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

Current concepts and controversies in OP management Dr Bishan Rajapakse PhD Candidate Australia National University, Emergency Medicine Registrar, SydneySouth 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 managementof 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 isthat I don’t know anything” - Socrates Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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

Agents of poisoning16001400 Death Cases12001000 800 600 400 200 0 Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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

Convenient: Source of Poison Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

Alcohol Use of alcohol during self-harm in Uda Walawe Men 68% Women ? Konradsen et al, 2004Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

High mortality & morbidity inpesticide 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)

Limited resources andinfrastructure for healthcare delivery Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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

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

Mechanism - Inhibition of Acetycholinesterase Dr Bishan Rajapakse - OP UpdateCNSForum.com 31st2012) Image accessed from (Port Hedland Jan

Mechanism - Inhibition of AcetycholinesteraseFigure from Chapter: “Organophosphorus and Carbamate Agents (Anti-cholinesterase pesticide poisoning)” – stB.Rajapakse, N. Buckley - Dr Bishan Rajapakse - OPTextbook” Ed S David, WoltersKluwer (In press) “Emergency Medicine Update (Port Hedland Jan 31 2012)

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)

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

CASE 0900 hrs • Drunk 100mls after (village) dispute36 yo female 0930 hrs • Found by familyIngestion 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)

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.

OP poison Management• Resuscitation! – A, B, C, D – Consider early intubation • IV Atropine – Stops lung secretions – Increases blood pressureEddleston M, Buckley NA, Eyer P, Dawson AH. Management ofacute organophosphorus pesticide poisoning. Lancet. Feb 162008;371(9612):597-607. - OP Update (Port Hedland Jan 31st2012) Dr Bishan Rajapakse

End points of atropinisationLung Secretions Clear Chest AHypotension T sBP > 80mmHg RBradycardia O HR > 80/min PSweating I Dry Axillae N E (Pupils no longer(Miosis) pinpoint) Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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)

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.

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)

But would you give Oximes? Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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)

Oxime SummaryHow 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)

Discussion: …..Time for your thoughts!Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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)

Acknowledgements – Thanks!SACTRCI would like to acknowledge all the staff at the South Asian clinical toxicologyresearch collaboration, and in particular:-Professor Nick Buckley, Professor Andrew Dawson, Dr IndikaGawarmanna, Dr Michael Eddleston, Dr Darren Roberts & Mr LalithSenarathnaSri Lanka Hospital StaffI would like to thank and acknowledge the patients and the hospitalstaff of Sri Lankan hospitals for their support in my researchNew Zealand Emergency PhysiciansDr Paul Quigley, Dr Craig Wallace, Dr Sandra RattenburyFunders & UniversityWelcome Trust (GR071669) & Australia National University Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

“Imagination is moreimportant than knowledge” Albert Einstein Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)

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

by Bishan Rajapakse

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