POISONING DUE TO ACETYLCHOLINESTERASE INHIBITORS IN THE MEDICAL EMERGENCY UNIT, CHRIS HANI BARAGWANATH ACADEMIC HOSPITAL, SOWETO, SOUTH AFRICA. Dr Patricia Marie Saffy Student No: 8110563 A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment for the degree of Master of Science in Medicine in Emergency Medicine. Johannesburg 2017 Declaration I, Patricia Marie Saffy, declare that this research report is my own work. It is being submitted for the degree of MSc in Medicine in Emergency Medicine at the University of Witwatersrand, Johannesburg. It has not been submitted before for any degree or examination at this or any other university. The 5th day of July 2017 II Dedication This report is dedicated to my father, Hans Beckenstrater, who died last year, but whose life was always an inspiration to me. You allowed us to pursue our dreams, and you showed us how to work to get there. III Abstract Introduction: Acetylcholinesterase Inhibitor (AChEI) poisoning is well described in chemical warfare and is commonly used for attempted suicide in many third world countries. Methods: This study serves to describe the demographic factors, temporal relationships and causes of acetylcholinesterase inhibitor overdose at a tertiary hospital emergency department in Gauteng, South Africa. Cross sectional chart review from the adult emergency unit overdose register was used to extract those patients with AChEI overdose and analysed for demographics, temporal relationships, presenting signs and blood results, treatment regimens and emergency department outcomes. Results: Of the 126 patients with AChEI overdose during this period over three- quarters (77%) had taken AChEI for attempted suicide. AChEI were usually taken alone without being mixed with other toxins, medicines or poisons. Males (54.3%) were more likely to attempt AChEI overdose than females. Younger people were more likely to overdose on AChEI with the majority (43.7%) being between 20-29 years, 24.6% between 30-39 years and 17.4% between 14-19 years. The remainder were over 40 years. Miosis was the most common sign of poisoning exhibited by 74% of patients. Emergency treatment was supportive with urgent use of high doses of atropine in escalating doses. Oximes and benzodiazepines were not used in the initial urgent treatment. Most patients (69%) were admitted to a high care, non- ventilated ward for observation and ongoing treatment but 19% of patients were severe enough to be ventilated and admitted into ICU. A small percentage, (12%) were sent to general wards. The mortality from AChEI poisoning in the unit was 2.4%. IV Conclusion: Typically, young healthy people were found to abuse AChEIs; the majority of which had suicidal intent. An average of 5 patients presented with AChEI poisoning per week. The mortality rate in the unit was very low. V Acknowledgements Thank you to the following people who have assisted me with this research report: my husband, parents and sons for their ongoing patience and support, my new supervisor, Martin Botha, who took over at a point when the previous supervisor left myself and others without support, Dr Maryam Rahban for extra help and support, Marcelle de Kock for her enormous patience and extra help with results and formatting, and support from Prof E Kramer and Prof A Bentley. VI Table of Content 1 Introduction 1 1.1 Motivation and rationale for this research....................................................... 1 1.2 Statement of the problem: .............................................................................. 2 1.3 Study Aim and Objectives: ............................................................................. 2 2 Literature review 3 2.1 History ............................................................................................................ 3 2.2 Structure and mechanism of interference of AChEI (OP & Carbamates) ....... 4 2.3 Cholinesterases ............................................................................................. 8 2.4 Causes and epidemiology of pesticide poisoning with AChEI ...................... 10 2.4.1 Causes of pesticide poisoning with AChEI in the South African context .. 12 2.5 Demographics of overdose with AChEI ........................................................ 15 2.5.1 Mortality associated with AChEI Overdose .............................................. 15 2.5.2 Gender differences ................................................................................... 16 2.5.3 Age distribution ........................................................................................ 17 2.5.4 Temporal distribution of AChEI overdose ................................................. 17 2.5.5 AChEI overdose in pregnancy .................................................................. 18 2.6 Clinical Presentation .................................................................................... 18 2.6.1 Signs and symptoms of AChEI toxicity (toxidrome) .................................. 18 2.6.2 Acute blood abnormalities ........................................................................ 22 2.6.3 ECG changes ........................................................................................... 23 2.7 Management ................................................................................................ 24 2.7.1 Decontamination ...................................................................................... 24 2.7.2 Treatment ................................................................................................. 26 VII 2.7.2.1 Symptomatic treatment 26 2.7.2.2 Specific treatment 30 2.7.3 Experimental treatments .......................................................................... 34 2.8 Risk factors for prognosis ............................................................................. 36 2.9 Long term effects of AChEI (specifically organophosphates) ....................... 36 2.10 Conclusion ................................................................................................... 37 3 Methods 39 3.1 Ethics ........................................................................................................... 39 3.2 Study Design ................................................................................................ 39 3.3 Study Setting ................................................................................................ 39 3.4 Study Population .......................................................................................... 40 3.5 Study Protocol .............................................................................................. 40 3.5.1 Data Collection ......................................................................................... 40 3.5.2 Outcome Measures .................................................................................. 41 3.5.3 Data analysis ............................................................................................ 43 3.5.4 Funding .................................................................................................... 43 3.5.5 Conflict of Interest .................................................................................... 43 4 Results 44 4.1 Demographics .............................................................................................. 44 4.2 Causes of AChEI Overdose ......................................................................... 45 4.3 Pregnancy .................................................................................................... 47 4.4 Type of exposure ......................................................................................... 48 4.5 Timing of presentation .................................................................................. 48 VIII 4.6 Temporal Distribution ................................................................................... 49 4.7 Signs and Symptoms ................................................................................... 51 4.7.1 Signs of poisoning .................................................................................... 51 4.7.2 Glasgow Coma Scale ............................................................................... 52 4.7.3 Pulse rate ................................................................................................. 53 4.7.4 Blood pressure ......................................................................................... 54 4.7.5 Respiratory rate ........................................................................................ 55 4.8 Blood results ................................................................................................ 56 4.8.1 Potassium ................................................................................................ 56 4.8.2 Lactate ..................................................................................................... 57 4.8.3 White Cell Count ...................................................................................... 58 4.8.4 Glucose .................................................................................................... 59 4.8.5 Pseudocholinesterase .............................................................................. 61 4.8.6 pH ............................................................................................................ 62 4.9 Electrocardiogram (ECG) analysis ..............................................................