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Presented by:
Dr. Mazen Baroudi
supervised by:
Dr. Mirella Halabi
Introduction:
- Organophosphates and carbamates are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity following cutaneous exposure, inhalation, or ingestion.
- World Wide:
3,000,000 per yr people are exposed.
up to 300,000 fatalities.
- 15 to 18 % of all poisoning in Aleppo.
- Chemical weapons (nerve gases) are organophosphate agents.
Mechanism Of Action:
- Organophosphorous compounds bind to acetylcholinesterase
- overabundance of acetylcholine in the synapse
- By time the compound undergoes a conformational change (aging) renders the enzyme irreversibly resistant to reactivation.
- Carbamate compounds unlike organophosphates, are transient cholinesterase inhibitors.
Clinical Features:
- Generally oral or respiratory exposures result in signs or symptoms within three hours.
- while symptoms of toxicity from dermal absorption may be delayed up to 12 hours.
Clinical Features (Acute Toxicity):
- Generally manifests in minutes to hours
- Evidence of cholinergic excess
- SLUDGE = Salivation,
Lacrimation,
Urination,
Defecation,
Gastric Emptying.
BBB = Bradycardia,
Bronchorrhea,
Bronchospasm.
Clinical Features (Acute Toxicity):
- Respiratory insufficiency can result from muscle weakness, decreased central drive, increased secretions, and bronchospasm and it is the lead cause of death.
- Cardiac arrhythmias, including heart block and QTc prolongation may be due to hypoxemia.
Clinical Features (Acute Toxicity):
In children
- Seizures are more common (22%-25%).
- Lethargy and coma (54%-96%).
- Flaccid muscle weakness, miosis, excessive salivation
are common presenting signs.
Clinical Features (Intermediate Syndrome):
- 10 to 40 % of organophosphorous agent poisoned patients.
- Occurs 24-96 hours after exposure.
- Bulbar, respiratory, and proximal muscle weakness are prominent features.
- Generally resolves completely in 1-3 weeks.
Clinical Features (Delayed Neurotoxicity):
- Organophosphate Induced Delayed Neuropathy (OPIDN).
- specific organophosphorous agents.
- Usually occurs several weeks after exposure.
- Primarily motor involvement (symmetrical motor polyneuropathy) flaccid weakness of lower extremities, ascends to involve upper extremities.
- Sensory disturbances are usually mild.
- May resolve spontaneously, but can result in permanent neurologic dysfunction.
Diagnosis:
- 88% of parents initially deny any exposure history.
- petroleum or garlic-like odor.
- If doubt exists a trial of Atropine (0.01 to 0.02 mg/kg) may be employed.
The absence of signs or symptoms of anticholinergic effects following atropine challenge strongly supports the diagnosis
Diagnosis (Laboratory abnormalities):
- RBC acetylcholinesterase activity:
- provides a measure of the degree of toxicity.
- determine the effectiveness of antidote therapy.
- plasma (or pseudo-) cholinesterase activity:
- more easily performed.
- not correlate well with the severity of poisoning.
- a depression of 25% or more is strong evidence of excessive organophosphate absorption.
Diagnosis (Laboratory abnormalities):
Do not delay the treatment until laboratory confirmation is obtained.
Management (Initial resuscitation):
- Deliver 100 % oxygen via facemask
- Strongly consider intubation:
- patients who appear mildly poisoned may rapidly develop respiratory failure.
- Consider volume resuscitation with normal saline or ringer to treat Bradycardia and hypotension.
- Use activated charcoal within one hour of an ingestion.
- In cases of dermal exposure aggressive decontamination with complete removal of the patient's clothes and vigorous irrigation of the affected areas should be performed.
Management (Atropine):
- Competes with acetylcholine at muscarinic receptors.
- Initial dose 0.05 mg/kg IV bolous.
- Doubled every 3 to 5 min until bronchial secretions and wheezing stop (SaO2).
- Repeat every 10 to 30 min until all absorbed organophosphate metabolized (few hours to several days; usually 2 to 12 hours).
Management (Atropine):
- Keep a maintenance dose of atropine for 2-3 days after disappearing of manifestation.
- Tachycardia and mydriasis are not appropriate markers for therapeutic improvement, as they may indicate continued hypoxia, hypovolemia, or sympathetic stimulation.
- Fever, muscle fibrillation, and delirium are the main signs of atropine toxicity that indicate that atropine administration should be discontinued, at least temporarily.
Management (Pralidoxime):
- Cholinesterase reactivating agent that are effective in treating both muscarinic and nicotinic symptoms.
- Use within 48 hours after poisoning.
- Use with concurrent of atropine.
- Use only for moderate to severe Organophosphate poisoning and not carbamate.
- Use if neuromuscular dysfunction is present.
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