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Organophosphate Pesticide Poisoning

Organophosphate Pesticide Poisoning. Bishan Rajapakse MBChB Otago Emergency Medicine Advanced Trainee Registrar, MPhil Student (ANU), South Asian Clinical Toxicology Research Collaboration (SACTRC). OP Poisoning - Overview. Epidemiology Mechanism Clinical features Management

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Organophosphate Pesticide Poisoning

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  1. OrganophosphatePesticidePoisoning Bishan Rajapakse MBChB Otago Emergency Medicine Advanced Trainee Registrar, MPhil Student (ANU), South Asian Clinical Toxicology Research Collaboration (SACTRC)

  2. OP Poisoning - Overview • Epidemiology • Mechanism • Clinical features • Management • Current developments in Oxime therapy

  3. 0900 hrs (village) 0930 hrs 1000 hrs 1115 hrs CASE • Drunk 100mls after dispute • Found by family vomiting • Taken to nearest peripheral hospital (1 doctor, 2 nurses) • Sent by Ambulance (no paramedics) to nearest General hospital 36 yo female Ingestion of Dimethoate (Severely Toxic OP) Village

  4. Management • Initial Management? • ABC’s • Atropine • Ongoing Assessment & Management • Oximes (Pralidoxime, Obidoxime) -yes/no? • Dose? Duration? • Acetylcholinesterase assays?

  5. Organophosphorus (OP) Pesticide Poisoning

  6. Organophosphate Poisoning in Sri Lanka • Organophosphorus poisoning • High acuity and fatality • 12,000 admissions • 800 deaths • Mostly self-ingestion in Young adults • South Asian Clinical Toxicology Research Colaboration (SACTRC) • 5 Hospitals

  7. Organophosphate Poisoning in Sri Lanka • Case Fatality rates (CFR) • 10-30% for most OP’s • In west CFR • 0.3% from all poisons • Multifactorial • Toxicity of OP’s • Patient transport • Lack of resources • Training • Although less common OP Poisoning is still a problem in West • Occupational exposure • Threat of Chemical warfare

  8. Mechanism of OP toxicity

  9. Inhibition of Acetycholinesterase

  10. Nicotinic, Muscurinic & Central Syndrome

  11. Simplified Acute OP ToxicityOP’s are Cholinomimetics Organophosphate

  12. } Respiratory failure + Death Clinical Features • Acute Cholinergic Syndrome: • Central • Peripheral Muscarinic • Peripheral Nicotinic • Intermediate Syndrome • OPIDN: Delayed peripheral neuropathy • Neurocognitive dysfunction

  13. Cholinergic Effects – “DUMBELS” • D iarrhoea • U rination • M iosis • B radycardia, Bronchorrhoea, Bronchospasm • E mesis • L acrimation • S alivation

  14. Nicotinic Effects • Muscle Weakness • Respiratory difficulty • diaphragmatic weakness • respiratory arrest • Stimulation of sympathetic nervous system

  15. CNS effects • Serious Effects • Coma • Respiratory centre depression • Seizures • Other effects • Confusion • Memory loss • Disorientation • Delirium

  16. Case 2 • 24 yo female ingested 50 mls of Chlorpyrifos after an argument with her husband • Forced emesis at the local hospital • Arrived at the district hospital 4 hours later

  17. A- Airway threatened,  secretions present • B - RR 20, O2 sats 79-90% on oxygen • Widespread creps and poor air entry • C- P80 BP 100/70  • D- Pupils 2mm • GCS 10/15 (M5 V2 E3) • about V on the A V P U scale

  18. Fasiculations

  19. Intermediate Syndrome • Delayed Respiratory Failure • Proximal muscle weakness and CN lesions • Typically 1-4 days after cholinergic crisis has resolved • Prolonged Effects on Nicotinic receptors • Primary motor end plate degeneration • Clinical importance • Delayed respiratory failure leads to death if not aware of it or prepared for it • Wadia et. al 1974 : “Type II Paralysis, Senanayake and Karalliedde 1987”

  20. Chronic Effects • Organophosphate induced delayed neuropathy (OPIDN) • 1-3weeks • Peripheral neuropathy • Axonopathy due to Neuropathy Target Esterases (NTE) • Chronic organophosphate induced neuropsychiatric disorder (COPIND)

  21. Difference in OPs - Toxicity • 3most common OP’s ingested in NCP • Chlorpyrifos (Diethly OP) • Dimethoate & Fenthion (Dimethly OP) • Higher case fatality and intubation rates • in Dimethoate (CFR 23%, Intu 35%) and Fenthion (CFR 16%, Intu 31%) • compared with Chlorpyrifos (CFR 8%, Intu 15%)

  22. Clinical Variation Risk: Relative human toxicity of pesticides in self-poisoning X dimethoate Dimethyl fenthion X X Diethyl chlorpyrifos 0 1 0 2 0 3 0 4 0 C a s e f a t a l i t y r a t i o ( 9 5 % C I ) Xsymptomatic Eddleston M et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005

  23. Difference in OPs - Toxicity • AChE inhibition responded poorly to oxime therapy in the 2 Dimethyl OP’s • Short half life of Ageing • (Dimethly vs Diethyl)

  24. t1/2 Spontaneous reactivation • 0.7 hr for diMethyl • 31 hrs for diEthyl • t1/2 of Ageing • 3.7 hrs for diMethyl • 33 hrs for diEthyl Different rates of OP - AChE inhibition, reactivation and ageing • t 1/2 inhibition • Milliseconds for both diMethyl and diEthyl OPs Eddleston M, Eyer P, Worek F, Mohamed F, et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005 Oct 22-28;366(9495):1452-9

  25. Time to Death Eddleston M, Eyer P, Worek F, Mohamed F, et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005 Oct 22-28;366(9495):1452-9

  26. Eddleston M, Eyer P, Worek F, Mohamed F, et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005 Oct 22-28;366(9495):1452-9

  27. Effectiveness of 1 gram pralidoxime treatment ChlorpyrifosDimethoate

  28. Dimethyl OPs - specific features • Oximes less effective • Dimethoate patients died sooner • Hypotensive shock • Fenthion patients had higher incidence of delayed respiratory failure • Initially few symptoms • Later required intubation

  29. Management ?

  30. Management The priorities in management are : Resuscitation! A,B,C,D,E Atropinisation of symptomatic patients Decontamination Other Treatments - Oximes

  31. Resuscitation of OP poisoned patients • ABCDE – Careful attention to management of “airway + breathing” • ATROPINE is part of A, B, and C and • administer simultaneously to resuscitation • GI Decontamination is NOT a life saving procedure! • Should not be performed before resuscitation

  32. Respiratory Failure in OP patients • Review of 376 OP poisoned patients in NCP1 • 90pts (24%) required intubation • 52 (58%) intubated within 2 hours • 46 (51%) died • 29 (32%) Well on admission but required intubation >24hrs • 1Eddleston M, Mohamed F, Davies JO, Eyer P, Worek F, Sheriff MH et al. Respiratory failure in acute organophosphorus pesticide self-poisoning. QJM. 2006;99(8):513-22.

  33. All OP’s >24hours <2hours 2-24hours Fenthion When OP Patients were intubated in NCP Eddleston et al. Respiratory failure in acute organophosphorus pesticide self-poisoning. QJM. 2006;99(8):513-22.

  34. Atropine administration in OP poisoning • Indications • How fast to give • For how long • Toxicity of Atropine

  35. Indications for AtropineSpeed of intial Atropinisation Indications Atropinisation – Endpoint Poor air entry in lungs caused bronchospasm and bronchorrhoea Hypotension Bradycardia Excessive sweating (Miosis) Chest Clear Systolic BP >80mmHg Heart rate >80/min Dry Axillae Pupils no longer pinpoint Atropine

  36. Speed of intial Atropinisation • Study looked at severely poisoned OP patients in Sri Lanka • 22 patients, all required intubation, but survived to discharge • Mean dose of atropine required 23.4mg (range 1-75mg) Eddleston et al. Speed of initial atropinisation in significant organophosphorus pesticide poisoning--a systematic comparison of recommended regimens. J.Toxicol.Clin.Toxicol. 2004;42(6):865-75. • Text book recommendations for atropinisation varied markedly • Average patient 23.4mg – (8 to 1380 mins) • Severely ill patient 75mg – (25 to 4440 mins)

  37. Suggested Atropine Regimen • Loading • Doubling dose regime e.g. 2 4 8 16 mgs every 5 minutes • Maintenance • Continuous infusion < 3mg/hr • 10-20% of loading dose/hour • Endpoints • Clear chest on auscultation with no wheeze • Heart rate >80 beats/min

  38. What if you give too much Atropine ? • Anticholinergic Syndrome: • Hot as hell • Blind as a bat • Red as a beet • Dry as a bone • Mad as a hatter • CVS - Severe Tachycardia (eg HR >120) • Risk of ischaemia in elderly patients • CNS - Confusion, Agitation • Hyperthemia

  39. Gastrointestinal Decontamination ?

  40. Benefits Gastrointestinal Decontamination Risks • Aspiration • Trauma • Electrolyte Imbalances • Cardiac Arrest • Cost • Removal of poison load • Prevention of ongoing poison absorption • More beneficial in Toxic OP’s

  41. Gastrointestinal Decontamination Options: • Nothing • Emesis • Gastric Lavage • Activated Charcoal

  42. Risk of Intervention • Aspiration • Trauma • Oesphageal Injury • Nasopharyngeal injury 1. Eddleston M, Haggalla S, Reginald K, Sudarshan K, Senthilkumaran M, Karalliedde L, et al. The hazards of gastric lavage for intentional self-poisoning in a resource poor location. Clin Toxicol (Phila) 2007;45(2):136-43.

  43. Risk of Intervention • Electrolyte Abnormalities • Cardiac Arrest • Increased Vagal Tone especially with toxin induced bradycardia • Induced emesis, Lavage • Cost

  44. Summary of Experimental Evidence • GI decontamination should be done in ideal settings • Means to protect airway • Expertise to carry out procedure safely • Little benefit in outcomes after 1 hour • Position statement: single-dose activated charcoal. J Toxicol Clin Toxicol 1997;35:721-41. • Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999;37:731-51.

  45. Decontamination for OPs • Within 1 hour • Gastric lavage if no contraindications • Able to protect airway • GCS >12 • Followed by single dose AC • 1-2 hours – debatable • In some centres the above treatment is acceptable • > 2 hours ingestion • No place for Gastric Lavage or AC

  46. Oximes ?

  47. Oximes • Ineffective in some situations • Ageing • Variation between organophosphates • Effective protocols not established • Variation in use • Zero – 24 grams a day • Expensive • USA $30-600 / gram • India $6- 9 / gram • Sri Lanka 55 cents / gram • Unlikely to address Non-ACh effects

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