ICU Fellowship Snippet – Organophosphate Poisoning

Organophosphate Poisoning

Written by Dr Madhuri Anupindi

A 50-year-old farmer with a history of alcohol abuse and depression is brought to the ED, having been found collapsed in his garage. He is semi-conscious and unable to move. What is your differential diagnosis?

My primary concern in this gentleman is organophosphate poisoning but other potential causes for his collapse and inability to move could be secondary to other toxins or envenomation, neurological causes, or metabolic or cardiac causes with subsequent trauma causing a spinal cord injury.

Toxins/envenomation:

• Organophosphate
• Toxic alcohol
• Botulism
• Carbamate poisoning
• Carbon monoxide poisoning
• Cyanide toxicity
• Snake bite: Tapian, tiger
• Tick paralysis

Neurological:

• Brain stem stroke
• Intracranial haemorrhage
• Seizure activity
• Meningitis/encephalitis
• Myasthenic crisis
• Epidural abscess
• Guillain barre syndrome
• Lambert-Eaton myasthenic syndrome
• Acute flaccid myelitis

Metabolic

• Hypoglycaemia
• Renal/hepatic failure
• Sepsis

Cardiac

• Arrhythmia
• Aortic stenosis

The paramedics report an empty bottle of insecticide found next to the patient and you are concerned about organophosphate toxicity. What clinical features and investigative findings would help confirm your diagnosis?

Clinical features: cholinergic excess

Muscarinic receptor effects:

• Salivation
• Lacrimation
• Urination
• Diarrhoea
• Vomiting
• Bronchorrhea and bronchospasm
• Bradycardia
• Miosis
• Diaphoresis

Nicotinic receptor effects:

• Fasciculations
• Flaccid paralysis
• May cause tachycardia and hypertension

CNS effects

• Agitation
• Confusion
• Ataxia
• Seizures
• Coma

Diagnosis generally is on history and examination findings – treatment generally instituted before laboratory confirmation (as not all labs able to perform test).

Investigation:

• Butyryl cholinesterase and red cell acetylcholinesterase activity: will be low
• Non-specific: ECG (QT prolongation, bradycardia), FBC (leucocytosis)
• Exclude other causes and evaluate severity: ABG (oxygenation/ventilation, hypoglycaemia, carbon monoxide levels), UEC/LFTS (organ function) CTB/c spine (intra-cranial causes, spinal lesion)

What is the mechanism of organophosphate toxicity?

Organophosphates are found in pesticides and some medications. They are highly lipid soluble and well absorbed through the lungs, skin and gastrointestinal tract with a high volume of distribution. They bind to and thereby block the activity of acetylcholinesterase which results in an excess of acetylcholine at the neuromuscular junction and neuronal synapses. This results in cholinergic crisis with excessive stimulation of muscarinic and nicotinic receptors as outlined earlier.

Initially, when organophosphates bind to acetylcholinesterase, it undergoes cleavage, forming a reversible bond but still inactivating the enzyme. Over time this bond becomes irreversible, a process known as aging, and enzyme regeneration is no longer possible.

What initial management would you institute?

Decontamination

• PPE for all staff is vital
• Remove and dispose of patient’s clothes and wash skin with soap and water à this should not delay resuscitation, should be done concurrently or afterwards
• If timeframe can be confirmed and is within 1 hour of ingestion give charcoal 50g once intubated

Resuscitation

• Pre-oxygenation and intubation with high dose rocuronium, avoid suxamethonium, sats > 92%, normal etco2 à sedation post involving benzos as likely to have agitation
• Appropriate access and monitoring: initial peripheral then CVC, arterial line, sats, etco2, IDC, NGT
• Circulatory support: IVF and vasopressors (hypotension common)

Antidotes

• Atropine: 1mg bolus à keep doubling every 5 minutes until cholinergic symptoms controlled. Then start infusion of 10 – 20% of total bolus dose per hour.
• Pralidoxime: 30mg/kg or 2g bolus then 8mg/kg/hr or 500mg/hr which should be continued for at least 24 hours

Logistics:

• Requires ICU bed
• Discuss with toxicology team
• Schedule as likely intentional overdose – will need psychiatric review

How do atropine and pralidoxime work in organophosphate toxicity?

Atropine: competes with acetylcholine at muscarinic receptors, thereby preventing cholinergic activation

Pralidoxime: reactivates acetylcholinesterase by cleaving the phosphate-ester bond between the organophosphate and acetylcholinesterase. This is only effective before irreversible binding takes place.