Pocket Medicine 7th Edition 2020 PDF

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Uploaded by MEDBOOKSVN.ORG Senior Acquisitions Editor: Sharon Zinner Development Editor: Ashley Fischer Production Project Manager: Sadie Buckallew Editorial Coordinator: Ingrid Greenlee Manufacturing Coordinator: Kathy Brown Design Coordinator: Stephen Druding Prepress Vendor: S4Carlisle Publishing Services Copyright © 2020, 2017, 2014, 2011, 2008, 2004, 2000 by Wolters Kluwer All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at [email protected], or via our website at shop.lww.com (products and services). 10 9 8 7 6 5 4 3 2 1 Printed in Mexico Library of Congress Cataloging-in-Publication Data ISBN-13: 978-1-975142-37-7 ISBN-10: 1-975142-37-3 eISBN: 978-1-975142-39-1 Library of Congress Control Number: 2019908668 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. shop.lww.com Uploaded by MEDBOOKSVN.ORG  CONTENTS Contributing Authors Foreword Preface CARDIOLOGY Rachel Frank, Shilpa Sharma, Nino Mihatov, Nilay Patel, Marc S. Sabatine, Michelle L. O’Donoghue Electrocardiography Chest Pain Noninvasive Evaluation of CAD Coronary Angiography and Revascularization Acute Coronary Syndromes PA Catheter and Tailored Therapy Heart Failure Cardiomyopathies Valvular Heart Disease Pericardial Disease Hypertension Aortic Aneurysms Acute Aortic Syndromes Arrhythmias Atrial Fibrillation Syncope Cardiac Rhythm Management Devices Cardiac Risk Assessment for Noncardiac Surgery Peripheral Artery Disease PULMONARY Miranda Theodore, Jason Maley, Walter J. O’Donnell Dyspnea Pulmonary Function Tests Asthma Anaphylaxis Chronic Obstructive Pulmonary Disease Solitary Pulmonary Nodule Hemoptysis Bronchiectasis Cystic Fibrosis Interstitial Lung Disease Pleural Effusion Venous Thromboembolism Pulmonary Hypertension Respiratory Failure Mechanical Ventilation Acute Respiratory Distress Syndrome Sepsis and Shock Toxicology Lung Transplant GASTROENTEROLOGY Stephanie M. Rutledge, Emily Walsh Lopes, Lawrence S. Friedman Esophageal and Gastric Disorders Gastrointestinal Bleeding Diarrhea Dysmotility & Nutrition Disorders of the Colon Inflammatory Bowel Disease Intestinal Ischemia Pancreatitis Abnormal Liver Tests Hepatitis Acute Liver Failure Cirrhosis Hepatic Vascular Disease Ascites Biliary Tract Disease NEPHROLOGY Alexander Blair, Harish Seethapathy, Andrew S. Allegretti Acid-Base Disturbances Sodium and Water Homeostasis Potassium Homeostasis Renal Failure Glomerular Disease Urinalysis Nephrolithiasis HEMATOLOGY-ONCOLOGY Melissa Lumish, Arielle Medford, Tanya E. Keenan, Harshabad Singh, Jean M. Connors, Daniel J. DeAngelo, David P. Ryan Anemia Disorders of Hemostasis Platelet Disorders Coagulopathies Hypercoagulable States Disorders of Leukocytes Transfusion Therapy Myelodysplastic Syndromes Myeloproliferative Neoplasms Leukemia Lymphoma Plasma Cell Dyscrasias Hematopoietic Stem Cell Transplantation Lung Cancer Breast Cancer Prostate Cancer Colorectal Cancer Pancreatic Tumors Hepatocellular Carcinoma (HCC) Oncologic Emergencies Chemotherapy & Immunotherapy Side Effects INFECTIOUS DISEASES Alison C. Castle, Kristen Hysell, Kimon C. Zachary Pneumonia Fungal Infections Infections in Immunosuppressed Hosts Uploaded by MEDBOOKSVN.ORG Urinary Tract Infections Soft Tissue and Bone Infections Infections of the Nervous System Bacteremia & Endocarditis Tuberculosis HIV/AIDS Tick-Borne Diseases Fever Syndromes ENDOCRINOLOGY Caitlin Colling, Armen Yerevanian, Michael Mannstadt Pituitary Disorders Thyroid Disorders Adrenal Disorders Calcium Disorders Diabetes Mellitus Lipid Disorders RHEUMATOLOGY Isaac D. Smith, Mazen Nasrallah, Robert P. Friday Approach to Rheumatic Disease Rheumatoid Arthritis Adult-Onset Still’s Disease & Relapsing Polychondritis Crystal Deposition Arthritides Seronegative Spondyloarthritis Infectious Arthritis & Bursitis Connective Tissue Diseases Systemic Lupus Erythematosus Vasculitis IgG4-Related Disease Cryoglobulinemia Amyloidosis NEUROLOGY Omar Al-Louzi, Leeann Brigham Burton, Kristin Galetta, Morgan Prust, Michael P. Bowley Change in Mental Status Seizures Alcohol Withdrawal Dizziness Stroke Weakness & Neuromuscular Dysfunction Headache Back and Spinal Cord Disease CONSULTS Sarah J. Carlson, Jennifer F. Tseng, Katherine T. Chen, Stella K. Kim Surgical Issues Ob/Gyn Issues Ophthalmic Issues APPENDIX ICU Medications & Treatment of Hypotension/Shock Antibiotics Formulae and Quick Reference ABBREVIATIONS INDEX PHOTO INSERTS Radiology Echocardiography & Coronary Angiography Peripheral Blood Smears & Leukemias Urinalysis ACLS Uploaded by MEDBOOKSVN.ORG  CONTRIBUTING AUTHORS Andrew S. Allegretti, MD, MSc Director of ICU Nephrology, Attending Physician, Nephrology Division, and Principal Investigator, Kidney Research Center, Massachusetts General Hospital Instructor of Medicine, Harvard Medical School Omar Al-Louzi, MD Neurology Resident, Partners Neurology Residency Alexander Blair, MD Internal Medicine Resident, Massachusetts General Hospital Michael P. Bowley, MD, PhD Instructor in Neurology, Massachusetts General Hospital Associate Program Director, Partners Neurology Residency Program Leeann Brigham Burton, MD Neurology Resident, Partners Neurology Residency Sarah J. Carlson Assistant Professor of Surgery, Boston University of Medicine Attending Surgeon, Boston Veterans Affairs Healthcare Alison C. Castle, MD Internal Medicine Resident, Massachusetts General Hospital Katherine T. Chen, MD, MPH Vice-Chair of Ob/Gyn Education, Career Development, and Mentorship Professor of Obstetrics, Gynecology, and Reproductive Science Professor of Medical Education Icahn School of Medicine at Mount Sinai, New York Caitlin Colling, MD Internal Medicine Resident, Massachusetts General Hospital Jean M. Connors, MD Medical Director, Anticoagulation Management Services Hematology Division, Brigham and Women’s Hospital & Dana-Farber Cancer Institute Associate Professor of Medicine, Harvard Medical School Daniel J. DeAngelo, MD, PhD Chief of the Division of Leukemia, Dana-Farber Cancer Institute Professor of Medicine, Harvard Medical School Rachel Frank, MD Internal Medicine Resident, Massachusetts General Hospital Robert P. Friday, MD, PhD Chief, Division of Rheumatology, Newton-Wellesley Hospital Affiliate Physician, Rheumatology Unit, Massachusetts General Hospital Instructor in Medicine, Harvard Medical School Lawrence S. Friedman, MD The Anton R. Fried, MD, Chair, Department of Medicine, Newton-Wellesley Hospital Assistant Chief of Medicine, Massachusetts General Hospital Professor of Medicine, Harvard Medical School Professor of Medicine, Tufts University School of Medicine Kristin Galetta, MD Neurology Resident, Partners Neurology Residency Kristen Hysell, MD Infectious Disease Fellow, Massachusetts General Hospital Tanya E. Keenan, MD, MPH Hematology-Oncology Fellow, Dana-Farber/Partners CancerCare Stella K. Kim, MD Joe M. Green Jr. Professor of Clinical Ophthalmology Ruiz Department of Ophthalmology and Visual Sciences Robert Cizik Eye Clinic University of Texas McGovern School of Medicine Emily Walsh Lopes, MD Gastroenterology Fellow, Massachusetts General Hospital Melissa Lumish, MD Internal Medicine Resident, Massachusetts General Hospital Jason Maley, MD Pulmonary Fellow, Massachusetts General Hospital Michael Mannstadt, MD Chief, Endocrine Unit, Massachusetts General Hospital Associate Professor of Medicine, Harvard Medical School Arielle Medford, MD Internal Medicine Resident, Massachusetts General Hospital Nino Mihatov, MD Cardiology Fellow, Massachusetts General Hospital Mazen Nasrallah, MD, MSc Rheumatology Fellow, Massachusetts General Hospital Walter J. O’Donnell, MD Staff Physician, Pulmonary/Critical Care Unit, Massachusetts General Hospital Assistant Professor of Medicine, Harvard Medical School Michelle L. O’Donoghue, MD, MPH Senior Investigator, TIMI Study Group Associate Physician, Cardiovascular Division, Brigham and Women’s Hospital Affiliate Physician, Cardiology Division, Massachusetts General Hospital Associate Professor of Medicine, Harvard Medical School Nilay Patel, MD Cardiology Fellow, Massachusetts General Hospital Morgan Prust, MD Neurology Resident, Massachusetts General Hospital Stephanie M. Rutledge, MBBCh, BAO, MRCPI Internal Medicine Resident, Massachusetts General Hospital David P. Ryan, MD Uploaded by MEDBOOKSVN.ORG Clinical Director, Massachusetts General Hospital Cancer Center Chief of Hematology/Oncology, Massachusetts General Hospital Professor of Medicine, Harvard Medical School Marc S. Sabatine, MD, MPH Chairman, TIMI Study Group Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine, Brigham and Women’s Hospital Affiliate Physician, Cardiology Division, Massachusetts General Hospital Professor of Medicine, Harvard Medical School Harish Seethapathy, MBBS Nephrology Fellow, BWH/MGH Joint Nephrology Fellowship Program Shilpa Sharma, MD Internal Medicine Resident, Massachusetts General Hospital Harshabad Singh, MBBS Instructor, Gastrointestinal Cancer Treatment Center, Dana-Farber Cancer Institute Isaac D. Smith, MD Internal Medicine Resident, Massachusetts General Hospital Miranda Theodore, MD Internal Medicine Resident, Massachusetts General Hospital Jennifer F. Tseng, MD, MPH Utley Professor and Chair, Boston University School of Medicine Surgeon-in-Chief, Boston Medical Center Armen Yerevanian, MD Endocrinology Fellow, Massachusetts General Hospital Kimon C. Zachary, MD Assistant Professor of Medicine, Infectious Disease Division, Massachusetts General Hospital  FOREWORD To the 1st Edition It is with the greatest enthusiasm that I introduce Pocket Medicine. In an era of information glut, it will logically be asked, “Why another manual for medical house officers?” Yet, despite enormous information readily available in any number of textbooks, or at the push of a key on a computer, it is often that the harried house officer is less helped by the description of differential diagnosis and therapies than one would wish. Pocket Medicine is the joint venture between house staff and faculty expert in a number of medical specialties. This collaboration is designed to provide a rapid but thoughtful initial approach to medical problems seen by house officers with great frequency. Questions that frequently come from faculty to the house staff on rounds, many hours after the initial interaction between patient and doctor, have been anticipated and important pathways for arriving at diagnoses and initiating therapies are presented. This approach will facilitate the evidence-based medicine discussion that will follow the workup of the patient. This well-conceived handbook should enhance the ability of every medical house officer to properly evaluate a patient in a timely fashion and to be stimulated to think of the evidence supporting the diagnosis and the likely outcome of therapeutic intervention. Pocket Medicine will prove to be a worthy addition to medical education and to the care of our patients. DENNIS A. AUSIELLO, MD Physician-in-Chief, Massachusetts General Hospital Jackson Professor of Clinical Medicine, Harvard Medical School Uploaded by MEDBOOKSVN.ORG  PREFACE To my parents, Matthew and Lee Sabatine, to their namesake grandchildren Matteo and Natalie, and to my wife Jennifer Written by residents, fellows, and attendings, the mandate for Pocket Medicine was to provide, in a concise a manner as possible, the key information a clinician needs for the initial approach to and management of the most common inpatient medical problems. The tremendous response to the previous editions suggests we were able to help fill an important need for clinicians. With this seventh edition come several major improvements. We have updated every topic thoroughly. In particular, we have included the newest diagnostic algorithms and pharmacotherapy for acute coronary syndromes, the revolutionary data for transcatheter aortic valve replacement (TAVR), and distilled the most recent guidelines for the classification and treatment of hypertension. We have added a dedicated section for the management of cystic fibrosis and updated the treatment of sepsis and shock. We continue to revise the approach to malignancies based on molecular classification and the corresponding biologic therapies, including dedicated sections on immunotherapy. We have incorporated the paradigm-shifting data for diabetes medications that lower cardiovascular risk and cover the newest classes of lipid-lowering therapies. As always, we have incorporated key references to the most recent high-tier reviews and important studies published right up to the time Pocket Medicine went to press. We welcome any suggestions for further improvement. This edition builds on the work of the many contributors to prior editions of Pocket Medicine. In addition, we appreciate the advice on specific topics from additional attendings including Dr. Adam Sperling. Of course, medicine is far too vast a field to ever summarize in a textbook of any size. Long monographs have been devoted to many of the topics discussed herein. Pocket Medicine is meant only as a starting point to guide one during the initial phases of diagnosis and management until one has time to consult more definitive resources. Although the recommendations herein are as evidence-based as possible, medicine is both a science and an art. As always, sound clinical judgement must be applied to every scenario. I am grateful for the support of the house officers, fellows, and attendings at the Massachusetts General Hospital. It is a privilege to work with such a knowledgeable, dedicated, and compassionate group of physicians. I always look back on my time there as Chief Resident as one of my best experiences. I am grateful to several outstanding clinical mentors, including Hasan Bazari, Larry Friedman, Nesli Basgoz, Eric Isselbacher, Mike Fifer, and Roman DeSanctis, as well as the late Charlie McCabe, Mort Swartz, and Peter Yurchak. This edition would not have been possible without the help of Melinda Cuerda and Abby Cange, my academic coordinators. They shepherded every aspect of the project from start to finish, with an incredible eye to detail to ensure that each page of this book was the very best it could be. Lastly, special thanks to my parents for their perpetual encouragement and love and, of course, to my wife, Jennifer Tseng, who, despite being a surgeon, is my closest advisor, my best friend, and the love of my life. I hope that you find Pocket Medicine useful throughout the arduous but incredibly rewarding journey of practicing medicine. MARC S. SABATINE, MD, MPH Cardiology ELECTROCARDIOGRAPHY Approach (a systematic approach is vital) Rate (? tachy or brady) and rhythm (? P waves, regularity, P & QRS relationship) Intervals (PR, QRS, QT) and axis (? LAD or RAD) Chamber abnormality (? LAA and/or RAA, ? LVH and/or RVH) QRST changes (? Q waves, poor R-wave progression V1–V6, ST ↑/↓ or T-wave Δs) Figure 1-1 QRS axis Left axis deviation (LAD) Definition: axis beyond –30° (S > R in lead II) Etiologies: LVH, LBBB, inferior MI, WPW Left anterior fascicular block (LAFB): LAD (–45 to –90°) and qR in aVL and QRS R in lead I) Etiologies: RVH, PE, COPD (usually not > +110°), septal defects, lateral MI, WPW Left posterior fascicular block (LPFB): RAD (90–180°) and rS in I & aVL and qR in III & aVF and QRS 20 mm in women Romhilt-Estes point-score system (4 points = probable; 5 points = diagnostic): ↑ volt: limb lead R or S ≥20 mm or S in V1 or V2 ≥30 mm or R in V5 or V6 ≥30 mm (3 pts) ST displacement opposite to QRS deflection: w/o dig (3 pts); w/ dig (1 pt) LAA (3 pts); LAD (2 pts); QRS duration ≥90 msec (1 pt) Intrinsicoid deflection (QRS onset to peak of R) in V5 or V6 ≥50 msec (1 pt) If LAFB present: S in III + max (R+S) in any lead ≥30 mm in men or ≥28 mm in women Right ventricular hypertrophy (RVH) (Circ 2009;119:e251; JACC 2014;63:672) Etiologies: cor pulmonale, congenital (tetralogy of Fallot, TGA, PS, ASD, VSD), MS, TR Criteria [all insensitive, but specific (except in COPD); all w/ poor PPV in general population] R > S in V1, R in V1 ≥6 mm, S in V5 ≥10 mm, S in V6 ≥3 mm, R in aVR ≥4 mm RAD ≥110° (LVH + RAD or prominent S in V5 or V6 → consider biventricular hypertrophy) Ddx of dominant R wave in V1 or V2 Ventricular abnl: RVH (RAD, RAA, deep S waves in I, V5, V6); HCM; Duchenne’s Myocardial injury: posterior MI (anterior R wave = posterior Q wave; often with IMI) Abnormal depolarization: RBBB (QRS >120 msec, rSR′); WPW (↓ PR, δ wave, ↑ QRS) Other: dextroversion; counterclockwise rotation; lead misplacement; nl variant Poor R wave progression (PRWP) (Am Heart J 2004;148:80) Definition: loss of anterior forces w/o frank Q waves (V1–V3); R wave in V3 ≤3 mm Possible etiologies (nonspecific): old anteroseptal MI (usually w/ R wave V3 ≤1.5 mm, ± persistent ST ↑ or TWI V2 & V3) LVH (delayed RWP w/ ↑ left precordial voltage), RVH, COPD (may also have RAA, RAD, limb lead QRS amplitude ≤5 mm, SISIISIII w/ R/S ratio 25% height of R wave in that QRS complex Small (septal) q waves in I, aVL, V5 & V6 are nl, as can be isolated Qw in III, aVR, V1 “Pseudoinfarct” pattern may be seen in LBBB, infiltrative dis., HCM, COPD, PTX, WPW ST elevation (STE) (NEJM 2003;349:2128; Circ 2009;119:e241 & e262) Acute MI: upward convexity STE (ie, a “frown”) ± TWI (or prior MI w/ persistent STE) Coronary spasm: Prinzmetal’s angina; transient STE in a coronary distribution Pericarditis: diffuse, upward concavity STE (ie, a “smile”); a/w PR ↓; Tw usually upright HCM, Takotsubo CMP, ventricular aneurysm, cardiac contusion 3 Uploaded by MEDBOOKSVN.ORG  Cardiology Pulmonary embolism: occ. STE V1–V3; classically a/w TWI V1–V4, RAD, RBBB, S1Q3T3 Repolarization abnormalities: LBBB (↑ QRS duration, STE discordant from QRS complex; see “ACS” for dx MI in LBBB) LVH (↑ QRS amplitude); Brugada syndrome (rSR′, downsloping STE V1–V2); pacing Hyperkalemia (↑ QRS duration, tall Ts, no P’s); epsilon waves (late afterdepol.) in ARVC aVR: STE >1 mm a/w ↑ mortality in STEMI; STE aVR > V1 a/w left main disease Early repolarization: most often seen in V2–V5 in young adults (Circ 2016;133:1520) 1–4 mm elev of peak of notch or start of slurred downstroke of R wave (ie, J point); ± up concavity of ST & large Tw (∴ ratio of STE/T wave 6), AI, widened mediast. on CXR (absence ⊖ LR 0.3); false lumen on imaging. (JAMA 2002;287:2262) Pulmonary Causes Pneumonia Pleuritic; dyspnea, fever, cough, sputum. ↑ RR, crackles. CXR infiltrate. Pleuritis Sharp, pleuritic pain. ± Pleuritic friction rub. PTX Sudden onset, sharp pleuritic pain. Hyperresonance, ↓ BS. PTX on CXR. PE Sudden onset pleuritic pain. ↑ RR & HR, ↓ SaO2, ECG Δs (sinus tach, RAD, RBBB, SIQIIITIII, TWI V1–V4, occ STE V1–V3), + CTA or V/Q, ± ↑ Tn. Pulm HTN Exertional pressure, DOE. ↓ SaO2, loud P2, RV heave, right S3 and/or S4. GI Causes Esophageal reflux Substernal burning, acid taste in mouth, water brash. ↑ by meals, recumbency; ↓ by antacids. EGD, manometry, pH monitoring. Esoph spasm Intense substernal pain. ↑ by swallowing, ↓ by NTG/CCB. Manometry. Mallory-Weiss Esoph tear precipitated by vomiting. ± Hematemesis. Dx w/ EGD. Boerhaave Esoph rupture. Severe pain, ↑ w/ swallow. Mediastinal air palpable & on CT. PUD Epigastric pain, relieved by antacids. ± GIB. EGD, ± H. pylori test. Biliary dis. RUQ pain, N/V. ↑ by fatty foods. RUQ U/S; ↑ LFTs. Pancreatitis Epigastric/back discomfort. ↑ amylase & lipase; abd CT. Musculoskeletal and Miscellaneous Causes Costochond Localized sharp pain. ↑ w/ movement. Reproduced by palpation. Zoster Intense unilateral pain. Pain may precede dermatomal rash. Anxiety “Tightness,” dyspnea, palpitations, other somatic symptoms (Braunwald’s Heart Disease, 11th ed, 2018; JAMA 2015;314:1955) Initial approach Focused history: quality, severity, location, radiation; provoking/palliating factors; intensity at onset; duration, freq, & pattern; setting; assoc sx; cardiac hx & risk factors Targeted exam: VS (incl. BP in both arms); gallops, murmurs, rubs; signs of vascular dis. 5 Uploaded by MEDBOOKSVN.ORG  Cardiology (carotid/femoral bruits, ↓ pulses) or CHF; lung & abd. exam; chest wall for reproducibility 12-lead ECG: obtain w/in 10 min; comp to priors & obtain serial ECGs; consider posterior leads (V7–V9) to ✔ for posterior STEMI if: hx c/w ACS but stnd ECG unrevealing; ST ↓ V1–V3 (ant ischemia vs. post STEMI) w/ refractory angina; or R/S >1 in V1–V2 CXR; other imaging (echo, PE CTA, etc.) as indicated based on H&P and initial testing Troponin: >99th %ile w/ rise and/or fall in approp. setting is dx of AMI (Circ 2018;138:e618) Detectable 1–6 h after injury, peaks 24 h, may be elevated for 7–14 d in STEMI ✔ at presentation & 3–6 h later; repeat if clinical or ECG Δs; ? sex-specific cutpoints If high-sens Tn (hsTn) assay, can ✔ at presentation & 1 h later; assess level & Δ Causes for ↑ Tn other than plaque rupture (= “type 1 MI”): (1) Supply-demand mismatch not due to Δ in CAD (= “type 2 MI”; eg, ↑↑ HR, shock, HTN crisis, spasm, severe AS), (2) non-ischemic injury (myocarditis/toxic CMP, cardioversion, cardiac contusion) or (3) multifactorial (PE, sepsis, severe HF, renal failure, Takotsubo, infilt dis.) CK-MB: less Se & Sp than Tn (other sources: skel. muscle, intestine, etc.); CK-MB/CK ratio >2.5 → cardiac source. Limited utility: ? higher bar for post-revasc MI; early reMI. Early noninvasive imaging Low prob of ACS (eg, ⊖ ECG & Tn) & stable → outPt or inPt noninv. fxnal or imaging test (qv) CCTA w/ high NPV, low PPV. ↓ LOS c/w fxnal testing (NEJM 2012;366:1393). In stable outPt w/ CP, CCTA added to standard of care ↑ early but not overall angiography/revasc; ↑ use of preventive med Rx, and ↓ coronary death/MI at 5 y (NEJM 2018;379:924). “Triple r/o” CT angiogram sometimes performed to r/o CAD, PE, AoD if dx unclear 6 Noninvasive Evaluation of CAD NONINVASIVE EVALUATION OF CAD Stress testing (JACC 2012;60:1828; J Nucl Cardiol 2016; 23:606) Indications: dx obstructive CAD, evaluate Δ in clinical status in Pt w/ known CAD, risk stratify after ACS, evaluate exercise tolerance, localize ischemia (imaging required) Contraindications (Circ 2002;106:1883; & 2012;126:2465) Absolute: AMI w/in 48 h, high-risk UA, acute PE, severe sx AS, uncontrolled HF, uncontrolled arrhythmias, myopericarditis, acute aortic dissection Relative (discuss with stress lab): left main CAD, mod symptomatic valvular stenosis, severe HTN, HCMP, high-degree AVB, severe electrolyte abnl Exercise tolerance test (w/ ECG alone) Generally preferred if Pt can meaningfully exercise; ECG Δs w/ Se ~65%, Sp ~80% Typically via treadmill w/ Bruce protocol (modified Bruce or submax if decond. or recent MI) Hold anti-isch. meds (eg, nitrates, βB) if dx’ing CAD but give to assess adequacy of meds Pharmacologic stress test (nb, requires imaging because ECG not interpretable) Use if unable to exercise, low exercise tolerance, or recent MI. Se & Sp ≈ exercise. Preferred if LBBB, WPW or V-paced, because higher prob of false ⊕ imaging with exercise Coronary vasodilator: diffuse vasodilation → relative “coronary steal” from vessels w/ fixed epicardial dis. Reveals CAD, but not if Pt ischemic w/ exercise. Regadenoson (↓ side effects), dipyridamole, adenosine. Side effects: flushing, ↓ HR, AVB, SOB, bronchospasm. Chronotropes/inotropes (dobuta): more physiologic, but longer test; may precip arrhythmia Imaging for stress test Use if uninterpretable ECG (V-paced, LBBB, resting ST ↓ >1 mm, digoxin, LVH, WPW), after indeterminate ECG test, or if pharmacologic test Use when need to localize ischemia (often used if prior coronary revasc) Radionuclide myocardial perfusion imaging w/ images obtained at rest & w/ stress SPECT (eg, 99mTc-sestamibi): Se ~85%, Sp ~80% PET (rubidium-82): Se ~90%, Sp ~85%; requires pharmacologic stress, not exercise ECG-gated imaging allows assessment of regional LV fxn (sign of ischemia/infarction) Echo (exercise or dobuta): Se ~85%, Sp ~85%; no radiation; operator dependent Cardiac MRI (w/ pharmacologic stress) another option with excellent Se & Sp Test results HR (must achieve ≥85% of max pred HR [220-age] for exer. test to be dx), BP response, peak double product (HR × BP; nl >20k), HR recovery (HRpeak – HR1 min later; nl >12) 7 Uploaded by MEDBOOKSVN.ORG  Cardiology Max exercise capacity achieved (METS or min); occurrence of symptoms ECG Δs: downsloping or horizontal ST ↓ (≥1 mm) 60–80 ms after QRS predictive of CAD (but does not localize ischemic territory); however, STE highly predictive & localizes Duke treadmill score = exercise min – (5 × max ST dev) – (4 × angina index) [0 none, 1 nonlimiting, 2 limiting]; score ≥5 → 110, SBP 90%; no mortality benefit if SaO2 ≥90% (NEJM 2017;377:1240) Other early adjunctive therapy High-intensity statin therapy (eg, atorva 80 mg qd; PROVE-IT TIMI 22, NEJM 2004;350:1495); ↓ ischemic events w/ benefit emerging w/in wks (JAMA 2001;285:1711 & JACC 2005;46:1405); ↓ peri-PCI MI (JACC 2010;56:1099); ? ↓ contrast-induced nephropathy (NEJM 2019;380:2156) Ezetimibe: ↓ CV events when added to statin (IMPROVE-IT, NEJM 2015;372:1500) 13 Uploaded by MEDBOOKSVN.ORG  Cardiology ACEI/ARB: start once hemodynamics and renal function stable Strong indication for ACEI if heart failure, EF 10 min; trauma/major surg. w/in 3 wk Active internal bleeding or known bleeding diathesis Internal bleed w/in 2–4 wk; active PUD Suspected aortic dissection Noncompressible vascular punctures Severe uncontrollable HTN Pregnancy For SK, SK Rx w/in 6 mo Current use of anticoagulants For SK, prior SK exposure Nonprimary PCI Rescue PCI if shock, unstable, failed reperfusion, or persistent sx (NEJM 2005;353:2758) Routine angio ± PCI w/in 24 h of successful lysis: ↓ D/MI/revasc (Lancet 2004;364:1045) and w/in 6 h ↓ reMI, recurrent ischemia, & HF compared to w/in 2 wk (NEJM 2009;360:2705); ∴ if lysed at non-PCI-capable hosp., consider transfer to PCI-capable hosp. ASAP espec if hi-risk (eg, ant. MI, IMI w/ ↓ EF or RV infarct, extensive STE/LBBB, HF, ↓ BP or ↑ HR) Late PCI (median day 8) of occluded infarct-related artery: no benefit (NEJM 2006;355:2395) Antiplatelet Therapy Aspirin 162–325 mg × 1 23% ↓ in death (Lancet 1988;ii:349) (crushed/chewed) then 81 mg qd Should not be stopped if CABG required P2Y12 inhibitor Lysis: clopidogrel 41% ↑ in patency, 7% ↓ mort, no Δ major bleed or ICH Give ASAP (do not wait for angio) b/c (NEJM 2005;352:1179; Lancet 2005;366:1607); no data for pras or ticag onset inhib delayed in STEMI pts w/ lytic Ticagrelor or prasugrel (if PCI) as PCI: prasugrel and ticagrelor ↓ CV events c/w clopi (Lancet 2009;373:723 & detailed above Circ 2010;122:2131) Clopidogrel: 600 mg pre-PCI; 300 mg if Prehospital ticagrelor may be safe & ? ↓ rate of stent thrombosis (NEJM lysis (no LD if >75 y) → 75 mg qd 2014;371:1016) GP IIb/IIIa inhibitors Lysis: no indication (Lancet 2001;357:1905) 17 Uploaded by MEDBOOKSVN.ORG  Cardiology abciximab, eptifibatide, tirofiban Peri-PCI: 60% ↓ D/MI/UR (NEJM 2001;344:1895) Adapted from ACC/AHA 2013 STEMI Guidelines Update (Circ 2013;127:529); Lancet 2013;382:633 Anticoagulant Therapy (choose one) UFH No demonstrated mortality benefit 60 U/kg IVB (max 4000 U) ↑ patency with fibrin-specific lytics 12 U/kg/h (max 1000 U/h initially) Titrate to aPTT 1.5–2× control (~50–70 sec) Enoxaparin Lysis: 17% ↓ D/MI w/ ENOX × 7 d vs. UFH × 2 d (NEJM 2006;354:1477) Lysis: 30 mg IVB → 1 mg/kg SC bid PCI: ↓ D/MI/revasc and ≈ bleeding vs. UFH (Lancet 2011;378:693) (adjust for age >75 & CrCl) PCI: 0.5 mg/kg IVB Bivalirudin PCI: similar bleeding, ± ↑ MI, ↑ stent thromb (Lancet 2014;384:599; NEJM 0.75 mg/kg IVB → 1.75 mg/kg/hr IV 2017;377:1132) Fondaparinux can be used (if CrCl >30 mL/min) in setting of lysis, where superior to UFH w/ less bleeding (JAMA 2006;295:1519). Adapted from ACC/AHA 2013 STEMI Guidelines (Circ 2013;127:529; Lancet 2013;382:633) LV failure (occurs in ~25%) Diurese to achieve PCWP ~14 → ↓ pulmonary edema, ↓ myocardial O2 demand ↓ Afterload → ↑ stroke volume & CO, ↓ myocardial O2 demand. Can use IV NTG or nitroprusside (although risk of coronary steal) → short-acting ACEI. Inotropes if HF despite diuresis & ↓ afterload; use dopamine, dobutamine, or milrinone Cardiogenic shock (~7%) = MAP 2 Intraaortic balloon pump (IABP) counterpulsation offers ~0.5 L/min CO and ↑ coronary perfusion, but no survival benefit if early revasc (NEJM 2012;367:1287) Axial flow pumps (eg, Impella) offer up to 3–5 L/min CO, but no data that improves clinical outcomes (JACC 2017;69:278) IMI complications (Circ 1990;81:401; NEJM 1994;330:1211; JACC 2003;41:1273) Heart block: ~20%, occurs in part because RCA typically supplies AV node 40% on present., 20% w/in 24 h, rest by 72 h; high-grade AVB can develop abruptly Rx: atropine, epi, aminophylline (100 mg/min × 2.5 min), temp pacing wire RV infarct: proximal RCA occlusion → ↓ flow to RV marginals Angiographically present in 30–50% of cases, but only ~1/2 clinically significant HoTN; ↑ JVP, ⊕ Kussmaul’s; ≥1 mm STE in V4R; RA/PCWP ≥0.8; RV dysfxn on TTE Rx: optimize preload (RA goal 10–14 mmHg; BHJ 1990;63:98); ↑ contractility (dobutamine); maintain AV synchrony (pacing as necessary); reperfusion (NEJM 1998;338:933); mechanical support (IABP or RVAD); pulmonary vasodilators (eg, inhaled NO) Mechanical complications (incid. 15 mmHg Optimize preload = LVEDV ≈ LVEDP ≈ LAP ≈ PCWP (NEJM 1973;289:1263) goal PCWP ~14–18 in acute MI, ≤14 in acute decompensated HF optimize in individual Pt by measuring SV w/ different PCWP to create Starling curve ↑ by giving NS (albumin w/o clinical benefit over NS; PRBC if significant anemia) ↓ by diuresis (qv), ultrafiltration or dialysis if refractory to diuretics Optimize afterload ≈ wall stress during LV ejection = [(~SBP × radius) / (2 × wall thick.)] and ∴ ∝ MAP and ∝ SVR = (MAP – CVP / CO); goals: MAP >60, SVR 800–1200 MAP >60 & SVR ↑: vasodilators (eg, nitroprusside, NTG, ACEI, hydral.) or wean pressors MAP 10 → PCWP >22) ⊕ hepatojugular reflux: ≥4 cm ↑ in JVP for ≥15 sec w/ abdominal pressure Se/Sp 73/87% for RA >8 and Se/Sp 55/83% for PCWP >15 (AJC 1990;66:1002) Abnl Valsalva response: square wave (↑ SBP w/ strain), no overshoot (no ↑ BP after strain) S3 (in Pts w/ HF → ~40% ↑ risk of HF hosp. or pump failure death; NEJM 2001;345:574) rales, dullness at base 2° pleural effus. (often absent in chronic HF due to lymphatic compensation) ± hepatomegaly, ascites and jaundice, peripheral edema Perfusion (“warm” vs. “cold”) narrow pulse pressure (2.2 (MVO2 >60%), SVR 50%) Utility of BNP-guided Rx (inPt and outPt) remains debated (Eur Heart J 2014;35:16) Implantable PA pressure sensor in NYHA III → ~33% ↓ risk of hosp (Lancet 2016;387:453) Treatment of Chronic HF with Reduced EF (JACC 2017;70:776) Diet, exercise Na 12), ⊖ LR 0.03 Ddx = PE, hypovolemia, severe COPD, auto-PEEP, periconstriction (~1/3), RV infarct ? absent if pre-existing ↑ LVEDP, irregular rhythm, severe AI, ASD, regional tamponade Distant heart sounds (28%), ± pericardial friction rub (30%) Tachypnea and orthopnea but clear lungs Diagnostic studies ECG: ↑ HR, ↓ voltage (seen in 42%), electrical alternans (20%), ± signs of pericarditis CXR: ↑ cardiac silhouette (89%) Echocardiogram: ⊕ effusion, IVC plethora, septal shift with inspiration diastolic collapse of RA (Se 85%, Sp 80%) and/or RV (Se left-sided heart failure (systemic congestion > pulmonary congestion) Physical exam ↑ JVP with prominent y descent, ⊕ Kussmaul sign [Ddx: tricuspid stenosis, acute cor pulmonale, RV dysfxn (CMP, RV MI), SVC syndrome] Hepatosplenomegaly, ascites, peripheral edema. Consider in Ddx of idiopathic cirrhosis. PMI usually not palpable, pericardial knock, usually no pulsus paradoxus Diagnostic studies ECG: nonspecific, AF common (up to 33%) in advanced cases CXR: calcification (MTb most common), espec in lateral view (although not specific) Echocardiogram: ± thickened pericardium, “septal bounce” = abrupt displacement of 51 Uploaded by MEDBOOKSVN.ORG  Cardiology septum during rapid filling in early diastole Cardiac catheterization: atria w/ Ms or Ws (prominent x and y descents) ventricles: dip-and-plateau or square-root sign (rapid ↓ pressure at onset of diastole, rapid ↑ to early plateau) discordance between LV & RV pressure peaks during respiratory cycle (Circ 1996;93:2007) CT or MRI: thickened pericardium (>4 mm; Se ~80%) w/ tethering (Circ 2011;123:e418) Treatment Diuresis if intravascular volume overload; surgical pericardiectomy if infectious or advanced Constrictive Pericarditis vs. Restrictive Cardiomyopathy Evaluation Constrictive Pericarditis Restrictive Cardiomyopathy ⊕ Kussmaul sign ± Kussmaul sign Physical exam Absent PMI Powerful PMI, ± S3 and S4 ⊕ Pericardial knock ± Murmurs of MR, TR ± Low voltage Low voltage if infiltrative myopathy ECG ± Conduction abnormalities Respirophasic variation (25–40%): 12 cm/sec) E′ ↓ ( RVEDP (esp. w/ vol.) RVSP 55 mmHg Cardiac RVEDP >⅓ RVSP (Se 93%, Sp 46%) RVEDP 1.1 (Se 97%, Sp 100%) Endomyocardial Usually normal ± Specific etiology of RCMP (fibrosis, infiltration, biopsy hypertrophy) 52 Hypertension HYPERTENSION JNC 8 Classification Category Systolic Diastolic Normal 1 y) vs. permanent (no plan for SR) Nonvalvular (AF absent rheumatic MS, prosthetic valve, or mitral valve repair) vs. valvular Epidemiology and etiologies (Circ 2011;124:1982; Nat Rev 2016;2:1) 1–2% of pop. has AF (10% of those age ≥80); M > F; lifetime risk ~25% Acute (up to 50% w/o identifiable cause) Cardiac: HF, new CMP, myo/pericarditis, ischemia/MI, HTN crisis, valve dis., cardiac surg Pulmonary: acute pulmonary disease or hypoxemia (eg, COPD flare, PNA), PE, OSA Metabolic: high catecholamine states (stress, infection, postop, pheo), thyrotoxicosis Drugs: alcohol, cocaine, amphetamines, theophylline, caffeine, smoking, ibrutinib Neurogenic: subarachnoid hemorrhage, ischemic stroke Chronic: ↑ age, HTN, ischemia, valve dis. (MV, TV, AoV), CMP, hyperthyroidism, obesity Evaluation H&P, ECG, CXR, TTE (LA size, thrombus, valves, LV fxn, pericardium), K, Mg, Cr, FOBT before anticoag, TFTs; r/o MI not necessary unless other ischemic sx In acute AF 48 h 2–5% risk stroke w/ cardioversion (pharmacologic or electric) ∴ either TEE to r/o thrombus or ensure therapeutic anticoagulation ≥3 wk prior If needs to cardiovert urgently, often anticoagulate acutely (eg, IV UFH) Likelihood of success ∝ AF duration & atrial size; control precipitants (eg, vol status, thyroid) Before electrical cardiovert, consider pre-Rx w/ AAD (eg, ibutilide), esp. if 1st cardiovert failed 68 Atrial Fibrillation For pharmacologic cardioversion, class III and IC drugs have best proven efficacy If SR returns (spont. or w/ Rx), atria may be mech. stunned; also, high risk of recurrent AF over next 3 mo. ∴ Anticoag postcardioversion ≥4 wk (? unless AF 3 min after Horiz/down ST ↓ ≥1 ST ↓ ≥1 mm or exertion mm 1–2 abnl leads SBP ↓ 10 mmHg or typical angina 3–4 abnl leads 1–3 min after exertion Additional preoperative testing (Circ 2014;130:e278) ECG if known cardiac disease and possibly reasonable in all, except if low-risk surgery TTE if any of following & prior TTE >12 mo ago or prior to Δ in sx: dyspnea of unknown origin; hx of HF w/ ↑ dyspnea; suspect (eg, murmur) or known ≥ moderate valvular dis. Coronary artery disease If possible, wait ~60 d after MI in the absence of revascularization before elective surgery Coronary revasc guided by standard indications. Has not been shown to Δ risk of death or postop MI when done prior to elective vasc. surgery (NEJM 2004;351:2795). Heart failure (JACC 2014;64:e77) Decompensated HF should be optimally Rx’d prior to elective surgery 30-d CV event rate: symptomatic HF > asx HFrEF > asx HFpEF > no HF Valvular heart disease If meet criteria for valve intervention, do so before elective surgery (postpone if necessary) If severe valve disease and surgery urgent, intra- & postoperative hemodynamic monitoring reasonable (espec for AS, because at ↑ risk even if sx not severe; be careful to maintain preload, avoid hypotension, and watch for atrial fibrillation) Cardiac implantable electronic devices Discuss w/ surgical team need for device (eg, complete heart block) & consequences if interference w/ fxn, and likelihood of electromagnetic interference Consider reprogramming, magnet use, etc. as needed Pre- & perioperative pharmacologic management ASA: continue in Pts w/ existing indication. Initiation prior to surgery does not ↓ 30-d ischemic events and ↑ bleeding (NEJM 2014;370:1494), but Pts w/ recent stents excluded. Dual antiplatelet therapy: delay elective surg 14 d after balloon angioplasty, 30 d after BMS and ideally 6 mo (min 3 mo) after DES (JACC 2016; 68:1082) unless risk of bleeding > risk of stent thrombosis or ACS. If must discontinue P2Y12 inh, continue ASA and restart P2Y12 inh ASAP; can consider IV cangrelor if high-risk (JAMA 2012;307:265). β-blockers (JAMA 2015;313:2486) Continue βB in Pts on them chronically. Do not stop βB abruptly postop (may cause reflex sympathetic activation). Use IV if Pt unable to take PO. Reasonable to initiate if intermed- or high-risk ⊕ stress test, or RCRI ≥3, espec if vasc surgery. Initiate ≥1 wk prior to surgery (not day of), use low-dose, short-acting βB, and titrate to achieve HR and BP goal (? HR ~55–65). Avoid bradycardia and 78 Cardiac Risk Assessment for Noncardiac Surgery HoTN. Statins: ↓ ischemia & CV events in Pts undergoing vascular surg (NEJM 2009;361:980). Consider if risk factors & non–low-risk surgery and in all Pts undergoing vascular surgery. ACEI/ARB: holding 24 h preop to ↓ intraop HoTN (Anes 2017;126:16). Restart ASAP. Amiodarone: ↓ incidence of postop AF if started prior to surgery (NEJM 1997;337:1785) Postoperative monitoring ECG if known CAD or high-risk surgery. Consider if >1 risk factor for CAD. Routine troponin prognostic (JAMA 2017;317:1642) but ✔ only if sx/ECG Δs suggestive of ACS 79 Uploaded by MEDBOOKSVN.ORG  Cardiology PERIPHERAL ARTERY DISEASE (PAD) Clinical features (NEJM 2016;374:861) Prev. ↑ w/ age: 1.4, non-dx possibly due to calcified noncompressible vessel → ✔ PVR, TBI (toe-brachial index). If ABI abnl → segmental ABI w/ PVR to localize disease. If ⊕ sx but nl ABI, ✔ for ↓ lower extrem BP after exercise (≥20% ↓ in ABI w/ exercise or ≥30 mmHg ↓ in ankle pressure). Duplex arterial U/S; CTA w/ distal run-off; MRA or angio if dx in ? or possible intervention Treatment (JACC 2013;61:1555; JAMA 2013;309:453 & 2015;314:1936) Risk factor modif. Screen for CAD/AAA. Structured exercise program (JAMA 2013;310:57). If sx or if asx with ABI ≤0.90, ASA, clopi, or ticag to ↓ D/MI/stroke (NEJM 2017; 376:32) More intensive antiplt Rx ↓ both MACE & limb ischemic events (JACC 2016;67:2719) Adding riva 2.5 mg bid to ASA ↓ MACE & death but ↑ bleeding (NEJM 2017;377:1319) Statins & PCSK9i ↓ MACE & limb ischemic events (Circ 2018;137:338). Cilostazol (if no HF). Endovascular (angioplasty vs. stent) or surgical revasc if limiting/refractory sx or CLI Acute limb ischemia (ALI) (Circ 2016;135:e686) Sudden decrement in limb perfusion (ie, acutely cold & painful) that threatens viability Etiologies: embolism > acute thrombosis (eg, athero, APS, HITT), trauma to artery Clinical manifestations (6 Ps): pain (distal to proximal, ↑ in severity), poikilothermia, pallor, pulselessness, paresthesias, paralysis Testing: pulse & neuro exam; arterial & venous Doppler; angiography, CTA or MRA Urgent consultation w/ vascular medicine and/or vascular surgery 80 Peripheral Artery Disease 81 Uploaded by MEDBOOKSVN.ORG  Cardiology NOTES 82 Pulmonary DYSPNEA Pathophysiology Etiologies Airway obstruction (↑ resistance to Asthma, COPD, bronchiectasis, cystic fibrosis, tumor, foreign body, vocal airflow) cord dysfunction, anaphylaxis Alveolar / Parenchymal disease Pulmonary edema: cardiogenic or noncardiogenic ILD; pneumonia; atelectasis Vascular Large vessel: PE, tumor emboli (V/Q mismatch) Small vessel: PHT, vasculitis, ILD, emphysema, PNA Chest wall Pleural disease: large effusion, fibrosis, pneumothorax (↑ resistance to expansion; weakness of Chest wall/diaphragm: kyphoscoliosis, ↑ abd girth respir. muscles) Neuromuscular disorders (ALS, GBS, MG) Hyperinflation (COPD, asthma) Stimulation of receptors Chemoreceptors: hypoxemia, metabolic acidosis Mechanoreceptors: ILD, pulmonary edema, PHT, PE ↓ O2 carrying cap. (but nl PaO2) Anemia, methemoglobinemia, CO poisoning Psychological Anxiety, panic attack, depression, somatization Evaluation History: quality of sensation, tempo, positional dependence, exac./allev. factors, exertion Cardiopulmonary exam, SaO2, CXR (see Appendix & Radiology inserts), ECG, ABG, U/S predictors of CHF: h/o CHF, PND, S3, CXR w/ venous congestion, AF (JAMA 2005;294:1944) dyspnea w/ nl CXR: CAD, asthma, PE, PHT, early ILD, anemia, acidosis, NM disease Based on results of initial evaluation: PFT, chest CT, TTE, cardiopulmonary testing BNP & NT-proBNP ↑ in CHF (also ↑ in AF, RV strain from PE, COPD flare, PHT, ARDS) BNP 400 to r/i (NEJM 2002;347:161) NT-proBNP 450 pg/mL (900 (50–75 y), >1800 (>75 y) (EHJ 2006;27:330) In chronic heart failure, ∴ need to compare to known “dry BNP” 83 Uploaded by MEDBOOKSVN.ORG  Pulmonary PULMONARY FUNCTION TESTS (PFTs) Spirometry: evaluate for obstructive disease Flow-volume loops: diagnose and/or localize obstruction Bronchodilator: indicated if obstruction at baseline or asthma clinically suspected Methacholine challenge: helps dx asthma if spirometry nl, > 20% ↓ FEV1 → asthma Lung volumes: evaluate for hyperinflation or restrictive disease including NM causes DLCO: evaluates functional surface area for gas exchange; helps differentiate causes of obstructive and restrictive diseases and screens for vascular disease & early ILD Figure 2-1 Approach to abnormal PFTs FEV1/FVC LLN typically 0.75. DLCO can be diminished due to secondary atelectasis. 84 Asthma ASTHMA Definition and epidemiology (Lancet 2018;391:783) Chronic inflam disorder w/ airway hyperresponsiveness + variable airflow obstruction Affects 5–10% population; ~85% of cases by age 40 y Clinical manifestations (NEJM 2013;369:549) Classic triad = wheezing, cough, dyspnea; others include chest tightness, sputum; symptoms typically chronic with episodic exacerbation Precipitants (triggers) respiratory irritants (smoke, perfume, etc.) & allergens (pets, dust mites, pollen, etc.) infections (URI, bronchitis, sinusitis) drugs (eg, ASA & NSAIDs via leukotrienes, βB via bronchospasm, MSO4 via histamine) emotional stress, cold air, exercise (increase in ventilation dries out airways) Physical examination Wheezing and prolonged expiratory phase Presence of nasal polyps, rhinitis, rash → allergic component Exacerbation → ↑ RR, ↑ HR, accessory muscle use, diaphoresis, pulsus paradoxus Diagnostic studies (JAMA 2017;318:279) Spirometry: ↓ FEV1, ↓ FEV1/FVC, coved flow-volume loop; lung volumes: ± ↑ RV & TLC ⊕ bronchodilator response (↑ FEV1 ≥12% & ≥200 mL) strongly suggestive of asthma methacholine challenge (↓ FEV1 ≥20%) if PFTs nl: Se >90% Allergy suspected → consider checking serum IgE, eos, skin testing/RAST Ddx (“all that wheezes is not asthma…”) Hyperventilation & panic attacks Upper airway obstruction or inh foreign body; laryngeal/vocal cord dysfxn (eg, 2° to GERD) CHF (“cardiac asthma”); COPD; bronchiectasis; ILD (including sarcoidosis); vasculitis; PE “Asthma plus” syndromes Atopy = asthma + allergic rhinitis + atopic dermatitis Aspirin-exacerbated respiratory disease (Samter’s syndrome) = asthma + ASA sensitivity + nasal polyps (J Allergy Clin Immunol 2015;135:676) ABPA = asthma + pulmonary infiltrates + allergic rxn to Aspergillus (Chest 2009;135:805) Dx: ↑ IgE to Asperg. & total (>1000), ↑ Asperg. IgG levels, ↑ eos, central bronchiectasis 85 Uploaded by MEDBOOKSVN.ORG  Pulmonary Rx: steroids ± itra-/voriconazole for refractory cases (NEJM 2000;342:756) Eosinophilic granulomatosis w/ polyangiitis (EGPA, previously Churg-Strauss) = asthma + eosinophilia + granulomatous vasculitis CHRONIC MANAGEMENT “Reliever” medications (used prn to quickly relieve sx) Short-acting inh β2-agonists (SABA): albuterol Rx of choice Short-acting inh anticholinergics (ipratropium) ↑ β2-agonist delivery → ↑ bronchodilation “Controller” meds (taken daily to keep control) (JAMA 2017;318:279) Inh corticosteroids (ICS) Rx of choice. Superior to LAMA if sputum w/ ≥2% eos (NEJM 2019;380:2009). PO steroids may be needed for severely uncontrolled asthma; avoid if possible b/c of systemic side effects. Long-acting inh β2-agonists (LABA; eg, salmeterol) safe & ↓ exacerbations when added to ICS (NEJM 2018;378:2497) Long-acting inh antimuscarinics (LAMA; eg, tiotropium, umeclidinium): may consider if sx despite ICS+LABA (JAMA 2018;319:1473) Leukotriene receptor antagonists (LTRA): some Pts very responsive, esp. ASA-sens (AJRCCM 2002;165:9) and exercise-induced (Annals 2000;132:97). May be noninferior to ICS initial Rx and LABA add-on Rx (NEJM 2011;364:1695). Nedocromil/cromolyn: limited use in adults. Useful in young Pts, exercise-induced bronchospasm; ineffective unless used before trigger or exercise exposure. Immunotherapies (NEJM 2017;377:965) Allergen ImmunoRx (“allergy shots”) may help if sig. allerg. component (JAMA 2016;315:1715) Anti-IgE (omalizumab) for uncontrolled mod-to-severe allergic asthma (w/ IgE >30) on ICS ± LABA (JAMA 2017; 318:279) Anti-IL5 (mepolizumab, reslizumab) ↓ exacerb in severe asthma (NEJM 2014;371:1189 & 1198) Anti-IL5Rα (benralizumab) ↓ steroid use, ↓ exac. in sev asthma w/ eos (NEJM 2017;376:2448) Anti-IL4Rα (dupilumab) blocks IL-4 & IL-13; ↓ exacerb in severe asthma, ↓ steroid use, ↑ FEV1 (NEJM 2018;378:2475 & 2486) Principles of treatment Education and avoidance of environmental triggers (Lancet 2015;386:1075); yearly flu shot Use quick-relief rescue medication as needed for all Pts Goal to achieve complete control = daily sx ≤2/wk, ∅ nocturnal sx or limitation of activity, reliever med ≤2/wk, nl peak expiratory flow rate or FEV1; partly controlled = 1–2 of the above present in a wk; uncontrolled = ≥3 of the above present in a wk Step up treatment as needed to gain control, step down as tolerated Can abort exacerb by quadrupling ICS if deteriorating control (NEJM 2018;378:902) 86 Asthma EXACERBATION Evaluation History: baseline PEF, steroid requirement, ED visits, hospital admissions, prior intubation Current exacerbation: duration, severity, potential precipitants, meds used Risk factors for life-threatening: prior intubation, h/o near-fatal asthma, ED visit/hosp for asthma w/in 1 y, current/recent PO steroids, not using ICS, overdependent on SABA, Ψ, h/o noncompliance Physical exam: VS, pulm, accessory muscle use, pulsus paradoxus, abdominal paradox Assess for barotrauma: asymmetric breath sounds, tracheal deviation, subcutaneous air → pneumothorax, precordial (Hamman’s) crunch → pneumomediastinum Diagnostic studies: peak expiratory flow (know personal best; 25 positive-pressure Results in 58% ↓ intubation, ↓ LOS by 3.2 d, 59% ↓ mortality ventilation Contraindications: Δ MS, inability to cooperate or clear secretions, hemodynamic instability, UGIB (NEJM 1995;333:817; Annals 2003;138:861; Cochrane 2004;CD004104; ERJ 2005;25:348) Endotracheal Consider if PaO2 1 ppd current smoker, no prior smoking cessation (NEJM 2003;348:2535 & 2013;369:910) Diagnostic studies PET: detects metabolic activity of tumors, 97% Se & 78% Sp for malig (esp if >8 mm) useful for surgical staging b/c may detect unsuspected mets (JAMA 2001;285:914) useful in deciding which lesions to bx vs. follow w/ serial CT (J Thor Oncol 2006;1:71) Transthoracic needle biopsy (TTNB): if tech feasible, 97% will obtain definitive tissue dx (AJR 2005;185:1294); if noninformative or malignant → resect Video-assisted thoracoscopic surgery (VATS): for percutaneously inaccessible lesions; highly sensitive and allows resection; has replaced thoracotomy Transbronchial bx (TBB): most lesions too small to reliably sample w/o endobronchial U/S (Chest 2003;123:604); bronch w/ brushings low-yield unless invading bronchus; navigational bronchoscopy w/ 70% yield, ↑ sens w/ larger nodules (Chest 2012;142:385) PPD, fungal serologies, ANCA Management (if >8 mm; if ≤8 mm, serial CT q6-12mo) (Chest 2013;143:840) Low risk (100 mL/h or >500 mL in 24 h; massive hemoptysis usually from tortuous or invaded bronchial arteries Etiologies (Crit Care Med 2000;28:1642) Infection/ Bronchitis (most common cause of trivial hemoptysis) Inflammation Bronchiectasis incl CF (common cause of massive hemoptysis) TB or aspergilloma (can be massive); pneumonia or lung abscess Neoplasm Usually primary lung cancer, sometimes metastasis (can be massive) Cardiovasc PE (can be massive), pulmonary artery rupture (2° to instrumentation), CHF, mitral stenosis, trauma/foreign body, bronchovascular fistula Other Vasculitis (GPA, Goodpasture’s, Behçet’s), AVM, anticoag (w/ underlying lung dis), coagulopathy, cocaine, pulm hemosiderosis Diagnostic workup Localize bleeding site (r/o GI or ENT source by H&P ± endo); determine whether unilateral or bilateral, localized or diffuse, parenchymal or airway by CXR/chest CT ± bronch PT, PTT, CBC to rule out coagulopathy Sputum culture/stain for bacteria, fungi and AFB; cytology to r/o malignancy ANCA, anti-GBM, urinalysis to ✔ for vasculitis or pulmonary-renal syndrome Treatment Death is from asphyxiation not exsanguination; maintain gas exchange, reverse coagulopathy and Rx underlying condition; cough suppressant may ↑ risk of asphyxiation Inhaled tranexamic acid promising (Chest 2018;154:1379) Massive hemoptysis: put bleeding side dependent; selectively intubate nl lung if needed Angiography: Dx & Rx (vascular occlusion balloons or selective embol of bronchial art) Rigid bronch: allows more options (electrocautery, laser) than flexible bronch Surgical resection 96 Bronchiectasis BRONCHIECTASIS Definition and epidemiology (NEJM 2002;346:1383) Obstructive airways disease of bronchi and bronchioles, chronic transmural inflammation w/ airway dilatation and thickening, collapsibility, mucus plugging w/ impaired clearance Initial workup H&P: cough, dyspnea, copious sputum production, ±hemoptysis, inspiratory “squeaks” CXR: scattered or focal; rings of bronchial cuffing; “tram track” of dilated, thick airways PFTs: obstructive; chest CT: airway dilation & thickening ± cystic Δs, infiltrates, adenopathy Etiology Other Features Diagnostic Testing Chronic infxns (eg, MTb, Chronic cough, freq/persist infiltrate, refract Sputum cx (incl mycobact, fungal), ± ABPA) asthma (ABPA) bronch/BAL, IgE & eos (ABPA) 1° ciliary dyskin Sinusitis, infertility, otitis Dynein mutations Immunodefic Recurrent infxns often as child IgA, IgG, IgM, IgG subclasses RA, SLE Resp sx may precede joint sx RF, ANA IBD Not relieved by bowel resection Colonoscopy, biopsy α1-AT deficiency Lower lobe emphysema α1-AT level Anatomic R middle lobe synd. from sharp takeoff, Bronchoscopy foreign body aspiration Treatment Acute exacerbations: antibiotics directed against prior pathogens; if no prior Cx data → FLQ Chronic mgmt: treat underlying condition, chest PT, inhaled hypertonic saline, bronchodil.; prophylactic azithro shown to ↓ exacerb in non-CF bronchiectasis (JAMA 2013:1251) Non-tuberculous mycobacterium (NTM; ubiquitous hydrophilic bacteria) Chronic cough, ↓ wt; Lady Windermere syndrome: R middle lobe bronchiectasis in elderly ♀ who suppress expectoration Dx: CT scan (tree-in-bud, nodules, cavities, bronchiect.), sputum ×3 or BAL, AFB stain + Cx Treatment: [azithro or clarithro] + rifamycin & ethambutol for ≥12 mo (Chest 2004;126:566) 97 Uploaded by MEDBOOKSVN.ORG  Pulmonary CYSTIC FIBROSIS Definition and pathophysiology (NEJM 2015;372:351) Autosomal recessive genetic disorder due to mutations in chloride channel (CFTR gene) ↑ mucus thickness, ↓ mucociliary clearance, ↑ infections → bronchiectasis Clinical features Recurrent PNA, sinus infections Distal intestinal obstruction syndrome (DIOS), pancreatic insufficiency (steatorrhea, malabsorption, failure to thrive, weight loss), CF-related diabetes, infertility Treatment (Lancet 2016;388:2519) Acute exacerbations: may be assoc w/ persistent drop in FEV1 (AJRCCM 2010;182:627); continue aggressive airway clearance, target abx based on sputum cx (incl double coverage for PsA); common pathogens include PsA, S. aureus, non-typeable H flu, Stenotrophomonas, Burkholderia, NTM Chronic mgmt: airway clearance with chest PT, inhaled hypertonic saline, inhaled DNAse (dornase alfa), SABA; oral azithromycin if chronic respiratory symptoms, inhaled tobramycin or aztreonam if persistent PsA infection CFTR potentiator (ivacaftor) or corrector (lumacaftor, tezacaftor) depending on mutation; combination approved for patients homozygous for ΔF508 (most common mutation) (NEJM 2011;365:1663; 2015;373:220; 2017;377:2013 & 2024) Lung transplantation; refer to lung transplant center when FEV1 12 mo peripheral, subpleural, & basal 5-y mort ~80% NSIP Homogenous ground-glass opacities or consolid., reticular irreg lines; Sx mos–y symmetric, peripheral, basal, subpleural. Cellular & fibrotic subtypes, latter 5-y mort 10% similar to UIP. COP Patchy, migratory consolidations; subpleural & peribronchial. Excessive Post-infxn, XRT, rxn proliferation of granulation tissue in small airways and alveolar ducts. to drug. 5-y mort 40, pleural bx ~70% Se Fungal, viral (usually small), parasitic (eg, amebiasis, echinococcosis, paragonimiasis) Malignancy (15%): primary lung cancer most common, metastases (esp. breast, lymphoma, etc.), mesothelioma (✔ serum osteopontin levels; NEJM 2005;353:15) Pulmonary embolism (10%): effusions in ~40% of PEs; exudate (75%) > transudate (25%); hemorrhagic—must have high suspicion b/c presentation highly variable Collagen vascular disease: RA (large), SLE (small), GPA, EGPA Abdominal diseases: pancreatitis, cholecystitis, esophageal rupture, abdominal abscess Hemothorax (Hcteff/Hctblood >50%): trauma, PE, malignancy, coagulopathy, leaking aortic aneurysm, aortic dissection, pulmonary vascular malformation Chylothorax (triglycerides >110): thoracic duct damage due to trauma, malignancy, LAM Other: Post-CABG: left-sided; initially bloody, clears after several wks Dressler’s syndrome (pericarditis & pleuritis post-MI), uremia, post-radiation therapy Asbestos exposure: benign; ⊕ eosinophils Drug-induced (eg, nitrofurantoin, methysergide, bromocriptine, amiodarone): ⊕ eos Uremia; post-XRT; sarcoidosis Meigs’ syndrome: benign ovarian tumor → ascites & pleural effusion Yellow-nail syndrome: yellow nails, lymphedema, pleural effusion, bronchiectasis 103 Uploaded by MEDBOOKSVN.ORG  Pulmonary Diagnostic studies (NEJM 2018;378:740) Thoracentesis (ideally U/S guided) (NEJM 2006;355:e16) Indications: all effusions >1 cm in decubitus view if suspect due to CHF, can diurese and see if effusions resolve (75% do so in 48 h); asymmetry, fever, chest pain or failure to resolve → thoracentesis parapneumonic effusions should be tapped ASAP (cannot exclude infxn clinically) Diagnostic studies: ✔ total protein, LDH, glucose, cell count w/ differential, Gram stain & culture, pH; remaining fluid for additional studies as dictated by clinical scenario Complications: PTX (5–10%), hemothorax (~1%), re-expansion pulm edema (if >1.5 L removed), spleen/liver lac.; post-tap CXR not routinely needed (Annals 1996;124:816) ↓ PTX w/ U/S and experienced supervisor; even with INR ~1.9, risk of bleed low w/ U/S & experienced operator (Chest 2009;135:1315 & 2013;144:456; Archives 2010;170:332) Transudate vs. exudate (JAMA 2014;311:2422) Light’s criteria: exudate = TPeff/TPserum >0.5 or LDHeff/LDHserum >0.6 or LDHeff >2/3 ULN of LDHserum; 97% Se, 85% Sp; best Se of all methods; however, will misidentify 25% of transudates as exudates; ∴ if clinically suspect transudate but meets criterion for exudate, confirm w/ test w/ higher Sp Exudative criteria w/ better Sp: choleff >55 mg/dL (95–99% Sp); choleff >45 mg/dL and LDHeff >200 (98% Sp); choleff/cholserum >0.3 (94% Sp); serum-effusion alb gradient ≤1.2 (92% Sp); serum-effusion TP gradient ≤3.1 (91% Sp) CHF effusions: TP may ↑ with diuresis or chronicity → “pseudoexudate”; alb gradient ≤1.2, choleff >60 mg/dL (Se 54%, Sp 92%) or clin judgment to distinguish (Chest 2002;122:1524) Complicated vs. uncomplicated parapneumonic (Chest 1995;108:299) complicated = ⊕ Gram stain or culture or pH 10%) → blood, air, drug rxn, asbestos, paragonimiasis, Churg- Strauss, PE RBC: Hcteff 1–20% → cancer, PE, trauma; Hcteff/Hctblood >50% → hemothorax AFB: yield in TB 0–10% w/ stain, 11–50% w/ culture, ~70% w/ pleural bx adenosine deaminase (ADA): seen w/ granulomas, >70 suggests TB, 60; seen in chronic effusions (eg, CHF, RA, old TB) 104 Pleural Effusion creatinine: effusion/serum ratio >1 → urinothorax fibulin-3: ↑ plasma and/or effusion levels → mesothelioma (NEJM 2012;367:1417) Chest CT; pleural biopsy; VATS Undiagnosed persistent pleural effusions (Clin Chest Med 2006;27:309) Transudative: most commonly CHF or hepatic hydrothorax. ✔ s/s CHF or cirrhosis, NT-proBNPeff; consider intraperitoneal injection of technetium-99m sulfur colloid Exudative (ensure using Sp test listed above): most commonly malig, empyema, TB, PE. ✔ s/s malig, chest CT (I+), ADA or IFN-γ release assay; consider thoracoscopy. Treatment Symptomatic effusion: therapeutic thoracentesis, treat underlying disease process Parapneumonic effusion (Chest 2000;118:1158) uncomplicated → antibiotics for pneumonia >½ hemithorax or complicated or empyema → tube thoracostomy (otherwise risk of organization and subsequent need for surgical decortication) loculated→ tube thoracostomy or VATS; intrapleural t-PA + DNase ↓ need for surgical referral (NEJM 2011;365:518) Malignant effusion: serial thoracenteses vs. tube thoracostomy + pleurodesis (success rate ~80–90%) vs. indwelling pleural catheter, which ↓ hosp days but ↑ adverse events 105 Uploaded by MEDBOOKSVN.ORG  Pulmonary systemic steroids & pH 6 h (NEJM 2001:779) injury to endothelium: trauma, surgery, prior DVT, inflam, central catheter thrombophilia: genetic disorders (qv), HIT, OCP, HRT, tamoxifen, raloxifene Malignancy (12% of “idiopathic” DVT/PE; Circ 2013;128:2614) History of thrombosis (greater risk of recurrent VTE than genetic thrombophilia) Obesity, smoking, acute infection, postpartum (JAMA 1997;277:642; Circ 2012;125:2092) Thromboprophylaxis (Chest 2012;141:e195S, 227S, 278S) Patient & Situation Prophylaxis Low-risk med; same-day surg & 3 cm c/w unaffected side), venous distention, erythema, warmth, tenderness, palpable cord, ⊕ Homan’s sign (calf pain on dorsiflexion, seen in 70%), crackles (51%), ↑ HR (30%), fever, cyanosis, pleural friction rub, loud P2 Massive: syncope, HoTN, PEA; ↑ JVP, R-sided S3, Graham Steell (PR) murmur Simplified Wells Pretest Probability Scoring for PE (Annals 2011;154:709) Prior PE or DVT Clinical signs of DVT Active cancer HR >100 bpm Immobilization (bed rest ≥3 d) or surgery w/in 4 wk Hemoptysis Alternative dx less likely than PE Dichotomized Wells Probability Assessment ≤1 Variable = “Unlikely” (13% probability) ≥2 Variables = “Likely” (39% probability) Diagnostic studies—PE (EHJ 2014;35:3033) CXR (limited Se & Sp): 12% nl, atelectasis, effusion, ↑ hemidiaphragm, Hampton hump (wedge-shaped density abutting pleura); Westermark sign (avascularity distal to PE) ECG (limited Se & Sp): sinus tachycardia, AF; signs of RV strain → RAD, P pulmonale, RBBB, SIQIIITIII & TWI V1–V4 (McGinn-White pattern; Chest 1997;111:537) ABG: hypoxemia, hypocapnia, respiratory alkalosis, ↑ A-a gradient (Chest 1996;109:78) 18% w/ room air PaO2 85–105 mmHg, 6% w/ nl A-a gradient (Chest 1991;100:598) 108 Venous Thromboembolism D-dimer: high Se, poor Sp (~25%); ELISA has >99% NPV ∴ use to r/o PE if “unlikely” pretest prob (JAMA 2006;295:172); cut-off 500 if 60L/min. (Adapted from Marino P. The ICU Book, 4th ed, Philadelphia: LWW, 2014:431) Noninvasive Positive Pressure Ventilation (NPPV) (NEJM 2015;372:e30) Indications (Lancet Clinical: mod–severe dyspnea, RR >24–30, signs of ↑ work of breathing, accessory muscle 2009;374:250) use, abd paradox Gas exchange: PaCO2 >45 mmHg (& significantly worse than baseline), hypoxemia, PaO2/FiO2 7.2. Acute ventilatory deterioration (usually ↑ PIP) Response to ↑ PIP: disconnect Pt from vent, bag, auscultate, suction, ✔ CXR & ABG Figure 2-7 Approach to acute ventilatory deterioration 120 Mechanical Ventilation (Adapted from Marino PL. The ICU Book, 4th ed., Philadelphia: LWW, 2014) Liberating from the ventilator (NEJM 2012;367:2233; Lancet 2016;387:1856) Perform daily assessment of readiness for spontaneous breathing trial (SBT) Clinical screening criteria: VS stable, minimal secretions, adequate cough, cause of respiratory failure or previously failed SBT reversed Vent parameters: PaO2/FiO2 >200, PEEP ≤5, f/VT 105 predicts failure, NPV 0.95 (NEJM 1991;324:1445) Daily awakening trial (d/c all sedation; Lancet 2008;371:126): open eyes & w/o: agitation, RR >35, SaO2 0.6) Ventilator-induced lung injury (see “ARDS”) Ventilator-associated pneumonia (~1%/d, mortality rate ~30%) typical pathogens: MRSA, Pseudomonas, Acinetobacter and Enterobacter species preventive strategies (AJRCCM 2005;171:388): wash hands, HOB elevated, non-nasal intub., enteral nutrition rather than TPN?, routine suction of subglottic secretions, avoid unnecessary abx & transfusions; routine oral antiseptic controversial Stress ulcers/GIB: prophylaxis w/ PPI ↓ GIB, but no Δ in overall course (NEJM 2018;379:2199) Laryngeal edema: for Pts vent >36 h; ? predicted by ⊕ cuff leak test. Methylprednisolone 20 mg IV q4h starting 12 h pre-extub. → ↓↓ edema and 50% ↓ in reintubation (Lancet 2007;369:1003). ulceration: consider tracheostomy for Pts in whom expect >14 d of mech vent → ↓ duration mech vent, ↓ # ICU days (BMJ 2005;330:1243); no benefit to performing at ~1 121 Uploaded by MEDBOOKSVN.ORG  Pulmonary wk vs. waiting until ~2 wk (JAMA 2010;303:1483) Malnutrition (for all critically ill Pts): enteral nutrition initiated early is safe but not necessary (JAMA 2012;307:795), but bolus may ↑ risk of VAP & C diff. (JPEN 2002;26:174); no clear benefit to ✔ing gastric residuals (JAMA 2013;309:249); permissive enteral underfeeding (~1/2 of calculated caloric req) & standard enteral feeding w/ similar outcomes (NEJM 2015;372:2398); parenteral nutrition should be delayed until after day 8 to ↓ risk of infections, cholestasis, RRT, ventilator days (NEJM 2011;365:506) Oversedation/delirium: BDZs and polypharmacy are risk factors propofol: HoTN in ~25%; propofol infusion syndrome (PRIS) ? espec w/ high (>5 mg/kg/h) & prolonged (>48 h) infusions & concom vasopressors → ↑ AG, cardiac dysfxn, rhabdomyolysis, ↑ triglycerides, & renal failure (Crit Care 2009;13:R169) dexmedetomidine: no clear benefit on vent-free days (JAMA 2016;315:1460 & 2017;317:1321); dosen't work as sole agent, but spares use of other (NEJM 2019;380:2506) 122 Acute Respiratory Distress Syndrome ACUTE RESPIRATORY DISTRESS SYNDROME Berlin definition (JAMA 2012;307:2526) Acute onset within 1 week of clinical insult or worsening respiratory status Bilateral infiltrates without alternative explanation (eg, effusion, atelectasis, nodules) Edema not fully explained by fluid overload or congestive heart failure Hypoxemia: PaO2/FiO2 determined with 5 cm H2O of PEEP PaO2/FiO2 200–300 = mild ARDS (may be on NPPV), 100–200 = mod, 20 or PaCO2 12k or 10% bands. No longer used. Shock (see “PA Catheter & Tailored Therapy” for subtypes; NEJM 2013;369:1726) Tissue hypoxia due to ↓ tissue perfusion and hence ↓ tissue O2 delivery and/or ↑ O2 consumption or inadequate O2 utilization Typical signs include HoTN (SBP 40 mmHg), tachycardia, oliguria (UOP 0.9 and pulse pressure [(SBP – DBP)/SBP] 10% ↑ in pulse pressure w/ passive leg raise. Static CVP poor surrogate. After early resuscitation, if ALI/ARDS, target CVP 4–6 mmHg because additional fluids may be harmful → ↑ ventilator/ICU days (NEJM 2006;354:2564; Chest 2008;133:252) Pressors & inotropes (also see “ICU Medications”) MAP target 65–70 mmHg as good as 80–85 and ↓ AF (NEJM 2014;370:1583) Norepinephrine: ↓ arrhythmia & mortality c/w dopamine (NEJM 2010;362:779; Crit Care Med 2012;40:725) and ∴ is pressor of choice in septic shock Vasopressin: adding to norepi (vs. using high-dose norepi) ↓ risk of AF & RRT by ~¼ (JAMA 2018;319:1889) If targets (see below) not reached after adequate fluids and pressors, consider inotropes 125 Uploaded by MEDBOOKSVN.ORG  Pulmonary Targets Lactate clearance (≥20%/2 h) as effective as ScvO2 to guide resusc. (JAMA 2010;303:739) Targeting capillary refill time ≤3 sec (check q30min) as good if not better than lactate clearance (JAMA 2019;321:654) Antibiotics Start empiric IV abx as soon as possible following recognition of severe sepsis or septic shock; every hr delay in abx admin a/w 7.6% ↑ in mortality (Crit Care Med 2006;34:1589), abx admin w/in 3 h of presentation in the ED a/w ↓ in-hospital mortality (NEJM 2017;376:2235) If possible, obtain 2 sets of BCx before urgently starting abx (but do not delay abx) Broad gram-positive (incl MRSA) & gram-neg (incl highly resistant) coverage, ± anaerobes Procalcitonin-guided cessation (not initiation) ↓ mortality (Crit Care Med 2018;46:684) Empiric micafungin in critically ill Pts w/ Candida colonization & sepsis of unknown etiology ↓ invasive fungal infxns & tended ↑ invasive fungal infxn-free survival, espec. in Pts w/ 1,3-b-D-glucan >80 (JAMA 2016;316:1555) Steroids (Crit Care Med 2018;46:1411) Hydrocortisone 50 mg IV q6 + fludrocortisone 50 µg via NGT daily in septic shock ↓ duration of shock and may ↓ mortality (NEJM 2018; 378:797 & 809) Consider in Pts w/ refractory shock on escalating doses of pressors Early Goal-Directed Therapy (EGDT) Historically: IVF & pressors for MAP ≥65 mmHg, CVP 8–12 mmHg, UOP ≥0.5 mL/kg/h; inotropes & PRBCs for ScvO2 ≥70% in 6 h (NEJM 2001;345:1368) However, now in era of early abx and adequate fluid resuscitation, no ↓ in mortality w/ EGDT vs. current usual care, and ↑ hospital costs (NEJM 2017; 376:2223) 126 Toxicology TOXICOLOGY Drug/Toxin Signs/Sx and Diagnostics Management Options Acetaminophen Vomiting, ↑ AG & nl OG metabolic N-acetylcysteine (NAC) infusion acidosis, hepatitis & hepatic failure, renal Hemodialysis if massive O/D failure See “Acute liver failure” Salicylates Tinnitus, hyperventilation, abd. pain, IVF resuscitation vomiting, ΔMS, Alkalinization w/ NaHCO3 mixed ↑ AG & nl OG metabolic acidosis + Maintain respiratory alkalemia respiratory alkalosis Consider hemodialysis Opioids ↓ mentation, ↓ RR, miosis IV naloxone Benzodiazepines ↓ mentation, ataxia, ↓ RR Flumazenil not rec (can precipitate withdrawal/seizures) Calcium channel blockers Bradycardia, AV block, hypotension, HF, IVF, vasopressors, Ca infusion, hyperglycemia hyperinsulinemic euglycemia, ? intralipid emulsion, pacing Beta blockers Bradycardia, AV block, hypotension, HF, Glucagon, vasopressors, pacing hypoglycemia Digoxin N/V, bradycardia, AV block, delirium, Correct hypokalemia xanthopsia Digibind if hyperkalemia, life-threatening ✔ serum dig level (but may be inaccurate dysrhythmia if cyclosporine (↓ incidence of acute rejection) + steroids + MMF/azathioprine Monitoring: clinic visits, serial PFTs, chest X-ray, bronchoscopy w/ transbronchial biopsy Complications Primary graft dysfunction (PGD): acute lung injury following txp; assoc w/ early mortality Anastomotic: vascular (stenosis, thrombosis) and airway (infection, necrosis, dehiscence, granulation tissue, tracheobronchomalacia, stenosis, fistula) Acute rejection: ↓ lung fxn, cough, SOB, fever; Dx w/ trans-bronch bx; Rx immunosupp Chronic rejection: bronchiolitis obliterans w/ obstruction; Dx w/ PFTs, trans-bronch bx; Rx limited (azithromycin, montelukast, Δ immunosuppressives) Infection: ↑ bacterial, fungal, viral pneumonia, systemic infections, CMV, OI Malignancy: 2× ↑ risk overall. 5.5× ↑ risk lung cancer. PTLD (assoc w/ EBV) common. Misc: GVHD, CKD, DM, CAD, CHF, stroke, encephalopathy, drug toxicity 128 Gastroenterology ESOPHAGEAL AND GASTRIC DISORDERS DYSPHAGIA Oropharyngeal: inability to propel food from mouth through UES into esophagus Esophageal: difficulty swallowing & passing food from esophagus into stomach Figure 3-1 Etiologies of and approach to dysphagia (NCP Gastrohep 2008;5:393; Neurogastro 2012;24:57) Structural dysphagia (solids > liquids; JAMA 2015;313:18; Gastro 2018;155:1022) Oropharyngeal Zenker’s divertic. (pharyngeal pouch): in elderly, a/w aspir., dx w/ video fluoro, Rx endo/surg Malignancy; proximal strictures/rings/webs; infection; radiation injury; goiter; osteophytes Esophageal Rings (intermittent dysphagia, concentric obstructing tissue, eg, Schatzki ring): near GE jxn, a/w food impaction, linked to GERD; Rx w/ PPI, dilation Webs (nonconcentric): usually prox, can be a/w Fe defic. (Plummer-Vinson synd.) Peptic or XRT strictures, foreign body, tumor, vascular compression (dysphagia lusoria) Infxn esophagitis: odynophagia > dysphagia; often immunosupp w/ Candida, HSV, 129 Uploaded by MEDBOOKSVN.ORG  Gastroenterology CMV Pill esophagitis: odynophagia > dysphagia; NSAID, KCl, bisphosp., doxy & tetracycline Eosinophilic esophagitis: often young/middle-aged ♂. Dx: >15 eos/hpf on bx, esoph dysfxn (ie, dysphagia, food impaction). Rx: 1st line is PPI (½ respond); alternative (or if fail PPI) is 3Ds: 1st try elimination Diet (∅ milk, soy, eggs, wheat, nuts, fish); if no Δ, Drugs (swallow inh steroids); if ongoing sx & stricturing, Dilation. Neuromuscular dysphagia (solids & liquids; Neurogastero Motil 2015;27:160 & 2016;22:6) Caused by aberrant motility or innervation of oropharynx/esophagus Oropharyngeal: consider CNS disorders (eg, stroke, ALS, myopathies, CNS tumors) Esophageal: motility disorder w/ dysphagia, chest pain, GERD; dx: conventional or high- res manometry w/ esophageal pressure topography. Chicago classification v3.0: 1. Incomplete LES relaxation: Isolated EGJ outflow obstruction or achalasia. Achalasia: simult. ↓ amp contractions & ↓ LES relaxation; barium swallow w/ dilated esophagus & distal “bird’s beak” narrowing; mostly idiopathic, although can be a/w Chagas; Rx: pneumatic dilation as effective as Heller myotomy (local expertise dependent) (Gut 2016;65:732); peroral endoscopic myotomy; CCB/nitrates/PDEi; Botox if ∅ surg cand. 2. Major motility disorders: Absent contractility; Distal spasm (uncord. peristalsis w/ simult. contractions); Hypercontractile (high amp contract.; Rx w/PPI, nitrates/CCB/PDEi, TCA) 3. Minor motility disorders: Fragmented peristalsis; Hypomotility (↓ amp of distal esoph contractions; seen in scleroderma, DM, hypothyroid.; Rx w/ underlying disorder & w/ PPI) GASTROESOPHAGEAL REFLUX DISEASE (GERD) Pathophysiology ↑ acid exposure in esophagus, caused by ↑ transient LES relaxations. Worsened by ↑ intraabd pressure (eg, obesity, pregnancy), ↓ esophagogastric motility, hiatal hernia. Rarely caused by ↑ acid production except in ↑ secretory states (eg, Zollinger-Ellison) Precipitants: supine position, fatty foods, caffeine, alcohol, cigarettes, CCB, pregnancy Clinical manifestations Esophageal: heartburn, atypical chest pain, regurgitation, water brash, dysphagia Extraesophageal: cough, asthma (often poorly controlled), laryngitis, dental erosions Diagnosis (Annals 2015;163:ITC1; Nat Rev Gastro Hepatol 2016;13:501) Clinical diagnosis based on sx and response to empiric trial of PPI (“PPI test”) EGD: if (1) ∅ response to PPI; or if (2) alarm features: dysphagia, vomiting, ↓ wt, anemia If dx uncertain & EGD nl → esoph manometry w/ 24-h pH monitoring ± impedance to dx: “Nonerosive reflux disease”: no erosion, ulceration or Barrett’s; ½ abnl pH. Unpredictable response to PPI. Most will not progress to erosive esophagitis or Barrett’s. 130 Gastroenterology “Reflux hypersensitivity”: nl acid exposure on pH/impedance w/ symptom–reflux assoc. “Functional heartburn”: nl acid exposure on pH/impedance w/o symptom–reflux assoc. Treatment (World J Gastrointest Endosc 2018;10:175) Lifestyle: avoid precipitants, lose weight, avoid large & late meals, elevate head of bed Medical: PPI achieve relief in 80–90% of Pts; H2 blockers for intermittent sx Refractory: confirm w/ pH testing (on PPI to assess need for ↑ Rx, or off PPI to verify dx). If acidic or sx correlate w/ reflux episodes: surgical fundoplication (emerging Rx: LES sphincter augmentation w/ radiofrequency, implantable magnetic or electrical devices) If nl pH or no sx correlation: Dx: ”functional heartburn”. Rx w/ TCA, SSRI or baclofen. Complications (Gastro Clin NA 2015;44:203; Gastro 2015;149:567 & 1599) Reflux esophagitis (erosions/ulcers above GE jxn), strictures (caused by chronic inflamm) Barrett’s esoph. (BE): metaplastic columnar mucosa above GE jxn replaces squam epithel. Screen if chronic (>5 y) and/or frequent GERD (≥1/wk) in ♂ w/ ≥2 risk factor for Barrett’s/esophageal adeno: >50 y, white, hiatal hernia, central adiposity, smoking, FHx of Barrett’s/esophageal adeno. In ♂, consider only if multiple RFs. 0.1–0.3%/y risk of esoph adenocarcinoma, ↑ if ↑ dysplasia (Am J Gastro 2016;111:30). Mgmt: PPI. W/o dysplasia: surveillance EGD q3–5y. Low-grade dysplasia: EGD q12mo; possible endoscopic eradication. High-grade dysplasia: endoscopic eradication; consider chemoprophylaxis w/ high-dose PPI & ASA (Lancet 2018;392:400). PEPTIC ULCER DISEASE (PUD) Definition & etiologies (Lancet 2017;390:613) Ulcers (break in mucosal lining >5 mm) & erosions ( NSAID/ASA use H. pylori infection: causes ~60–70% of duodenal ulcers (DU) & ~30–40% of gastric ulcers (GU). ~50% of world colonized w/ H. pylori, but only 5–10% will develop PUD. ASA & NSAIDs: damage to mucosa caused by ↓ prostaglandin synthesis. Cause majority of non–H. pylori-related DU & GU. Regular use a/w 5–6× ↑ odds of GIB. Other: smoking, stress, excessive EtOH, gastric cancer/lymphoma, Crohn’s, viral infxn (eg, CMV/HSV in immunosupp), bisphosphonates, steroids (in combo w/ NSAIDs, but not risk factor alone); rarely gastrinoma (Zollinger-Ellison synd.), mastocytosis, idiopathic Stress ulcer: risk factors = ICU & coagulopathic, mech vent, h/o GIB, steroid use; Rx w/ PPI Clinical manifestations Epigastric gnawing abdominal pain: relieved with food (DU) or worsened by food (GU) Complications: UGIB, perforation & penetration, gastric outlet obstruction Diagnostic studies 131 Uploaded by MEDBOOKSVN.ORG  Gastroenterology Testing for H. pylori: stool Ag, urea breath testing (UBT) or EGD + rapid urease test (RUT) False ⊖ Ag, UBT, RUT if on abx, bismuth, PPI; ∴ stop prior to testing if possible Serology: ↓ utility, useful only to exclude infection in low prevalence areas (most of U.S.) EGD (definitive dx): if fail empiric Rx or alarm features (see “GERD”); bx GU to r/o malig & H. pylori; relook in 6–12 wk if >2 cm, malig features, risk factors for gastric cancer (ie, ⊕ FHx, ⊕ H. pylori, atrophic gastritis, dysplasia/ metaplasia on bx, >50 y), or sx persist Treatment (Lancet 2016;388:2355; Gastro 2016;151:51; Gut 2017;66:6; AJG 2017;112:212) If H. pylori ⊕ → eradicate (“test and treat”); if ⊖ → gastric acid suppression w/ PPI 1st line: Quad. Rx: 14d x [MNZ + TCN + bismuth + PPI] or [MNZ + amox + clarith + PPI] Besides PUD, test & Rx if: gastric MALT lymphoma, s/p resection for early gastric ca, FHx gastric ca, unexplained iron def. anemia, ITP, uninvestigated dyspepsia in Pt 60 y, steroids or dyspepsia; prior to start test & Rx H. pylori Consider Δ non-selective NSAID to selective COX-2 inhibitor (↓ PUD & UGIB but ↑ CV events) if low CV risk & not on ASA 132 Gastrointestinal Bleeding GASTROINTESTINAL BLEEDING Definition Intraluminal blood loss anywhere from the oropharynx to the anus Classification: upper = above the ligament of Treitz; lower = below the ligament of Treitz “Severe” GIB: defined as having associated shock, orthostatic hypotension, ↓ Hct by 6% (or ↓ Hb by 2 g/dL), or requiring transfusion ≥2U PRBCs. Requires hospitalization. Clinical manifestations Hematemesis = blood in vomitus (UGIB) Coffee-ground emesis = emesis of blood exposed to gastric acid (UGIB) Melena = black, tarry stools from digested blood (usually UGIB, but can be from R colon) Hematochezia = bloody or maroon-colored stools (LGIB or rapid UGIB) Initial management Assess severity: VS including orthostatic Δs, JVP. Tachycardia (can be masked by βB use) suggests 10% volume loss, orthostatic hypotension 20% loss, shock >30% loss. Scoring systems predict rebleeding & mortality: AIMS65 & Glasgow-Blatchford. History: prior GIB, tempo of current bleed, specific bleeding manifestations (see above), other GI s/s (eg, abd pain, Δ in bowel habits, weight loss, N/V), NSAID/ASA or EtOH use, anticoag/antiplt drugs, h/o or risk factors for cirrhosis, radiation, prior GI or aortic surgery Physical exam: localizable abd tenderness, peritoneal signs, masses, LAN, prior surgery, signs of liver disease (hepatosplenomegaly, ascites, jaundice, telangiectasias), rectal exam: masses, hemorrhoids, anal fissures, stool appearance, color Resuscitation: placement of 2 large-bore (18-gauge or larger) intravenous lines Volume replacement: NS or LR to achieve normal VS, UOP, & mental status Lab studies: Hct (may be normal in first 24 h of acute GIB before equilibration) 2–3% → 500 mL blood loss; low MCV → Fe deficient and chronic blood loss; plt, PT, PTT; BUN/Cr (ratio >36 in UGIB b/c GI resorption of blood ± prerenal azotemia); LFTs Transfuse: type & cross; use O-neg if emerg; for UGIB (esp. w/ portal HTN) transfuse w/ more restrictive Hb goal (eg, 7 g/dL) or >8 g/dL if CAD (JAMA 2016;316:2025) Reverse coagulopathy: consider FFP to normalize PT; plts to keep count >50,000 Triage: alert endoscopist. Consider ICU if unstable VS or poor end organ perfusion. Intubation for: emergent EGD, ongoing hematemesis, shock, poor resp status, Δ MS ? OutPt management if SBP ≥110, HR 95% of cases (GI Endo 2015;81:889). Imaging: if too unstable for endo or recurrent bleeding, can then → IR procedure or surgery tagged RBC scan: can identify general luminal location if bleeding rate ≥0.04 mL/min CT angiography: faster to obtain than RBC scan, detects bleeding ≥0.3 mL/min arteriography: can localize exact vessel if bleeding rates ≥0.5 mL/min, allows for IR Rx Emergent exploratory laparotomy (last resort) if no localization and life-threatening bleed Etiology UGIB Comment & Treatment PUD (20–67%) Treatment: PPI: 40 mg PO or IV BID. ? Octreotide if suspect varices. (Am J Gastro 2014;109:1005; Endoscopic therapy: epi inj + bipolar cautery or hemoclip. Bx for ? H. pylori and NEJM 2016;374:2367; Br J Clin treat if ⊕. Pharm 2017;83:1619) High-risk (for rebleeding) ulcer: arterial spurting, adherent clot, visible vessel. Endo See “PUD” Rx, IV PPI × 72 h post EGD, then Δ to high-dose oral PPI. If fail, arteriography w/ embolization; surgery (last resort). Intermediate-risk ulcer: oozing, in o/w stable Pt. Endo Rx, can Δ to oral PPI after EGD and observe 24–48 h. Low-risk ulcer: clean-based or flat. Oral PPI & ? discharge. Hold anticoag & antiplatelet Rx until hemostasis; can resume after hemostasis & PPI on board (Endoscopy 2015;47:a1) Erosive gastropathy Precipitants: NSAIDs, ASA, EtOH, cocaine, gut ischemia, XRT (4–31%) Stress-related mucosal injury in ICU Pts. Risk factors include severe coagulopathy, mech vent >48 h, high-dose glucocorticoids Treatment: high-dose PPI Erosive esopha-gitis (5–18%) Risk factors: cirrhosis, anticoagulation, critical illness. Rx offending cause + high- dose PPI; repeat EGD later to r/o underling Barrett’s. Esophageal or gastric varices (4– 2° to portal HTN. If isolated gastric → r/o splenic vein thrombosis. 20%) Pharmacologic (Clin Gastro Hepatol Start octreotide pending EGD if suspect varices: 50 µg IVB → 50 µg/h (84% 2015;13:2109; J Gastro Hepatol success). Rx for 2–5 d, but most benefit w/in 24–48 h. 2016;31:1519; Hep 2017;65:310) Abx: 20% cirrhotics p/w GIB have infxn, & ~50% develop infxn during See “Cirrhosis” hospitalization; Ppx w/ IV CTX, cipro, or levoflox × 7 d Nonpharmacologic Esophageal varices: endoscopic band ligation (>90% success). Covered esophageal stent placement or balloon tamponade if refractory as bridge to TIPS (consider early espec. if Child-Pugh C). Gastric varices: arteriography w/ coiling, or if available, endoscopic injection of cyanoacrylate (glue). If refractory: TIPS or balloon-retrograde transvenous obliteration. Portal HTN gastropathy ↑ portal venous pressure → ectatic vessels, hyperemia in prox. gastric body. No endoscopic option; Rx portal HTN (octreotide), βB. Angioectasia AVMs, AVMs congenital. Angioectasia (ectatic submucosal vessels) a/w ↑ age, CKD, HHT (see below) cirrhosis, CTD, severe CV dis. Heyde syndrome: GIB due to angioectasias + aortic stenosis. Endo Rx. Dieulafoy’s lesion Large (1–3 mm) submucosal artery protruding through fundal mucosa → sudden, Vascular massive UGIB. Difficult to identify. Endo Rx. (2–8%) Gastric antral vasc. “Watermelon stomach”; ectatic gastric vessels, often a/w cirrhosis, CTD, typically ectasia (GAVE) older ♂. Rx w/ EGD w/ thermal hemostasis, repeat q4–8wk to eradicate lesions. 134 Gastrointestinal Bleeding TIPS does not improve outcomes. Aortoenteric fistula AAA or aortic graft erodes into 3rd portion of duodenum. P/w “herald bleed”; if suspected, diagnose by endoscopy or CT. Malignancy (2–8%) Endoscopic hemostasis of mass temporizing measure till cancer Rx Mallory-Weiss tear (4–12%) GE jxn lacerations due to vomiting → ↑ intraabd pressure & shearing effect. Can self-resolve w/o endo Rx. Rx w/ antiemetics, PPI. Cameron’s lesions Linear erosions in hiatal hernia due to mech trauma of diaphragm Post-sphincter-otomy bleeding Occurs in ~2% of ERCP w/ sphincterotomy; ↑ risk w/ more complic. procedure. Bleeding into duodenum. Rx w/ endo hemostasis. (GI Endosc Clin N Am 2015;25:415) Etiology LGIB Comment & Treatment (NEJM 2017;376:1054) Diverticular bleed Pathophysiology: Intimal thickening and medial thinning of vasa recta as they course over dome (30%)