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Organophosphate Poisoning Treatment - port headland doctor teaching (31-1-12)

This is an educational talk about the treatment of organophosphorus poisoning (OP) based upon a talk given at the Australasian college of Emergency Medicine, Annual scientific sessions Nov 2010, canberra. If you liked this presentation; please also check out this page created by one of my senior colleagues (and watch the video) :- http://curriculum.toxicology.wikispaces.net/2.2.7.4.5+Organophosphates

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Current concepts and
  controversies in OP
     management




                 Dr Bishan Rajapakse
     PhD Candidate Australia National University,
       Emergency Medicine Registrar, Sydney
South Asian Clinical Toxicology Research Collaboration
                       (SACTRC)
       Abbreviated version of talk from -ACEM
         21st -25th November 2010, Canberra
        Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
PhD - “Improving the emergency management
of OP poisoning through research and medical
           education ” (2006-2010)
•   Advanced Trainee
     – Wellington NZ 2005 (1st year Ad Tr)
     – Sydney Oz, Aug 2010 – April 2011
     – Locuming June 2010 onwards until
       PhD submitted

•   South Asian Clinical Toxicology
    Research Collaboration (SACTRC)
     – Research collaboration
     – 5 Hospitals in Sri Lanka


• PhD Topics
     – Use of biomarkers in OP
       poisoning (RBC-AChE)
     – Rural doctor resuscitation
       education

               Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
Management of OP poisoning is
        Important in Emergency Medicine!
• Prevalent in developing
  world
   – 200,000 deaths /year
   – Self–poisoning
     predominates
• 15-30% mortality
   – (0.3% for all poisoning in
     the west)
• Also affects developed
  world nations
   – Occupational exposure &
     HAZMAT incidents
   – Nerve gas attacks

    Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning.
    Lancet. Feb 16 2008;371(9612):597-607.
                      Dr can we learn from - OP Update sarin attacks? Przegl st2012)
    Vale A. What lessons Bishan Rajapakse the Japanese (Port Hedland Jan 31 Lek. 2005;62(6):528-532.
PhD Paradox


“The only thing I know is
that I don’t know anything”

                                              - Socrates


    Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
Poisoning Problem




Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
Agents of poisoning
1600


1400                                           Death      Cases
1200


1000


 800


 600


 400


 200


   0




       Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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Organophosphate Poisoning Treatment - port headland doctor teaching (31-1-12)

  • 1. Current concepts and controversies in OP management Dr Bishan Rajapakse PhD Candidate Australia National University, Emergency Medicine Registrar, Sydney South Asian Clinical Toxicology Research Collaboration (SACTRC) Abbreviated version of talk from -ACEM 21st -25th November 2010, Canberra Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 2. PhD - “Improving the emergency management of OP poisoning through research and medical education ” (2006-2010) • Advanced Trainee – Wellington NZ 2005 (1st year Ad Tr) – Sydney Oz, Aug 2010 – April 2011 – Locuming June 2010 onwards until PhD submitted • South Asian Clinical Toxicology Research Collaboration (SACTRC) – Research collaboration – 5 Hospitals in Sri Lanka • PhD Topics – Use of biomarkers in OP poisoning (RBC-AChE) – Rural doctor resuscitation education Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 3. Management of OP poisoning is Important in Emergency Medicine! • Prevalent in developing world – 200,000 deaths /year – Self–poisoning predominates • 15-30% mortality – (0.3% for all poisoning in the west) • Also affects developed world nations – Occupational exposure & HAZMAT incidents – Nerve gas attacks Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. Feb 16 2008;371(9612):597-607. Dr can we learn from - OP Update sarin attacks? Przegl st2012) Vale A. What lessons Bishan Rajapakse the Japanese (Port Hedland Jan 31 Lek. 2005;62(6):528-532.
  • 4. PhD Paradox “The only thing I know is that I don’t know anything” - Socrates Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 5. Poisoning Problem Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 6. Agents of poisoning 1600 1400 Death Cases 1200 1000 800 600 400 200 0 Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 7. Impulsive Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 8. Convenient: Source of Poison Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 9. Alcohol Use of alcohol during self-harm in Uda Walawe Men 68% Women ? Konradsen et al, 2004 Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 10. High mortality & morbidity in pesticide poisoning is Multi-factorial • High toxicity of agents (15-30% mortality in OPs) – Lack of 100% effective antidote for the biggest killers Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 11. Limited resources and infrastructure for health care delivery Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 12. Dangerous GI decontamination • “Iatrogenic” component of mortality & morbidity • 14 consecutive OP poisonings – 7 Aspiration Pneumonia – 2 Deaths Images courtesy of Dr Michael Eddleston The Hazards of Gastric Lavage for Intentional Self-Poisoning in a Dr Poor LocationClinTox Hedland Jan 31st2012) ResourceBishan Rajapakse - OP Update (Port2007;45(2):136-43
  • 13. OP Poisoning Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 14. Mechanism - Inhibition of Acetycholinesterase Dr Bishan Rajapakse - OP UpdateCNSForum.com 31st2012) Image accessed from (Port Hedland Jan
  • 15. Mechanism - Inhibition of Acetycholinesterase Figure from Chapter: “Organophosphorus and Carbamate Agents (Anti-cholinesterase pesticide poisoning)” – st B.Rajapakse, N. Buckley - Dr Bishan Rajapakse - OPTextbook” Ed S David, WoltersKluwer (In press) “Emergency Medicine Update (Port Hedland Jan 31 2012)
  • 16. OP Poisoning – Complex Multi-system presentation Life threatening Cholinergic Effects on features Neuro:  GCS Central - Seizure (CNS) Resp:  Lung Secretions - Respiratory muscle weakness P Autonomic Peripheral S CVS:  HR (PNS)  BP Somatic + Death Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 17. OP Poisoning – Complex Multi-system presentation Life threatening Cholinergic Effects on features Neuro:  GCS Central - Seizure (CNS) Resp:  Lung Secretions - Respiratory muscle weakness P Autonomic Peripheral S CVS:  HR (PNS)  BP Somatic + Death Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 18. Clinical cases Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 19. CASE 0900 hrs • Drunk 100mls after (village) dispute 36 yo female 0930 hrs • Found by family Ingestion of vomiting Dimethoate (Severely Toxic OP) 1000 hrs • Taken to nearest Village peripheral hospital (1 doctor, 2 nurses) • Sent by Ambulance 1115 hrs (no paramedics) to nearest General hospital Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 20. Spectrum of disease • Acute cholinergic syndrome – Immediate onset • Intermediate Syndrome – Delayed respiratory failure (24-96hrs) – Nerve conduction can predict weakness • OP induced delayed peripheral neuropathy Jayawardane P, Dawson AH, Weerasinghe V, Karalliedde L, Buckley NA, Senanayake N. The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka.Rajapakse - OP Update (Port Hedland Jan 31st2012) Dr Bishan PLoS Med. Jul 15 2008;5(7):e147.
  • 21. OP poison Management • Resuscitation! – A, B, C, D – Consider early intubation • IV Atropine – Stops lung secretions – Increases blood pressure Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. Feb 16 2008;371(9612):597-607. - OP Update (Port Hedland Jan 31st2012) Dr Bishan Rajapakse
  • 22. End points of atropinisation Lung Secretions Clear Chest A Hypotension T sBP > 80mmHg R Bradycardia O HR > 80/min P Sweating I Dry Axillae N E (Pupils no longer (Miosis) pinpoint) Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 23. Atropine - Doubling Dose regime • Large doses of Atropine are required – Mean dose in severe OP poisoning 23.4mg (range 1- 75mg) • Text book recommendations vary – Upto 1,380 minutes to administer 23.4mg • Doubling IV bolus doses most effective – Eg. 2mg, then 4mg, then 8mg etc every 5 minutes until “clinical response” – Continue with 10-20% of loading dose/hour 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. Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 24. Antidotes in OP poisoning Rx • Acute Cholinergic Syndrome: ATROPINE A • Neuro: Low GCS, Coma, Seizure B • Resp: Lung Secretions C Respiratory Muscle Weakness D • CVS: Bradycardia and Hypotension DIAZEPAM Oximereactivators Roberts DM, Aaron CK. Management of acute organophosphorus pesticide st2012) poisoning. Bmj. Mar Bishan Rajapakse - OP Update (Port Hedland Jan 31 Dr 24 2007;334(7594):629-634.
  • 25. Oxime RCT – concluding statements • No evidence for benefit (WHO dose regime of Pralidoxime) • Reasons for failure were not apparent • Further studies needed – Different dose regimes (OP specific) – Different Oximes Eddleston M, Eyer P, Worek F, et al. Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial. PLoS Med. Jun 30 2009;6(6):e1000104. Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 26. But would you give Oximes? Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 27. Practicing Evidence Based Medicine Three factors: –The Evidence –Clinical Expertise –The Patient Source: Discussion with Prof Tony Celenza - UWA Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 28. Oxime Summary How would I treat a symptomatic OP pt? • Patient responding to atropine - would use this alone and not use pralidoxime. • If they are not getting better or decompensating with atropine, then treat with pralidoxime Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 29. Discussion: …..Time for your thoughts! Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 30. Conclusions • Pesticide poisoning large global public health problem • Treatment of OP poisoning = Atropine (++) & Resuscitation (Simultaneously) • Endpoints of atropinisation; BP, P, Lung secretions, secretions • Oxime therapy is controversial – use if not improving with atropine Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 31. Acknowledgements – Thanks! SACTRC I would like to acknowledge all the staff at the South Asian clinical toxicology research collaboration, and in particular:- Professor Nick Buckley, Professor Andrew Dawson, Dr Indika Gawarmanna, Dr Michael Eddleston, Dr Darren Roberts & Mr Lalith Senarathna Sri Lanka Hospital Staff I would like to thank and acknowledge the patients and the hospital staff of Sri Lankan hospitals for their support in my research New Zealand Emergency Physicians Dr Paul Quigley, Dr Craig Wallace, Dr Sandra Rattenbury Funders & University Welcome Trust (GR071669) & Australia National University Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
  • 32. “Imagination is more important than knowledge” Albert Einstein Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

Editor's Notes

  1. It’s the same in medicine – we just keep finding out how much we thought was correct perhaps isnt, and how much we don’t really know, the only difference is that as we get qualificaitons we are more confident about saying what we don’t know!
  2. The most common group are OP and one of the most deadly, next to paraquat which is also seen in high numbers.
  3. EASY ACCCESS
  4. The other important
  5. Also worthy of mention when considering why the Mortality and morbidity is high is the Iatrogenic componentForced emesis and gastric lavage were we accepted practice of poison management world world wide many decades ago, but during the last 3 decades in the west the was the realisation that forced emesis was a dangerous practice, and the benefits of even Gastric lavage which is slightly more controlled is still limited, and still dangerous if there is a decreased level of consciousness when performed in a non intubated patient. However, despite this there is still the widespread practice of both these procedures throughout asia, and this early reserch by Michael eddleston conducted in Sri Lanka documented that in 14 consecutive OP poisonings that there were 7 cases of aspiration pneumonia and 2 deaths related to this. This gives an idea of the magnitude of a potentially iatrogenic component to the high mortality and morbidity – this also suggests the importance of both good education in poisoning management and also the importance of resuscitation education. Knowledge / practice GapDangerous GI decontamination despite established poison treatment protocolsIneffective resuscitation practice and trainingAnother factor is the dangerous decontamination practices – such as the widespread use of forced emesis – which involves often the patient drinking 3 litres of bicarbonate until they vomit. Also other practices include using a widebore orogastric tubes or nasogastric tubes in patients with low leves of consciousness who are not intubated. One study looked at 14 consetcutive patients with OP poisong where there was an incidence of aspiration pneumonia in 7 and death in 2.
  6. We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoningTwo hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). N=235CONCLUSIONS: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.