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Organophosphate Toxicity Lessons from Anuradhapura

Organophosphate Toxicity Lessons from Anuradhapura. Andrew Dawson Program Director Sri Lanka. www.asiatox.org. Wellcome Trust & Australian National Health and Medical Research Council International Collaborative Capacity Building Research Grant (GR071669MA ). Organophosphate Poisoning.

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Organophosphate Toxicity Lessons from Anuradhapura

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  1. Organophosphate Toxicity Lessons from Anuradhapura Andrew Dawson Program Director Sri Lanka www.asiatox.org Wellcome Trust & Australian National Health and Medical Research Council International Collaborative Capacity Building Research Grant (GR071669MA )

  2. Organophosphate Poisoning • Asia 300,000 deaths /year • Sri Lanka • 17000 admissions • 35% ICU • 10% Die (20% of symptomatic)

  3. Past Pivotal Points : Pesticide Restriction Personal Communication Gunnell D, Fernando R, Heganawathna N et al

  4. Clinical Challenges

  5. Expensive: Costs Anuradhapura General Hospital Steel et al APAMT August 2006, Colombo. www.asiatox.org

  6. OP Case Fatality Rates

  7. Lesson 1Influence of Initial Care

  8. Gastric emptying – what happens if you stop?

  9. The results of observational data on gastric emptying (GE) in pesticide self-poisoning

  10. Lesson 2Variability of Toxicity

  11. Predictors of Death Case Fatality Rates of pesticides in self-poisoning

  12. Lesson 3Predictors of Mortality

  13. Clinical Signs and Mortality

  14. Glasgow Coma Score & Mortality • Normal GCS 5% • GCS <14 30% • GCS <10 60% OP Type & Mortality • Chlorpyrifos 7% • Fenthion 14% • Dimethoate 21%

  15. Review of OP Mechanism

  16. Normal Nerve Function ACh

  17. Normal Nerve Function ACh

  18. Normal Nerve Function AChE ACh

  19. How OP Work: Reversible & Aged Binding AChE OP ACh

  20. Nicotinic, Muscurinic & Central Syndrome

  21. Muscarinic Diarrhoea Urination Miosis Bronchospasm Emesis Lacrimation Salivation CNS CNS depression, coma Respiratory Centre Dysfunction Seizures Nicotinic Paralysis Sweating Mydriasis Hypertension Tachycardia Cardiovascular Arrhythmias Hypertension Tachycardia Tissue ischaemia

  22. Lesson 4Use of Atropine

  23. How Atropine Works AChE Atropine OP ACh

  24. Range of times it would take to give adequate doses of atropine (23mg and 75 mg) following the expert advice from each text

  25. A t r o p i n i z a t i o n A t r o p i n e r e q u i r e m e n t 2 4 1 6 8 C l e a r l u n g s P o o r a i r e n t r y i n t o l u n g s c a u s e d b y b r o n c h o s p a s m a n d b r o n c h o r r h o e a 4 0 D r y a x i l l a e E x c e s s i v e s w e a t i n g 3 0 S y s t o l . B P > ( H y p o t e n s i o n ) 8 0 m m H g 2 0 H e a r t r a t e > ( B r a d y c a r d i a ) 8 0 / m i n N o m i o s i s 1 0 ( M i o s i s ) 0 0 5 1 0 1 5 m i n a f t e r f i r s t a t r o p i n e d o s e Scheme of atropinization (endpoints to be reached) • Eddleston M, Buckley NA, Mohamed F, Senarathna L, Hittarage A, Dissanayake W, Azhar S, Sheriff MHR, Dawson AH. Speed of initial atropinisation in significant organophosphorus pesticide poisoning - a comparison of recommended regimens. Journal of Toxicology – Clinical Toxicology 2004;6:865-875.

  26. Results

  27. Clinical Challenges

  28. Lesson 5Reasons for Variation

  29. Most common organophosphorus pesticides

  30. X X X Xsymptomatic Clinical Variation Risk: Relative human toxicity of pesticides in self-poisoning • 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

  31. Time to Death

  32. Effectiveness of 1 gram pralidoxime treatment ChlorpyrifosDimethoate

  33. OPs are different • Differing Toxicity & Kinetics • Different Clinical Syndromes • Different Response to Antidotes • ? Need Different Treatment Responses

  34. Alternate Sites for Antidotes • Protect AChE • Supply AChE • Reduce ACh • Protect ACh Receptor • Reduce OP Load

  35. Magnesium • Reduces acetylcholine release • Blockage pre-synaptic calcium channels • Central and Peripheral Nervous System • Decrease toxicity in animal models • Limited human studies • Singh G. Electroencephalogr.Clin.Neurophysiol. 1998;107(2):140-8. • Magnesium sulfate in acute human OP poisoning Pajoumand A et al Hum Exp Toxicol. 2004 23(12):565-9

  36. Lessons from Anuradhapura • Influence of Initial Care on Mortality • Risk of decontamination • Variability of Toxicity • Applied to regulatory decisions, pesticide withdrawal • Predictors of Mortality • Pesticide type & Clinical Status • Use of Atropine: • The doubling protocol • Reasons for Variation • Chemical and Kinetic:Oxime Failure • Implications for where, how and what treatment is delivered

  37. Conclusion • OP Poisoning remains a complex problem • There are many reasons contributing to death • Multiple Points of Intervention (Medical, Regulatory & Social) requires Research

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