Algorithms of Common Poisonings, Third Edition PDF

EW VI RE ALGORITHMS OF COMMON POISONINGS OR Third Edition 2F FT A DR  The printing of Algorithms of Common Poisonings, Third Edition, EW...

EW VI RE ALGORITHMS OF COMMON POISONINGS OR Third Edition 2F FT A DR  The printing of Algorithms of Common Poisonings, Third Edition, EW is financed by the National Poison Management and Control Center. Proceeds from your purchase go to a fund for the development of future editions of this book as well as other manuals on the management of poisoning. VI Please do not photocopy. If you would like to order more copies, contact us at 63-2-5241078 RE or visit our website www.uppoisoncenter.org. OR 2F First published 1991 FT Second edition published 1998 Copyright © 2011, 1998, 1991 by the National Poison Management and Control Center www.uppoisoncenter.org A Book design by Maria Lurenda S. Westergaard, M.D. All rights reserved. No part of this publication may be reproduced, DR stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior permission from the National Poison Management and Control Center. Printed in the Philippines. ISBN 978-971-8650-24-0  EDITORS EW Nelia P. Cortes-Maramba, MD, FPPS, FPSCOT, FPSECP Professor Emeritus, Department of Pharmacology & Toxicology, University of the Philippines College of Medicine Adviser, UP National Poison Management & Control Center VI Lynn Crisanta R. Panganiban, MD, DPAFP, FPSCOT Professor, Department of Pharmacology & Toxicology, University of the Philippines College of Medicine RE Head, UP National Poison Management & Control Center Joselito C. Pascual, MD, MSc, FRSAP, FPSCOT Associate Professor, Department of Psychiatry & Behavioral Medicine, University of the Philippines College of Medicine/Philippine OR General Hospital Consultant, UP National Poison Management & Control Center Carissa Paz C. Dioquino, MD, MPH, FPNA, FPSCOT Associate Professor, Department of Neurosciences, University of the 2F Philippines College of Medicine/ Philippine General Hospital Consultant, UP National Poison Management & Control Center Maria Lurenda S. Westergaard, MD, MMed Project Assistant, UP National Poison Management & Control Center FT CONTRIBUTORS A Allan R. Dionisio, MD, FPAFP, FPSCOT Associate Professor, Department of Family & Community Medicine, DR University of the Philippines College of Medicine/Philippine General Hospital Consultant, UP National Poison Management & Control Center iii Danilo G. Villamangca, MD, FPCP, DPSCOT Associate Professor, Department of Pharmacology, Emilio Aguinaldo EW College of Medicine Coordinator, Rizal Medical Center Poison Control Center Irma R. Makalinao, MD, FPPS, FPSCOT Professor & Chair, Department of Pharmacology & Toxicology VI University of the Philippines College of Medicine Nerissa M. Dando, MD, FPPS, DPSCOT Professorial Lecturer, Department of Pharmacology & Toxicology, RE University of the Philippines College of Medicine Consultant, UP National Poison Management & Control Center Erle S. Castillo, MD, FPSCOT Associate Professor, Department of Emergency Medicine, University of OR the Philippines College of Medicine/ Philippine General Hospital Consultant, UP National Poison Management & Control Center Kenneth Y. Hartigan-Go, MD, MD (UK), FPCP, FPSECP, FPSCOT 2F President, Philippine Society of Experimental and Clinical Pharmacology Aeesha Yahcob-Pingli, MD, DPAFP Clinical Toxicology Fellow, UP National Poison Management & Control FT Center, 2006-2008 A DR iv  CONTENTS EW Preface vii Preface to the Second Edition ix Preface to the First Edition x VI ACRONYMS AND ABBREVIATIONS xii INTRODUCTION 1 RE DEFINITION OF TERMS 5 GENERAL MEASURES IN THE MANAGEMENT OF POISONING 9 Readily Available Agents Used as Antidotes 38 OR OVERDOSE OF COMMON PHARMACEUTICALS 49 Antidepressants Lithium 51 Selective Serotonin Reuptake Inhibitors - SSRIs 54 Tricyclic antidepressants 58 2F Antipsychotics Typical antipsychotics 63 Atypical antipsychotics 69 Barbiturates 74 Benzodiazepines 78 FT Digitalis 82 Iron / Ferrous sulfate 87 Isoniazid 93 Opiates and Opioids 98 A Paracetamol 104 Salicylates 109 Theophylline 115 DR HOUSEHOLD AND WORKPLACE CHEMICALS 121 Caustic and Corrosive Agents 123 Caustics: Acids 125 Caustics: Alkalis 130 Sodium hypochlorite 135 v  Jewelry cleaning agents (cyanide containing) 138 Kerosene 145 EW Pesticides Coumatetralyl / Warfarin 150 N-methyl carbamates 155 Organochlorines 156 Organophosphates 160 Pyrethroids 166 VI Watusi / Dancing Firecracker 170 SUBSTANCE ABUSE 173 RE Amphetamines (Shabu) 175 Cannabis (Marijuana) 181 Ethanol 184 ANIMAL TOXINS 191 Ciguatera 193 OR Cobra bite 198 Paralytic Shellfish 202 PLANT TOXINS 207 Herbal supplements 209 2F Jatropha seed (Tuba-tuba) 215 Talampunay (Angel’s trumpet, Datura) 218 ANNEX A. Properties of Common Drugs Involved in Poisoning 225 ANNEX B. Approximate Duration of Detectability of Chemicals FT in Urine 226 ANNEX C. Specimen Time Collection - Blood and Urine 227 ANNEX D. Common Antidotes - Formulation and Dose 228 ANNEX E. Drugs for Supportive Therapy - Formulation and Dose 230 A ANNEX F. Minimum Required Drugs and Devices for the Management of Poisoning - Assembling a Poison Kit 232 ANNEX G. Rumack-Matthew Paracetamol Nomogram 233 DR ANNEX H. Units, Concentrations and Conversions 234 IMPORTANT CONTACT NUMBERS 235 vi  PREFACE EW In 1989, a study involving 20 tertiary hospitals in Metro Manila was done to determine the accuracy of response among Emergency Room (ER) personnel to telephone inquiries on poisoning. Results showed that ER personnel were giving correct advice in only 38% of calls regarding poisoning due to isoniazid (INH) and 55% of calls about kerosene VI ingestion. It became evident that there was a problem in both diagnosis and management of poisoning cases. The National Poison Management and Control Center (NPMCC) has RE been working towards upgrading the competencies of health professionals in the management of poisoning through symposia, conferences, training programs and fellowships. The Center has also published various handbooks on poisoning prevention, management and control. This handbook, fondly called “the Black Book,” remains the most popular and widely used of the Center's publications. OR The practice of toxicology is constantly evolving as it responds to the changing character and growing number of chemicals being used for agricultural, industrial, recreational and medical purposes. Although the list of most commonly encountered poisons has remained consistent over the past ten years, new products and new toxicants have emerged, 2F including new designer drugs of abuse. Over the past decade, clinical practice and research in toxicology have strengthened support for a number of approaches in the management of acutely poisoned patients (such as the use of activated charcoal), and withdrawn support from others (such as forced diuresis). FT All these developments present the health care provider with many challenges, and unfortunately, very little guidance. This third edition of the Black Book is a major revision of the second. The editors and contributors reviewed general principles in managing poisoned patients as well as treatment algorithms for specific poisons. A The algorithms have been revised according to information gleaned from recent research, current consensus and position statements, as well as DR the growing body of local experience in the management of poisoning. There are sections on new toxicants encountered in the clinics. The first part of the book describes general measures that apply to all cases of poisoning. This is followed by algorithms for the management of specific poisons. Information is presented succinctly. Steps to be taken in the acute management of poisoning are shown in vii flow charts. The design of this book is hinged on enhancing efficiency through appropriate action within the shortest period of time. EW It is our hope that this book will continue to serve as a good resource for health care providers attending to the acutely poisoned patient. However, it should be used in the context of holistic care, taking into consideration underlying medical conditions and psychosocial issues. We are grateful to be given the opportunity to share our expertise in the field of toxicology. More so, we continue to thank our families in VI supporting us in this endeavor. The beginning of wisdom is to acquire wisdom; and with all your RE acquiring, get understanding. (Proverbs 4:7) January 2011 OR 2F A FT DR viii  PREFACE EW TO THE SECOND EDITION The management of an acutely poisoned patient is a challenge to the first contact physician because early recognition and management of a poisoning case contributes greatly to better patient outcome. Thus, it is VI important that the physician should have within reach available guides for the treatment of an acutely intoxicated patient. The contents of this book have been reviewed and data have been updated based on the clinical experience and researches conducted by RE the toxicology staff of the National Poison Control and Information Service. The agents discussed are the most commonly encountered poisons in clinical practice and the treatment guidelines have been used in effectively managing patients. The format has been revised to make it more “user friendly” for the OR physician who wishes to avail of relevant information quickly, particularly in the emergency room setting. The authors and contributors encourage physicians to use these algorithms as guides to treatment. However, in managing acute poisoning cases, we should take into consideration the uniqueness of 2F every patient. Thus, treatment interventions should always be individualized. Furthermore, the caring physician should always remember that behind a poisoned patient, whether the nature of poisoning is occupational, accidental, suicidal or substance abuse, lies a much deeper problem which deserves equal attention. We would like to thank our families who have always been supportive FT of our endeavors, for their love and understanding during the hours and days of absence from them because we had to attend to our sick patients, both in the hospital and in the community. A For wisdom is more precious than rubies, and nothing you desire can compare with her. (Proverbs 8:11) DR August 1998 ix  PREFACE EW TO THE FIRST EDITION This initial guidebook on the management of poisoning focuses on the most common types we have seen over the last 25 years in the Philippines. An algorithmic approach to diagnosis and management is VI presented. It must be realized, however, that this process can only be utilized after a thorough history and complete physical examination of the patient have been undertaken. The first part of the book deals with general considerations in the RE diagnosis and management of poisoning with specific boxed guidelines for easy recall. The individual poisoning algorithms deal with the general management followed by a flow chart of the most common complications. The boxed precautions take into account the adverse interactions and special conditions to watch out for in the management OR of the patient. The annexes include the most common toxidromes one encounters in the practice of clinical toxicology, the approximate duration of detectability of chemicals in the urine, and common drug dosages, among others. We are grateful for the inputs of all the residents who rotated in 2F toxicology and the practicing physicians who referred their actual cases to us. I am grateful most especially to my co-authors. We hope that the medical officer who faces the dilemma of diagnosing and managing a poisoning case will find this book a handy friend. We further hope that he/she will stay cool yet warm at heart towards troubled patients and their families, and in the process, become FT a more knowledgeable physician. Nelia P. Cortes-Maramba October 4, 1991 A DR x  EW VI NOTICE RE The data in this book have been verified with reliable sources, and treatment modalities discussed have been utilized in clinical practice. However, new researches, changes in the medical sciences, and human error should be considered. Readers are advised to confirm data herein with other sources such as drug information sheets for OR dosage, contraindications to administration, and other data relevant to treatment. Updates may also be available at the NPMCC website: www.uppoisoncenter.org. The editors are not responsible for errors or omissions in patient management due to inaccuracies or incompleteness of the information that may be present in this book. 2F A FT DR xi  ACRONYMS and EW ABBREVIATIONS AACT American Academy of Clinical Toxicology ABG Arterial blood gas extraction and analysis ACE Angiotensin-converting enzyme VI ALD Acute lethal dose ALT Alanine aminotransferase, also known as serum glutamic pyruvic transaminase (SGPT) APTT Activated partial thromboplastin time RE ARDS Acute respiratory distress syndrome ASA Acetylsalicylic acid AST Aspartate aminotransferase, also known as serum glutamic oxaloacetic transaminase (SGOT) BAL British anti-Lewisite BID Bis in die, two times a day OR BP Blood pressure BUN Blood urea nitrogen cap Capsule CBC Complete blood count CHF Congestive heart failure CNS Central nervous system 2F COPD Chronic obstructive pulmonary disease CPK Creatine phosphokinase CVA Cardiovascular accident CVP Central venous pressure CVS Cardiovascular system CXR Chest x-ray FT CXR-PA Chest x-ray posteroanterior view DB Direct bilirubin DBP Diastolic blood pressure DMPS 2,3 Dimercapto-1-propane sulphonate DMSA Dimercaptosuccinic acid A DOC Drug of choice DTPA Diethylene triamineopiate pentaacetic-N-N-N-N-N acid DR ECG Electrocardiogram EDTA Disodium edetate EAPCCT European Association of Poisons Centres and Clinical Toxicologists EEG Electroencephalogram ELISA Enzyme-linked immunosorbent assay FBS Fasting blood sugar FPN Ferric chloride, perchloric acid and nitric acid (Forrest test; xii  phenotiazine screen) GABA Gamma-amino butyric acid EW GI Gastrointestinal GIT Gastrointestinal tract HPLC High-performance liquid chromatography h, hr, hrs Hour/s IB Indirect bilirubin ICU Intensive Care Unit VI INH Isoniazid IV Intravenous IM Intramuscular KBW Kilogram body weight RE LD Loading dose LFTs Liver function tests MAO Monoamine oxidase mcg Microgram MD Maintenance dose mEq Milliequivalent mg Milligram OR mins Minutes mL Milliliter mmol Millimole mcmol Micromole NAPA N-acetyl penicillamine 2F NAC N-acetyl cysteine ng Nanogram NGT Nasogastric tube NPO Non/nil/nihil per os/orem, nothing by mouth NPCIS National Poison Control and Information Service. NPCIS and the PGH Poison Control and Information Unit were merged in January 2005, FT creating the NPMCC. NPMCC National Poison Management and Control Center NSAIDs Non-steroidal anti-inflammatory drugs NSS Normal saline solution OPIDN Organophosphate induced delayed neuropathy A PAT Paroxysmal atrial tachycardia PEEP Positive end-expiratory pressure PCP Phencyclidine DR PEG Polyethylene glycol PEN Penicillamine PGH Philippine General Hospital PO Per os/orem, by mouth PPA Phenyl propanolamine PRN Pro re nata (take as needed) xiii PSP Paralytic shellfish poisoning PT Protime (prothrombin time) EW PTT Partial thromboplastin time PVC Premature ventricular contraction QD Quaque die, once a day QID Quater in die, four times a day RBC Red blood cell RBS Random blood sugar VI RR Respiratory rate RUQ Right upper quadrant SBP Systolic blood pressure SC Subcutaneous SR Sustained release RE SSRI Selective serotonin re-uptake inhibitor SV Supraventricular T4 Thyroxine TB Total bilirubin TCAD Tricyclic antidepressant TIA Transient ischemic attack OR TID Ter in die, three times a day TR Therapeutic level TX Toxic level UP University of the Philippines 2F A FT DR xiv  INTRODUCTION EW Establishing a Network for Poison Management and Control In 1975, the science of toxicology was introduced in the Philippines with the establishment of a poison control center at the Philippine General Hospital (PGH). This was in response to the increasing incidence of VI poisoning due to indiscriminate use of pesticides. Activities of the Center focused on the management of acute poisoning cases and research. The true picture of poisoning in the country was unknown during those RE years. There were very limited data on poisoning cases from other hospitals in the different regions. The number of poisoning cases seen at the PGH from 1984-1989 only averaged 190 per year. The 1987 statistics from the Department of Health (DOH) reported 279 poisoning cases with an incidence of 0.5/100,000 population. In 25% of these cases, the type of poison was OR not specified or identified. The limited poisoning data for the country was mainly due to underreporting and misdiagnosis of cases. Health professionals handling poisoning cases did not have any access to an information system nor training in toxicology through which they would be able to gain knowledge on poisoning and its appropriate 2F management. At that time, the University of the Philippines (UP) College of Medicine was the only institution that included the teaching of toxicology in its curriculum. Activities to improve public and health sector awareness of the hazards of chemicals and their toxicities were limited. Furthermore, a standardized system of data collection, monitoring and FT evaluation of poisoning cases did not exist. This situation highlighted the urgency of setting up a national poison control center and its network of satellite centers to take responsibility and assume the lead role for all matters related to poisoning in the country. A In 1991, the Poisons Control and Information Service Network (PCISN) was created through a grant from the International Development DR Research Centre (IDRC) of Canada. Additional support was received from the Gesselschaft fur Technische Zusammenarbeit (GTZ). The UP- PGH Poison Control Center was renamed to become the National Poison Control and Information Service (NPCIS) with the Philippine General Hospital serving as the training and service hospital, and the Department of Pharmacology coordinating related efforts of other 1 clinical departments, namely Family Medicine, Emergency Medicine Services, Internal Medicine, Pediatrics, Surgery, and Psychiatry. The EW main objectives of the project were to advocate for poisoning prevention, and to improve the management of poisoning cases. With the establishment of NPCIS, a memorandum of agreement on partnership was signed by the Department of Health Secretary (then Dr. Antonio Periquet) and the Chancellor of UP Manila (Dr. Ernesto Domingo) in June 2, 1992. The memorandum of agreement was reaffirmed on VI September 25, 1992 by the new Health Secretary who assumed office a few months later, Dr. Juan Flavier. Through this partnership, satellite poison centers were established in different regions of the country. RE The NPCIS thus became the focal point of a nationwide network that has since been involved in managing poisoning cases, conducting health assessment activities on the health effects of chemical exposure among high-risk communities, conducting training courses and research that are relevant for policy formulation. The NPCIS was recognized as a unit of the College of Medicine during OR the term of Dean Ramon L. Arcadio on March 21, 2003. Soon after, the PGH-Poison Control and Information Unit (PICU) was created by then Director Juan Pablo R. Nañagas. On January 27, 2005, the Board of Regents of the University of the Philippines approved the merging of the NPCIS and the PGH-PCIU. The 2F unit was named National Poison Management and Control Center (NPMCC). From 2002 to 2007, the NPMCC managed 4,263 in-patients; an average of 711 patients a year. During the same period, the Center assisted in the management of 16,195 poisoning cases through FT telephone referrals; an average of 2,699 a year. Although majority of telephone calls (>90%) were from health facilities, increasing numbers also came from the general public. These developments point to the growing awareness of the public regarding poisoning consultation, and the broadening reach of the Center's poison information service. A The Center continues to be based at the University of the Philippines- Manila, working with the different clinical departments of the PGH in DR managing poisoning cases and training resident physicians and clinical fellows. It also collaborates with the basic science departments, particularly the Department of Pharmacology and Toxicology, on the academic training of clinical fellows, the conduct of postgraduate courses, and the strengthening of the analytical toxicology laboratory. 2  Poisoning as a Health Problem EW The leading causes of poisoning managed at the NPMCC are exposures to alcohol, kerosene, methamphetamine, sodium hypochlorite, mixed household pesticide (propoxur and/or pyrethroid), hydrochloric acid, isoniazid, paracetamol, and ferrous sulfate. In the early 1990s, new toxicants, such as dancing firecrackers (”watusi”) and jatropha (tuba- tuba), were added to the list. More recently, poisoning due to cyanide- VI containing jewelry cleaning agents, slimming pills, and herbal products, have been reported. Alcoholic beverages remain in the top 5 commonly encountered RE toxicants. Aggressive advertising and social acceptability significantly influence alcohol use. Admissions from methamphetamine (”shabu”) intoxication have decreased through the years, that is, from being the 2nd or 3rd most commonly encountered toxicant in 2002-2004 to becoming 8th in 2006 and 13th in 2007. There are several reasons for this development. One is the strict implementation of the law on illegal OR substances. Another is the shift in the choice of recreational substance. Over the past two years, there have been increasing admissions from newer stimulants such as methylenedioxymethamphetamine (MDMA) or “ecstasy” as well as older toxicants such as marijuana. There are two age groups that are at highest risk for poisoning: 2F young people aged 20 to 35 years (about one third of cases), and children under 6 years (about a quarter of cases). Accidental poisoning in children occurs most often because of the accessibility and availability of toxicants in the home. Children are by nature inquisitive. They can reach into unlocked cabinets (for example, storage spaces under the FT kitchen sink) which are used to store household chemicals like kerosene or cleaning agents. Often, these toxic substances are stored in unlabelled bottles that normally contain cola, water or juice. As much as 35% of cases managed by the NPMCC involve accidental exposures A involving children who ingest household chemicals and therapeutic agents. Majority of cases (60%) managed by the NPMCC are non-accidental DR or intentional in nature. These include suicide attempts and substance abuse. The reason for self-harm is often relational, that is, conflict between the patient and a parent, or between the patient and someone he or she is romantically involved with. There are as yet no local studies on the impact of economic hardship or workplace stresses on the incidence of intentional poisoning. Socio-cultural factors that increase 3 the propensity for self-harm, as well as factors that protect against such behavior, need to be studied. EW Slightly more male than female patients consult for poisoning. Annual data from the 1980s onward show that mortality rates range from 2% to 9%, although the rates are as much as three times higher for males compared to females. Strategies in poisoning prevention and control VI The NPMCC engages in various strategies to minimize the risks and occurrence of poisoning. These include training of health personnel in RE the early recognition and management of poisoning cases, and the development of information materials on poisons and poisoning management. Health advisories are issued to the general public when there is a sharp rise in the incidence of certain types of poisoning. In recent years, the NPMCC and other poison centers in the country have been taking a more active role in chemical safety and poisoning OR prevention in industrial and community settings. The work of the poison control centers goes beyond the corners of the hospitals where these are located. The staff are involved in responding to chemical incidents and raising awareness about community exposure to hazardous chemicals. Lessons from these experiences have been translated into local as well 2F as national policies. Challenges ahead Throughout the years, the NPMCC has realized the importance of FT networking and partnership in dealing with the problem of poisoning. Addressing toxicologic issues is not solely the job of the toxicologist. Diagnosis, treatment and rehabilitation of the single poisoned patient, a group of workers exposed to hazardous substances, or a community with index cases of poisoning, requires a multidisciplinary team. Ensuring a A safe and healthy environment is everybody’s business. The challenge is not only to preserve the networks that have been DR established in the past 35 years, but also to develop new partnerships between health professionals, policy makers and the general public. Strength comes in numbers: “A cord of three strands is not quickly torn apart.” 4  DEFINITION OF TERMS EW TOXICITY: inherent ability of a substance to cause injury to biologic material RISK: the potential (likelihood) that injury (biological damage) will occur VI in a given situation EXPOSURE: contact with a chemical which may or may not enter the RE body POISON: any agent that is capable of producing deleterious or harmful effects in a biological system, seriously injuring function or producing death OR POISONING: an event where a living organism is exposed to drugs, medicaments, chemicals or biological substances that adversely affect the function of that organism SELF-POISONING AND PARASUICIDE: refers to the deliberate ingestion 2F of more than the therapeutic dose of a drug or a substance not intended for consumption, usually by an adult in a moment of distress. Those who die are classed as suicides rather than parasuicides regardless of whether or not this was the intended outcome. FT ACCIDENTAL POISONING: non-intentional ingestion, overdose or exposure to drugs, medicaments or poisonous substances SUBSTANCE ABUSE: (DSM-IV-TR criteria) A. A maladaptive pattern of drug use leading to clinically significant A impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period: DR (1) recurrent drug use resulting in a failure to fulfil major role obligations at work, school, or home (2) recurrent drug use in situations in which it is physically hazardous (3) recurrent drug-related legal problems (4) continued drug use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects 5  of the drug B. The symptoms have never met the criteria for drug dependence. EW SUBSTANCE DEPENDENCE: (DSM-IV-TR criteria) A maladaptive pattern of drug use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period: (1) tolerance, as defined by either of the following: VI (a) a need for markedly increased amounts of the drug to achieve intoxication or desired effect (b) markedly diminished effect with continued use of the same RE amount of the drug (2) withdrawal, as manifested by either of the following: (a) the characteristic withdrawal syndrome for the drug (b) the same (or closely related) drug is taken to relieve or avoid withdrawal symptoms (3) the drug is often taken in larger amounts or over a longer period OR than was intended (4) there is a persistent desire or unsuccessful efforts to cut down or control drug use (5) a great deal of time is spent in activities necessary to obtain the drug, use the drug or recover from its effects 2F (6) important social, occupational or recreational activities are given up or reduced because of drug use (7) drug use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the drug FT Note: The definitions for substance dependence and substance abuse exclude acute drug intoxication in the absence of substance dependence or abuse. A SUBSTANCE WITHDRAWAL: (DSM-IV-TR criteria) A. The development of a substance-specific syndrome due to the DR cessation of (or reduction in) substance use that has been heavy or prolonged. B. The substance-specific syndrome causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. 6  C. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder. EW SUBSTANCE INTOXICATION: (DSM-IV-TR criteria) A. The development of a reversible substance-specific syndrome due to recent ingestion of (or exposure to) a substance. Note: Different substances may produce similar or identical syndromes. B. Clinically significant maladaptive behavior or psychological changes VI that are due to the effect of the substance on the central nervous system (e.g., belligerence, mood lability, cognitive impairment, impaired judgment, impaired social or occupational functioning) and RE develop shortly after use of the substance. C. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder. OR 2F A FT DR 7 DR AFT 2F OR RE VI EW  EW VI RE GENERAL MEASURES OR IN THE MANAGEMENT OF POISONING 2F FT A DR DR AFT 2F OR RE VI EW  The general approach to the poisoning patient involves the following: I. Emergency stabilization EW II. Clinical evaluation III. Minimizing absorption of the poison IV. Enhancing elimination of the absorbed poison V. Administration of antidotes VI. Supportive therapy and observation VII. Disposition VI I. EMERGENCY STABILIZATION RE As in any other serious medical emergency, life-saving measures should take priority in poisoning cases. In a suspected or frank case of poisoning, management is directed towards the immediate life- threatening problems of airway obstruction, breathing difficulties, circulatory inadequacy, CNS disturbances, and electrolyte or metabolic OR abnormalities. ABCs of Life Support for Poisoned Patients A - Airway. Maintain adequate airway 2F B - Breathing. Provide adequate oxygenation/ventilation C - Circulation. Maintain adequate circulation D - Drug- or toxicant-induced CNS disturbances. Treat convulsions, coma E - Electrolytes. Correct metabolic abnormalities FT A. Maintain adequate airway Assess all patients for airway patency. A patient who is awake is likely to have an intact airway. However, decreasing sensorium due to worsening A intoxication may compromise airway patency. In patients with decreased sensorium, the gag or cough reflex may give an indirect estimate of the patient's ability to keep the airway clear. DR If the airway is obstructed, place the patient in supine position. Perform the chin-lift and jaw-thrust maneuvers to position the tongue away from the airway. Remove any foreign bodies (dentures, oropharyngeal secretions). 11 Rule out cervical fracture before attempting endotracheal intubation. If there is respiratory insufficiency, loss of consciousness, impaired or EW absent gag reflex or status epilepticus, endotracheal intubation should be done by trained or experienced personnel. Once a tube is inserted, administer humidified air to prevent drying, crusting and sloughing of the tracheal mucosa. Do bronchial toilet on a regular basis, depending on the volume of secretions. VI B. Provide adequate oxygenation / mechanical ventilation Inadequate oxygen delivery to the lungs may be due to ventilatory failure, RE hypoxia or bronchospasm. In all cases, check ABGs to accurately assess ventilation. If the patient manifests clinical signs of poor oxygenation, or pO2 is less than 80 mmHg, give oxygen via nasal cannula, face mask, or with a mechanical ventilator, depending on the availability of equipment and the FiO2 level required by the patient. If the patient manifests with bronchospasm, evaluate the need for bronchodilators. OR Common Toxicants that Can Cause Hypoxia · Alcohol · Opiates · Quinine · Carbon monoxide · Organophosphates 2F Modes of Oxygen Delivery with Equivalent FiO2 Nasal cannula 44% Plastic mask 60% Rebreathing mask 60 to 80% FT Ventilator 100% IMPORTANT: Oxygen may be contraindicated in the initial management of watusi poisoning. Watusi is a flammable substance which can explode in the presence of oxygen. Oxygen may also be contraindicated in the A management of paraquant poisoning because it increases the risk of pulmonary fibrosis. DR C. Maintain adequate circulation Secure venous access and initiate intravenous infusion of the appropriate fluids. In case of hypotension (SBP 2 ng/mL and >40 ng/mL, respectively. In cases of chronic intake of digoxin, acute toxicity occurs when the drug OR dosage is not adjusted in such conditions as hypothyroidism, hepatic and renal disease, electrolyte imbalances, alkalosis, hypoxemia, myocardial disease and cor pulmonale. Treatment is generally supportive. 2F Specific Precautions Drug interactions. The following drugs increase digoxin levels: Amiodarone Macrolide antibiotics Carvedilol Quinidine Diltiazem Spironolactone Indomethacin Verapamil FT The following metabolic imbalances enhance digoxin toxicity: Hypokalemia Hypernatremia Hyperkalemia Alkalosis Hypomagnesemia Hypoxemia A Repeated administration of cholestyramine or activated charcoal lavage is beneficial in removing the drug. Cardioversion is generally not recommended in cases of digitalis toxicity DR because of the possibility of malignant ventricular arrhythmias. Use of forced diuresis or dialysis is not effective because of the large volume of distribution of the drug. Digitalis does not have a threshold effect; therefore, the narrow toxic- therapeutic margin is not well defined. Thus, in chronic intake, predis- posing factors to toxicity should be taken into consideration. 82  DIGITALIS Management EW Amount taken Time and mode of exposure Intake of other drugs (calcium channel blockers, diuretics, etc.) Presence of disease conditions (cor pulmonale, renal or hepatic disease, etc.) VI Symptoms of acute poisoning: HISTORY GI disturbances - anorexia, nausea, vomiting, abdominal pain Cardiovascular symptoms RE CNS manifestations - headache, convulsions, visual disturbances (yellow halos or xanthopsia) Symptoms of chronic poisoning: CNS manifestations - weakness, visual disturbances Cardiovascular symptoms OR Focus on GI, CV and CNS Acute poisoning Chronic poisoning Dysrhythmias Dysrhythmias Extra systoles - PVCs Sinus bradycardia Ventricular flutter Atrial fibrillation with PHYSICAL Ventricular fibrillation SVR or junctional 2F EXAMINATION Tachyarrhythmias escape rhythm Bradycardia, AV block Ventricular arrhythmias Mental status changes Accelerated junctional Drowsiness tachycardia and PAT Confusion, disorientation with block Hallucinations FT Toxicologic Examination Serum total digoxin levels 6 hrs after ingestion. After the use of digoxin-specific Fab then only free digoxin concentrations are meaningul (see p. 86). A General Examinations LABORATORY Serial ECG Protime Urinalysis EXAMINATIONS ABG RBS CBC DR Serial electrolytes BUN CXR Na+, K+, Ca++, Mg++ Creatinine T4 Acute poisoning Chronic poisoning Hyperkalemia Hypokalemia Hypomagnesemia Hyperkalemia in severe cases 83 DIGITALIS ABCs of life support. Maintain vital signs. Oxygen inhalation, if necessary. EW Put patient on NPO. Give intravenous fluids. Adult: D5 0.9NaCl or AR 1 liter x 8 hrs Pedia: D5 0.3NaCl or AR according to KBW Hook to cardiac monitor Insert nasogastric tube (appropriate size for age) For acute poisoning VI Gastric lavage with activated charcoal Adult: 100 g in 200 mL water Pedia: 1 g/kg to make a slurry GENERAL Repeat every 6 hrs for 48 hrs at ½ individual dose. MEASURES RE OR Cholestyramine (as alternative to activated charcoal) 1 gm sachet every 6 hrs For chronic poisoning Activated charcoal lavage is not done unless acute poisoning occurs on top of chronic intoxication. After lavage, give sodium sulfate. OR Adult: 15 g in 100 ml water Pedia: 250 mg/kg in water to make a 10% solution May be repeated only once if initial dose does not result in bowel movement after one hour. May give after 4 doses of activated charcoal if there is still no bowel movement. 2F Amount ingested < 0.05 mg/kg > 0.05 mg/kg Asymptomatic Symptomatic Asymptomatic Observe for 24h. Repeat Observe for 24h. FT Refer to Psych if cholestyramine Repeat non-accidental. or activated cholestyramine If still asymptom- charcoal or activated atic, discharge. lavage.every charcoal SPECIFIC 6 hours. lavage. MEASURES Cardiac monitoring. Refer to Psych if A Treat specific non-accidental problems. If still asymptom- Give digoxin- atic, discharge. DR specific antibody (Fab fragment) if available for severe cases. Admit to ICU. 84  DIGITALIS Treatment of Specific Problems EW PVCs Phenytoin 5-7 mg/kg slow IV or Lidocaine 50 mg IV push (1 mL/min) then drip at 1-4 mg/min Ventricular fibrillation/flutter/ventricular CARDIAC tachycardia DYSRHYTHMIAS Lidocaine 50 mg IV push (1 mL/min) VI Symptomatic bradyarrhythmias Atropine 0.5-2.0 mg IV AV block - Pacemaker Supraventricular tachycardia - Carotid massage RE See discussion on pp. 14-15. Hypokalemia KCl solution up to 40 mEq/hr Hypomagnesemia Magnesium sulfate ++ OR Loading dose: 600 mg of elemental Mg in D5W over 3 hours Maintenance dose: 600-900 mg of elemental Mg++ per 24 hours IV or IM In emergency situations, the loading dose should ELECTROLYTE not exceed 15 mg/min 2F IMBALANCE Magnesium sulfate can be administered IM at 200 mg every 4 hours for 24 hours then 100 mg every 4 hours. Monitor parameters for magnesium toxicity. Hyperkalemia Glucose-insulin infusion FT 50 mL D50-50 and 10 units regular insulin Followed by sodium bicarbonate 1 mEq/kg/dose Hypernatremia Adjust fluids A HYPOVOLEMIC SHOCK Fluid challenge more next page DR 85 DIGITALIS Diazepam Adult: 2.5-5.0 mg slow IV push EW Pedia: 0.3 mg/kg/dose IV May be repeated q 2-5 min up to 20 mg. Be ready to intubate patient before giving additional doses. SEIZURES Lorazepam Adult: 2.5-10 mg/dose repeated twice at intervals VI of 15-20 min prn. Usual dose is 4-5 mg/dose. Pedia: 0.05-0.1 mg/kg/dose IV up to a max of 4 mg/dose repeated twice at intervals of 10-15 min prn. Compatible with D5W RE Digoxin-Specific Antibody Indications for digoxin-specific antibody Significant poisoning Severe hyperkalemia (>5 mEq/L) OR Symptomatic arrhythmias not responsive to usual drugs Massive oral overdose with high serum levels Intake of >10 mg in healthy adults or 4 mg in children Steady state serum concentration >10 ng/mL (6 hrs post-ingestion) Dosage computation for digoxin-specific antibody Dose = Total body load (in mg) 2F 0.6 mg where total body load = (Serum digoxin conc.)(Vd)(weight in kg) 1000 and Vd = volume of distribution = 5.6 L/kg Note: Each vial of Digibind contains 40 mg of digoxin-specific antibody fragments that will bind 0.6 mg digoxin or digitoxin. FT REFERENCES Antman EM et al. “Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments.” Circulation. June 1990, 81:6: 1744-1751. Dreisbach RH et al. Handbook of Poisoning, 12th ed. Norwalk: Appleton and Lange. A 1987. Ellenhorn MJ. Ellenhorn’s Medical Toxicology, 2nd ed. Baltimore: Lippincott Williams & Wilkins. 1997. Flomenbaum N, Goldfrank LR, et al. Goldfrank's Toxicologic Emergencies. New York: DR McGraw Hill Companies, Inc. 2006. Gossel TA et al. Principles of Clinical Toxicology 3rd ed. New York: Raven Press 1994. Klaasen CD, Amdur MO, Doull J. (eds.). Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th ed. New York: MacGraw-Hill. 1996. Olson KR, ed. Poisoning and Drug Overdose. Norwalk: Appleton and Lange. 1994. Shannon MW, Borron SW, Burns MJ (eds). Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th Ed. Philadelphia: Saunders. 2007. 86  IRON IRON EW Iron is absorbed in the small intestines in the ferrous (+2) state and further oxidized to the ferric (+3) state. It binds with the storage protein, ferritin. It is widely distributed in the tissues attached to the globulin, transferrin. Serum iron reflects the amount of iron bound to transferrin (normal VI concentration of iron = 50-150 mcg/dL; serum transferrin concentration = 300-400 mcg/dL). Excretion of iron occurs by blood loss or desquamation of the gastrointestinal mucosa. Iron toxicity results from direct corrosive effects on mucosal tissue, RE and cellular dysfunction. These occur when serum iron levels exceed the iron-binding capacity of transferrin. Free circulating iron causes damage to systemic blood vessels. A dose of 20-30 mg/kg of elemental iron can cause abdominal pain, vomiting and diarrhea; 40 mg/kg is potentially serious; 60 mg/kg is potentially fatal. OR Ferric chloride is a caustic substance. In cases of ingestion, use the acid protocol. Specific Precautions Iron tablets (especially the slow-release types) may form concretions in 2F the stomach and duodenum. This may result in delayed elevation of iron levels. Liquid iron preparations and chewable tablets are not radio-opaque but are as toxic as the tablet form. Activated charcoal does not bind iron effectively. Drug-drug interactions: FT Antacids decrease absorption of iron. Ascorbic acid increases absorption of iron. Iron enhances absorption of tetracycline. Hemodialysis removes the iron-deferroxamine complex but not iron itself. Exchange transfusion removes both free and bound iron. A DR 87 IRON Clinical Features EW Initial period - up to 6 hrs post ingestion Severe hemorrhagic gastritis with diarrhea and vomiting Lethargy, pallor tachycardia, hypotension Quiescent period - up to 12 hrs Deceptive improvement and stabilization occur Recurrent period - 12 to 48 hrs VI Hematemesis, melena, gastrointestinal perforation Increased lethargy, coma, convulsion Vasomotor collapse, cyanosis, pulmonary edema Hepatorenal failure, metabolic acidosis, hypoglycemia Late period - 2 to 6 weeks RE Gastric scarring, pyloric obstruction Computation for ingested elemental Fe Elemental Fe (No. of tabs)(mg of Fe salt per tab)(%elemental Fe) = OR (mg/kg) weight of patient in kg Salt Elemental Iron (Fe) Gluconate anhydrous 12.0% Sulfate crystalline 20.0% Sulfate anhydrous 36.8% 2F Fumarate 33.0% Guidelines for Use of Deferoxamine Indications for deferoxamine treatment FT Peak serum iron concentration >500 mcg/dL Significant clinical manifestations: lethargy, coma, hypovolemia, metabolic acidosis, coagulopathy (+) abdominal radiograph for tablets or capsules despite gastrointestinal decontamination A Peak serum iron concentration between 350-500 mcg/dL, AND presence of persistent vomiting, diarrhea, severe abdominal pain Indications for deferoxamine treatment termination DR Serum iron concentration below 150 mcg/dL 24 hours after return of normal urine color (if vin rose colored initially) Absence of radio-opaque formulation (if initially present) Resolution of clinical signs and symptoms of systemic iron poisoning 88  IRON Management EW Amount and formulation of elemental iron ingested HISTORY Time of ingestion Intake of other substances GI, CV, CNS manifestations PHYSICAL Complete physical examination with emphasis on GI EXAMINATION and CV systems and CNS - see Clinical Features VI Toxicologic Examination 10 mL clotted blood for Total Serum Iron (TSI) 3 to 5 hrs post ingestion RE Gastric aspirate LABORATORY General Examinations EXAMINATIONS CBC including hematorcrit Typing BUN LFTs ABG Creatinine Protime RBS Na+, K+, Cl- Plain abdomen OR Fecalysis with occult blood ABCs of life support Maintain vital signs. Put patient on NPO. Give intravenous fluids. Adult: D5 0.9NaCl or AR 1 liter x 8 hrs 2F Pedia: D5 0.3NaCl or AR according to KBW Insert nasogastric tube (appropriate size for age) Do gastric lavage using 1.5% sodium bicarbonate solution: 2 vials of 8.4% sodium bicarbonate to 1 liter of water OR baking soda: 1 Tbsp in 1 liter of water FT After lavage, give sodium sulfate. GENERAL Adult: 15 g in 100 ml water MEASURES Pedia: 250 mg/kg in water to make a 10% solution May be repeated only once if initial dose does not result in bowel movement after one hour. A If abdominal film is (+) for radioopaque tablets or capsules, repeat gastric lavage followed by sodium sulfate. Then repeat abdominal film to check if DR opacities have disappeared. Give antacids: aluminum-magnesium hydroxide or H2 blocker Refer for emergency endoscopy. Start 8.4% sodium bicarbonate 1 mEq/kg/dose IV or based on acid-base deficits 89 IRON Amount ingested < 20 mg/kg Give oral antacid (Al-Mg OH) EW Adult: 60 mL q 6 hrs Older child: 30 mL q 6 hrs Pedia: 15 mL q 6 hrs Observe for 24 hrs. SPECIFIC Refer to Psychiatry if necessary. MEASURES If asymptomatic after observation, discharge. VI Amount ingested unknown or > 20 mg/kg Mild Moderate Severe RE TSI=450-400 Heroin Agonist 4 rapid 3-4 --- 10-100 >400 Pethidine Agonist 100 3 2-4 30-100 500 1000-3000 FT Fentanyl Agonist 0.2 4 1-2 Codeine Agonist 60 3 3-4 1-12 20-50 >60 Oxycodone Agonist 4.5 4 3-4 1-10 20-500 --- Propoxyphene Agonist 100 15 4-5 5-20 30-60 80-210 Pentazocine Mixed 50 3 3-4 10-60 200-500 1000-2000 2F Nalbuphine Mixed 10 3.5 3-6 197-459 ng/mL Butorphanol Mixed 2 3 3-4 0.9-1.04 ng/mL Naloxone Antagonist 1-2 1 — 11.3-34.7 ng/mL (neonates) OR RE VI EW  OPIATES AND OPIOIDS Management EW Amount taken Time and mode of exposure HISTORY Intake of other substances (barbiturates, ethanol, methanol, etc.) Symptoms (see Clinical Features) Emphasis on examination of the CNS, respiratory and VI PHYSICAL EXAMINATION cardiovascular systems (see Clinical Features) Toxicologic Examinations Blood levels: 10 mL RE LABORATORY Urine levels: 200 mL (first void) EXAMINATIONS General Examinations ABG BUN Urinalysis RBS Creatinine ECG Na+, K+, Cl- OR ABCs of life support Maintain vital signs. GENERAL Put patient on NPO. Give intravenous fluids. MEASURES Adult: D5 0.9NaCl or AR 1 liter x 8 hrs Pedia: D5 0.3NaCl or AR according to KBW 2F Oral Preparation Insert NGT (appropriate size for age) Do gastric lavage with activated charcoal. Adult: 100 g in 200 mL water Pedia: 1 g/kg to make a slurry After lavage, give sodium sulfate. FT Adult: 15 g in 100 ml water SPECIFIC Pedia: 250 mg/kg in water to make a 10% solution MEASURES May be repeated only once if initial dose does not result in bowel movement after one hour. Repeat lavage q 6 hrs for 48 hrs using half of initial A dose for cases of meperidine or diphenoxylate toxicity. DR Parenteral Preparation Check sensorium more next page 101 OPIATES AND OPIOIDS EW Check sensorium Awake, Depressed non-toxic Awake, toxic Sensorium Observe 24 hrs. Refer to Psych VI Naloxone if non-acciden- Adult: 2 to 10 mg IV bolus at 5 min tal. intervals Neonates and infants: 0.01 mg/kg/dose RE Depressed Start naloxone drip sensorium or Compatible fluids: D5W or 0.9 NaCl respiration Dose: 2/3 of waking up dose to be given hourly or 2.5 ug/kg/hr Incompatibilities: Do not mix with bisulfite, sulfite or long chain or high molecular weight anions, or OR any solution with an alkaline pH. Respiratory support: oxygen, assisted ventilation If asymptomatic, discharge. 2F Treatment of Specific Problems Phenytoin 15 to 25 mg/kg ARRHYTHMIAS HYPOTHERMIA FT Can also hasten metabolism of opioids CIRCULATORY Insert CVP line FAILURE Give IV fluids A HYPOTHERMIA Keep patient warm DR Hypoxia Respiratory support METABOLIC Assisted ventilation DISTURBANCES Hypoglycemia D50-50 for adults; dilute to 10% for children 102  OPIATES AND OPIOIDS Furosemide 1 mg/kg PULMONARY Anti-pulmonary edema regimen EW EDEMA PEEP RENAL If with poor urine output: Dialysis FAILURE If with good urine output: Observe Diazepam Adult: 2.5-5.0 mg slow IV push VI Pedia: 0.3 mg/kg/dose IV May be repeated q 2-5 min up to 20 mg. Be ready to intubate patient before giving additional doses. RE SEIZURES Lorazepam Adult: 2.5-10 mg/dose repeated twice at intervals of 15-20 min prn. Usual dose is 4-5 mg/dose. Pedia: 0.05-0.1 mg/kg/dose IV up to a max of 4 mg/dose repeated twice at intervals of 10-15 min prn. OR Compatible with D5W REFERENCES Aronow R. Handbook of Common Poisonings in Children. American Academy of Pediatrics. 1993. 2F Ellenhorn MJ. Ellenhorn’s Medical Toxicology, 2nd ed. Baltimore: Lippincott Williams & Wilkins. 1997. Flomenbaum N, Goldfrank LR, et al. Goldfrank's Toxicologic Emergencies. New York: McGraw Hill Companies, Inc. 2006. Gossel TA, Bricker JD, et al. Principles of Clinical Toxicology, 3rd ed. New York: Raven Press. 1994. Henry J and Volans G. ABC of Poisoning, Part 1: Drugs. London: British Medical FT Association. McEvoy GK. AHFS Drug Information. American Society of Hospital Pharmacies. 1993. Olson KR, (ed). Poisoning and Drug Overdose. Norwalk: Appleton and Lange. 1994. Shannon MW, Borron SW, Burns MJ (eds). Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th Ed. Philadelphia: Saunders. 2007. A Viccello P. Handbook of Medical Toxicology. Boston: Little, Brown and Company. 1993. DR 103 PARACETAMOL PARACETAMOL EW Paracetamol is a widely used analgesic-antipyretic present in many prescription and over-the-counter medications. While generally safe in therapeutic doses, in overdose, it can produce hepatocellular necrosis leading to liver failure and death if untreated. The term “acute overdosage” refers to a single ingestion, or several VI episodes of ingestion occuring within a single 4-hour period. Doses of 150 mg/kg in children and 7.5 gm in adults are generally considered the lowest dose capable of producing significant toxicity. The toxic dose during repeated supratherapeutic ingestion (RSI) is still controversial. RE In therapeutic doses, the cytochrome P-450 system (mainly, CYP2E1) produces a small amount of toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), that can be readily detoxified by the reduced glutathione stores of the liver. In overdoses, however, the reduced glutathione stores can be overwhelmed and NAPQI will covalently bind to hepatic OR macromolecules resulting in hepatocellular necrosis. Specific Precautions Antidotal therapy with N-acetylcysteine (NAC) is most effective when given within 10 hours of ingestion of paracetamol. After this time, NAC can still 2F be used but its effectiveness diminishes. Intravenous NAC should only be given to cases with clear clinical indica- tions because it may cause rate-related anaphylactoid reactions. Patients with history of asthma or atopy are at higher risk. Intravenous diphenhy- dramine may be given prophylactically to prevent anaphylactoid reaction. Risk of hepatotoxicity is probably increased among chronic heavy FT alcoholics. The Rumack-Matthew nomogram is applicable only for acute overdosage presenting within 24 hours of ingestion (see nomogram in Annex G.) RSI of paracetamol is defined as more than one ingestion over a period of more than 8 hours that results in a cumulative dose of >4 gm/day A (>150 mg/kg/day in children). NAC is started if serum paracetamol level is >10 mcg/mL or serum AST is >50 IU/L. NAC is US FDA pregnancy category B. When used in pregnant women, it DR crosses the placenta and levels achieved in fetus are similar to maternal levels. Consider liver transplantation for patients who develop liver failure with hepatic encephalopathy. 104  PARACETAMOL Clinical Features EW Stages Symptoms and Signs Stage I (0-24 hrs) Asymptomatic, some vomiting, AST may be normal Stage II (24-72 hrs) Asymptomatic, some RUQ abdominal pain, elevated AST (>1,000 IU/L) Stage III (72-96 hrs) Onset of hepatic failure + renal failure, very high AST (>10,000 IU/L) VI Stage IV (day 7-10, Resolution of signs and symptoms, AST returns to variable) normal in a few weeks Management RE Amount taken Time and mode of exposure HISTORY Intake of other substances (phenobarbital, ethanol, rifampicin, barbiturates, diphenydramine, etc.) Symptoms: vomiting, aspiration, seizures (see Clinical Features) OR PHYSICAL Emphasis on examination of the heart, liver, kidneys. EXAMINATION Do a complete Neuro Exam (see Clinical Features) Toxicologic Examinations 2F Blood levels: 5-10 mL LABORATORY General Examinations EXAMINATIONS CBC LFTs RBS Creatinine ABG + + - Urinalysis Protime BUN Na , K , Cl ECG ABCs of life support Maintain vital signs. FT Put patient on NPO. Give intravenous fluids. Adult: D5 0.9NaCl or AR 1 liter x 8 hrs Pedia: D5 0.3NaCl or AR according to KBW Insert nasogastric tube (appropriate size for age). Do gastric lavage with activated charcoal. A GENERAL Adult: 100 g in 200 mL water MEASURES Pedia: 1 g/kg to make a slurry Activated charcoal may be repeated, especially if DR antidote (NAC) is not available. After lavage, give sodium sulfate Adult: 15 g in 100 ml water Pedia: 250 mg/kg in water to make a 10% solution May be repeated only once if initial dose does not result in bowel movement after one hour. 105 PARACETAMOL Serum levels known - see next page SPECIFIC EW MEASURES Serum levels unknown Amount Amount Unknown, Unknown, ingested ingested asympto- symptomatic >150 mg/kg 200 8 hours 60-100 >100 12 hours 30-50 >50 VI No Slight Possible Probable risk risk risk risk RE Observe for 72 hours. 20% N-acetylcysteine (NAC) Monitor AST, ALT and Test dose: 0.1 mL in 0.9 mL D5W protime daily. IV. If no hypersenstivity, give: Adult: Phase 1: 150 mg/kg in 200 mL Abnormal D5W to run for 1 hr Give NAC. Phase 2: 50 mg/kg in 500 mL OR D5W to run for 4 hrs Phase 1: 100 mg/kg in 1000 mL D5W to run for 16 hrs Normal Adjust IV fluid in the presence after 72 hrs of renal failure or congestive 2F heart failure. Pedia: Use adult dose. However, IV fluid administration must consider body weight. Give diphenhydramine 1 mg/kg IV (different site) prior to giving FT initial NAC. Continue monitoring AST, ALT and protime. If still not clinically improving, give second course of NAC. After second course, watch out for signs of A coagulopathy. Check partial thromboplastin time (PTT). Treat hepatitis and coagulopathy. DR Significant decrease in AST and ALT compared to baseline levels and patient is clinically improving. Refer to Psychiatry if non-accidental. Discharge 107 PARACETAMOL Treatment of Specific Problems EW ACUTE RENAL Adjust IV fluids FAILURE Hemodialysis BLEEDING Give Phytonadione 10 mg IV every 6 to 8 hrs if protime TENDENCIES is 150 mg/kg. Ingestion of >300 mg/kg will most likely OR produce an acute severe intoxication. Chronic intoxication is more commonly a result of repeated overmedication for several days and generally occurs with ingestion of >100 mg/kg/day for two or more days. Diagnosis is usually missed because manifestations may be non- specific and may be attributed to pneumonia, gastroenteritis, or sepsis. 2F Hence, mortality is higher than in acute overdose. Ingestion of large amounts of salicylate may produce gastric irritation. Once absorbed, salicylates cause direct stimulation of the medullary respiratory center resulting in hyperventilation and respiratory alkalosis (may not be prominent in children 40 mg/dL Chronic Non-specific manifestations such as confusion, dehydration, hyperthermia, metabolic acidosis, renal failure, cerebral and pulmonary edema are more RE common than in acute Specific Precautions Systemic acidemia promotes salicylate entry into the brain, worsening toxicity. OR Since there is no specific antidote for salicylate poisoning, sodium bicarbonate administration to treat acidemia and alkalinize the urine, and supportive therapy are the mainstays of treatment. Alkalemia is not a contraindication to bicarbonate therapy. Single determinations of serum salicylate level are not sufficient because 2F of possibility of prolonged or delayed absorption. In general, the toxicity of salicylates correlates poorly with serum concentrations, especially in chronic poisoning. In chronic poisoning, decontamination is seldom necessary. The indications for hemodialysis are: Acute ingestion with serum levels >100 mg/dL with severe acidosis and other manifestations FT Chronic intoxication with serum levels >60 mg/dL with acidosis, confusion, lethargy (especially if elderly or debilitated) Severe manifestations in any patient In small children, if hemodialysis is indicated but unavailable, consider A exchange transfusion. Multiple-dose activated charcoal (MDAC) can reduce serum salicylate half-life but not as effectively as hemodialysis. DR MDAC and/or whole bowel irrigation are also useful for gut decontam- ination with large ingestions (>30 g). 110  SALICYLATES Management EW Amount and form of salicylate taken Time and mode of exposure HISTORY Acute or chronic intake Intake of other substances (e.g., acetazolamide can worsen acidosis) Note level of sensorium, presence of respiratory VI PHYSICAL distress, hyperpyrexia, gastrointestinal bleed or EXAMINATION perforation Toxicologic Examinations RE Stat and serial serum salicylate levels: 0.5 mL blood Bedside Toxicologic Test FeCl3 test: To 2 mL urine, add 0.5 ml FeCl3. Positive LABORATORY test: purple color EXAMINATIONS General Examinations CBC LFTs RBS Creatinine ABG + + - OR Urine pH Protime BUN Na , K , Cl ECG CPK-MM Plain abdomen (for enteric coated tablets) Chest xray ABCs of life support Maintain vital signs. 2F GENERAL Keep patient in a quiet room. MEASURES Put patient on NPO. Give intravenous fluids. Adult: D5 0.9NaCl or AR 1 liter x 8 hrs Pedia: D5 0.3NaCl or AR according to KBW If ASA or methylsalicylate If salicylic acid, examine FT oropharynx for signs of burns. more next page A DR 111 SALICYLATES EW If ASA or methylsalicylate If salicylic acid, examine oropharynx for signs of burns. + for burns OR If no burns, do + signs of GI bleeding endoscopy. VI Manage as Caustic Poisoning + for burns No burns Give 8.4% sodium bicarbonate 2 mEq/kg IV bolus RE followed by continuous infusion of D5W 1 liter + 100 mEq sodium bicarbonate to run at 200 mL/hr. Pedia: adjust volume to run at 3 to 4 mL/kg/hr Maintain urinary pH > 7.5 Insert nasogastric tube (appropriate size for age). OR Do gastric lavage with activated charcoal. Adult: 100 g in 200 mL water Pedia: 1 g/kg to make a slurry After lavage, give sodium sulfate Adult: 15 g in 100 ml water Pedia: 250 mg/kg in water to make a 10% solution 2F May be repeated only once if initial dose does not result in bowel movement after one hour. To prevent enterohepatic recirculation, if possible, give activated charcoal q 6 hours for 8 doses per NGT at half of initial dose. Give sodium sulfate cathartic if there is no bowel movement after 4 doses. SPECIFIC FT MEASURES Asymptomatic, Asymptomatic, Symptomatic, Symptomatic, Non-toxic Toxic dose Mild Severe dose Observe Observe Admit to ICU. A Refer to for 12 hrs. for 12 hrs. Treat acidosis. Psych if Refer to Refer to Repeat ABG. non-acciden- Psych if Psych if Consider tal. non-accid- DR non-accid- hemo- or Discharge. ental. ental. peritoneal If still asymp- dialysis or tomatic, exchange If still asymp- If symptom- discharge. transfusion. tomatic, atic, assess discharge. if mild or severe. 112  SALICYLATES Treatment of Specific Problems EW GASTROINTESTINAL Give proton pump inhibitors IV. BLEEDING Temperature > 40 degrees C Hydrotherapy HYPERPYREXIA IV fluids VI Cooling measures Protime < 70%: Fresh frozen plasma Phytonadione LOW PROTIME RE Adult: 10 mg IV q 8 hours Pedia: 1mg/kg IV q 8 hours Sodium bicarbonate METABOLIC 1 mEq/kg or based on base deficit to maintain ACIDOSIS serum pH > 7.4 OR Hypoglycemia Adult: 50 to 100 mL D50-50 IV METABOLIC Pedia: 2 mL/kg D10W DISTURBANCES Hypokalemia Correlate with ABG and correct appropriately 2F NON-CARDIOGENIC Endotracheal intubation with mechanical ventilation, PULMONARY if warranted. Hyperventilate to prevent iatrogenic EDEMA respiratory acidosis. Diazepam Adult: 2.5-5.0 mg slow IV push FT Pedia: 0.3 mg/kg/dose IV May be repeated q 2-5 min up to 20 mg. Be ready to intubate patient before giving additional doses. SEIZURES Lorazepam A Adult: 2.5-10 mg/dose repeated twice at intervals of 15-20 min prn. Usual dose is 4-5 mg/dose. DR Pedia: 0.05-0.1 mg/kg/dose IV up to a max of 4 mg/dose repeated twice at intervals of 10-15 min prn. Compatible with D5W 113 SALICYLATES REFERENCES Dart RC (ed.). Medical Toxicology, 3rd ed. Philadelphia: Lippincott Williams and Wilkins. EW 2004. Hoffman RS, et al. (eds.). Goldfrank’s Manual of Toxicologic Emergencies. New York: McGraw-Hill, 2007. Leikin JB and Paloucek FP (eds.). Poisoning and Toxicology Handbook, 4th edition. New York: Lexi-Comp. 2008. Olson KR (ed.). Poisoning and Drug Overdose, 5th edition. New York: McGraw-Hill, 2007. VI RE OR 2F A FT DR 114  THEOPHYLLINE THEOPHYLLINE EW Theophylline is a methylxanthine derivative which is readily absorbed in the gastrointestinal tract. Its uncoated tablet or liquid forms reach peak plasma concentration within 1 to 5 hours. However, the sustained- release preparation may form concretions in the gastrointestinal tract, with prolonged and delayed absorption up to 24 hours, thereby VI increasing blood theophylline levels for a longer period of time. With single IV administration, peak serum concentration is obtained after 30 minutes. Its metabolism is age-related and is affected by factors such as smoking, presence of chronic obstructive lung disease, liver or heart RE dysfunction, and a number of drugs such as cimetidine, erythromycin, rifampicin, phenytoin, and oral contraceptives. The incidence of theophylline toxicity has declined in the past years since newer ß-agonists and leukotriene antagonists have replaced theophylline in the treatment of asthma. Toxicity has three clinically OR distinct forms (acute, chronic, and acute on top of chronic) with varying presentations and treatment. Ingestion of > 10 mg/kg (serum level > 20 ug/mL) of the drug is potentially toxic in acute overdose. However, in chronic overmedication, toxicity can occur even with low serum theophylline levels. Clinical presentation centers on the gastrointestinal 2F tract, cardiovascular and central nervous systems. Management is generally supportive. Experimental and clinical studies have shown that multiple-dose activated charcoal administration significantly increases the elimination of life-threatening amounts of theophylline. In patients presenting with seizures, IV pyridoxine is recommended. FT Specific Precautions For sustained-release preparations, toxicity may develop several hours after ingestion. Peak plasma levels may be seen >12 hours post ingestion. This is because the drug forms bezoars in the GI tract. A With chronic use of theophylline, toxicity may occur even at much lower blood levels. There is decreased clearance of theophylline with concommitant use of DR the following enzyme inhibiting drugs: Allopurinol Cimetidine Beta blockers (Propranolol) Ciprofloxacin Caffeine Erythromycin Contraceptives more next page 115 THEOPHYLLINE Specific Precautions (continued) EW Theophylline clearance is decreased under the following conditions: Concommitant illnesses - CHF, COPD, hepatic cirrhosis, acute hepatitis, acute influenza, pneumonia High carbohydrate diet Old age There is increased clearance of theophylline with concommitant use of VI the following enzyme inducing drugs: Carbamazepine Phenobarbital Ethanol (chronic intake) Isoniazid Phenytoin Marijuana Rifampicin Theophylline clearance is increased under the following conditions: RE Concommitant illnesses: hyperthyroidism, cigarette smoking High protein, low carbohydrate diet Intake of barbecued meat Childhood Hypoalbuminemia increases unbound theophylline in the blood. Administration of an anti-emetic agent may be necessary to control OR nausea/vomiting for effective administration of multiple-dose activated charcoal. Whole bowel irrigation has not been found to have additional benefit over activated charcoal alone in sustained-release theophylline toxicity. Hemodialysis is considered if serum theophylline levels in moderately 2F toxic range are increasing despite activated charcoal administration. Other indications include: Seizures Hypotension Cardiac arrhythmias Acute overdose with serum levels > 100 ug/mL FT Chronic toxicity and patient is not tolerating the present level Chronic toxicity in a patient < 60 years of age with serum level >60 ug/mL or patient > 60 years of age with serum level > 40 ug/mL Since theophylline-induced hypotension is due to excessive ß-adrenergic agonism, administration of dopamine, dobutamine, epinephrine to A correct hypotension are not preferred. Administration of phenytoin as anticonvulsant has been found to be ineffective in the treatment of theophylline-induced seizures. DR Rapid IV administration of aminophylline produces severe manifestations