blood cultures: at least three sets from different sites over a span of several hours
Echo (TTE vs TEE)
- It can be reasonable to start with TEE if pretest probability is high enough, if patient has known valvular abnormalities, or TTE will be technically difficult -
EKG: new heart block or prolonged PR raises concern for endocardial/perivalvular abscess. Endocarditis patients should be on telemetry, monitored closely by team
CXR: infiltrates suggestive of septic pulmonary emboli, pulmonary edema, cardiomegaly
Imaging of distant affected site if concerned for septic emboli
Other advanced imaging in select scenario: cardiac CTA, cardiac MRI, FDG-PET/CT

Management¶

Empiric antibiotics:
- If bacteria isolated from blood, reference bacteremia section for abx choice
- If awaiting cultures
  - Native valve: Vancomycin
  - Prosthetic valve: Vancomycin and cefepime, consider gentamicin
Duration: determined by ID, often 4-6 weeks
Surgical consult, if valve dysfunction, perivalvular abscess, large (>20mm) vegetations

Additional Information:¶

Complications:
- Cardiac:
  - Heart failure: usually secondary to valve dysfunction. Most common when aortic valve involved, risk also depends on organism (worst is Staph aureus )
  - Perivalvular abscess: suspect when there are conduction abnormalities on EKG; most likely when aortic valve involved, less likely with mitral valve.
  - Pericarditis: can be suppurative or non-suppurative
  - Intracardiac Fistula
- Septic emboli and metastatic abscesses
- Mycotic aneurysm: usually occurs at vessel branch points
Follow Up
- Repeat TTE at completion of treatment to establish new baseline
- Followed for valvular dysfunction with frequency determined by nature of the dysfunction. (MR caused by IE should be followed on a timeline like other MR)
- Regular dental care, Prior IE is an indication for SBE prophylaxis with dental work.
Episode of IE is an indication for PDA or VSD closure

Fungal Infections¶

Justin Smith

Histoplasmosis¶

Background¶

Endemic to Ohio and Mississippi river valley
Pulmonary infiltrate with hilar or mediastinal LAD, pulmonary nodule/cavitary lesion, pulmonary syndrome with erythema nodosum
DDx: TB, malignancy, sarcoidosis (if considering sarcoidosis, rule out histoplasmosis as sarcoidosis treatment can induce disseminated histoplasmosis)

Evaluation¶

Antigen (requires attending approval): For acute pulmonary histoplasmosis, 65% urine sensitivity, 69% serum sensitivity, and 83% sensitivity when co-tested. Thus, both serum and urine Ag are usually sent together
- Lower rates of positivity when disease is localized, versus diffuse throughout the lungs or disseminated.
- There are relatively high rates of cross-reactivity, where histoplasma antigen will be positive with blastomycosis; therefore, do not order blasto Ag if ordering histo Ag in MOST cases
Serology: Consider Histoplasma Ab if evaluating for pulmonary disease
Culture: most useful in chronic infections, sensitivity is low in acute/localized and may take >6 weeks to grow.
Bronchoscopy: If clinical suspicion is high and work up negative, consider interventional pulmonology consult for consideration of bronchoscopy

Management¶

Outpatient/Mild disease:
- Tx not required if symptoms \<4 weeks, initiate if symptomatic beyond 4 weeks
- Itraconazole: 200mg TID x3 days loading, then BID (adjusted by levels which are drawn 2 weeks post-start) for 6-12 weeks minimum
- Can use oral formulation or capsules (capsules require high acidity, give with food consumption or OJ or coke; do not use capsules if patient is on H2 blockers/PPI)
- Voriconazole, Posaconazole: used if not tolerating itraconazole or as salvage therapy
Inpatient/Moderate to Severe Disease:
- Amphotericin: 1-2 weeks induction, followed by PO itraconazole for 12 weeks (total)
- Methylprednisolone: help to prevent ARDS with significant lung involvement

Additional Information¶

Complications: Pericarditis, arthritis/arthralgias with erythema nodosum, chronic cavitary lesions, fibrosing mediastinitis, broncholithiasis
Disseminated Histoplasmosis:
- Typically found in immunocompromised populations
- Clinical presentations: FUO, weight loss, disseminated LAD, cutaneous manifestations, bone marrow suppression/pancytopenia, liver enzymes elevation, various solid organ involvement on imaging (liver, spleen, adrenals, nodes)
- Management
  - Mild: itraconazole
  - Moderate to Severe: amphotericin induction followed by itraconazole
  - CNS involvement: amphotericin for 4-6 weeks as induction

Blastomycosis¶

Background¶

Endemic to Mississippi/Ohio river valley, southern and midwestern US, great lakes
Pulmonary syndrome: cough, fever, hemoptysis, chest pain, dyspnea
- Can result in both an acute or chronic pneumonia, as well as ARDS
Cutaneous: raised verrucous lesion, varying in color, with irregular borders
MSK: osteolytic lesion, draining sinus, soft tissue swelling
Multi-system: up to 20-40% of cases, most typically lung/skin involvement.

Evaluation¶

Culture: typically takes 1-4 weeks
Ag: urine >serum. ~90% sensitive, but only 80% specific because of cross-reactivity
Serology: available, but not very useful because of high degree of cross-reactivity

Management¶

Mild: PO itraconazole for 6-12 months with loading, check level at 2 weeks
Moderate to Severe: induction with Amphotericin, followed by 6-12 months of PO itraconazole

Candida¶

Background¶

Oropharyngeal: white plaques in mouth, change in taste, erythema without plaques
- Usually seen in infants, older adults, immunocompromised host (HIV or chemotherapy), inhaled steroid users
Esophageal: odynophagia, especially retrosternal pain (AIDS defining illness)
Vulvovaginitis: itching, burning, vaginal discharge, vulvar erythema, vulvar edema, dyspareunia, dysuria
Balanitis: painful white plaques with burning and itching on the glans penis
Mastitis: erythema, tenderness in breast feeding woman.

Management¶

Depends on specifics, but typically nystatin or fluconazole EXCEPT C. glabrata (proof of fluconazole susceptibility needed) and C. krusei (intrinsically resistant to fluconazole)
Cx generally not indicated unless complicated pt with extensive tx history for Candida

Additional Information¶

Disseminated disease
- Presentation: Primarily immunocompromised populations (hematologic malignancies, solid organ transplant recipients, receiving chemotherapy, TPN, steroid use, broad spectrum antibiotics) and ICU settings (especially, burn, trauma, and neonatal)
- Diagnosis: Candida in a bacterial blood culture (NEVER contaminant)
- Start micafungin 100mg IV and consult ID for candidemia or if concerned for disseminated disease

General Tips¶

Vanderbilt Antibiotics Stewardship Program (VASP) has a website with much of the below guidance as well as Vanderbilt antibiograms, with our resistance patterns
Does your pt need to be on precautions? Check the Infection Prevention Website under ‘isolation’ tab or page the infection control pager in E-star paging for additional questions
Page 317-4376 for approval of restricted antimicrobials at VUMC (page the VA ID fellow at the VA)
The lab will automatically update the Tennessee health department with reportable diseases

Genitourinary Infection – VASP¶

Asymptomatic Bacteriuria¶

Background¶

Isolation of bacteria in an appropriately collected urine specimen from an individual without symptoms or signs of urinary tract infection. Bacteriuria, foul odor, urine appearance, pyuria and/or bacteriuria alone are not indicative of infection.
Anuric ESRD patients may have bacteriuria from colonization due to lack of flushing of bladder, avoid sending UA/Ucx unless patient is symptomatic
Treatment only required for specific populations:
- Pregnant women (screening performed at 12 – 16 weeks)
- Anticipated urologic intervention
- Some renal transplant recipients, depending on time since transplant

Uncomplicated Urinary Tract Infection (UTI)¶

Background¶

Clinical symptoms of UTI (dysuria/urgency/frequency/ hematuria) in non-pregnant, immunocompetent, neurologically-intact pts with normal urologic anatomy and no indwelling urinary catheters

Management¶

Empiric therapy
- Nitrofurantoin monohydrate: 100 mg PO BID x 5 days (avoid if any concern for pyelonephritis or if creatinine clearance \<60)
- Cephalexin 250-500mg q6h x5-7 days
Alternative therapies
- Fosfomycin: 3 grams of powder mixed in water as a single PO dose (avoid if any concern for ascending UTI or pyelonephritis). Susceptibility test results must be requested of micro lab and are only possible for E. coli and E. Faecalis.
- Amoxicillin-clavulanate: 875-125mg PO BID x5 days
- Ciprofloxacin: 250mg PO BID x3 days
  - FQ’s should be reserved for more serious infections than uncomplicated cystitis, and only after susceptibility results are confirmed given high rates of resistance from overuse (~25% of E. coli are resistant to ciprofloxacin at VUMC)
  - Adverse effect profile >> beta-lactams (i.e. QT-prolongation, tendinopathies)

Additional Information¶

MDR cystitis: ESBL isolates are increasingly common due to antibiotic overuse
- Before treating, decide if this is a TRUE UTI
- If true, consider Fosfomycin (if E. coli ) or nitrofurantoin (if susceptibility is confirmed – K. pneumoniae and Enterobacter spp are usually resistant), gentamicin or tobramycin 5-7mg/kg IV once, or ID consultation
- Ask the lab to check susceptibility results to these antibiotics, for the future reference

Complicated UTI and Pyelonephritis¶

Background¶

Fever, pyuria, and costovertebral angle tenderness suggest pyelonephritis.
Consider it a complicated UTI if any of the following are present:
- Renal calculi or other obstructive disease, immunosuppressed host, abnormal urological anatomy or physiology (including stents), presence of a urinary catheter
- Malse sex alone does NOT qualify as complicated

Evaluation¶

UA with reflex urine culture
BCx and UCx prior to antibiotics
If there is no pyuria, consider an alternative diagnosis, or proximal ureteral obstruction
- Pyuria is common in the presence of a urinary catheter, kidney stones, urostomy, ileal conduit and other invasive devices, and may not indicate infection

Management¶

Duration: 7-14 days, depending on antibiotic choice
Tailor therapy once/if cultures are available. If no improvement in 48h, consider imaging to rule out complications (e.g., perinephric abscess)

0	1	2
NaN	First Line	Alternative
Outpatient	Ciprofloxacin 750 BID (or 500 BID if bacteremia r/o) x 7d	NaN
Inpatient	- CTX 2g q24h - Cefepime 2g q8h - Meropenem 2g q8h (if h/o or confirmed ESBL w/in last 90 d)	- Ertapenem 1g q24 instead of Meropenem if no Pseudomonas - Ciprofloxacin 750 PO BID (500 PO BID if bacteremia ruled out) OR 400 IV BID (if suscept confirmed)*

*FQ’s have same bioavailability if given PO or IV so oral is preferred

Catheter Associated Urinary Tract Infection (CAUTI)¶

Background¶

Culture growth of > 10 ³ cfu/mL of uropathogenic bacteria + signs or symptoms consistent with infection (without another identified etiology) + indwelling urethral/suprapubic catheter or intermittent catheterization.
- This includes pts with catheters in place during the preceding 48 hours
Duration = greatest risk factor (Increases 3-10% per day of catheterization)
- Other risks: female sex, diabetes, elderly, colonization of catheter bag, poor care
Bacteriuria, foul odor, pyuria, urine appearance and/or bacteriuria alone are not indicative of infection in patients who are otherwise asymptomatic.
Ensure clean sample collected
- Ideally, catheter is removed and midstream sample obtained
- If catheterization required; removal of old catheter and sample taken from new

Management¶

Distinguish uncomplicated vs complicated UTI (see above)
Antimicrobial management:
- Guided by cultures and susceptibilities
- Empiric guidance as per management of uncomplicated/complicated UTI and per prior culture data/susceptibilities when available
- Duration: 7 – 14 days depending on antibiotic, clinical response and whether infection constitutes complicated vs uncomplicated UTI
- Special note regarding Candida UTI management: Candida Is generally not pathogenic
- Presence in urine does not indicate infection (unless perinephric abscess, renal transplant, or complex fistulous disease)
- Fluconazole achieves excellent urinary penetration
- Echinocandins do not, and other azoles are not well studied in UTIs
- If fluconazole resistant Candida cultured or suspected, consult ID
- Susceptibilities are not routinely run on Candida from urine cultures and would need to be requested if concern for true infection.
Catheter management
- At the least, catheters should be replaced at the time of antibiotic initiation (preferably removed)
- Preferably, catheters should be removed
- If catheterization is necessary, intermittent catheterization is preferred over continuous use. Condom catheters and pure wicks also preferred over foley catheter

HIV/AIDS and ART¶

Kathryn Snyder and Quinton Taylor

Background¶

Why is ART important?
- Clear morbidity and mortality benefits across all CD4 counts
- Decreases subsequent infections (both common and opportunistic)
- Decreased HIV related comorbid conditions, viral reservoirs, and transmission
New HIV Diagnosis
- ID consult if patient is not on Rogers ID service (important for initiation, follow up [CCC], social work assistance)
- ART is indicated for all HIV+ patients, regardless of CD4; however, starting ART requires appropriate outpatient follow up
- Lab evaluation:
  - HIV viral load, genotype, and resistance testing
  - T cell subsets (CD4 Count), CBC with differential, CMP, UA
  - HLA*B5701 testing before using abacavir containing regimen
  - QuantiFERON Gold
  - Pregnancy testing
  - Viral hepatitis serologies
  - Toxoplasma serologies
  - Other STI screening (Syphilis, Gonorrhea/Chlamydia)
Timing of ART initiation
- Factors affecting timing of initiation
  - Drug toxicity and interactions, risks for resistance, adherence barriers
  - Treatment of opportunistic infections may delay initiation of ART given associated risk of immune reconstitution inflammatory syndrome (IRIS)
    - Delay ART for several weeks after initiation of therapy for cryptococcal meningitis, tuberculosis, and CMV retinitis
ART plan for overnight admits: okay to continue home ART, special consideration for:
- Patients with hepatic or renal dysfunction may need dose adjustment
- Interactions with other newly initiated medications
- If there is concern for non-adherence, can hold morning dose
- Combination pills may need to be ordered as separate components
Common key regimens for initiation
- Most regimens consist of an NRTI backbone (2 agents) plus a 3^rd agent
- Some dual therapy regimens (such as Dovato@) are non-inferior to standard 3-drug therapy
- Many patients are started on combination pill regimens, including Integrase Inhibitor based regimens: Biktarvy®, Dovato®, Triumeq®, Genvoya®, dolutegravir + Descovy®

Inpatient COVID-19 Management¶

Kathryn Snyder

Background¶

COVID-19 is the novel coronavirus responsible for the ongoing pandemic that started in late 2019. The virus has ongoing mutations resulting in new dominant strains.

Evaluation¶

Please see the most updated VUMC and VA guidance due to frequently evolving recommendations.
Please refer to the hospital’s current maximum oxygen requirement allowed on the floor to ensure patient is appropriately triaged.
Basic admission workup for symptomatic, confirmed COVID-19
- Labs: CBC with diff, CMP, d-dimer, ferritin, CRP, ESR, PT/INR, PTT, procalcitonin, RPP
- Imaging: portable CXR
- Nursing: Strict I/O
- Enhanced precautions (contact, airborne, eye protection)

Management¶

Fluid balance goal slightly net negative to even
Anticoagulation/DVT prophylaxis:
- Please see latest VUMC or VA guidance based on clinical status (supplemental O2 requirements, ICU vs floor, etc.)
Pharmacologic therapies
- Note: Therapies, indications, and contraindications are frequently changing, please see latest VUMC/VA guidelines for specific indications for these medications or others
Remdesivir
- Loading dose 200mg IV x1 then 100mg daily x 4 days
- For use in patients hospitalized for COVID within 7 days of symptom onset
- Contraindications: known hypersensitivity, ALT >/= 10x ULN, high-flow NC, PPV, intubated, or on ECMO
- Monitoring: baseline CBC, INR, q48h CMP
Dexamethasone
- 6mg PO/IV x 10 days; consideration of longer taper if no clinical improvement or persistently elevated CRP
- Contraindications: no hard contraindications, use clinical judgement if concomitant serious bacterial/fungal infection
Antibiotics:
- The incidence of superimposed bacterial infection in the setting of COVID-19 is low
- The majority of patients do not need additional coverage for bacterial pneumonia
- You can use procalcitonin to guide decision
Other pharmacologic therapies include baricitinib (JAK inhibitor), tocilizumab (IL-6 inhibitor) and monoclonal antibodies

Additional Information

Complications and special considerations for COVID-19 patients
- High PE/DVT risk
- Superimposed bacterial PNA
- AKI
- GI symptoms/abnormalities (see GI section on COVID-19)

Joint Infections and Osteomyelitis – VASP¶

Evaluation¶

Blood cultures prior to antibiotics
MRI is the most sensitive and specific imaging modality for osteomyelitis.
Ortho consult for joint fluid aspirate or bone bx; send for culture and send fluid for cell count/differential.

Management¶

Hold antibiotics until culture obtained, if patient is clinically stable
Osteomyelitis is a 6-week treatment course, can consider early transition (at 2-3 weeks) to oral if good bioavailability and susceptibility.
For prosthetic joint infection, procedure/retention of hardware determines duration
First line empiric: Vancomycin + ciprofloxacin 750mg BID
Antimicrobial therapy will ultimately be guided by culture data, ID consult recommended for joint infection treatment due to need for prolonged antibiotic therapy

Pulmonary Infections¶

VASP, Evan Schwartz

Acute Bronchitis¶

Background¶

1-3 wks productive cough, often preceded by URI, may have wheezing/rhonchi
Distinct from chronic bronchitis (>3 mos of consecutive cough x 2 consecutive yrs)
Distinct from PNA (parenchymal consolidation, fever >100.4F, hypoxia, tachypnea)
DDx: COVID-19, post-nasal drip, GERD, undertreated/new asthma, ACE-i induced bradykinin cough, undertreated CHF, acute PE, or new lung cancer
Clinical dx; CXR/labs not necessary unless PNA suspected

Management¶

Supportive: lozenges, cough suppressants (guaifenesin or dextromethorphan), smoking cessation. Consider albuterol inhaler for wheezing
No indication for antibiotics

Influenza¶

Background¶

Dx often clinical w/cough, sore throat, #sputum/nasal discharge, HA, fever, myalgias, and malaise; ± N/V/D. Exam with increased flushing, rarely with lower respiratory symptoms

Evaluation¶

During flu season: Obtain COVID/RPP or dedicated influenza PCR; testing is more accurate if obtained within 96 hour of symptom onset
CXR if concerned for bacterial superinfection

Management¶

Antivirals most effective when given <48 hours from symptom onset; however, recommended to be given if symptomatic despite duration and to all hospitalized patients
Oseltamivir 75mg BID x 5 days, peramivir 600mg IV x 1 (needs renal adjustment), or baloxavir (age ≥12) 40mg once (use 80 mg if >80kg)
Amantadine and rimantadine are no longer used due to emerging resistance

Community Acquired Pneumonia (CAP)¶

Background¶

All PNA that does not otherwise meet criteria for Hospital Acquired Pneumonia (PNA that develops ≥48 hours after hospital admission), Ventilator Associated Pneumonia (PNA that develops ≥48-72 hours after endotracheal intubation), or aspiration PNA
Healthcare-associated pneumonia is no longer a clinical entity per 2016 IDSA guidelines
MRSA Risk Factors: recent history, cavitary lesion, post-influenza bacterial PNA, pts with IDU, severe hypoxemia requiring intubation
Pseudomonas: Double coverage is not indicated in general population; LVQ has 82% sensitivity so not recommended unless isolate proven susceptible

Evaluation¶

Sputum cultures prior to abx, consider BCx in select groups (severe pneumonia, ICU admission, cavitary disease, immunosuppression).
Rule out flu if the right season, COVID-19, consider RVP if it will change management
CURB-65 or PSI can aid in decision between outpatient vs inpatient therapy
- CURB65: Confusion, Uremia (BUN >=19 mg/dL), RR (>30/min), BP(\<90/60 mmHg), Age ≥ 65 If ≥ 2, hospitalization is recommended.

Consider urine pneumococcal Ag, urine Legionella Ag in severe CAP and in certain pts (e.g., neutropenia, asplenia, obstructive lung disease, hyponatremia, diarrhea, or heavy alcohol use); these are performed at reference labs and will take several days to return.
CRP, ESR, and pro-calcitonin have not been shown to reliably improve outcomes; however, pro-calcitonin \< 0.25 suggests against bacterial respiratory infection and antibiotic discontinuation is encouraged
PA/ lateral CXR to evaluate for and localize infiltrate. If immunocompromised, consider CT chest w/o contrast (does not improve outcomes)
- Lobar Consolidation - likely bacterial
- Interstitial Infiltrate - likely atypical vs. viral vs. non-infectious
- Cavitation - concerning for fungal vs. necrotizing vs. mycobacterial

Management¶

Antibiotic Duration: 5-7 days (at least 5 days and improvement with clinical stability)

No MRSA or Pseudomonas suspected

Low Risk\*:

-Amoxicillin 1g TID

High Risk:

-Amoxicillin-clavulanate 875/125 BID + Macrolide

-Cefdinir 300 BID + Macrolide

-Amoxicillin 1g TID + Macrolide

-Levofloxacin 750 daily

CTX 2g q24 + Azithromycin 500 daily OR Levofloxacin 750 daily

MRSA or Pseudomonas suspected

MRSA: Vancomycin OR Linezolid

(if no bacteremia)

Pseudomonas: Cefepime 2g q8h

*No chronic heart, lung, liver, renal disease, DM, alcoholism, immunocompromise

Additional Information¶

MRSA nasal swab has reported negative predictive value for MRSA pneumonia ranging 95% to >99%; consider sending and if negative, discontinue MRSA agent
CTX is generally adequate coverage for aspiration PNA without evidence of abscess, empyema, or cavitary lesion on imaging
Aspiration pneumonia can be confused for aspiration pneumonitis which does not need to be treated with antibiotics. Rapid resolution of leukocytosis and stabilization of vitals suggest aspiration pneumonitis and consideration of stopping antibiotics.
There is low sensitivity of S. pneumoniae to azithromycin (42%) and doxycycline (72%), so these should not be used as monotherapy
Check for drug interactions with linezolid (e.g., SSRI, methadone, methamphetamine use)

Hospital Acquired Pneumonia (HAP) and Ventilator Associated Pneumonia (VAP)¶

Background¶

HAP: Pneumonia that develops >48 hours after admission
VAP: Pneumonia that develops >48 hours after endotracheal intubation

Evaluation¶

Cultures of blood, sputum, endotracheal aspirate and/or bronchoscopy specimen
Consider MRSA nares to help with de-escalation
If there is concern for respiratory viruses: send influenza, COVID, RVP

Management¶

Initially cover for MRSA and Pseudomonas
Antibiotic Duration: 7 days in uncomplicated cases, although specific pathogens (e.g., Pseudomonas) may require longer duration and ID guidance
Consider ID consultation if the patient is not clinically improving on empiric therapy or if an MDR pathogen grows from culture
If no MRSA isolated and pt is improving, consider stopping vancomycin ASAP
There is concern for nephrotoxicity with combination Vancomycin and piperacillin-tazobactam, but data controversial

	MRSA Coverage	Pseudomonas Coverage
First Line	Vancomycin (Pharmacy dosing)	Cefepime 2g q8h OR Piperacillin-tazobactam 3.375 q8h extended infusion OR Ceftazidime 2g q8h
Alternative	Vancomycin allergy: Linezolid 600 mg PO q12h	True PCN allergy: Aztreonam 2g q8h

Skin and Soft Tissue Infection (SSTI) - VASP¶

Cellulitis¶

Background¶

DDx: erysipelas, pyomyositis, necrotizing fasciitis, osteomyelitis, venous stasis, shingles, gout
Pathogens: Streptococcus species: Group A (most common), B, C, G, Staphylococcus aureus (including MSSA and MRSA)
- Non-purulent, lymphangitis, or erysipelas? Think Streptococcus
- - Purulence (abscess or boil)? Think Staphylococcus
Unique clinical scenarios and associated organisms/organisms to consider:
- Dog/cat bite: Pasteurella multicoda, Capnocytophaga canimorsus
- Human bite: Eikenella corrodens, oral anaerobes, S. aureus
- Fresh water exposure: Aeromonas hydropholia, Plesiomonas shigelloides
- Saltwater exposure: Vibrio vulnificus
- Neutropenia, presence of ecthyma: Gram negatives (Pseudomonas aeruginosa)
- Immunocompromised: Fungal (Candida spp, Cryptococcus), Nocardia, non-tubercular mycobacteria)
- Burn patients: Pseudomonas, Acinetobacter, Fusarium

Evaluation¶

Outline border of erythema and obtain urgent surgery consultation if rapid spread of infection, crepitus, air in tissues or pain dramatically out of proportion to exam
Blood cultures (BCx): ONLY needed if systemic signs/symptoms of infection or immunocompromised (most pts will not need BCx or imaging)
Ultrasound for underlying abscess
CT/MRI w/contrast: if necrotizing fasciitis, pyomyositis or osteomyelitis suspected
Bilateral lower extremity cellulitis is RARE and warrants further consideration of other non-infectious etiologies
Elevation test: if erythema improves after elevating leg above the level of the heart for 1-2 minutes, less likely to be infectious cellulitis

Management¶

Antibiotics for 5 days for uncomplicated; can extend to 10-14 days if little to no improvement, more extensive/serious infection, or if immunosuppressed
Typically improvement is not seen until >48 hours of antibiotics, usually longer
Provide anti-Staphylococcal antibiotics for purulent cellulitis in addition to I&D, if abscess present
Clinical appearance may often appear to worsen initially despite adequate therapy
Always elevate the extremity for more rapid clinical improvement!

Mild/Moderate

(Outpatient)

Cephalexin 500 QID

Amoxicillin 500 TID

Cefadroxil 1g BID

Cephalexin 500 QID

Cefadroxil 1g BID

Dicloxacillin 500 QID

\*Clindamycin 300-450 q6

TMP/SMX 1-2 DS tabs BID

Doxycycline 100 BID

Severe (Inpatient)

Cefazolin 2g q8h

CTX 2g q24h

Cefazolin 2g q8h

Nafcillin 2g q4h

Vancomycin

\*Consider for PCN allergy; check antibiogram (VUMC vs VA) for Staph sensitivities; clindamycin should NOT be used for strep coverage

Necrotizing Fasciitis¶

Background¶

Infection of the deeper soft tissues that causes necrosis along the muscle fascia and overlying subcutaneous fat that is rapidly progressive and lethal if not addressed
Clinical cues include rapid spread, pain out of proportion to exam, crepitus and hemorrhagic bullae

Evaluation/Management¶

SURGICAL EMERGENCY!
- STAT consult to surgical service for emergent debridement (generally EGS vs ortho)
- Imaging does NOT rule out necrotizing fasciitis and should not delay these consultations
ID consult
- Blood cultures, but this should not delay antibiotic administration
- Contact and droplet precautions x first 24h of abx therapy; after this, contact precautions only if draining or contained wounds
- Vancomycin + either piperacillin-tazobactam 3.375g IV q8h extended infusion OR cefepime 2gm IV q8h + clindamycin 600mg-900mg IV q8h (for antitoxin effects)

Ended: Infectious diseases

Nephrology ↵

Acid-Base¶

Ned Hardison and Trey Richardson

Background¶

Abnormal serum H+ concentrations lead to impaired cellular function (cardiac arrest, vasodilation, decreased response to catecholamines), electrolyte abnormalities (e.g. hypo- and hyperkalemia, hypo- and hypercalcemia), impaired glucose metabolism, impaired drug metabolism, and a whole host of other complications that translate to increased morbidity and mortality
ABG/VBG reference ranges:
- pH = 7.36-7.44 (~7.32-7.40)
- PCO2 = 36-44 mmHg
- pO2: 60-100 mmHg
- HCO3 = 22-26 mEq/L
Useful formulas
- pH on ABG = VBG pH + 0.035
- Anion Gap= Na-(Cl+Bicarb)
- Normal Anion Gap= 12-14
- Calculated Osmolarity= 2[Na]+ ([Glucose]/18) + ([BUN]/2.8)
- Osmolar gap= Measured osmolarity – Calculated osmolarity
- Winter’s formula for respiratory compensation for AGMA: expected pCO2 = 1.5 (serum bicarb) +8 ± 2
- Shortcut: Expected p**C**O₂ ≈ last two digits of pH

General Approach to Acid-Base Derangements¶

Step 1: Determine if the patient is acidemic or alkalemic (look at the pH)
Step 2: Determine the primary disorder (metabolic or respiratory)
Step 3: Calculate anion gap (see section below)
Step 4: Is there appropriate compensation?
Step 5: Evaluate for secondary disorders

Anion Gap Metabolic Acidosis¶

Background¶

Na+ is the predominant cation in normal plasma. Cl- and HCO3- are the predominant anions. There are anions that are not directly measured (e.g. most binding globulins, immunoglobulins, clotting factors, and other proteins). These unmeasured anions are responsible for the normal anion gap of ~12 meq/L. When there are extra unmeasured anions within the plasma, the anion gap increases

Differential¶

GOLDMARK: Glycols, oxyproline (acetaminophen metabolite), L-lactate, D-lactate, methanol, ASA, renal failure/uremia, ketoacids

Evaluate for secondary disorders¶

Corrected bicarbonate
- Corrected H**C**O₃ = patient’s H**C**O₃ + (patient’s anion gap - 12)
  - Corrected H**C**O₃ > 26, coexisting metabolic alkalosis,
  - Corrected HCO3 \<22 coexisting non-AG metabolic acidosis

Osmolar Gap¶

If there is an anion gap, it is worthwhile to always calculate an osmolar gap. You will be surprised the number of toxic ingestions you catch this way

Non-anion gap metabolic acidosis (NAGMA)¶

There are two places from which people can waste bicarbonate- the kidneys and the gut
- The urine anion-gap, which corresponds to unmeasured urinary NH4+ (primary means of renal acid excretion), can differentiate between the two
- Urine anion gap = Unmeasured cations (NH4+) – unmeasured anions = UNa + UK – UCl
- Positive value-> low NH4+-> renal losses
  - RTA
  - Carbonic anhydrase inhibition: acetazolamide, topiramate
  - Adrenal insufficiency
  - Normal saline infusion
- Ne-GUT-ive value->high NH4+->kidneys working appropriately-> GI losses
  - Diarrhea
  - Pancreatic fistula
  - Ureterosigmoidostomy
Caveat: Proximal RTA has a normal distal urine acidification and has a negative urine AG

Managing Metabolic Acidosis¶

Lactic acidosis is the most common cause of anion gap metabolic acidosis that we encounter
In general, avoid use of bicarbonate to treat lactic acidosis
Remember: H⁺ + HCO3^- \<-> H2CO3 \<-> H2O + CO2. While administering bicarbonate will transiently improve pH, carbonic acid will eventually form and ultimately worsen acidemia
In acute NAGMA, reasonable to give bicarbonate when bicarb \<12 or pH \<7.1-7.2
Pay close attention to other electrolyte levels, especially potassium as it shifts back into cells

Metabolic Alkalosis¶

Background¶

Metabolic alkalosis occurs as a primary disorder or as compensation for respiratory acidosis. A thorough history and exam can usually clarify which of these two scenarios is occurring
In order for metabolic alkalosis to occur, there has to be both an inciting phase (e.g. volume depletion) and a maintenance phase (e.g. hypochloremia or hypokalemia)

Presentation¶

Most symptoms of metabolic alkalosis (confusion, nausea, vomiting, tremors) occur as a result of other electrolyte abnormalities (hypocalcemia, hypokalemia)
Serum pH of >7.55 is likely the threshold where symptoms will develop

Causes¶

Saline responsive (e.g. hypochloremia)
- True volume depletion
- NG suction/Nausea/vomiting
- Diuretic use
Saline refractory
- Hypokalemia
- Milk-Alkali syndrome
- Mineralocorticoid excess states
- Bartters Syndrome
- Gitelman’s Syndrome

Treatment¶

Saline Responsive/Hypochloremia
- If volume deplete, then normal saline is treatment of choice
- If alkalosis develops in setting of diuresis, then make sure replacing KCl and consider acetazolamide
Saline refractory
- Hypokalemia- replenish potassium stores
- Hyperaldosteronism- covered in more detail in the endocrinology section
- Bartter syndrome and Gitelman syndrome - replace electrolytes and refer to nephrology

Kidney Transplant Rejection¶

Background¶

Rejection is divided into acute vs chronic and T-cell mediated or antibody mediated
- Pathologists can determine the type of rejection and the chronicity by observing the structures that are acutely involved (e.g. tubulitis, glomerulitis, arteritis, and capillaritis) as well as the time course of involvement (e.g. presence of fibrosis)
- Structures exhibiting fibrosis represent chronic rejection that is unlikely to respond to treatment, whereas acute inflammation may be amenable to acute therapies
- This section will focus on acute rejection since this is the clinical entity we will most likely manage while on the wards

Acute Rejection¶

Acute T cell mediated rejection
- Infiltration of the graft by lymphocytes and inflammatory cells characterized by tubulitis, interstitial inflammation, and arteritis (on occasion)
- Treatment:
  - High dose glucocorticoids (methyl prednisolone) is first line (~ 5 days)
  - Thymoglobulin (polyclonal Ig anti-T cell)
    - Use depends on severity of rejection
    - Indicated if Cr fails to improve after steroids
    - T cell subsets are measured during treatment until depleted
  - Tacro target levels are reset to ~8-10 if treated for acute T cell mediated rejection
Acute antibody mediated rejection (ABMR)
- Donor specific antibody mediated rejection characterized by glomerulitis, peri-tubular capillaritis (microcirculation inflammation), complement deposition (C4d staining), and presence of DSA
- Treatment = B-cell depletion therapy
  - IV methyl prednisone 500 mg IV x 3-5 days
  - Plasmapheresis (If with high titers of DSA)
  - IVIG 2 g/kg (max 140 g)
  - Rituximab 375 mg/m2

Acute Kidney Injury (AKI)¶

Terra Swanson

Background:¶

Definition based on 2012 KDIGO Guidelines:
- Rise in serum creatinine (sCr) > 0.3 mg/dL within 48 hours, or increase > 1.5 x baseline in 7 days
- Urine volume \<0.5 cc/Kg/H for at least 6 H

Framework for AKI¶

Pre-renal/hemodynamic AKI:
- Volume depletion: GI losses, hemorrhage, burns, critical illness increased insensible losses
- Decreased effective circulating volume: cardiorenal, hepatorenal, hemodynamic effects of ACEi/ARB
- Afferent arteriole constriction [NSAIDs, Iodinated contrast]
- Renal vein thrombus
Intra-renal: Glomerular, tubular, or interstitial diseases
- ATN = Most common form of intrinsic AKI. Can be Ischemic or toxic
  - Toxins can be broken down further into endogenous (e.g. rhabdo) and exogenous (e.g. drugs)
- Acute Interstitial Nephritis (AIN): Usually drug induced (NSAIDs, PPIs, beta lactam abx)
- Glomerulonephritis
- Other causes:
  - Crystalline nephropathy: IV acyclovir, tumor lysis, ethylene glycol
  - Small vessel disease: MAHA, TTP, HUS
  - Large vessel disease: Aortic dissection, renal artery stenosis
Post-renal: Can occur at any level of the GU system
- Ureteral: stones, external compression (malignancy, LAD, abscess)
- Bladder: neurogenic bladder, malignancy, obstructing blood clot
- Urethra: BPH, prostate cancer, prostatitis
Pre-renal azotemia and acute tubular necrosis comprise the majority of inpatient acute kidney injuries

Evaluation¶

History and volume exam
Labs: CMP, urinalysis, protein/Cr ratio
500cc-1L IV fluid challenge: If sCr improves to baseline in \<48H then the insult was likely pre-renal. If not, then look for other etiologies
Evaluate for obstruction: I/O cath, Foley, Post Void Residual >250 cc
Who needs a renal ultrasound?
- No obvious cause of AKI
- Abrupt oliguria or anuria (think renal vein thrombus or obstruction)
- High suspicion for bladder outlet obstruction (PVRs might give you same data)
- Add doppler to evaluate for renal artery stenosis (or if working up resistant hypertension)
Urine Electrolytes
- FENa \<1% or FEUrea \<33% (if on diuretics) suggest pre-renal physiology
- Caveat, only validated in oliguric patients and more difficult to interpret after fluids, diuretics, etc
- Not needed in the initial work-up of all patients with AKI. If high suspicion for pre-renal etiology, trial fluid challenge and assess response first
Urine sodium can be used to assess Na avidity: UNa > 40 suggests ATN and UNa \< 20 suggests pre-renal

Management¶

All causes
- Minimize fluctuations in blood pressure
- Consider holding anti-hypertensive medications, especially ACEi/ARB (remember to determine plan to resume at/after discharge)
- Avoid unnecessary nephrotoxins
- Dose-adjust medications for changing renal function
Pre-Renal
- True volume depletion- Intravenous volume expansion
- Cardiorenal syndrome- Decongestion/diuresis
- Hepatorenal syndrome- See Hepatology section for more information
Post-renal
- Relieve Obstruction: I/O cath, foley, Urostomy (Urology), percutaneous nephrostomy (IR)
- Monitor for post-obstructive diuresis
Intra-renal
- ATN- supportive care, monitor for post-ATN diuresis. If delayed recovery, may need outpatient dialysis
- Glomerulonephritis- Consult AKI service for assistance with biopsy and selecting immunosuppressive agents if needed
- AIN- Review meds, consult nephrology for possible biopsy and recommendations for steroids
Monitor for renal recovery
- Suspect concomitant ATN if sCr declines with volume expansion, diuresis, or relief of obstruction but remains a few points above baseline
When to consult Nephrology
- Urgent indication for dialysis (see “Renal Replacement Therapy”)
- Abrupt anuria
- Cr worsening or urine output inadequate w/o clear cause
- Need for kidney biopsy

Additional Information¶

Rhabdomyolysis: UA positive for blood but no RBCs on microscopy
- Toxic damage due to myoglobin
- Serologic markers of muscle injury: elevated CK, AST>AST with normal ALK Phos
- Fluids adjusted to urine output goal of 200-300 mL/hr until CK declines
  - Consider isotonic bicarb for initial 1-2L of IVF urine alkalinization to reduce precipitation
- Avoid calcium repletion for hypocalcemia unless symptomatic
Post-obstructive diuresis
- Necessary process to clear accumulated uremic toxins
- Replace ~50% of urine output to prevent pre-renal azotemia
- Monitor calcium, phosphorus, and magnesium in severe post-obstructive diuresis

Contrast Induced AKI (CI-AKI)¶

Trey Richardson

Background¶

When someone develops an AKI do your due diligence and evaluate for the usual causes of AKI, regardless of when they were given contrast
Mechanism of injury: direct toxic effect leading to tubular necrosis and arteriolar vasoconstriction leading to medullary ischemia

KDIGO Criteria for CI-AKI:¶

sCr increase by 0.5mg/dl or 25% increase in sCr from baseline 48 H after radiologic procedure where intravenous contrast was administered

Who is at risk for CI-AKI?¶

Normal kidney function: incidence of CI-AKI is 1-3%
Pre-existing CKD: Incidence of CI-AKI may be as high as 20% in patients with CKD 4-5
Other risk factors include: diabetes, heart failure, and advanced age
No real sCr or eGFR threshold below which iodinated contrast is contraindicated, especially in patients for whom imaging will alter management (e.g. acute stroke, PE, STEMI)

Risk reduction strategies¶

Volume expansion with isotonic crystalloid (PRESERVE Trial) in patients with AKI or eGFR \<30 ml/min/1.73m^2 who are clinically hypo or euvolemic
- 1cc/kg/hr for 6-12 hours before/during and 6-12 hours after the procedure in patients at high risk for CI-AKI. This rate can be decreased based on the risk for hypervolemia
If the patient is volume overloaded, they probably should not receive volume expansion prior to a contrasted study
Never delay a necessary procedure out of concern for worsening renal function. If in doubt, talk to nephrology

Iodinated contrast in CKD-5/ESRD patients¶

Iodinated contrast does not need to be dialyzed immediately
Avoid giving if you are trying to preserve residual kidney function in ESRD on PD

Gadolinium contrast for MRI¶

Contraindicated in any AKI or if GFR \<30 in CKD given risk of nephrogenic systemic fibrosis.

Approach to Chronic Kidney Disease¶

Terra Swanson

Definition of CKD¶

Decreased kidney function or one or more markers of kidney damage for 3 or more months
History of kidney transplant
GFR \< 60; Staging helps risk-stratify pts likely to progress or develop complications of CKD
- CKD IIIa: eGFR 45-60
- CKD IIIb: eGFR 30-44
- CKD IV: eGFR 15-30
- CKD V: eGFR \< 15
Markers of kidney damage
- Albumin/Cr ratio
  - Mild: 0-30 mg/g
  - Moderate: 30-300 mg/g
  - Severe: >300 mg/g
Urine sediment: RBC casts, WBC casts, oval fat bodies or fatty casts, granular casts
Electrolyte derangements
Abnormalities on histology
Structural abnormalities: (cysts, hydronephrosis, scarring, masses, renal artery stenosis)

When to refer to nephrology clinic¶

eGFR \< 45
Persistent urine albumin/creatinine ratio > 300 mg/g
Urine protein/creatinine ratio greater than 500 mg/g
Rapid loss of kidney function (> 30% decline over 4 months)
Hematuria not 2/2 urologic condition or if there are RBC casts on UA
Inability to identify presumed cause of renal dysfunction
Difficult to manage complications (hyperkalemia, anemia, bone-mineral disease, HTN)
Confirmed or presumed hereditary kidney disease (PCKD suspected)

Complications of CKD¶

Imbalance of water homeostasis
- As renal mass declines the ability to both concentrate and dilute the urine is impaired
- This manifests as hyponatremia (no end-organ to respond to ADH) and edema
- Treat this with water restriction, diuretics or, eventually, ultrafiltration

Metabolic acidosis¶

Correcting serum bicarbonate to a goal of 23-30 meq/L slows decline in renal function and protects against bone-mineral complications of chronic metabolic acidosis
Can calculate bicarbonate deficit to estimate dose of bicarbonate
If bicarb \< 22, consider:
- Sodium bicarb 650 mg TID (8mEq bicarb per 650mg tablet) up to 5850mg/day (70 mEq or 3 tabs TID)
- Sodium citrate (Bicitra): 1mL = 1 mEq * Careful in cirrhosis since citrate cannot be metabolized
- Baking soda (sodium bicarbonate): 1 teaspoon = 59 mEq HCO3 (careful of Na load)

HTN in CKD¶

Goal BP \< 120/80 (Class 2B recommendation) based on SPRINT trial, ACC/AHA 2017, and KDIGO 2021 guidelines
All comers: Diet (e.g. DASH) and lifestyle modifications
CKD without albuminuria or DM:
- Start pharmacotherapy based on ASCVD risk as well as risk for other target organ damage
CKD with moderate to severe albuminuria w/ or w/out DM
- ACEi or ARB titrated to maximally tolerated dose (Class 1B recommendation)
- Thiazide-like diuretics (see CLICK trial for chlorthalidone in advanced CKD)
- Loop diuretics can assist with volume driven HTN in patients with CKD 4-5
HTN in kidney transplant
- CCBs or ARBs are first line (Class 1C recommendation)
Consider stopping ACE-i/ARB if:
- GFR declines >30% over 4 months. Consider evaluation for renal artery stenosis
- K > 5.5 despite low K diet, optimizing dose of diuretics, or adding K-binders

Anemia in CKD¶

Multifactorial: decreased EPO production, impaired iron absorption, uremic toxins suppressing bone marrow, loss of blood in dialysis circuit, and from GI AVMs
Indications for iron supplementation in non-dialysis patients:
- ALL patients with TSAT \<20% and ferritin \<100 ng/mL
- Patients with Hb \<13 and TSAT \<30% and ferritin \<500 ng/mL
- Can start with PO supplementation (see Anemia section). Reassess iron levels in 1-3 mos; if not appropriately ↑, consider IV iron repletion
Dialysis patients:
- IV Iron preferred method of repletion for HD patients with
  - TSAT \< 20% and ferritin \< 200
  - TSAT \<30% and ferritin \<500 AND with Hb \< 10 OR are on EPO
Dosing: usually administered at HD sessions - 125 mg ferric gluconate at consecutive HD sessions x 8 doses - 100 mg iron sucrose at consecutive HD sessions x 10 doses - Ferumoxytol 510mg at the end of two HD sessions 1-4 weeks apart
Indications for EPO
- Pts w/ Hb \<10 who are not iron deficient (ferritin >500) or who’s anemia persists despite adequate iron repletion

Hyperkalemia (Goal K \< 5.5)¶

Patients with diabetic nephropathy (T4 RTA) and CKD 5-ESRD are at the highest risk
Strategies to mitigate hyperK
- Low K diet (\< 40-70 mEq/day or 1500-2700 mg/day)
- Loop diuretics
- GI cation exchangers
  - Patiromer (Veltassa): binds K in colon in exchange for calcium
  - Sodium zirconium cyclosilicate (Lokelma): binds K throughout intestine in exchange for sodium and H+
  - Do not use Kayexelate as chronic therapy
Treat metabolic acidosis

Mineral bone disease in ESRD¶

Avoid calcium supplementation in mild or asymptomatic hypocalcemia
Replace vitamin D to >20 (weak evidence)
Phos goal \< 5.5
- Sevelamer: use lowest dose effective to achieve Phos \< 5.5
  - Phos 5.5-7.5: initial dose 800 TID with meals
  - Phos 7.5-9.0: initial dose 1200-1600 TID with meals
  - Phos > 9: initial dose 1600 TID
  - Can titrate dosing by 400 to 800 mg per meal at 2-week intervals
- Restrict dietary phos to 900 mg/day
PTH goal in CKD3: 2x ULN
PTH Goal in ESRD: 2-10x ULN

Diabetes in CKD¶

Individualize A1C goals. Both the ADA and VA-DOD have guidelines for selecting A1C targets
Treatment:
- Metformin remains first-line but should be dose-reduced based on eGFR
  - eGFR > 45: Maximum daily dose of 2000mg/day (1000mg bid)
  - eGFR \< 45: Reduce max daily dose to 1000mg/day (500mg bid)
  - eGFR \< 30: Discontinue if high risk for volume mediated AKI/chronically ill
- SGLT-2 inhibitors for patients with eGFR > 30 reduces progression to ESRD and death from renal or cardiovascular cause (Evidence: DAPA-CKD, CREEDENCE)
- Finerenone (non-steroidal MRA)- would ask nephrology for help if considering this option since relatively new and increased risk for hyperkalemia. (Evidence: FIDELIO)

Dialysis initiation¶

Early (CKD3a or 3b) referral to nephrology has better outcomes
Uremic symptoms: fatigue, sleep disturbance, N/V, decreased appetite, dysgeusia, itching, hiccupping
Refractory hyper K
Refractory hypertension
Plot your patient’s eGFR using the graph function in EPIC or CPRS to determine trajectory (normal age-related decline after age 60 is ~ 1ml/min/m2)

Hematuria¶

Laura Binari/Patrick Steadman

Background¶

Definition: 3 urinalyses with three or more RBC/hpf; 1 urinalysis with 100 RBC/hpf or gross hematuria (1 cc blood/L urine can induce color change)
Causes:
- Can be transient (exercise-induced, menses, trauma)
- Concurrent pyuria/dysuria: consider urinary tract infection or bladder malignancy
  - Malignancy risk factors: male sex, age > 50, smoking Hx, exposures to benzene/aromatic amine, cyclophosphamide, indwelling foreign body, pelvis irradiation, chronic UTIs, heavy NSAID use, urologic disorders (nephrolithiasis, BPH)
- Recent URI: think infection related glomerulonephritis, IgA, vasculitis, anti-GBM
- Positive Family Hx of Hematuria: consider PKD, Sickle Cell Disease
- Bleeding from other sites: think inherited/acquired bleeding disorder, anticoagulation
- Unilateral Flank Pain: Ureteral calculus, renal malignancy, IgA Nephropathy

Glomerular	Extraglomerular (Non-Glomerular Source)
Glomerular	Kidney	Ureter/ Bladder	Prostate/ Urethra	Other
IgA Nephropathy IgA Vasculitis	Pyelo	Cystitis	BPH	Exercise-Induced
Lupus Nephritis	Renal Cell Carcinoma	Urothelial Malignancy	Prostate Cancer	Bleeding Diathesis
Infection-related glomerulonephritis	PKD	Nephrolithiasis	TURP	Meds (AC)
Anti-GBM Disease (Goodpasture’s)	Sickle Cell Papillary Necrosis	Ureteral Stricture	Urethritis (STI)	Menses
ANCA-associated	Malignant HTN	Hemorrhagic Cystitis (chemo/rads)		TB Schistoso-miasis
Genetic (Thin Basement Membrane Nephropathy/Alport Syndrome)	Arterial embolism Vein thrombus	Traumatic Foley/procedure

Evaluation

Step 1: Confirm the presence of hematuria
- Dipstick positive heme: urinary RBCs (hematuria), free myoglobin or free hemoglobin
- Centrifuge the urine
  - Red sediment -> true hematuria (urinary RBCs)
  - Red supernatant +
    - Positive dipstick: myoglobulin or hemoglobin
    - Negative dipstick porphyria, Pyridium, beets, rhubarb, or ingestion of food dyes

	Glomerular	Extraglomerular
Color (if gross hematuria)	Red, Cola, Smoky	Red/Pink
Clots	Absent	Present/Absent
Proteinuria	May be >500 mg/day	\<500 mg/day
RBC morphology	Dysmorphic RBCs present	Normal (isomorphic)
RBC casts	May be present	Absent

Step 2: Determine if there is a GLOMERULAR or NON-GLOMERULAR source of bleeding
- Glomerular Bleeding:
  - Isolated Hematuria: Differential includes IgA Nephropathy, thin BM dx, Alport’s
  - Nephritic syndrome (new proteinuria, pyuria, HTN, edema, rise in Cr): post-infectious GN, MPGN, ANCA vasculitis, Goodpasture’s, lupus nephritis
  - Workup: anti-GMB, anti-DNase/ASO, ANA, ANCA, C3, C4, cryo, Hep B & C, HIV
  - Indications for Renal Biopsy: glomerular bleeding + risk factors for progressive disease, including albuminuria > 30 mg/day, new hypertension > 140/90 or significant elevation over baseline BP, rise in serum creatinine
- Extraglomerular Bleeding (Imaging Section)
  - If historical clues suggest nephrolithiasis, start with non-con CT A/P
  - Gross Hematuria otherwise should be evaluated with CT A/P w/ and w/o contrast (CT urography); consult urology for cystoscopy (often done as outpatient referral)
  - If clots are passed, more likely to be secondary to lower urinary source, and if a high burden of clots poses a risk of obstruction (urologic emergency)
  - If extraglomerular bleeding with clots: hematuria catheter needs to be placed ASAP (2 valve catheter, 20-24 Fr (!); page urology if nursing unable to obtain)
CT Urography is more sensitive than IV pyelogram for renal masses and stones.
Prefer Renal and Bladder Ultrasound in pregnant patients
All pts w/gross hematuria that is non-glomerular in source, in whom infection has been ruled out, warrant cystoscopy. Additionally, all patients with clots need cystoscopy

Hypercalcemia¶

Rebecca Choudhry and Trevor Stevens

Background¶

Total serum Calcium >10.5
Most (99%) Ca+2 is anhydrous and stored in bone. The remaining 1% is 60% bound (mostly to albumin), and 40% ionized and able to exert a physiologic effect
Remember, there is an inverse relationship between pH and Ca2+. As pH declines, serum Ca increases due to H+ binding to albumin and releasing Ca2+
Don’t forget to correct calcium level if hypoalbuminemia (or check ionized calcium level),
- Corrected Ca2+ = ((Normal albumin – Patient’s albumin) x 0.8)) + Patient’s Ca2+
  - This equation Is less reliable at very low albumin

Presentation¶

Ca+2 > 12 can cause shortened QT interval, 2^nd and 3^rd degree heart block, ventricular arrhythmias, and ST elevations mimicking MI
Severe manifestations uncommon at Ca+2 \<14
“Stones, bones, thrones, belly groans, and psychiatric overtones”
- Bone pain
- Polydipsia/polyuria- due to nephrogenic DI
- Nausea/constipation
- Depressed mood/cognitive impairment
- Decreased level of consciousness

Evaluation¶

Measure PTH
- Normal or ↑ PTH
  - Primary hyperparathyroidism: ↑ Ca+2 and ↓ PO4-3
  - Tertiary hyperparathyroidism (autologous secretion of PTH in CKD/ESRD)
  - Familial hypercalciuric hypercalcemia (often asymptomatic, no treatment required).
  - Li toxicity
- ↓ PTH
  - Humoral hypercalcemia of malignancy (PTHrP)
  - Malignancy (boney metastases)
  - Excess vitamin D intake
  - Granulomatous disease: 1,25 dihydroxy vitamin D, 25 hydroxyvitamin D, or ACE level
  - Milk-alkali syndrome
  - Medications (classically HCTZ)
  - Thyrotoxicosis
  - Adrenal insufficiency

Management¶

If Ca+2 \< 12 and asymptomatic
- Encourage PO hydration
- Normal saline if hypovolemic
- Evaluate for underlying cause
If Ca+2 > 12 with symptoms or Ca > 14
- Trend Ca q8 hrs, EKG, monitor on telemetry; strict I/Os ± foley catheter
- Volume expansion w/ NS bolus followed by continuous infusion at ~ 200cc/hr
  - Goal UOP 100-150cc/hr
- Add loop diuretic (Lasix) once patient is volume expanded
- Bisphosphonates
  - Zoledronic acid 4mg IV (EGFR >60), Pamidronate 90mg IV (EGFR 15-60)
If Ca+2 >14 or neurologic symptoms, consider subq (not intranasal) calcitonin
- VUMC: requires approval from an oncology or endocrine attending
- Tachyphylaxis after ~48H
Additional Information
- In CHF pt, consider early addition of a loop diuretic, especially if volume overloaded
- In ESRD pt with hypercalcemia (rare), patient with oliguric AKI not responsive to IVF, or pt with severely elevated Ca 16-18, consult endocrine and nephrology early
- In pts with sarcoidosis or lymphoma, consider glucocorticoids

Hyperkalemia¶

Mengyao Tang and Amanda Morrison

Background¶

Causes:
- Cellular shifts: Acidemia, Rhabdomyolysis, TLS, beta blockade
- Aldosterone deficient states: T4 RTA, Primary adrenal insufficiency
- Decreased distal tubular delivery: Volume depletion
- Decreased clearance: AKI, CKD, ESRD
- Excessive intake
- Medication-related: ACEi, ARB, MRA, NSAIDs, TMP/SMX, digoxin, heparin
Pseudo-Hyperkalemia: hemolysis, severe leukocytosis
Symptoms are rare, but usually manifest as cardiac dysrhythmias

Evaluation¶

Confirm hyperkalemia with repeat BMP
Check EKG for hyperkalemic changes (sensitivity for EKG findings in hyper K is poor)
- K+ 5.5-6.5: peaked T waves, prolonged PR interval
- K+ 6.5-8: prolonged QRS, loss of P wave, ST elevation, ectopic beats
- K+ >8: sine wave pattern, asystole, PEA, VF

Management¶

If EKG changes or signs of instability
- Calcium gluconate 1g IV (effective within 3-5 min)
  - Stabilizes cardiac membrane for ~60mins
  - SHOULD BE REPEATED HOURLY while hyperkalemic
Shift K+ (temporizing measures)
- D50 w/ regular insulin 10 units (can order using Adult Hyperkalemia order set in epic)
  - Use 5 units if there is renal impairment
  - Lasts for 4-6hrs (can be longer in renal impairment)
Correct acidosis- Consider using isotonic bicarb
Beta Agonists (e.g. high-dose albuterol nebulizer); lasts 2-4 hrs
- Note that typical albuterol nebulizer is 2.5mg, need 10-20mg to have an effect
Increase K+ Excretion
- Loop diuretic- if the kidneys work, use them
  - If there is