Organophosphate Pesticide Poisoning

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Organophosphate Pesticide Poisoning

• Bishan Rajapakse
• MBChB Otago
• Emergency Medicine Advanced Trainee, MPhil
  Student (ANU),
• South Asian Clinical Toxicology Research
  Collaboration
• Sri Lanka

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The Case.

• Picture yourself in Anuradhapura hospital Sri
  Lanka ED/ Medical SHO
• Ward 6 , teaming with patients.
• Charge Sister tells you there is a sick patient
• 36yo F
• Taken 100mls of Dimethoate after a domestic
  argument
• Theres nowhere to run, or hide. So you see the
  patient what do you do?

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Organophosphate Pesticide Poisoning
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Organophosphate Poisoning in Sri Lanka

• Organophosphate pesticide (OP) poisoning kills
  300,000 worldwide
• In Sri Lanka these are mostly impulsive
  deliberate self-poisoning in young people

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Organophosphate Poisoning in Sri Lanka

• Case Fatality rates (CFR)
• 10-20 for most
• 50-70 for some OPs
• In west CFR
• 0.3 from all poisons
• Multifactorial
• Toxicity of OPs
• Patient transport
• Lack of resources
• Training

• Although less common OP Poisoning is still a
  problem in West
• Occupational exposure
• Threat of Chemical warfare

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Poisoning at Anuradhapura Hospital in 2005
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Mechanism of OPs
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Simplified Acute OP Toxicity

• Inactivation of acetylcholinesterase enzyme

Organophosphate
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Pharmacology of Cholinomimetics according to
Katzung

• Structure
• Simple Alcohols eg edrophonium
• Carbamates Eg Neostigmine and Physostigmine
  (tertiary)
• Organophosphates eg Parathion

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Clinical Syndrome

• Clinical Syndrome
• Acute Cholinergic
• Central
• Peripheral Muscarinic
• Peripheral Nicotinic
• Intermediate Syndrome
• OPIDN Delayed peripheral neuropathy
• Neurocognitive dysfunction

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Cholinergic Effects

• D iarrhoea
• U rination
• M iosis
• B radycardia, Bronchorrhoea, Bronchospasm
• E mesis
• L acrimation
• S alivation

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Nicotinic Effects

• Respiratory difficulty
• respiratory arrest
• diaphragmatic weakness
• Muscle Weakness
• fasiculations
• clonus
• tremor
• Stimulation of sympathetic nervous system
• Mydriasis, hypertension, tachycardia
• re-entrant dysrhythmias
• cardiorespiratory arrest

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CNS effects

• Malaise
• Memory loss
• Confusion
• Disorientation
• Delirium
• Seizures
• Respiratory centre depression or dysfunction
• Coma

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Intermediate Syndrome

• Delayed Respiratory Failure
• Proximal muscle weakness and cranial nerve
  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

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Chronic Effects

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

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Management

• The priorities in management are to
• Resuscitation
• Atropinisation of symptomatic patients
• Decontamination
• Other Treatments - Oximes

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Antidotes

• Atropine
• Oximes
• Expensive
• Does treatment affect outcome
• Intermediate Syndrome?
• OPIDN?

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Does the patient need atropine?

• How much and for how long

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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
  20046865-875.

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Atropine

• Loading
• Doubling dose regime e.g. 2 4 8 16 mgs every 5
  minutes
• Maintenance
• Continuous infusion lt 3mg/hr
• 10-20 of loading dose/hour
• Endpoints
• Clear chest on auscultation with no wheeze
• Heart rate gt80 beats/min
• Withdrawal
• Atropine toxicity
• Clinical Improvement

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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
• A sensitive indicator for ingestion, but poor
  predictor for toxicity.
• Full syndrome is rare

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Gastrointestinal Decontamination

• ?

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Our Decision should depend on a risk/benefit
analysis

• Nothing
• Emesis
• Gastric Lavage
• Activated Charcoal
• Whole bowel irrigation

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Risk of Intervention

• Aspiration
• Impaired GCS Unprotected Airway
• Emesis, Lavage, Charcoal (worse with cathartics)
• Trauma
• Oesphageal Injury
• Emesis, Lavage, Charcoal
• Electrolyte Abnormalities
• Forced Emesis, Cathartics
• Cardiac Arrest
• Toxin induced bradycardia Vagal Tone
• Induced emesis, Lavage
• Cost

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Summary of Experimental Evidence

• Ideal settings
• Little benefit in outcomes after 1 hour
• Activated Charcoal is equivalent or better than
  emesis or lavage
• Position statement single-dose activated
  charcoal. J Toxicol Clin Toxicol 199735721-41.
• Position statement and practice guidelines on the
  use of multi-dose activated charcoal in the
  treatment of acute poisoning. J Toxicol Clin
  Toxicol 199937731-51.

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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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Alternate sites for antidotes

• Protect AChE
• Supply AChE
• Reduce ACh
• Protect ACh Receptor
• Reduce OP Load
• Multiple Mechanisms

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Other Treatments under investigation

• Magnesium
• Reduces acetylcholine release
• Blockage pre-synaptic calcium channels
• Limited human studies
• Clonidine
• Decrease the presynaptic synthesis and release of
  acetylcholine.
• Central nervous system gt peripheral cholinergic
  synapses
• Diazepam
• Diazepam reduces respiratory failure (rats) and
  cognitive deficit (primates)
• Postulate uncoordinated stimulation of the
  respiratory centres decreases phrenic nerve
  output.

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The Case.

• Picture yourself in Anuradhapura hospital Sri
  Lanka ED/ Medical SHO
• Ward 6 , teaming with patients.
• Charge Sister tells you there is a sick patient
• 36yo F
• Taken 100mls of Dimethoate after a domestic
  argument
• Theres nowhere to run, or hide. So you see the
  patient what do you do?

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Summary

• OPs are Indirect Cholinomimetic
• Block AChE, prolonged duration of ACh in synapse
• Effects
• Muscarinic, Nicotinic, CNS
• Respiratory failure and Death result from this
• Treatment
• ABCs, Atropine, Decontaminate, Oximes
• Important also in West