habeas NOTEBOOK POCKET MEDICINE SIXTH EDITION Marc S. Sabatine The Massachusetts General Hospital Handbook of Internal Medicine SE AW ollie AUN lga | CONTESTS... | Contributing Authors vi Foreword ix Preface x CARDIOLOGY Nino Mihatoy, John D. Serfas, J. Sawalla Guseh, William J. Hucker, Marc S. Sabatine, Michelle L. O'Donoghue Electrocardiography 14 Chest Pain 1-3 Noninvasive Evaluation of CAD 14 Coronary Angiography and Revascularization 15 Acute Coronary Syndromes 16 PA Catheter and Tailored Therapy 1-12 Heart Failure 1-14 Cardiomyopathies 1-17 Valvular Heart Disease 1-20 Pericardial Disease 1-25 Hypertension 1.28 Aortic Aneurysms 130 Acute Aortic Syndromes 1-31 Arrhythmias 41a, Atrial Fibrillation 1-35 Syncope 137 Cardiac Rhythm Management Devices 1-39 Cardiac Risk Assessment for Noncardiac Surgery 1-40 Peripheral Artery Disease 1-41 PULMONARY Alyssa Sclafani, Elias N. Baedorf Kassis, Walter J. O'Donnell Dyspnea 2-1 Pulmonary Function Tests 21 Asthma 2-2 Anaphylaxis 2-4 Chronic Obstructive Pulmonary Disease 2-5 Hemoptysis 2-7 Bronchiectasis 27 Solitary Pulmonary Nodule 28 Sleep Apnea 2-8 Interstitial Lung Disease 2-9 Pleural Effusion 2-11 Venous Thromboembolism 2-13 Pulmonary Hypertension 2-16 Respiratory Failure 218 Mechanical Ventilation 2-19 Acute Respiratory Distress Syndrome 2-22 Sepsis and Shock 2-23 Toxicology 2-24 Lung Transplant 2-24 GASTROENTEROLOGY Vanessa Mitsialis, Nneka N. Ufere, Lawrence S. Friedman Esophageal and Gastric Disorders 3-1 Gastrointestinal Bleeding 3-3 Diarrhea 3-5 Dysmotility & Nutrition 3-8 Disorders of the Colon 3-9Tick-Borne Diseases Fever Syndromes ENDOCRINOLOGY Taher Modarressi, Kelly Lauter Roszko, Michael Mannstadt Pituitary Disorders Thyroid Disorders Adrenal Disorders Calcium Disorders Diabetes Mellitus Lipid Disorders RHEUMATOLOGY Sarah Keller, Zachary S.Wallace, 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 Jessica M. Baker, Michael G. Erkkinen, Mark R. Etherton, Khaled Moussawi, Tracey A. Cho Change in Mental Status Seizures Alcohol Withdrawal 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 6-20 6-22 yy Sak 9-6 9-10 9-11 10-1 10-3 10-4 11-1 11-3 11-4 12-1 1-1 P-1 P-9 P-13 P-15 ACLS-1Inflammatory Bowel Disease Intestinal Ischemia Pancreatitis Abnormal Liver Tests Hepatitis Acute Liver Failure Cirrhosis Hepatic Vascular Disease Ascites Biliary Tract Disease NEPHROLOGY Jacob Stevens, Andrew S. Allegretti, Hasan Bazari Acid-Base Disturbances Sodium and Water Homeostasis Potassium Homeostasis Renal Failure Glomerular Disease Urinalysis Nephrolithiasis HEMATOLOGY-ONCOLOGY Edmond M. Chan, Tanya E. Keenan, Andrew M. Brunner, Sheheryar K. Kabraj 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 Chemotherapy Side Effects Pancreatic Tumors Oncologic Emergencies Cancer of Unknown Primary Site INFECTIOUS DISEASES Michael S.Abers, Ana A. Weil, Nesli Basgoz Pneumonia Fungal Infections Infxns in Immunosuppressed Hosts Urinary Tract Infections Soft Tissue and Bone Infections Infections of the Nervous System Bacterial Endocarditis Tuberculosis HIV/AIDS 3-10 3-12 3-13 3-15 3-17 3-20 3-21 3-25 3-26 3-27 4-1 4-6 4-10 4-12 4.17 4-19 4-20 6-1 6-3 6-4 65 6-6 6-9 6-12 6-15 6-17REWOR To the st Edition It is with the greatest enthusiasm that | 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 ofa 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 hand- book should enhance the ability of every medical house officer to properly evalu- ate 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. AusigLLo, MD Physician-in-Chief, Massachusetts General Hospital Jackson Professor of Clinical Medicine, Harvard Medical School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 sixth edition come several major improvements. We have updated every topic thoroughly. In particular, we have included the latest pharmacotherapy for acute coronary syndromes, heart failure, pulmonary hypertension, hepatitis C, HIV, and diabetes, as well as the latest device- based treatments for valvular heart disease, atrial fibrillation, and stroke. Recent paradigm shifts in the guidelines for hypertension and cholesterol have been distilled and incorporated. We have expanded coverage of the molecular classification of malignancies and the corresponding biologic therapies. We have added new sections ‘on mechanical circulatory support, angioedema, non-invasive ventilation, toxicology, lung transplantation, Gl motility disorders, and the cardiorenal syndrome, just to name a few. We have also updated the section on Consults in which non-internal medicine specialists provide expert guidance in terms of establishing a differential diagnosis for common presenting symptoms and initiating an evaluation in anticipa- tion of calling a consult. 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. 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. | 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 knowl- edgeable, dedicated, and compassionate group of physicians. | always look back on my time there as Chief Resident as one of the best experiences | have ever had. | am grateful to several outstanding clinical mentors, including Hasan Bazari, Larry Friedman, Nesli Basgoz, Eric Isselbacher, Bill Dec, 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, my academic coordinator. She 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. | hope that you find Pocket Medicine useful throughout the arduous but incredibly rewarding journey of practicing medicine. Marc S. SaBaTINE, MD, MPHELECTROCARDIOGRAPHY a 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 Vi-Vs, ST 1/1 or Ewave As) Figure 1-1. QRS axis Left axis deviation (LAD) + Definition: axi + Etiologies: LVH, LBBB, inferior MI, WPW + Left anterior fascicular block (LAFB): LAD (AS to -90) and gR in aVL and QRS <120 msec and no other cause of LAD (eg, IMI) Right axis deviation (RAD) + Definition: axis beyond +90° (S > R in lead |) + Etiologies: RVH, PE, COPD (usually not > +110*), septal defects, lateral MI, WPW 2° aE 60 + Left posterior fascicular block (LPFB): RAD (90- 490" 180°) and rS in | & aVL and gR in Ill & aVF and QRS < 120 msec and no other cause of RAD Bundle Branch Blocks (Circ 2009;119:¢235) vi V. Initial depol. left-to-right across septum (r inV1 & q inVe; nb, Normal a el | Steere LBBB) followed by LV & RV free wall, with LV dominating (nb, RV depol. later and visible in RBBB). STL or TW1 in R precordial leads QRS 2120 msec (110-119 = IVCD or “incomplete”) |. Displacement of ST & Tw opposite major QRS deflection 5. +t PRWP.LAD, Qw’s in inferior leads vo aes Wide § wave in | and Vs . Absence of Q in I,Vs and Vs (may have narrow q in aVL) FSR’ in R precordial leads (V:,V2) LBBB af Ka Vs-¥e if cardiomegaly) naw - QRS 2120 msec (110-119 = IVCD or “incomplete”) RBBB ay 4 Broad, slurred, monophasic R in |, aVL,Vs—Ve (+ RS in Bifascicular block: RBBB + LAFB/LPFB. “Trifascicular block": bifascicular block + 1° AVB. Prolonged QT interval (NEJM 2008:358:169; www:torsades.org) + QT measured from beginning of QRS complex to end of T wave (measure longest QT) + QT varies w/ HR -> corrected w/ Bazett formula: QTc = QT/YRR (RR in sec), overcorrects at high HR, undercorrects at low HR (nl QTc <440 msec 3, <460 msec @) + Fridericia’s formula preferred at very high or low HR: QTc = QTAIRR * QT prolongation a/w f risk TAP (espec >500 msec); establish baseline QT and monitor if using QT prolonging meds, no estab guidelines for stopping Rx if QT prolongs + Etiologies: Antiarrhythmics: class la (procainamide, disopyramide), class Ill (amio, sotalol, dofet) Psych drugs: antipsychotics (phenothiazines, haloperidol, atypicals), Li, ? SSRIL,TCA Antimicrobials: macrolides, quinolones, azoles, pentamidine, atovaquone, atazanavir Other: antiemetics (droperidol, 5-HTs antagonists), alfuzosin, methadone, ranolazine Electrolyte disturbances: hypoCa (nb, hyperCa alw | QT), + hypoK, ? hypoMg Autonomic dysfxn: ICH (deep TW), Takotsubo, stroke, CEA, neck dissection ‘Congenital (long QT syndrome): K, Na, & Ca channelopathies (Circ 2013;127:126) Misc: CAD, CMP bradycardia, high-grade AVB, hypothyroidism, hypothermia, BBB Left Atrial Abnormality (LAA) Right Atrial Abnormality (RA) ECG a0 a0 me T P-wave ae a i (Crikerianope ints Mn rsp aie m i: | or Mo \ eet Left ventricular hypertrophy (LVH) (circ 2009:119:251) + Etiologies: HTN, AS/Al, HCM, coarctation of aorta + Criteria (all w/ Se <50%, Sp >85%: accuracy affected by age, sex, race, BMI) Romhilt-Estes point-score system (4 points = probable; 5 points = diagnostic): 4 volt limb lead R or § 220 mm or $ in; or V2 230 mm or R inVs orVs 230 mm (3 pts) Perl tL1359) ST displacement opposite to QRS deflection: w/o dig (3 pts); w/ dig (1 pt) LAA (3 pts); LAD (2 pts); QRS duration 290 msec (1 pt) Intrinsicoid deflection (QRS onset to peak of R) inVs or Vz 250 msec (1 pt) Sokolow-Lyon: S inV; +R inVs or Vs >35 mm or R in aVL 211 mm (1 Se wi 1 BMI) Cornell: R in aVL +S in >28 mm in men or >20 mm in women If LAFB present: Sin Ill + max (RS) in any lead 230 mm in men or 228 mm in women Right ventricular hypertrophy (RVH) (Circ 2009:119:e251;JACC 201463672) + Etiologies: cor pulmonale, congenital (tetralogy, TGA, PS,ASD, VSD), MS,TR + Criteria fall insensitive, but specific (except in COPD); all w/ poor PPV in general population] R>SinV;, V1 26 mm,S inVs 210 mm, $ inV, 23 mm, R in aVR 24 mm RAD 2110° (LVH + RAD or prominent $ ins or Vs -» consider biventricular hypertrophy) Ddx of dominant R wave inV; or V2 + Ventricular enlargement: RVH (RAD, RAA, deep S waves in 1, Vs, Ve); HCM + Myocardial injury: posterior MI (anterior R wave = posterior Q wave; often with IMI) + Abnormal depolarization: RBBB (QRS >120 msec, rR’); WPW (1 PR, 5 wave, ? QRS) + Other: dextroversion; counterclockwise rotation; Duchenne’s; lead misplacemnent; nl variant Poor R wave progression (PRWP) (Am Heort / 2004:14880) + Definition: loss of anterior forces w/o frank Q waves (Vi-V3);R wave inV3 <3 mm + Possible etiologies (nonspecific): old anteroseptal MI (usually w/ R wave V3 <1.5 mm,+ persistent ST 7 or TWIV2 &V3) LVH (delayed RWP w/ T left precordial voltage), RVH, COPD (may also have RAA, RAD, limb lead QRS amplitude <5, SiSiSu1 w/ R/S ratio <1 in those leads) LBBB; WPW; clockwise rotation of the heart; lead misplacement; CMP; PTX Pathologic Q waves * Definition: 230 msec (220 msec V2-Vs) or >25% height of R wave in that QRS complex + Small (septal) q waves in |, aVLVs &Ve are nl, as can be isolated Qw in Ill, VR,Vi + “Pseudoinfarct” pattern may be seen in LBBB, infiltrative dis., HCM, COPD, PTX, WPW. ST elevation (STE) (Neo 2003:349:2128; Cre 2008;119:0241 & 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 J;Tw usually upright HCM, Takotsubo CMP, ventricular aneurysm, cardiac contusion Pulmonary embolism: occ. STEV1-Vs; classically aw TWIV1-Vs, RAD, RBBB, S1Q:Ts Repolarization abnormalities: LBBB ( QRS duration, STE discordant from QRS complex; see “ACS” for dx MI in LBBB) LVH (7 QRS amplitude); Brugada syndrome (rSR’, downsloping STE V1-V2); pacing Hyperlalemia (1 QRS duration, tall Ts, no Ps) aVR: STE >1 mm alw T mortality in STEMI; STE aVR >V1 alw left main disease Early repolarization: most often seen in V2-Vs in young adults (JACC 2015:66:470) 1-4 mm elev of peak of notch or start of slurred downstroke of R wave (ie,) point);:+ up concavity of ST & large Tw (-. ratio of STE/T wave <25%; may disappear w/ exercise) 2 early repol in inf leads may be alw T risk of VF (NEJM 2009;361:2529; Circ 201 1;124:2208) ST depression (STD) + Myocardial ischemia (+ Tw abn!) + Acute true posterior Mk: posterior STE appearing as anterior STD (#1 R wave) inV;-V3 ¥ posterior ECG leads; manage as a STEMI with rapid reperfusion (see “ACS") * Digitalis effect (downsloping ST + Tw abnl, does not correlate w/ dig levels) + Hypokalemia (+ U wave) * Repolarization abni a/w LBBB or LVH (usually in leads Vs,Ve, , aVL) T wave inversion (TWI; generally 21 mm; deep if 25 mm) (Circ 2002:119:241) Ischemia or infarct; Wellens’ sign (deep, symm precordial TW1) -> critical prox LAD lesion Myopericarditis; CMP (Takotsubo, ARVC, apical HCM); MVP; PE (espec if TWIV;-V4) Repolarization abnl in alw LVH/RVH (“strain pattern”), BBB Posttachycardia or postpacing (“memory” T waves) Electrolyte, digoxin, PaQ2, PaCOz, pH or core temperature disturbances Intracranial bleed (“cerebral T waves,” usually w/ 1 QT) Normal variant in children (V1-Vs) and leads in which QRS complex predominantly © Low vol * QRS amplitude (R +S) <5 mm in all limb leads & <10 mm in all precordial leads + Etiol: COPD, pericard./pleural effusion, myxedema, t BMI, amyloid, diffuse CAD Electrolyte abnormalities + TK: tented Tw, | QT, T PR,AVB, wide QRS, STE; | K: flattened Tw, U waves, T QT + T Ca: | QT, flattened Tw & Pw, | point elevation; | Ca: t QT;Tw Astt, Disorder Typical Characteristics & Diagnostic Studies Cardiac Causes acs Substernal “pressure” (® LR 1.3) -» neck, jaw, arm (® LR 1.3-2.6) (15-25% of Sharp, pleuritic, positional, or reprod. w/ palp all w/ ® LR <0.35, chest pain in Diaphoresis (® LR 1.4), dyspnea (® LR 1.2), alw exertion (® LR 1.5~1.8) ED) = prior MI (2 LR 2.2); wi NTG/rest (but not reliable; Anat £M 2005:45:581) +ECG As: STE, STD,TWI, Qw. + ? Troponin. Pericarditis Sharp pain — trapezius, 1 w/ respiration, | w/ sitting forward. + Pericardial & myo- friction rub. ECG As (diffuse STE & PR 1, opposite in aVR) + pericardial pericarditis effusion. If myocarditis, same as above + 1Tn and + s/s HF and | EF Aortic Sudden severe tearing pain (absence © LR 0.3). Asymm (+20 mmHg) dissection _BP or pulse (® LR 5.7), focal neuro deficit (2 LR >6), Al, widened mediast. on CXR (absence © LR 0.3); false lumen on imaging. (AMA 200228722262) Pulmonary Causes Pneumonia __Pleuritic; dyspnea, fever, cough, sputum, 7 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. 1 RR & HR, 1 $,O2, ECG As (sinus tach, RAD, RBBB, SiQuiTu, TWIV1-Vs, occ STE V1-V3), ® CTA or V/Q, + TT Pulm HTN: Exertional pressure, DOE. | S,Oz, loud P2, RV heave, right Ss and/or S«. GI Causes Esophageal Substernal burning, acid taste in mouth, water brash. T by meals, reflux recumbency; | by antacids. EGD, manometry, pH monitoring Esoph spasm Intense substernal pain. t by swallowing, | by NTGICCB, Manometry. Mallory-Weiss Esoph tear precipitated by vomiting. + Hematemesis. Dx w/ EGD. Boerhaave Esoph rupture. Severe pain, T w/ swallow. Mediastinal air palpable & on CT. PUD Epigastric pain, relieved by antacids. + GIB. EGD, + H. pylori test. Biliary dis. RUQ pain, NIV. by fatty foods. RUQ UIS; t LFTs. Pancreatitis _Epigastric/back discomfort. 1 amylase & lipase; abd CT. Musculoskeletal and Miscellaneous Causes Costochond Localized sharp pain. 1 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, 10 ed, 2014; 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. (carotid/femoral bruits, | pulses) or CHF; lung & abd. exam; chest wall for reproducibility * 12-lead ECG: obtain w/in 10 min; dw priors & obtain serial ECGs; consider posterior leads (Vz-Vs) to ¥ for posterior STEM if hx ciw ACS but stnd ECG unrevealing or ST LV1-V3 (ant ischemia vs. post STEMI) and angina that is hard to relieve or R/S >1 in VV» + CXR; other imaging (echo, PE CTA, etc.) as indicated based on H&P and initial testing * Troponin: / at baseline & 3-6 h after sx onset; repeat 6 h later if clinical or ECG As; level >99th %ile w/ rise & fall in appropriate setting is dx of Ml; >95% Se, 90% Sp detectable 1-6 h after injury, peaks 24 h, may be elevated for 7-14 d in STEMI high-sens, assays (not yet available in U.S.) offer NPV >99% at 1 h (Loncet 2015:386:2481) Causes for 1Tn other than plaque rupture (="type 1 MI"):(1) Supply-demand mismatch not due to A in CAD (= “type 2 MI"; eg, TT HR, shock, HTN crisis, spasm, severe AS), (2) non-ischemic injury (myocarditis/toxic CMP. cardiac contusion) or (3) multifactorial (PE, sepsis, severe HF renal failure, Takotsubo, infilt dis.) (Circ 2012:126:2020) + CK-MB: less Se & Sp than Tn (other sources: skel. muscle, intestine, etc); CK-MB/CK ratio >2.5 — cardiac source. Useful for dx of post-PCI/CABG MI or (re)MI if Tn already high. Early noninvasive imaging + flow prob of ACS (eg, ECG &Tn) & stable —> outPt or inPt noninvasive fxnal or imaging test (qv).CCTA w! high NPV but low PPV; | LOS cfw fxnal testing (NEM 20123661393). + “Triple r/o” CT angiogram sometimes performed to r/o CAD, PE,AoD if dx unclear eet) eh