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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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Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Current concepts and controversies in OP
management
Dr Bishan RajapaksePhD Candidate Australia National University,
Emergency Medicine Registrar, SydneySouth Asian Clinical Toxicology Research Collaboration
(SACTRC)
Abbreviated version of talk from -ACEM21st -25th November 2010, Canberra
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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 31st 2012)
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.
Vale A. What lessons can we learn from the Japanese sarin attacks? Przegl Lek. 2005;62(6):528-532.
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
PhD Paradox
“The only thing I know is that I don’t know anything”
- Socrates
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Poisoning Problem
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Agents of poisoning
Carba
mat
e
Organ
opho
spha
te
Unkno
wn Pes
ticid
e
Other
Her
bicid
es
Paraq
uat
0
200
400
600
800
1000
1200
1400
1600
Death Cases
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Impulsive
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Convenient: Source of Poison
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Men
Women
68%
Konradsen et al, 2004
Use of alcohol during self-harm in Uda Walawe
Alcohol
?
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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 31st 2012)
Limited resources and infrastructure for health care delivery
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Dangerous GI decontamination
• “Iatrogenic” component of mortality & morbidity
• 14 consecutive OP poisonings– 7 Aspiration
Pneumonia– 2 Deaths
The Hazards of Gastric Lavage for Intentional Self-Poisoning in a Resource Poor Location Clin Tox 2007;45(2):136-43
Images courtesy of Dr Michael Eddleston
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
OP Poisoning
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Mechanism - Inhibition of Acetycholinesterase
Image accessed from CNSForum.com
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Mechanism - Inhibition of Acetycholinesterase
Figure from Chapter: “Organophosphorus and Carbamate Agents (Anti-cholinesterase pesticide poisoning)” – B.Rajapakse, N. Buckley - “Emergency Medicine Textbook” Ed S David, WoltersKluwer (In press)
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
OP Poisoning – Complex Multi-system presentation
Cholinergic Effects on
Central(CNS)
Peripheral(PNS)
Somatic
AutonomicP
S
Life threatening features
+ Death
Neuro: - GCS- Seizure
Resp:
CVS:
- Lung Secretions
- HR- BP
- Respiratory muscle weakness
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
OP Poisoning – Complex Multi-system presentation
Cholinergic Effects on
Central(CNS)
Peripheral(PNS)
Somatic
AutonomicP
S
Life threatening features
+ Death
Neuro: - GCS- Seizure
Resp:
CVS:
- Lung Secretions
- HR- BP
- Respiratory muscle weaknessToxicology
Emergency
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
Clinical cases
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
CASE
36 yo femaleIngestion of Dimethoate
(Severely Toxic OP)
Village
• 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
0930 hrs
1000 hrs
0900 hrs(village)
1115 hrs
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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. PLoS Med. Jul 15 2008;5(7):e147.
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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.
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
End points of atropinisation
Lung Secretions
Hypotension
Bradycardia
Sweating
(Miosis)
Clear Chest
sBP > 80mmHg
HR > 80/min
Dry Axillae
(Pupils no longer pinpoint)
ATROPINE
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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 31st 2012)
ABCD
• Acute Cholinergic Syndrome:
• Neuro: Low GCS, Coma, Seizure• Resp: Lung Secretions
Respiratory Muscle Weakness• CVS: Bradycardia and Hypotension
Antidotes in OP poisoning Rx
ATROPINE
DIAZEPAM
Oxime reactivators
Roberts DM, Aaron CK. Management of acute organophosphorus pesticide poisoning. Bmj. Mar 24 2007;334(7594):629-634.
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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 31st 2012)
But would you give Oximes?
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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 31st 2012)
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 31st 2012)
Discussion: …..Time for your thoughts!
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
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 31st 2012)
SACTRCI 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 StaffI 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 PhysiciansDr Paul Quigley, Dr Craig Wallace, Dr Sandra Rattenbury
Funders & University Welcome Trust (GR071669) & Australia National University
Acknowledgements – Thanks!
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st 2012)
“Imagination is more important than knowledge”
Albert Einstein