Washington Manual of Medical Therapeutics 2014 PDF

THE WASHINGTON MANUAL® OF MEDICAL THERAPEUTICS 34th Edition Department of Medicine Washington University School of Medicine St. Louis, Missouri Editors Hemant Godara, MD Angela Hirbe, MD Michael Nassif, MD...

THE WASHINGTON MANUAL® OF MEDICAL THERAPEUTICS 34th Edition Department of Medicine Washington University School of Medicine St. Louis, Missouri Editors Hemant Godara, MD Angela Hirbe, MD Michael Nassif, MD Hannah Otepka, MD Aron Rosenstock, MD Executive Editor: Rebecca S. Gaertner Senior Product Manager: Kristina Oberle Production Manager: David Saltzberg Manufacturing Manager: Beth Welsh Senior Marketing Manager: Kimberly Schonberger Design Coordinator: Teresa Mallon Production Service: Absolute Service, Inc. Editorial Coordinator: Katie Sharp 34th Edition © 2014 by Department of Medicine, Washington University School of Medicine © 2010 by Department of Medicine, Washington University School of Medicine © 2007 by Department of Medicine, Washington University School of Medicine © 2004, 2001 by Department of Medicine, Washington University School of Medicine All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form by any means, including photocopying, 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. Printed in China Adhesive binding: ISBN: 978-1-4511-8851-6 ISBN: 1-4511-8851-X The Washington Manual® is an intent-to-use mark belonging to Washington University in St. Louis to which international legal protection applies. The mark is used in this publication by LWW under license from Washington University. Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of the information in a particular situation remains the professional responsibility of the practitioner. The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in the publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice. To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320. International customers should call (301) 223-2300. Visit Lippincott Williams & Wilkins on the Internet: at LWW.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST.  We dedicate this manual to the outstanding medicine house staff at Washington University and Barnes-Jewish Hospital— their wisdom, dedication, and compassion continue to inspire us each and every day. www.ketabpezeshki.com 66485457-66963820 www.ketabpezeshki.com 66485457-66963820 Contents DEDICATION iii CONTRIBUTORS xxvi CHAIRMAN’S NOTE xxix PREFACE xxx 1 Patient Care in Internal Medicine 1 Mark Thoelke, John Cras, Nathan Martin, and Amy Sheldahl General Care of the Hospitalized Patient 1 Prophylactic Measures 2 Venous Thromboembolism Prophylaxis 2 Decubitus Ulcers 3 Other Precautions 4 Acute Inpatient Care 4 Chest Pain 5 Dyspnea 6 Acute Hypertensive Episodes 6 Fever 7 Pain 8 Altered Mental Status 12 Insomnia and Anxiety 14 Perioperative Medicine 17 Preoperative Cardiac Evaluation 17 Perioperative Anticoagulation and Antithrombotic Management 25 Perioperative Management of Specific Conditions 28 Hypertension 28 Pacemakers and Implantable Cardioverter Defibrillators (ICDs) 29 Pulmonary Disease and Preoperative Pulmonary Evaluation 30 Anemia and Transfusion Issues in Surgery 34 Liver Disease 36 Diabetes Mellitus 38 Adrenal Insufficiency and Corticosteroid Management 41 Chronic Renal Insufficiency and End-Stage Renal Disease 43 Acute Renal Failure 44 v www.ketabpezeshki.com 66485457-66963820 vi CONTENTS 2 Nutrition Support 46 Dominic Reeds and Ben P. Bradenham, Jr. Nutrient Requirements 46 Assessment of Nutritional Status 48 Enteral Nutrition 61 Parenteral Nutrition 67 Refeeding the Severely Malnourished Patient 72 3 Preventive Cardiology 76 Angela L. Brown, Timothy J. Fendler, and Anne C. Goldberg Hypertension 76 Dyslipidemia 97 4 Ischemic Heart Disease 112 Mohammad Kizilbash, Jeffrey R. Parker, Muhammad A. Sarwar, and Jason D. Meyers Coronary Heart Disease and Stable Angina 112 Acute Coronary Syndromes, Unstable Angina, and Non−ST-Segment Elevation Myocardial Infarction 126 ST-Segment Elevation Myocardial Infarction 142 5 Heart Failure and Cardiomyopathy 171 Shane J. LaRue, Susan M. Joseph, and Gregory A. Ewald Heart Failure 171 Acute Heart Failure and Cardiogenic Pulmonary Edema 183 Cardiomyopathy 185 Dilated Cardiomyopathy 185 Heart Failure with Preserved Ejection Fraction 187 Hypertrophic Cardiomyopathy 187 Restrictive Cardiomyopathy 190 Peripartum Cardiomyopathy 192 6 Pericardial and Valvular Heart Disease 194 Jay Shah and Brian R. Lindman Pericardial Disease 194 Constrictive Pericarditis 194 Cardiac Tamponade 196 www.ketabpezeshki.com 66485457-66963820  CONTENTS vii Valvular Heart Disease 198 Mitral Stenosis 198 Aortic Stenosis 203 Mitral Regurgitation 207 Aortic Regurgitation 213 Prosthetic Heart Valves 217 7 Cardiac Arrhythmias 220 Shivak Sharma, Daniel H. Cooper, and Mitchell N. Faddis Tachyarrhythmias 220 Approach to Tachyarrhythmias 220 Supraventricular Tachyarrhythmias 223 Atrial Fibrillation 230 Ventricular Tachyarrhythmias 242 Bradyarrhythmias 251 Syncope 263 Cardiac Resynchronization Therapy 265 8 Critical Care 268 Anthony Boyer, Scott T. Micek, and Marin H. Kollef Respiratory Failure 268 Noninvasive Oxygen Therapy 270 Airway Management and Tracheal Intubation 271 Mechanical Ventilation 275 Shock 284 Hemodynamic Monitoring 290 9 Obstructive Lung Disease 293 Jeffrey J. Atkinson, Robert M. Senior, Ajay Sheshadri, and Mario Castro Chronic Obstructive Pulmonary Disease 293 Asthma 306 www.ketabpezeshki.com 66485457-66963820 viii CONTENTS 10 Pulmonary Diseases 322 Murali Chakinala, Colleen McEvoy, Tonya D. Russell, Rachel Bardowell, Alexander Chen, and Daniel B. Rosenbluth Pulmonary Hypertension 322 Obstructive Sleep Apnea–Hypopnea Syndrome 334 Interstitial Lung Disease 339 Solitary Pulmonary Nodule 348 Pleural Effusion 355 Hemoptysis 362 Cystic Fibrosis 369 11 Allergy and Immunology 377 Sarena Sawlani, Jennifer M. Welch, and Andrew L. Kau Adverse Drug Reactions 377 Anaphylaxis 381 Eosinophilia 386 Urticaria and Angioedema 392 Immunodeficiency 396 12 Fluid and Electrolyte Management 400 Judy L. Jang and Steven Cheng Fluid Management and Perturbations in 400 Volume Status The Euvolemic Patient 401 The Hypovolemic Patient 402 The Hypervolemic Patient 404 Disorders of Sodium Concentration 405 Hyponatremia 405 Hypernatremia 411 Potassium 415 Hypokalemia 415 Hyperkalemia 418 Calcium 421 Hypercalcemia 421 Hypocalcemia 424 www.ketabpezeshki.com 66485457-66963820  CONTENTS ix Phosphorus 427 Hyperphosphatemia 427 Hypophosphatemia 429 Magnesium 430 Hypermagnesemia 430 Hypomagnesemia 431 Acid−Base Disturbances 433 Metabolic Acidosis 436 Metabolic Alkalosis 439 Respiratory Acidosis 440 Respiratory Alkalosis 441 13 Renal Diseases 442 Seth Goldberg and Daniel Coyne Evaluation of the Patient with Renal Disease 442 Acute Kidney Injury 444 Glomerulopathies 451 Primary Glomerulopathies 452 Minimal Change Disease 452 Focal Segmental Glomerulosclerosis 453 Membranous Nephropathy 453 Membranoproliferative Glomerulonephropathy 454 IgA Nephropathy/Henoch−Schönlein Purpura 455 Pulmonary−Renal Syndromes 456 Secondary Glomerulopathies 457 Diabetic Nephropathy 457 Lupus Nephritis 457 Postinfectious Glomerulonephropathy 458 Deposition Disorders/Dysproteinemias 459 HIV-Associated Nephropathy 459 Polycystic Kidney Disease 460 Progressive Loss of Renal Function 461 Chronic Kidney Disease 461 www.ketabpezeshki.com 66485457-66963820 x CONTENTS Renal Replacement Therapies 465 Approach to Dialysis 465 Hemodialysis 466 Peritoneal Dialysis 468 Transplantation 470 Nephrolithiasis 470 Approach to Kidney Stones 470 14 Treatment of Infectious Diseases 472 Stephen Y. Liang, Sara L. Cross, and Nigar Kirmani Principles of Therapy 472 Toxin-Mediated Infections 474 Clostridium Difficile Infection 474 Tetanus 474 Toxic Shock Syndrome 475 Staphylococcal Toxic Shock Syndrome 475 Streptococcal Toxic Shock Syndrome 476 Skin, Soft Tissue, and Bone Infections 477 Abscesses, Furuncles and Carbuncles 477 Cellulitis 477 Erysipelas 478 Complicated Skin and Soft Tissue Infections 478 Infected Decubitus Ulcers and Limb-Threatening Diabetic Foot Ulcers 478 Necrotizing Fasciitis 479 Anaerobic Myonecrosis (Gas Gangrene) 480 Osteomyelitis 480 Central Nervous System Infections 481 Meningitis 481 Ventriculitis and Ventriculoperitoneal Shunt Infections 483 Encephalitis 483 Brain Abscess 484 Neurocysticercosis 485 www.ketabpezeshki.com 66485457-66963820  CONTENTS xi Cardiovascular Infections 485 Infective Endocarditis 485 Myocarditis 492 Pericarditis 494 Upper Respiratory Tract Infections 494 Pharyngitis 494 Epiglottitis 495 Sinusitis 496 Influenza Virus Infection 497 Lower Respiratory Tract Infections 498 Acute Bronchitis 498 Community-Acquired Pneumonia 499 Lung Abscess 500 Tuberculosis 501 Gastrointestinal and Abdominal Infections 504 Peritonitis 504 Hepatobiliary Infections 506 Other Infections 507 Diverticulitis 507 Appendicitis 508 Genitourinary Infections 508 Lower Urinary Tract Infections 508 Pyelonephritis 513 Sexually Transmitted Infections, Ulcerative 513 Diseases Genital Herpes 513 Syphilis 514 Chancroid 518 Lymphogranuloma Venereum 518 www.ketabpezeshki.com 66485457-66963820 xii CONTENTS Sexually Transmitted Infections, Vaginitis and 518 Vaginosis Trichomoniasis 518 Bacterial Vaginosis 519 Vulvovaginal Candidiasis 519 Cervicitis/Urethritis 520 Pelvic Inflammatory Disease 520 Systemic Mycoses and Atypicals 521 Candidiasis 521 Cryptococcosis 527 Histoplasmosis 527 Blastomycosis 528 Coccidioidomycosis 528 Aspergillosis 529 Sporotrichosis 530 Mucormycosis 530 Nocardiosis 531 Actinomycosis 531 Atypical (Nontuberculous) Mycobacteria 532 Tick-Borne Infections 532 Lyme Borreliosis (Lyme Disease) 532 Rocky Mountain Spotted Fever 533 Ehrlichiosis and Anaplasmosis 534 Tularemia 535 Babesiosis 535 Mosquito-Borne Infections 536 Arboviral Meningoencephalitis 536 Malaria 536 Zoonoses 538 Cat-Scratch Disease (Bartonellosis) 538 Leptospirosis 538 Brucellosis 539 Bite Wounds 539 Animal Bites 539 Human Bites 541 www.ketabpezeshki.com 66485457-66963820  CONTENTS xiii Health Care – Associated Infections 541 Catheter-Related Bloodstream Infections 541 Hospital- and Ventilator-Associated Pneumonia 543 Methicillin-Resistant Staphylococcus aureus Infections 543 Vancomycin-Resistant Enterococcus Infections 544 Multidrug-Resistant Gram-Negative Infections 544 Emerging Infections and Bioterrorism 544 Anthrax 545 Smallpox 546 Plague 546 Botulism 547 Viral Hemorrhagic Fever 548 Severe Acute Respiratory Syndrome 549 Pandemic, Avian, and Swine Influenza 549 15 Antimicrobials 550 Bernard C. Camins and David J. Ritchie Antibacterial Agents 550 Penicillins 550 Cephalosporins 552 Monobactams 554 Carbapenems 554 Aminoglycosides 555 Vancomycin 557 Fluoroquinolones 558 Macrolide and Lincosamide Antibiotics 559 Sulfonamides and Trimethoprim 561 Tetracyclines 562 Antimicrobial Agents, Miscellaneous 563 Chloramphenicol 563 Colistin and Polymyxin B 563 Daptomycin 564 Fosfomycin 565 Linezolid 565 Methenamine 566 Metronidazole 566 Nitrofurantoin 567 www.ketabpezeshki.com 66485457-66963820 xiv CONTENTS Quinupristin/Dalfopristin 567 Telavancin 568 Tigecycline 568 Antimycobacterial Agents 569 Isoniazid 569 Rifamycins 569 Pyrazinamide 570 Ethambutol 570 Streptomycin 570 Antiviral Agents 571 Anti-Influenza Agents 571 Antiherpetic Agents 572 Anticytomegalovirus Agents 572 Antifungal Agents 574 Amphotericin B 574 Azoles 574 Echinocandins 576 Miscellaneous 577 16 Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome 578 Sara L. Cross and E. Turner Overton HIV Type 1 578 Opportunistic Infections 592 Cytomegalovirus Infection 593 Mycobacterium Tuberculosis 594 M. Avium Complex Infection 595 Pneumocystis Jiroveci Pneumonia 595 Candidiasis 596 Cryptococcus Neoformans 597 Histoplasma Capsulatum Infections 597 Protozoal Infections 598 Toxoplasma Gondii 598 Cryptosporidium 599 Cyclospora 599 Isospora Belli 599 Microsporidia 599 www.ketabpezeshki.com 66485457-66963820  CONTENTS xv Associated Neoplasms 600 Kaposi Sarcoma 600 Lymphoma 600 Cervical and Perianal Neoplasias 600 Sexually Transmitted Diseases 601 Genital Herpes 601 Genital Warts 601 Syphilis 606 17 Solid Organ Transplant Medicine 608 Christina L. Klein and Brent W. Miller Solid Organ Transplant Basics 608 Graft Rejection 612 Acute Rejection, Kidney 612 Acute Rejection, Lung 613 Acute Rejection, Heart 614 Acute Rejection, Liver 614 Acute Rejection, Pancreas 615 Chronic Allograft Dysfunction 616 Complications 616 18 Gastrointestinal Diseases 620 C. Prakash Gyawali and Amit Patel Gastrointestinal Bleeding 620 Dysphagia and Odynophagia 626 Nausea and Vomiting 628 Diarrhea 629 Constipation 632 Luminal Gastrointestinal Disorders 634 Gastroesophageal Reflux Disease 634 Esophageal Motor Disorders 638 Peptic Ulcer Disease 640 Inflammatory Bowel Disease 643 Functional Gastrointestinal Disorders 649 Acute Intestinal Pseudo-Obstruction (Ileus) 651 www.ketabpezeshki.com 66485457-66963820 xvi CONTENTS Pancreatobiliary Disorders 653 Acute Pancreatitis 653 Chronic Pancreatitis 655 Gallstone Disease 657 Other Gastrointestinal Disorders 658 Anorectal Disorders 658 Celiac Sprue 659 Diverticulosis and Diverticulitis 660 Gastroparesis 661 Ischemic Intestinal Injury 662 19 Liver Diseases 664 M. Katherine Rude, Thomas Kerr, and Mauricio Lisker-Melman Evaluation of Liver Disease 664 Viral Hepatitis 667 Hepatitis A Virus 667 Hepatitis B Virus 671 Hepatitis C 677 Hepatitis D 682 Hepatitis E 683 Drug-Induced Liver Injury 684 Alcoholic Liver Disease 686 Immune-Mediated Liver Diseases 688 Autoimmune Hepatitis 688 Primary Biliary Cirrhosis 691 Primary Sclerosing Cholangitis 692 Complications of Cholestasis 694 Nutritional Deficiencies 694 Osteoporosis 695 Pruritus 695 www.ketabpezeshki.com 66485457-66963820  CONTENTS xvii Metabolic Liver Diseases 696 Wilson’s Disease 696 Hereditary Hemochromatosis 698 a1-Antitrypsin Deficiency 701 Miscellaneous Liver Disorders 702 Nonalcoholic Fatty Liver Disease 702 Ischemic Hepatitis 704 Hepatic Vein Thrombosis 705 Sinusoidal Obstruction Syndrome 706 Portal Vein Thrombosis 707 Pyogenic Abscess 708 Amebic Abscess 708 Granulomatous Hepatitis 709 Acute Liver Failure 710 Chronic Liver Diseases 712 Cirrhosis 712 Portal Hypertension 712 Ascites 713 Spontaneous Bacterial Peritonitis 714 Hepatorenal Syndrome 716 Hepatic Encephalopathy 717 Hepatocellular Carcinoma 718 Liver Transplantation 720 20 Disorders of Hemostasis and Thrombosis 722 Roger Yusen, Charles Eby, Kristen Sanfilippo, and Brian F. Gage Hemostatic Disorders 722 Platelet Disorders 725 Thrombocytopenia 725 Immune Thrombocytopenia 726 Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome 728 Heparin-Induced Thrombocytopenia 730 Posttransfusion Purpura 732 Gestational Thrombocytopenia 733 www.ketabpezeshki.com 66485457-66963820 xviii CONTENTS Thrombocytosis 734 Qualitative Platelet Disorders 735 Inherited Bleeding Disorders 736 Hemophilia A 736 Hemophilia B 738 von Willebrand Disease 739 Acquired Coagulation Disorders 741 Vitamin K Deficiency 741 Liver Disease 742 Disseminated Intravascular Coagulation 743 Acquired Inhibitors of Coagulation Factors 744 Venous Thromboembolic Disorders 745 Approach to Venous Thromboembolism 745 21 Hematologic Disorders and Transfusion Therapy 760 Ronald Jackups, Kristen Sanfilippo, Tzu-Fei Wang, and Morey Blinder Anemia 760 Anemias Associated with Decreased Red Blood 762 Cell Production Microcytic Anemia 762 Thalassemia 765 Sideroblastic Anemias 768 Macrocytic/Megaloblastic Anemia 768 Anemia of Chronic Renal Insufficiency 770 Anemia of Chronic Disease 772 Anemia in Cancer Patients 773 Anemia Associated with HIV Infection 773 Aplastic Anemia 774 Anemias Associated with Increased Red Blood 775 Cell Destruction Anemias Associated with Increased Erythropoiesis 775 Sickle Cell Disease 776 www.ketabpezeshki.com 66485457-66963820  CONTENTS xix G6PD Deficiency 779 Autoimmune Hemolytic Anemia 780 Drug-Induced Hemolytic Anemia 783 Microangiopathic Hemolytic Anemia 783 White Blood Cell Disorders 784 Leukocytosis and Leukopenia 784 Platelet Disorders 786 Bone Marrow Disorders 786 Myelodysplastic Syndrome 786 Myeloproliferative Disorders 786 Monoclonal Gammopathies 788 Monoclonal Gammopathy of Unknown Significance 788 Multiple Myeloma 790 Waldenström Macroglobulinemia 790 Amyloidosis 790 Transfusion Medicine 791 22 Medical Management of Malignant Disease 796 Saiama N. Waqar, Janakiraman Subramanian, George Ansstas, and Ramaswamy Govindan Medical Management of Malignant Disease 796 Approach to the Cancer Patient 796 Lung Cancer 801 Breast Cancer 805 Head and Neck Cancer 807 Sarcoma 808 Gastrointestinal Malignancies 809 Esophageal Cancer 809 Gastric Cancer 810 Colorectal Cancer 811 Pancreatic Cancer 812 Hepatocellular Carcinoma 813 www.ketabpezeshki.com 66485457-66963820 xx CONTENTS Genitourinary Malignancies 814 Renal Cancer 814 Bladder Cancer 816 Prostate Cancer 817 Testicular Cancer and Germ Cell Tumors 818 Gynecologic Malignancies 819 Cervical Cancer 819 Endometrial Cancer 820 Ovarian Cancer 821 Cancer of Unknown Primary 822 Hematologic Malignancies 822 Myelodysplastic Syndrome 822 Acute Myeloid Leukemia 825 Acute Lymphoblastic Leukemia 827 Chronic Myeloid Leukemia 829 Chronic Lymphocytic Leukemia 830 Hairy Cell Leukemia 831 Hodgkin’s Lymphoma 832 Non-Hodgkin’s Lymphoma 833 Multiple Myeloma 835 Principles of Stem Cell Transplant 836 Oncologic Emergencies 837 Febrile Neutropenia 837 Tumor Lysis Syndrome 839 Malignant Hypercalcemia 840 Malignant Spinal Cord Compression 840 Brain Metastases with Increased Intracranial Pressure 841 Superior Vena Cava Syndrome 842 Management of Treatment Toxicities 842 Nausea 842 Diarrhea 843 Cytopenias 843 Mucositis 844 Pneumonitis 844 www.ketabpezeshki.com 66485457-66963820  CONTENTS xxi Supportive Care: Complications of Cancer 845 Cancer Pain 845 Bone Metastasis 846 Pleural Effusion 847 Venous Thromboembolism 847 Fatigue 848 Anorexia and Cachexia 848 23 Diabetes Mellitus and Related Disorders 849 Janet B. McGill Diabetes Mellitus 849 Diabetes Mellitus in Hospitalized Patients 853 Type 1 Diabetes and Diabetic Ketoacidosis 856 Type 1 Diabetes 856 Diabetic Ketoacidosis 859 Type 2 Diabetes and Nonketotic Hyperosmolar 863 Syndrome Type 2 Diabetes 863 Nonketotic Hyperosmolar Syndrome 871 Chronic Complications of Diabetes Mellitus 873 Diabetic Retinopathy 873 Diabetic Nephropathy 874 Diabetic Neuropathy 876 Macrovascular Complications of Diabetes Mellitus 877 Coronary Heart Disease 877 Peripheral Vascular Disease 879 Miscellaneous Complications 880 Erectile Dysfunction 880 Diabetic Foot Ulcers 880 Hypoglycemia 882 www.ketabpezeshki.com 66485457-66963820 xxii CONTENTS 24 Endocrine Diseases 885 William E. Clutter Disorders of the Thyroid Gland 885 Evaluation of Thyroid Function 885 Hypothyroidism 887 Hyperthyroidism 890 Euthyroid Goiter and Thyroid Nodules 895 Disorders of Adrenal Function 896 Adrenal Failure 896 Cushing’s Syndrome 899 Incidental Adrenal Nodules 900 Disorders of Anterior Pituitary Function 901 Hypopituitarism 902 Hyperprolactinemia 903 Acromegaly 905 Metabolic Bone Disease 906 Osteomalacia 906 Paget’s Disease 907 25 Arthritis and Rheumatologic Diseases 909 Hector Molina and Zarmeena Ali Basic Approach to the Rheumatic Diseases 909 Infectious Arthritis and Bursitis 915 Septic Bursitis 917 Lyme Disease 917 Crystal-Induced Synovitis 918 Rheumatoid Arthritis 922 Osteoarthritis 929 Spondyloarthropathies 930 Ankylosing Spondylitis 930 Arthritis of Inflammatory Bowel Disease 931 Reactive Arthritis 932 Psoriatic Arthritis 933 Systemic Lupus Erythematosus 934 Systemic Sclerosis 937 Raynaud’s Phenomenon 938 www.ketabpezeshki.com 66485457-66963820  CONTENTS xxiii Necrotizing Vasculitis 939 Polymyalgia Rheumatica 942 Cryoglobulin Syndromes 943 Polymyositis and Dermatomyositis 944 26 Neurologic Disorders 946 Robert C. Bucelli and Beau Ances Alterations in Consciousness 946 Alzheimer’s Disease 952 Seizures 953 Cerebrovascular Disease 958 Headache 966 Head Trauma 968 Acute Spinal Cord Dysfunction 971 Parkinson’s Disease 974 Neuromuscular Disease 976 Guillain–Barré Syndrome 976 Myasthenia Gravis 979 Other Neuromuscular Disorders 983 Neuromuscular Disorders with Rigidity 984 27 Medical Emergencies 986 Jason Wagner, Christopher Sampson, and Rebecca Bavolek Airway Emergencies 986 Acute Upper Airway Obstruction 986 Emergent Airway Adjuncts 988 Pneumothorax 988 Drowning 991 Heat-Induced Injury 993 Heat Exhaustion 993 Heat Syncope 994 Heat Stroke 994 Cold-Induced Illness 996 Chilblains 996 Immersion Injury (Trench Foot) 997 Frostnip (Superficial Frostbite) 997 Deep Frostbite 997 Hypothermia 998 www.ketabpezeshki.com 66485457-66963820 xxiv CONTENTS 28 Toxicology 1002 S. Eliza Halcomb, Evan Schwarz, and Michael E. Mullins Overdoses 1002 Overdose, General 1002 Acetaminophen 1006 Colchicine 1011 Nonsteroidal Anti-Inflammatory Drugs 1013 Opioids 1014 Salicylates 1015 Phenytoin and Fosphenytoin 1018 Carbamazepine/Oxcarbazepine 1020 Lamotrigine 1022 Levetiracetam 1023 Valproic Acid 1023 Monoamine Oxidase Inhibitors 1024 Tricyclic Antidepressants 1027 Selective Serotonin Reuptake Inhibitors 1029 Serotonin Syndrome 1030 Lithium 1032 Bupropion 1034 Antipsychotics, General 1034 Phenothiazines 1035 Clozapine 1036 Olanzapine 1037 Risperidone, Ziprasidone, and Quetiapine 1037 b-Adrenergic Antagonists 1038 Calcium Channel Blockers 1040 Clonidine 1042 Other Antihypertensives 1044 Parasympathetic Agents 1044 Anticholinergics 1044 Cholinesterase Inhibitors 1046 Organophosphates 1046 Carbamates 1049 Barbiturates 1051 Benzodiazepines 1052 Sympathomimetics, General 1053 Amphetamines 1054 Cocaine 1055 www.ketabpezeshki.com 66485457-66963820  CONTENTS xxv Theophylline 1057 Toxic Alcohol, General 1059 Methanol 1060 Ethylene Glycol 1063 Ethanol 1065 Cyanide 1066 Carbon Monoxide 1068 Appendix A Immunizations and Postexposure Therapies 1070 Carlos A. Q. Santos and Victoria J. Fraser Appendix B Infection Control and Isolation Recommendations 1088 Carlos A. Q. Santos and Victoria J. Fraser Appendix C Advanced Cardiac Life Support Algorithms 1094 INDEX 1097 www.ketabpezeshki.com 66485457-66963820 Contributors Zarmeena Ali, MD Steven Cheng, MD Instructor of Medicine Division of Assistant Professor of Medicine Division of Rheumatology Renal Diseases Beau Ances, MD, PhD, MS William E. Clutter, MD Assistant Professor Division of Neurology Associate Professor of Medicine Division of George Ansstas, MD Medical Education Instructor of Medicine Hospitalist-BMT Daniel H. Cooper, MD Jeffrey J. Atkinson, MD Assistant Professor of Medicine Division of Assistant Professor of Medicine Division of Cardiovascular Medicine Pulmonary Medicine Daniel Coyne, MD Rachel Bardowell, MD Professor of Medicine Division of Renal Instructor in Medicine Hospitalist Service Diseases Rebecca Bavolek, MD John Cras, MD Instructor in Emergency Medicine Division Assistant Professor of Medicine Hospitalist of Emergency Medicine Service Morey Blinder, MD Sara L. Cross, MD Associate Professor of Medicine Division of Clinical Fellow Division of Infectious Hematology Diseases Anthony Boyer, MD Charles Eby, MD Clinical Fellow Division of Pulmonary Professor Department of Pathology & Medicine Immunology Ben P. Bradenham, Jr., MD Gregory A. Ewald, MD Resident Department of Medicine Associate Professor of Medicine Division of Cardiovascular Medicine Angela L. Brown, MD Assistant Professor of Medicine Division of Mitchell N. Faddis, MD, PhD Cardiology Associate Professor of Medicine Division of Cardiovascular Medicine Robert C. Bucelli, MD, PhD Assistant Professor Department of Neurology Timothy J. Fendler, MD Resident Department of Medicine Bernard C. Camins, MD Assistant Professor of Medicine Division of Victoria J. Fraser, MD Infectious Diseases Adolphus Busch Professor of Medicine and Chairman Department of Medicine Mario Castro, MD Professor of Medicine Division of Brian F. Gage, MD Pulmonary and Critical Care Professor of Medicine Division of General Medical Sciences Murali Chakinala, MD Associate Professor of Medicine Division of Anne C. Goldberg, MD Pulmonary and Critical Care Associate Professor of Medicine Division of Endocrinology and Metabolism Alexander Chen, MD Assistant Professor of Medicine Division of Pulmonary and Critical Care xxvi www.ketabpezeshki.com 66485457-66963820  CONTRIBUTORS xxvii Seth Goldberg, MD Stephen Y. Liang, MD Assistant Professor of Medicine Division of Instructor in Medicine Division of Nephrology Infectious Diseases Ramaswamy Govindan, MD Brian R. Lindman, MD Professor of Medicine Division of Medical Assistant Professor of Medicine Division of Oncology Cardiovascular Medicine C. Prakash Gyawali, MD Mauricio Lisker-Melman, MD Professor of Medicine Division of Professor of Medicine Division of Gastroenterology Gastroenterology S. Eliza Halcomb, MD Nathan Martin, MD Assistant Professor Department of Instructor in Medicine Hospitalist Service Emergency Medicine Colleen McEvoy, MD Ronald Jackups, MD Clinical Fellow Division of Pulmonary and Assistant Professor of Pathology and Critical Care Immunology Laboratory and Genomic Janet B. McGill, MD Medicine Professor of Medicine Division of Judy L. Jang, MD Endocrinology Assistant Professor of Medicine Division of Jason D. Meyers, MD Renal Diseases Clinical Fellow Division of Cardiovascular Susan M. Joseph, MD Medicine Assistant Professor of Medicine Division of Scott T. Micek, PharmD, BCPS Cardiovascular Medicine Department of Pharmacy Barnes-Jewish Andrew L. Kau, MD Hospital Clinical Fellow Division of Allergy and Brent W. Miller, MD Immunology Associate Professor of Medicine Division of Thomas Kerr, MD Nephrology Assistant Professor of Medicine Division of Hector Molina, MD Gastroenterology Associate Professor of Medicine Division of Nigar Kirmani, MD Rheumatology Professor of Medicine Division of Infectious Michael E. Mullins, MD Diseases Associate Professor of Emergency Medicine Mohammad Kizilbash, MD Department of Medicine Assistant Professor of Medicine Division of E. Turner Overton, MD Cardiovascular Medicine Adjunct Assistant Professor of Medicine Christina L. Klein, MD Division of Infectious Diseases Assistant Professor of Medicine Division of Renal Diseases Jeffrey R. Parker, MD Instructor in Medicine Division of Marin H. Kollef, MD Hospitalist Medicine Professor of Medicine Division of Pulmonary & Critical Care Amit Patel, MD Resident Department of Medicine Shane J. LaRue, MD Clinical Fellow Division of Cardiovascular Dominic Reeds, MD Medicine Assistant Professor in Medicine Director, Clinical Nutrition Support Service www.ketabpezeshki.com 66485457-66963820 xxviii CONTRIBUTORS David J. Ritchie, PharmD Jay Shah, MD Clinical Pharmacist Division of Infectious Instructor in Medicine Division of Diseases Cardiovascular Medicine Daniel B. Rosenbluth, MD Shivak Sharma, MD Professor of Medicine and Pediatrics Clinical Fellow Division of Cardiovascular Division of Pulmonary and Critical Care Medicine M. Katherine Rude, MD Amy Sheldahl, MD Clinical Fellow Division of Instructor in Medicine Hospitalist Service Gastroenterology Ajay Sheshadri, MD Tonya D. Russell, MD Clinical Fellow Division of Pulmonary and Associate Professor of Medicine Division of Critical Care Pulmonary and Critical Care Janakiraman Subramanian, MD Christopher Sampson, MD Instructor in Medicine Division of Medical Assistant Professor of Emergency Medicine Oncology Division of Emergency Medicine Mark Thoelke, MD Kristen Sanfilippo, MD Associate Professor Division of Hospital Clinical Fellow Division of Medical Medicine Oncology Jason Wagner, MD Carlos A. Q. Santos, MD Assistant Professor of Emergency Medicine Assistant Professor of Medicine Division of Division of Emergency Medicine Infectious Diseases Tzu-Fei Wang, MD Muhammad A. Sarwar, MD Clinical Fellow Division of Medical Research Fellow Division of Cardiovascular Oncology Medicine Saiama N. Waqar, MD Sarena Sawlani, MD Instructor in Medicine Division of Medical Clinical Fellow Division of Allergy and Oncology Immunology Jennifer M. Welch, MD Evan Schwarz, MD Clinical Fellow Division of Immunology Assistant Professor of Emergency Medicine Roger Yusen, MD, MPH Division of Emergency Medicine Associate Professor of Medicine Division of Robert M. Senior, MD Pulmonary and Critical Care D & H Moog Professor of Pulmonary Diseases Division of Pulmonary and Critical Care www.ketabpezeshki.com 66485457-66963820 Chairman’s Note The rate of increase of medical knowledge places an enormous burden on physicians to keep up with recent advances, particularly in novel therapies that will improve patient outcomes. The Washington Manual ® of Medical Therapeutics provides an easily accessible source of current information that covers a practical clinical approach to the diagnosis, investigation, and treatment of common medical conditions that internists encounter on a regular basis. The pocketbook size of the Manual ensures that it will continue to be of enormous assistance to interns, residents, medical students, and other practitioners in need of readily accessible practical clinical informa- tion. It meets an important unmet need in an era of information overload. I acknowledge the authors, who include house officers, fellows, and attendings, at Washington University/Barnes-Jewish Hospital. Their efforts and outstanding skill are evident in the quality of the final product. In particular, I am proud of our editors—Hemant Godara, Angela Hirbe, Michael Nassif, Hannah Otepka, and Aron Rosenstock—and the series editors—Tom De Fer and Katherine Henderson—who have worked tirelessly to produce another outstanding edition of the Manual. I also recognize Melvin Blanchard, MD, Chief of the Division of Medical Education in the Department of Medicine at Washington University, for his guidance and advice. I am confident that this Manual will meet its desired goal of providing practical knowledge that can be directly applied to improving patient care. Victoria J. Fraser, MD Adolphus Busch Professor of Medicine Chairman, Department of Medicine Washington University School of Medicine St. Louis, Missouri xxix www.ketabpezeshki.com 66485457-66963820 Preface We have the pleasure of introducing the 34th edition of The Washington Manual of Medical Therapeutics. “The Manual,” as it has been labeled here at Washington University, has a proud tradition of being edited by the Internal Medicine Chief Residents. It was initially intended for use by local medical students and house staff but has now grown to be the best-selling medical text in the world. Beyond the increase in production, the Manual has grown in size and complexity, mirroring the practice of medicine. Wayland MacFarlane served as the initial editor in 1943, and numerous revisions have occurred in its 70 years of existence, moving from a short textbook to a portable reference. Today, we hope to continue that evolution in providing the rich text in both written and electronic form with availability on portable electronic devices. We continue the virtues that made the work a success: a concise discussion of pathophysiology, an evidence-based presentation of current therapies, and a sensible format. Additionally, we have diligently updated the content to reflect ever-changing advances in medicine. The Washington Manual of Medical Therapeutics has established a tradition of excellence that we aspire to preserve. Throughout this year, the medicine house staff, fellows, medical students, and attendings have inspired us. Their brilliance, commitment, and compassion are truly remarkable. We are honored that they turn to the Manual for guidance. We are deeply indebted for the substantial support and direction that Tom De Fer, the series editor, provided in the creation of this edition of the Manual. We also thank Katie Sharp and the editorial staff at Lippincott Williams & Wilkins for their assistance and patience with our busy schedules. We have had the honor and pleasure of serving as Chief Residents of Shatz- Strauss, Karl-Flance, Kipnis-Daughaday, North Campus firms, and The Primary Care Medicine Clinic in the Barnes-Jewish Center for Outpatient Health. Our Firm Chiefs, Megan Wren, William Clutter, Geoffrey Cislo, and E-P Barrette, have been instrumental over the course of the year, serving as mentors and role models. Our program director, Melvin Blanchard, has been a great help in the production of the Manual. Our Chairman of Medicine, Vicky Fraser, provided guidance and support in the creation of this text. We thank our families for their support and inspiration. To Ram Kumar, Malka, and Robbie; Patrick and Carla, TJ and Gabriel; Edward, Cecelia, and Karla; Steve, Karen, and Arun; Julio, Katty, and Jessi … our gratitude is beyond measure. Hemant Godara, MD Angela Hirbe, MD, PhD Michael Nassif, MD Hannah Otepka, MD Aron Rosenstock, MD xxx www.ketabpezeshki.com 66485457-66963820  Patient Care in Internal 1 Medicine Mark Thoelke, John Cras, Nathan Martin, and Amy Sheldahl General Care of the Hospitalized Patient GENERAL PRINCIPLES Although a general approach to common problems can be outlined, therapy must be individualized. All diagnostic and therapeutic procedures should be explained carefully to the patient, including the potential risks, benefits, and alternatives. This explanation minimizes anxiety and provides the patient and the physician with appropriate expectations. The period of hospitalization represents a complex interplay of multiple caregivers that subjects the patient to potential harm by medical errors and iatrogenic complications. Every effort must be made to minimize these risks. Basic mea- sures include:  Use of standardized abbreviations and dose designations  Excellent communication between physicians and other caregivers  Institution of appropriate prophylactic precautions  Prevention of nosocomial infections, including attention to hygiene and discontin- uation of unnecessary catheters  Medicine reconciliation at all transfers of care Hospital orders  Admission orders should be written promptly after evaluation of a patient. Each set of orders should bear the date and time of writing and the legible signature of the physician. Consideration should be given to including a printed signature and a contact number. All orders should be clear, concise, organized, and legible. Computer order entry facilitates aspects of this process.  To ensure that no important therapeutic measures are overlooked, the content and organization of admission orders may follow the outline that follows (the mnemonic ADC VANDISMAL): Admitting service, location, and physician responsible for the patient Diagnoses Condition of the patient Vital signs with frequency Activity limitations Nursing instructions (e.g., Foley catheter to gravity drainage, wound care, daily weights) Diet. Remember that “NPO” may preclude oral medications unless specified Intravenous (IV) fluids, including composition and rate Sedatives, analgesics, and other as needed (PRN) medications Medications, including dose, frequency, route, and indication; state “first dose now” when appropriate 1 www.ketabpezeshki.com 66485457-66963820 2 Chapter 1 Patient Care in Internal Medicine Allergies, sensitivities, and previous drug reactions Laboratory tests and radiographic studies  Orders should be reevaluated frequently and altered as patient status dictates.  Daily rounds should include assessment for ongoing need of IV fluids, medica- tions, telemetry, and supplemental oxygen. Discharge  Discharge planning begins at the time of admission. Assessment of the patient’s social situation and potential discharge needs should be made at this time.  Early coordination with nursing, social work, and case coordinators/managers facilitates efficient discharge and a complete postdischarge plan.  Patient education should occur regarding changes in medications and other new therapies. Compliance with treatment is influenced by patient’s understanding of that treatment.  Prescriptions should be written for all new medication, and the patient should be provided with a complete medication list including instructions and indications.  Communication with physicians who will be resuming care of the patient after discharge is important for optimal follow-up care. PROPHYLACTIC MEASURES Venous Thromboembolism Prophylaxis GENERAL PRINCIPLES Epidemiology Venous thromboembolism (VTE) is among the most common preventable causes of death in hospitalized patients. Between 70% and 80% of fatal pulmonary emboli occur in nonsurgical patients (Chest 2007;132:936 ). Approximately 40% of medical inpatients are considered high risk for VTE by risk factors ($4 points) described in the following and would therefore benefit from VTE prophylaxis ( J Thromb Haemost 2010;8:2450 ). Risk Factors Weighted risk factors for VTE in hospitalized medical patients include: 3 points: active cancer, previous VTE (excluding superficial vein thrombosis), known thrombophilic condition, bed rest for at least 3 days 2 points: trauma or surgery ,1 month ago 1 point: age over 70, obesity (body mass index [BMI].30), heart and/or respiratory failure, acute myocardial infarction (MI), ischemic stroke, acute infection and/or rheumatologic disorder, ongoing hormonal treatment Prevention Pharmacologic prophylaxis results in a 50% decrease in VTE risk. All able patients should be encouraged to ambulate several times a day. Acutely ill patients at high risk of VTE using risk factors described previously without active bleeding or high risk for bleeding should be initiated on prophylactic dosing of low-dose unfractionated heparin (UFH), 5,000 units SC q8h or q12, or low–molecular-weight heparin (LMWH), enoxaparin, 40 mg SC daily or daltep- arin, 5,000 units SC daily, or fondaparinux, 2.5 mg SC daily. Aspirin alone is not sufficient for prophylaxis (Chest 2012;141:e195S). www.ketabpezeshki.com 66485457-66963820  Prophylactic Measures Decubitus Ulcers 3 At-risk patients with contraindications to anticoagulation prophylaxis may receive mechanical prophylaxis with intermittent pneumatic compression or graded compression stockings, although evidence of benefit is lacking in medical patients (Chest 2012;141:e195S; Ann Intern Med 2011;155:625). Decubitus Ulcers GENERAL PRINCIPLES Epidemiology Decubitus ulcers typically occur within the first 2 weeks of hospitalization and can develop within 2 to 6 hours. Once they develop, decubitus ulcers are difficult to heal and have been associated with increased mortality ( J Gerontol A Biol Sci Med Sci 1997;52:M106 ). Risk factors for the development of decubitus ulcers include, advanced age, paralysis, and severe illness (Clin Dermatol 2010;28(5):527). Prevention Prevention is the key to management of decubitus ulcers. While the majority of decubitus ulcers are preventable, evidence for best practices is lacking, and it is likely not all decubitus ulcers are avoidable). Measures include: Risk factor assessment, including immobility, limited activity, incontinence, im- paired nutritional status, impaired circulation, and altered level of consciousness. Skin care, including daily inspection with particular attention to bony prominences, minimizing exposure to moisture from incontinence, perspiration, or wound drain- age, and applying moisturizers to dry sacral skin. Nutritional supplements should be provided to patients at risk. Interventions aimed at relieving or redistributing pressure, including frequent repositioning (minimum of every 2 hours, or every 1 hour for wheelchair-bound patients), pillows or foam wedges between bony prominences, maintenance of the head of the bed at the lowest degree of elevation, and use of lifting devices when moving patients. Pressure-reducing and relieving devices (foam, dynamic air mattresses, low–air-loss and air-fluidized beds) can also be used ( JAMA 2006; 296:974 ). DIAGNOSIS Clinical Presentation National Pressure Ulcer Advisory Panel Staging: Suspected deep tissue injury: Purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear. The area may be preceded by tissue that is painful, firm, mushy, boggy, warmer, or cooler as compared to adjacent tissue. Stage I: Intact skin with nonblanchable redness of a localized area usually over a bony prominence. Darkly pigmented skin may not have visible blanching; its color may differ from the surrounding area. Stage II: Partial thickness loss of dermis presenting as a shallow open ulcer with a red pink wound bed without slough. May also present as an intact or open/ ruptured serum-filled blister. Stage III: Full thickness tissue loss. Subcutaneous fat may be visible but bone, tendon, or muscle are not exposed. Slough may be present but does not obscure the depth of tissue loss. May include undermining and tunneling. www.ketabpezeshki.com 66485457-66963820 4 Chapter 1 Patient Care in Internal Medicine Stage IV: Full thickness tissue loss with exposed bone, tendon, or muscle. Slough or eschar may be present on some parts of the wound bed. Often include undermin- ing and tunneling. Unstageable: Full thickness tissue loss in which the base of the ulcer is covered by slough (yellow, tan, gray, green, or brown) and/or eschar (tan, brown, or black) in the wound bed. TREATMENT Initial interventions include use of pressure-relieving devices, pain control, normal saline for cleansing, avoidance of agents that delay healing (antiseptic agents [Dakin solution, hydrogen peroxide, chlorhexidine] and wet-to-dry gauze), and removal of necrotic debris. Moist wounds heal best, and occlusive dressings (such as hydrocolloid dressings) should be used to maintain a moist environment while controlling exudate. Topical agents can also be used (silver sulfadiazine [Silvadene], bacitracin, Neosporin, Polysporin) to optimizing healing or for minor slough debridement (Santyl, Xenaderm). Adequate nutrition is recommended, although there is insufficient data to recom- mend a specific supplement regimen (Cochrane Database Syst Rev. 2003;(4): CD003216 ). Infected decubitus ulcers with evidence of cellulitis or lymphangitis require systemic antibiotics, but there is no role for antibiotics to aid healing of a noninfected ulcer. Other adjunctive therapies for nonhealing ulcers include electrical stimulation, radiant heat, negative pressure therapy, and surgical intervention ( JAMA 2008; 300:2647 ). Other Precautions GENERAL PRINCIPLES Fall precautions should be written for patients who have a history of falls or are at high risk of a fall (i.e., those with dementia, syncope, orthostatic hypotension). Falls are the most common accident in hospitalized patients, frequently leading to injury. Fall risk should not be equated with confinement to bed, which may lead to debilitation and higher risk of future falls. Seizure precautions should be considered for patients with a history of seizures or those at risk of seizing. Precautions include padded bed rails and an oral airway at the bedside. Restraint orders are written for patients who are at risk of injuring themselves or interfering with their treatment due to disruptive or dangerous behaviors. Restraint orders must be reviewed and renewed every 24 hours. Physical restraints may exacerbate agitation. Bed alarms or sitters are alternatives in appropriate settings. ACUTE INPATIENT CARE New or recurrent symptoms that require evaluation and management frequently develop in hospitalized patients. Evaluation should generally include a directed history, including a complete descrip- tion of the symptom (i.e., alleviating and precipitating factors, quality of the www.ketabpezeshki.com 66485457-66963820  Acute Inpatient Care Chest Pain 5 symptom, associated symptoms, and the course of the symptom, including acuity of onset, severity, duration, and previous episodes), a directed physical examination, review of the medical problem list, review of medications with attention to recent medication changes, and consideration of recent procedures. Further evaluation should be directed by the initial assessment, the acuity and severity of the complaint, and the diagnostic possibilities. An approach to selected common complaints is presented in this section. Chest Pain GENERAL PRINCIPLES Chest pain is a common complaint in the hospitalized patient, and the severity of chest discomfort does not always correlate with the gravity of its cause. DIAGNOSIS Clinical Presentation History History should be taken in the context of the patient’s other medical conditions, particularly previous cardiac or vascular history, cardiac risk factors, and factors that would predispose the patient to a pulmonary embolus. Physical Examination Physical examination is ideally conducted during an episode of pain and includes vital signs (with bilateral blood pressure [BP] measurements if considering aortic dissection), a careful cardiopulmonary and abdominal examination, and inspection and palpation of the chest for possible trauma, rash, and reproducibility of the pain. Differential Diagnosis Causes of chest pain in the medical inpatient range from life-threatening causes such as MI, aortic dissection, and pulmonary embolism to other causes including esopha- geal reflux, peptic ulcer disease, pneumonia, costochondritis, shingles, trauma to chest wall, and anxiety. Diagnostic Testing Assessment of oxygenation status, chest radiography, and electrocardiogram (ECG) is appropriate in most patients. Serial cardiac enzymes should be obtained if there is suspicion of ischemia. Spiral computed tomography (CT) and ventilation/ perfusion (VQ) scans are employed to diagnose pulmonary embolus. TREATMENT If cardiac ischemia is a concern, initial therapy should include supplemental oxygen, aspirin, and administration of nitroglycerin, 0.4 mg SL, or morphine sulfate, 1 to 2 mg IV, or both. (See Chapter 4, Ischemic Heart Disease.) If a gastrointestinal (GI) source of chest pain is suspected, a combination of Maalox and diphenhydramine (30 mL of each in a 1:1 mix) can be administered. www.ketabpezeshki.com 66485457-66963820 6 Chapter 1 Patient Care in Internal Medicine Musculoskeletal pain typically responds to acetaminophen or nonsteroidal anti- inflammatory drug (NSAID) therapy. Prompt empiric anticoagulation while awaiting testing should be considered if there is high suspicion for MI or pulmonary embolism (barring contraindication). Dyspnea GENERAL PRINCIPLES Dyspnea is most commonly caused by a cardiopulmonary abnormality, such as congestive heart failure (CHF), cardiac ischemia, bronchospasm, pulmonary embolus, infection, mucus plugging, and aspiration. Dyspnea must be promptly and care- fully evaluated. DIAGNOSIS Clinical Presentation History Initial evaluation should include a review of the medical history for underlying pulmonary or cardiovascular disease and a directed history. Physical Examination A detailed cardiopulmonary examination should take place, including vital signs with comparison of current findings to those documented earlier. Auscultation of the heart and lungs are vital to the exam in patients with dyspnea. Diagnostic Testing Oxygen assessment should take place promptly. Arterial blood gas measurement provides more information than pulse oximetry. Chest radiography is useful in most patients. Other diagnostic and therapeutic measures should be directed by the findings in the initial evaluation and the severity of the suspected diagnosis. TREATMENT Therapeutic measures should be directed by the findings in the initial evaluation and the severity of the suspected diagnoses. If the patient is hypoxic, oxygen administration should be delivered in a prompt fashion. Acute Hypertensive Episodes GENERAL PRINCIPLES Acute hypertensive episodes in the hospital are most often caused by inadequately treated essential hypertension. Volume overload and pain may exacerbate hypertension and should be recognized appropriately and treated. Hypertension associated with withdrawal syndromes (e.g., alcohol, cocaine) and rebound hypertension associated with sudden withdrawal of antihypertensive medi- www.ketabpezeshki.com 66485457-66963820  Acute Inpatient Care Fever 7 cations (i.e., clonidine, a-adrenergic antagonists) should be considered. These entities should be treated as discussed in Chapter 3, Preventive Cardiology. TREATMENT Treatment decisions should consider baseline BP, presence of symptoms (e.g., chest pain or shortness of breath), and current and baseline antihypertensive medications. Overtreatment with IV medications should be avoided. Fever GENERAL PRINCIPLES Fever accompanies many illnesses and is a valuable marker of disease activity. DIAGNOSIS Clinical Presentation History History should include chronology of the fever and associated symptoms, medications, potential exposures, and a complete social and travel history. Physical Examination Physical examination should include oral or rectal temperature monitoring from a consistent site. In the hospitalized patient, special attention should be paid to any rash, new murmur, abnormal fluid accumulation, IV lines, and indwelling devices such as gastric tubes or Foley catheters. In the neutropenic patient, the skin, oral cavity, and perineal area should be examined carefully for breaches of mucosal integrity. For management of neutro- penic fever, see Chapter 22, Medical Management of Malignant Disease. Differential Diagnosis Infection is a primary concern. Drug reaction, malignancy, VTE, vasculitis, central fever, and tissue infarction are other possibilities but are diagnoses of exclusion. The pace and complexity of the workup depends on the diagnostic considerations taken in the context of the clinical stability and immune status of the patient. Diagnostic Testing Testing includes culture of blood and urine, complete blood count (CBC) with differential, serum chemistries with liver function tests, and urinalysis. Diagnostic evaluation generally includes chest radiography. Cultures of abnormal fluid collections, sputum, cerebrospinal fluid, and stool should be sent if clinically indicated. Cultures are ideally obtained prior to initiation of antibiotics; however, antibiotics should not be delayed if serious infection is sus- pected. TREATMENT Not all fevers require treatment. Antipyretic drugs may be given to decrease associated discomfort. Aspirin, 325 mg, and acetaminophen, 325 to 650 mg PO www.ketabpezeshki.com 66485457-66963820 8 Chapter 1 Patient Care in Internal Medicine or per rectum q4h, are the drugs of choice. Aspirin should be avoided in adoles- cents with possible viral infections because this combination has been associated with Reye syndrome. Tepid water baths are effective in treating hyperpyrexia. Use of hypothermic (cooling) blankets and ice packs are uncomfortable and should generally be discour- aged. Empiric antibiotics should be considered in hemodynamically unstable patients in whom infection is a primary concern, as well as in neutropenic and asplenic patients. Heat stroke and malignant hyperthermia are medical emergencies that require prompt recognition and treatment (see Chapter 27, Medical Emergencies). Pain GENERAL PRINCIPLES Definition Pain is subjective, and therapy must be individualized. Chronic pain may not be associated with any objective physical findings. Pain scales should be employed for quantitation. Classification Acute pain usually requires only temporary therapy. For chronic pain, a combination of basal pain medication with bolus as needed doses may be needed. Anticonvulsants and antidepressants, such as gabapentin and tricyclic antidepres- sants (TCAs), are useful adjuncts for neuropathic pain. If pain is refractory to conventional therapy, then nonpharmacologic modalities, such as nerve blocks, sympathectomy, and cognitive behavioral therapy, may be appropriate. TREATMENT Medications Acetaminophen  Effects: Antipyretic and analgesic actions but no anti-inflammatory or antiplate- let properties.  Preparations and dosage: Acetaminophen, 325 to 1,000 mg q4–6h (maximum dose, 4 g/d), is available in tablet, caplet, liquid, intravenous, and rectal suppository form. It should be used at low doses in patients with liver disease (less than 2 g/d).  Adverse effects The principal advantage of acetaminophen is its lack of gastric toxicity. Hepatic toxicity may be serious, and acute overdose with 10 to 15 g can cause fatal hepatic necrosis (see Chapter 19, Liver Diseases, and Chapter 27, Medical Emergencies). Aspirin  Effects: Aspirin has analgesic, antipyretic, anti-inflammatory, and antiplatelet effects.  Preparations and dosages 325 to 650 mg PO q4h PRN (maximum dose, 4 g/d). www.ketabpezeshki.com 66485457-66963820  Acute Inpatient Care Pain 9 Rectal suppositories, 300 to 600 mg q3–4h may be irritating to the mucosa and have variable absorption. Enteric-coated tablets may cause less injury to the gastric mucosa than buffered or plain aspirin.  Adverse effects Dose-related side effects include tinnitus, dizziness, and hearing loss. Dyspepsia and GI bleeding can develop and may be severe. Hypersensitivity reactions, including bronchospasm, laryngeal edema, and urti- caria, are uncommon, but patients with asthma and nasal polyps are more suscep- tible. Patients with allergic or bronchospastic reactions to aspirin should not be given NSAIDs. Chronic excessive use can result in interstitial nephritis and papillary necrosis. Aspirin should be used with caution in patients with hepatic or renal disease, bleeding disorders, pregnancy, and those who are receiving anticoagulation therapy. Antiplatelet effects may last for up to 1 week after a single dose. NSAIDs  Effects: NSAIDs have analgesic, antipyretic, and anti-inflammatory properties mediated by inhibition of cyclooxygenase. All NSAIDs have similar efficacy and toxicities, with a side-effect profile similar to that of aspirin.  Adverse effects NSAIDs may blunt the cardioprotective effects of aspirin. NSAIDs should be used with caution in patients with impaired renal or hepatic function (see Chapter 25, Arthritis and Rheumatologic Diseases). The U.S. Food and Drug Administration (FDA) has issued a boxed warning that all NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors) are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. NSAIDs are contraindicated immediately postoperative from coronary artery bypass surgery. Ketorolac is an NSAID analgesic that can be given intramuscularly (IM) or IV, 15 to 30 mg q8h, and is often used postoperatively; however, parenteral therapy should not exceed 5 days. Nephrotoxicity is more pronounced with IM than with PO administration. Cyclooxygenase-2 (COX-2) inhibitors  Effects: COX-2 inhibitors act primarily on COX-2, an inducible form of cyclooxy- genase and an important mediator of pain and inflammation. COX-2 inhibitors have little significant effect on the gastric mucosa. COX-2 inhibitors offer no analgesic advantage over other NSAIDs.  Preparations and dosages: The currently available selective COX-2 inhibitor is celecoxib. Meloxicam is also available but is less selective for COX-2.  Adverse effects Chronic, high-dose COX-2 inhibitor increased the risk of adverse cardiovascular events in one study, but a subsequent meta-analysis of randomized controlled trials showed no increased risk of adverse cardiovascular outcomes, although most patients in these studies received only a short course of celecoxib (N Engl J Med 2006;355:873; Am J Cardiol 2007;99:91). While pharmacologic data suggest celecoxib has no effects on the platelet inhibitory effects of aspirin or Plavix, there is some concern for increased thrombotic risk when celecoxib is www.ketabpezeshki.com 66485457-66963820 10 Chapter 1 Patient Care in Internal Medicine used after cardiac stenting ( J Clin Pharmacology 2002;42:1027; KoreanCircJ2010; 40(7):321; Eur Heart J 2012 Mar 8. [Epub ahead of print]). COX-2 inhibitors should not be used in patients who have allergic or bronchos- pastic reactions to aspirin or other NSAIDs. Celecoxib is contraindicated in patients with allergic-type reactions to sulfon- amides. Opioid analgesics  Effects: Opioid analgesics are pharmacologically similar to opium or morphine and are the drugs of choice when analgesia without antipyretic action is desired.  Preparations and dosages: Table 1-1 lists equianalgesic dosages.  Constant pain Constant pain requires continuous (basal) analgesia with supplementary, PRN doses for breakthrough pain at doses of roughly 5% to 15% of the daily basal dose. Medication dosages should be maintained at the lowest level that provides adequate analgesia. If frequent PRN doses are required, the maintenance dose should be increased, or the dosing interval should be decreased. If adequate analgesia cannot be achieved at the maximum recommended dose of one narcotic or if the side effects are intolerable, the patient should be changed to another preparation beginning at one half of the equianalgesic dose to account for incomplete cross-tolerance. Oral medications should be used when possible. Parenteral and transdermal administration are useful in the setting of dyspha- gia, emesis, or decreased GI absorption. Continuous IV administration provides steady blood levels and allows for rapid dose adjustment. Agents with short half-lives, such as morphine, should be used. Narcotic-naïve patients should be started on the lowest possible doses, whereas patients with demonstrated tolerance will require higher doses. Patient-controlled analgesia is often used to control pain in a postoperative or terminally ill patient. Advantages of patient-controlled analgesia include enhancement in pain relief, and decrease in anxiety. Opioid-naïve patients should not have basal rates prescribed due to risk of overdose. Table 1-1 Equipotent Doses of Opioid Analgesics Drug Onset (min) Duration (hr) IM/IV/SC (mg) PO (mg) Fentanyl 7–8 1–2 0.1 NA Levorphanol 30 – 90 4–6 2 4 Hydromorphone 15 – 30 2–4 1.5 – 2.0 7.5 Methadone 30 – 60 4 – 12 10 20 Morphine 15 – 30 2–4 10 30a Oxycodone 15 – 30 3–4 NA 20 Codeine 15 – 30 4–6 120 200 Note: Equivalences are based on single-dose studies. a An IM:PO ratio of 1:2 to 1:3 used for repetitive dosing. NA, not applicable. www.ketabpezeshki.com 66485457-66963820  Acute Inpatient Care Pain 11  Selected drugs Codeine is usually given in combination with aspirin or acetaminophen. It is also an effective cough suppressant at a dosage of 10 to 15 mg PO q4–6h. Oxycodone and hydrocodone are also usually prescribed orally in combination with acetaminophen. Available tablets include oxycodone with acetaminophen, 5 mg/325 or 7.5 mg/325 PO q6h, and hydrocodone with acetaminophen, 5 mg/325, 5 mg/500, 7.5 mg/325, or 7.5 mg/500 PO q4–6h. Care should be taken to avoid acetaminophen overdose with these formulations. Oxycodone is avail- able without acetaminophen and should be used for patients requiring higher opioid doses to avoid acetaminophen toxicity. Immediate-release and sustained-release morphine sulfate preparations (immediate-release, 5 to 30 mg PO q2–8h, sustained-release, 15 to 120 mg PO q12h or a rectal suppository) can be used. The liquid form can be useful in patients who have difficulty in swallowing pills. Larger doses of morphine may be necessary to control pain as tolerance develops. Morphine should be used with caution in renal insufficiency. Meperidine is no longer recommended for pain treatment due to limited efficacy and a very short duration of analgesia with significant euphoria. Methadone is very effective when administered orally and suppresses the symp- toms of withdrawal from other opioids because of its extended half-life. Despite its long elimination half-life, its analgesic duration of action is much shorter. Hydromorphone, 2 to 4 mg PO q4–6h; 1 to 2 mg IM, IV, or SC q4–6h, is a potent morphine derivative. It is also available as a 3-mg rectal suppository. Fentanyl is available in a transdermal patch with sustained release over 72 hours. Initial onset of action is delayed. Respiratory depression may occur more frequently with fentanyl. Mixed agonist–antagonist agents (butorphanol, nalbuphine, oxymorphone, pentazocine) offer few advantages and produce more adverse effects than do the other agents.  Precautions Opioids are relatively contraindicated in acute disease states in which the pattern and degree of pain are important diagnostic signs (e.g., head injuries, abdominal pain). They may also increase intracranial pressure. Opioids should be used with caution in patients with hypothyroidism, Addi- son disease, hypopituitarism, anemia, respiratory disease (e.g., chronic obstruc- tive pulmonary disease [COPD], asthma, kyphoscoliosis, severe obesity), severe malnutrition, debilitation, or chronic cor pulmonale. Opioid dosage should be adjusted for patients with impaired hepatic function. Drugs that potentiate the adverse effects of opioids include phenothiazines, antidepressants, benzodiazepines, and alcohol. Tolerance develops with chronic use and coincides with the development of physical dependence. Physical dependence is characterized by a withdrawal syndrome (anxiety, irritability, diaphoresis, tachycardia, GI distress, and temperature instability) when the drug is stopped abruptly. It may occur after only 2 weeks of therapy. Administration of an opioid antagonist may precipitate withdrawal after only 3 days of therapy. Withdrawal can be minimized by tapering the medication slowly over several days. www.ketabpezeshki.com 66485457-66963820 12 Chapter 1 Patient Care in Internal Medicine  Adverse and toxic effects Although individuals may tolerate some preparations better than others, at equianalgesic doses, few differences in side effects exist. Central nervous system (CNS) effects include sedation, euphoria, and pupil- lary constriction. Respiratory depression is dose related and is especially pronounced after IV administration. Cardiovascular effects include peripheral vasodilation and hypotension, espe- cially after IV administration. GI effects include constipation, nausea, and vomiting. Patients who are receiving opioid medications should be provided with stool softeners and laxatives. Benzo- diazepines, dopamine antagonists (e.g., prochlorperazine, metoclopramide), and ondansetron can be used as antiemetics. Opioids may precipitate toxic megaco- lon in patients with inflammatory bowel disease. Urinary retention may be caused by increased bladder, ureter, and urethral sphincter tone. Pruritus occurs most commonly with spinal administration.  Opioid overdose Naloxone, an opioid antagonist, should be readily available for administration in the case of accidental or intentional overdose. For details of administration, see Chapter 27, Medical Emergencies. Side effects include hypertension or hypotension, irritability, anxiety, restless- ness, tremulousness, nausea, and vomiting. Naloxone can also precipitate seizure activity and cardiac arrhythmias. Alternative medications  Tramadol is an opioid agonist, and a centrally acting nonopioid analgesic that acts on pain processing pathways. Preparations and dosages: Between 50 and 100 mg PO q4–6h can be used for acute pain. For elderly patients and those with renal or liver dysfunction, dosage reduction is recommended. Adverse effects: Because CNS effects include sedation, concomitant use of alcohol, sedatives, or narcotics should be avoided. Nausea, dizziness, constipa- tion, and headache may also occur. Respiratory depression has not been described at prescribed dosages but may occur with overdose. Tramadol should not be used in patients who are taking a monoamine oxidase inhibitor, as it can contribute to serotonin syndrome.  Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine and oxcarbazep- ine), tricyclic antidepressants (e.g., amitriptyline), and duloxetine are PO agents that can be used to treat neuropathic pain.  Topical anesthetics (e.g., lidocaine) may provide analgesia to a localized region (e.g., postherpetic neuralgia). Altered Mental Status GENERAL PRINCIPLES Mental status changes have a broad differential diagnosis that includes neurologic (e.g., stroke, seizure, delirium), metabolic (e.g., hypoxemia, hypoglycemia), toxic (e.g., drug effects, alcohol withdrawal), and other etiologies. Infection (e.g., urinary www.ketabpezeshki.com 66485457-66963820  Acute Inpatient Care Altered Mental Status 13 tract infections, pneumonia) is a common cause in the elderly and patients with underlying neurologic disease. Sundown syndrome refers to the appearance of worsening confusion in the evening and is associated with dementia, delirium, and unfamiliar environments. DIAGNOSIS Clinical Presentation History Focus particularly on medications, underlying dementia, cognitive impairment, neurologic or psychiatric disorders, and a history of alcohol and drug use. Directed history should be obtained from the patient. Family and nursing personnel may be able to provide additional details. Physical Examination Physical examination generally includes vital signs, a search for sites of infection, a complete cardiopulmonary examination, and a detailed neurologic examination including mental status evaluation. Diagnostic Testing Testing includes blood glucose, serum electrolytes, creatinine, CBC, urinalysis, oxygen assessment, and chest radiograph. Other evaluation, including culture, lumbar puncture, toxicology screen, thyroid function tests, and B12 levels, should be directed by initial findings and diagnos- tic possibilities. If indicated by initial findings and diagnostic possibilities, the following should be obtained:  CT of the head (initially, a noncontrast study is appropriate)  Electroencephalogram (EEG)  ECG TREATMENT Management of specific disorders is discussed in Chapter 26, Neurologic Disorders. Medications Agitation and psychosis may be features of a change in mental status. The antipsy- chotic, haloperidol, and the benzodiazepine, lorazepam, are commonly used in the acute management of these symptoms. Second-generation antipsychotics (risperi- done, olanzapine, quetiapine, clozapine, ziprasidone, aripiprazole, paliperidone) are alternative agents that may lead to decreased incidence of extrapyramidal symp- toms. All of these agents pose risks to elderly, demented patients if given for long term. Haloperidol is the initial drug of choice for acute management of agitation and psychosis. The initial dose of 0.5 to 5 mg (0.25 mg in elderly patients) PO and 2 to 10 mg IM or IV can be repeated every 30 to 60 minutes until the desired effect is achieved. Sedation is usually achieved with 10 to 20 mg PO or IM. IV infusions (1 to 40 mg/hr) can also be used as an alternative to bolus injections. Haloperidol has fewer active metabolites and fewer anticholinergic, sedative, and hypotensive effects than other antipsychotics but may have more extrapyramidal www.ketabpezeshki.com 66485457-66963820 14 Chapter 1 Patient Care in Internal Medicine side effects. In low dosages, haloperidol rarely causes hypotension, cardiovascular compromise, or excessive sedation.  Prolongation of the QT interval with development of torsades de pointes may be seen with high-dose IV therapy. In patients who are receiving IV therapy, QTc and electrolytes (primarily potassium and magnesium) should be monitored. Use should be discontinued with prolongation of QTc.450 milliseconds or 25% above baseline.  Postural hypotension may occasionally be acute and severe after IM administra- tion. If significant hypotension occurs, administration of IV fluids with the patient in the Trendelenburg position is usually sufficient. If vasopressors are required, dopamine should be avoided, as it may exacerbate the psychotic state.  Neuroleptic malignant syndrome is an infrequent, potentially lethal complica- tion of antipsychotic drug therapy. Clinical manifestations include rigidity, akine- sia, altered sensorium, fever, tachycardia, and alteration in BP. Severe muscle rigidity can cause rhabdomyolysis and acute renal failure. Laboratory abnormali- ties include elevations in creatine kinase, liver function tests, and white blood cell count (see Chapter 26, Neurologic Disorders). Lorazepam is a benzodiazepine that is useful for agitation and psychosis in the setting of hepatic dysfunction and sedative or alcohol withdrawal, and in patients who are refractory to monotherapy with antipsychotics. The initial dose is 0.5 to 2.0 mg IV. The key features of lorazepam are its short duration of action and few active metabolites. The use of lorazepam, as with all benzodiazepines, is limited by excess sedation and respiratory depression. Caution is advised when using benzodiazepines in the elderly as they may paradoxically worsen agitation. Nonpharmacologic Therapies Patients with delirium of any etiology often respond to frequent reorientation, observance of the day–night light cycle, and maintenance of a familiar environ- ment. Insomnia and Anxiety GENERAL PRINCIPLES Insomnia and anxiety may be attributed to a variety of underlying medical or psychiatric disorders, and symptoms may be exacerbated by hospitalization. Causes of insomnia include environmental disruptions, mood and anxiety disor- ders, substance abuse disorders, common medications (i.e., b-blockers, steroids, bronchodilators), sleep apnea, hyperthyroidism, and nocturnal myoclonus. Anxiety may be seen in anxiety disorder, depression, substance abuse disorders, hyperthyroidism, and complex partial seizures. DIAGNOSIS The diagnosis of insomnia and anxiety is a clinical one. No laboratory or imaging tests help in establishing the diagnosis; however, they can help to rule out other etiologies. A thorough history is essential. www.ketabpezeshki.com 66485457-66963820  Acute Inpatient Care Insomnia and Anxiety 15 TREATMENT Selected medications for insomnia or anxiety or both: Benzodiazepines are frequently used in management of anxiety and insomnia. Table 1-2 provides a list of selected benzodiazepines and their common uses and dosages.  Pharmacology: Most benzodiazepines undergo oxidation to active metabolites in the liver. Lorazepam, oxazepam, and temazepam undergo glucuronidation to inactive metabolites; therefore, these agents may be particularly useful in the elderly and in those with liver disease. Benzodiazepine toxicity is heightened by malnutrition, advanced age, hepatic disease and concomitant use of alcohol, other CNS depressants, and CYP3A4 inhibitors. Benzodiazepines with long half- lives may accumulate substantially in the elderly, in whom the half-life may be increased manyfold.  Dosages Relief of anxiety and insomnia is achieved at the doses outlined in Table 1-2. Therapy should be started at the lowest recommended dosage with intermittent dosing schedules. Side effects include drowsiness, dizziness, fatigue, psychomotor impairment, and anterograde amnesia. The elderly are more sensitive to these agents and may experience falls, paradoxi- cal agitation, and delirium. IV administration of diazepam and midazolam can be associated with hypo- tension, bradycardia, and respiratory or cardiac arrest. Respiratory depression can occur even with oral administration in patients with respiratory compromise. Tolerance to benzodiazepines can develop. Dependence may develop after only 2 to 4 weeks of therapy. Seizures and delirium may also occur with sudden discontinuation of benzodi- azepines. A withdrawal syndrome consisting of agitation, irritability, insomnia, tremor, palpitations, headache, GI distress, and perceptual disturbance begins 1 to 10 days after a rapid decrease in dosage or abrupt cessation of therapy and may last for several weeks. Although the severity and incidence of withdrawal symptoms appears to be related to dose and duration of treatment, withdrawal symptoms have been reported even after brief therapy at doses in the recommended range. Short-acting and intermediate-acting drugs should be decreased by 10% to 20% every 5 days, with a slower taper in the final few weeks. Long-acting preparations can be tapered more quickly.  Overdose Flumazenil, a benzodiazepine antagonist, should be readily available in case of accidental or intentional overdose. For details of administration, see Chapter 27, Medical Emergencies. Common side effects include dizziness, nausea, and vomiting. Flumazenil should be used with caution in patients with a history of seizure disorder or if overdose with tricyclic antidepressants is suspected. Trazodone  Trazodone is a serotonin receptor antagonist antidepressant that may be useful for the treatment of severe anxiety or insomnia. Common dosing is 50 to 100 mg at bedtime. www.ketabpezeshki.com 66485457-66963820 16 Chapter 1 Patient Care in Internal Medicine Table 1-2 Characteristics of Selected Benzodiazepines Usual Half-life Drug Route Common Uses Dosage (hr)a Alprazolam PO Anxiety disorders 0.75 – 4.0 12 – 15 mg/24 hr (in three doses) Chlordiazepoxide PO Anxiety 15 – 100 mg/ 5 – 30 disorders, 24 hr (in alcohol divided withdrawal doses) Clonazepam PO Anxiety 0.5 – 4.0 mg/ 18 – 28 disorders, 24 hr (in seizure two doses) disorders Diazepam PO Anxiety 6 – 40 mg/24 20 – 50 disorders, hr (in one seizure to four disorders, doses) preanesthesia IV 2.5 – 20.0 20 – 50 mg (slow IV push) Flurazepam PO Insomnia 15 – 30 mg 50 – 100 at bedtime Lorazepamb PO Anxiety disorders 1 – 10 mg/24 10 – 20 hr (in two to three doses) IV or Preanesthetic 0.05 mg/kg 10 – 20 IM medication (4 mg max) Midazolam IV Preanesthetic 0.01 – 0.05 1 – 12 and mg/kg intraoperative medication IM 0.08 mg/kg 1 – 12 Oxazepamb PO Anxiety disorders 10 – 30 mg/ 5 – 10 24 hr (in three to four doses) Temazepamb PO Insomnia 15 – 30 mg 8 – 12 at bedtime Triazolam PO Insomnia 0.125 – 2–5 0.250 mg at bedtime a Half-life of active metabolites may differ. b Metabolites are inactive. www.ketabpezeshki.com 66485457-66963820  Perioperative Medicine Preoperative Cardiac Evaluation 17  Side effects Highly sedating, causes postural hypotension, and is rarely associated with pria- pism. Levels may be substantially increased when used with CYP3A4 inhibitors. Nonbenzodiazepine hypnotics appear to act on the benzodiazepine receptor. These agents have been shown to be safe and effective for initiating sleep. All should be used with caution in patients with impaired respiratory function. Zolpidem in high, chronic doses is rarely associated with withdrawal syndromes, rebound insom- nia, and tolerance (Drug Saf 2009;32(9):735 ). Zaleplon and eszopiclone have not been shown to be associated with rebound insomnia or tolerance. All three agents are associated with abuse potential and are therefore Schedule IV drugs by the U.S. Drug Enforcement Administration (DEA).  Zolpidem is an imidazopyridine hypnotic agent that is useful for the treatment of insomnia. It has no withdrawal syndrome, rebound insomnia, or tolerance. Side effects include headache, daytime somnolence, and GI upset. The starting dose is 5 mg PO every night at bedtime for the elderly and 10 mg for other patients, titrating up to 20 mg as needed. Doses should be reduced in cirrhosis.  Zaleplon has a half-life of approximately 1 hour and has no active metabolites. Side effects include drowsiness, dizziness, and impaired coordination. Zaleplon should be used with caution in those with compromised respiratory function. The starting dose is 5 mg PO at bedtime for the elderly or patients with hepatic dysfunction and 10 to 20 mg PO at bedtime for other patients.  Eszopiclone offers a longer half-life compared to the previous agents. Side effects include headache, somnolence, and dizziness. Starting dose is 2 mg, with reduced dosing in the elderly, debilitated, and patients with liver disease.  Ramelteon is a melatonin analog with similar efficacy as the nonbenzodiazepine hypnotics. The usual dose is 8 mg PO at bedtime. There is no evidence for withdrawal, tolerance, rebound insomnia, or abuse potential, and it is therefore not a scheduled drug.  Antihistamines: Over-the-counter antihistamines can be used for insomnia and anxiety, particularly in patients with a history of drug dependence. Anticholinergic side effects limit the utility, especially in the elderly. PERIOPERATIVE MEDICINE Preoperative Cardiac Evaluation GENERAL PRINCIPLES The role of the medical consultant is to estimate the level of cardiac risk associated with a given procedure. “Clearance” cannot be readily granted, as there is always some level of risk. Based on the estimated risk, the consultant should then determine the need for further evaluation and prescribe possible interventions to mitigate risk. Though preoperative consultations often focus on cardiac risk, it is essential to remember that poor outcomes can result from significant disease in other organ systems. Evaluation of the entire patient is necessary to provide optimal periop- erative care. www.ketabpezeshki.com 66485457-66963820 18 Chapter 1 Patient Care in Internal Medicine Definition Perioperative cardiac complications are generally defined as cardiac death, MIs (both ST and non-ST elevation), CHF, and clinically significant rhythm disturbances. Epidemiology The incidence of perioperative cardiac complications varies markedly depending on the definitions employed and the population studied. Overall, an estimated 50,000 perioperative infarctions and 1 million other cardiovascular complications occur annually (N Engl J Med 2001;345:1677 ). Of those who have a perioperative MI, the risk of in-hospital mortality is estimated at 10% to 15% (Chest 2006;130:584 ). Perioperative MI (PMI) is believed to occur via two distinct mechanisms:  Type I PMI occurs via erosion or rupture of unstable atherosclerotic plaque, leading to coronary thrombosis, ischemia, and infarction.  Type II PMI results from an imbalance in myocardial oxygen supply/demand, leading to prolonged ischemia and ST-segment depression. Angiographic data suggest that existing stenoses may play a role with some perioper- ative events; however, a significant number of PMIs are “stress” related (Type II PMI) and not due to plaque rupture (Am J Cardiol 1996;77:1126; J Cardiothorac Vasc Anesth 2003;17:90). Autopsy data suggest fatal PMIs occur predominantly in patients with multivessel and especially left main disease, via the same mechanism as non-PMIs (Int J Cardiol 1996;57:37 ). DIAGNOSIS Clinical Presentation History The focus of the history is to identify factors and comorbid conditions that will affect perioperative risk. Current guidelines focus on identification of active cardiac disease and known risk factors for perioperative events.  Evidence of active cardiac conditions for which the patient should undergo evaluation and treatment: Unstable coronary syndromes Unstable or severe angina Recent MI (defined as more than 7 but less than 30 days) Decompensated CHF (NY Heart Association [NYHA] class IV, worsening or new-onset heart failure [HF]) Significant arrhythmias Severe valvular disease  Clinical risk factors Preexisting, stable coronary artery disease (CAD) Compensated or prior CHF Diabetes mellitus Prior cerebrovascular accident (CVA) or transient ischemic attack (TIA) Renal insufficiency www.ketabpezeshki.com 66485457-66963820  Perioperative Medicine Preoperative Cardiac Evaluation 19  Other Age.70 years has been identified in several studies as a significant risk factor ( JAMA 2001;285:1865; Eur Heart J 2008;29:394 ). Not uniformly accepted as an independent risk factor. Abnormal ECG (e.g., LVH, LBBB, ST-T wave abnormalities) Nonsinus rhythm (rate controlled and stable) Poorly controlled hypertension Physical Examination A complete physical exam is essential. Specific attention should be paid to:  Vital signs, particularly evidence of hypertension. Systolic blood pressure (SBP) ,180 and diastolic blood pressure (DBP) ,110 are generally considered acceptable. The management of stage III hypertension (SBP.180 or DBP.110) is controversial. Postponing elective surgery to allow adequate BP control in this setting is acceptable, but this is poorly studied and how long to wait after treatment is instituted is unclear.  Evidence of CHF (elevated JVP, crackles, S3, etc.).  Murmurs suggestive of significant valvular lesions. Symptomatic stenotic lesions such as mitral and aortic stenosis (AS) are thought to be associated with the greatest risk. ę Severe AS (valve area ,0.7 cm2 or mean gradient $50 mm Hg) is associated with an approximate 30% incidence of cardiac morbidity with a mortality of approximately 10% (Am J Med 2004;116:8; Am J Cardiol 1998;81:448). ę The risk of asymptomatic, moderate AS appears to be less, and surgery can be considered in this group with careful evaluation (Chest 2005;128:2944 ). ę Mitral stenosis is not well studied in the perioperative setting. Percutaneous valvotomy should be considered with severe stenosis. Symptomatic regurgitant lesions are generally tolerated perioperatively and can be managed medically as long as the patient is well compensated preoperatively. Diagnostic Criteria Risk Stratification The 2007 American College of Cardiology/American Heart Association (ACC/ AHA) Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery offer a stepwise approach to preoperative evaluation (Figure 1-1). Step 1: Establish the urgency of surgery. Important to note that many surgeries, though not absolutely emergent, are urgent and are unlikely to allow for a time-consuming evaluation. Step 2: Assess for active cardiac conditions (see History section previously). Step 3: Determine the surgery-specific risk.  Though professional judgement is required, surgical risk can generally be divided as follows: Low-risk surgeries (,1% expected risk of adverse cardiac events) include superficial procedures, cataract surgery, breast surgery, endoscopic procedures, and most procedures that can be performed in an ambulatory setting. Intermediate risk surgeries (1% to 5% risk of adverse cardiac events) include carotid endarterectomy, intraperitoneal surgeries, intrathoracic surgeries, orthopedic surgeries, head and neck surgeries, and prostate surgery. www.ketabpezeshki.com 66485457-66963820 20 Chapter 1 Patient Care in Internal Medicine Proceed to OR Yes Emergency surgery? Postoperative evaluation for Step 1 ischemia and risk factor modification No Yes Postpone surgery Any active cardiac Step 2 Evaluate and treat cardiac conditions? conditions as indicated No Yes Proceed with surgery Step 3 Low-risk surgery?