![]() Carbamazepine coma is the most common indication for multiple-dose activated charcoal (MDAC).In patients with established CNS toxicity, charcoal is only given once the patient has been intubated and nasogastric tube position has been confirmed on chest x-ray.Įnhanced elimination techniques are used with aim of reducing the duration of mechanical ventilation and ICU stay.Oral activated charcoal (50g) may be given to patients who present early and asymptomatic with ingestions Serial ECGs to assess for cardiotoxicity.Serum carbamazepine level (repeat every 6 hours in comatose patients).Paracetamol level, 12-lead ECG, blood sugar (= routine toxicological screening tests).Ventricular dysrhythmias due to sodium-channel blockade are treated with boluses of IV sodium bicarbonate.Barbiturates are second-line agents for refractory toxicological seizures (e.g. Paradoxical seizures are managed with titrated doses of benzodiazepines (e.g.Intubation and ventilation may be required for coma with loss of airway reflexes or for florid combative delirium not responsive to other measures.Excretion: Approximately 70% of an ingested dose is excreted in the urine as epoxidated, hydroxylated or conjugated metabolites the remaining 30% is excreted in the faeces.This is further metabolised to inactive metabolites that are excreted in the urine. Metabolism: Metabolised in the liver by cytochrome P450 3A4 to an active metabolite, carbamazepine 10,11 epoxide.Distribution: Small volume of distribution (0.8 – 1.2 L/kg), hence may be cleared by dialysis.Bioavailability is approximately 100% for the standard release preparation and 85% for the controlled release preparation.There are reports of peak levels being delayed by up to 96 hours following massive overdose with controlled-release tablets. In overdose, ileus secondary to anticholinergic effects may result in ongoing absorption over several days. Peak plasma concentrations are typically delayed for 8-12 hours following ingestion. Absorption: Carbamazepine is slowly and erratically absorbed.Subsequently it emerged that he had been admitted under Toxicology earlier in the year for a large olanzapine overdose. In this case, physostigmine was avoided as the patient had a history of seizures. He ultimately required intubation for florid delirium unresponsive to benzodiazepine sedation. The response to therapy may be very dramatic (“end of the needle” response), with patients converted from a “fumbling, mumbling mess” into well-behaved, coherent individuals within seconds. Delirium may reoccur in 1-4 hours as the effects of physostigmine wear off, at which time the dose may be cautiously repeated.The clinical end-point of therapy is resolution of delirium.Give IV physostigmine 0.5 – 1mg as a slow push over 5 mins repeat every 10 mins up to a maximum of 4mg.Ensure there is no bradycardia / AV block / broad QRS on the 12-lead ECG.Must be given in a monitored setting with appropriate staff and resources to manage adverse effects such as seizures, bradyarrhythmias and respiratory distress.Muscle weakness due to excess acetylcholine at the neuromuscular junction (suxamethonium-like effect).Seizures may occur with rapid IV administration due to central cholinergic hyperactivity.“SLUDGE syndrome” with excess Salivation, Lacrimation, Urinary incontinence, Diarrhoea, Gastrointestinal upset and Emesis.Bronchospasm, Bronchorrhoea and Bradycardia (the “killer bees”).Interventricular conduction abnormality (QRS >100ms)Įxcessive dosing may produce side-effects due to excess cholinergic activity, resulting in a clinical picture similar to organophosphate poisoning.Poisoning with a pure anticholinergic agent (e.g.Severe anticholinergic delirium unresponsive to benzodiazepine sedation.This increased cholinergic activity overcomes muscarinic receptor blockade, transiently reversing the effects of the anticholinergic agents.It temporarily blocks the breakdown of acetylcholine, thus enhancing its effects at muscarinic and nicotinic receptors.Physostigmine is a reversible acetylcholinesterase inhibitor (similar to carbamate insecticides).Physostigmine is the specific antidote to anticholinergic delirium and may be used for behavioural control in carefully selected cases.
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