Barbiturate Poisoning

Barbiturate poisoning causes central nervous system and respiratory depression, hypotension, hypothermia and coma. It is now uncommon but remains seen with phenobarbital, thiopental, pentobarbital and in veterinary euthanasia agents, and is dangerous in combination with alcohol and opioids.

Fatal ingestions occur at around 10 times the hypnotic dose; for short acting agents (pentobarbital) 3 g is potentially lethal, for phenobarbital 6 to 10 g. Poisoning occurs mostly in intentional overdose and in people with access to veterinary or hospital stock.

Classes. Ultra-short (thiopental), short and intermediate (pentobarbital, secobarbital, amobarbital) and long acting (phenobarbital). Long acting drugs are eliminated by the kidney and are more suited to enhanced elimination.

Course. Coma may last 1 to 5 days after large ingestions of long acting agents; complications include aspiration, hypothermia and pressure injury.

Pathophysiology.

Barbiturates enhance GABA-A receptor chloride channel opening and directly gate the channel at high doses, causing profound central nervous system depression.

Medullary respiratory suppression and myocardial depression with vasodilatation cause hypoxia and shock.

• Drowsiness, slurred speech and ataxia, progressing to coma with absent reflexes.
• Respiratory depression, hypoxia and apnoea.
• Hypotension, bradycardia, hypothermia and pupil changes (small early, then fixed and dilated).
• Skin bullae over pressure areas; ileus and urinary retention.
• Withdrawal seizures if long term use stops abruptly.

Red flags.

• Glasgow Coma Scale under 9, apnoea or hypoxia.
• Hypotension unresponsive to fluids, or temperature under 32 degrees Celsius.
• Coma with absent brainstem reflexes (can mimic brain death).

• History of agent, dose and co-ingestants (alcohol, opioids, benzodiazepines); paracetamol and salicylate levels.
• Serum barbiturate level (phenobarbital) when available; glucose, electrolytes, renal and liver function, creatine kinase, venous gas and lactate.
• Chest imaging for aspiration; ECG; temperature.
• Urine toxicology screen may confirm exposure.

Differential diagnosis. Opioid overdose, benzodiazepine overdose, alcohol intoxication, stroke, hypoglycaemia, hypothermia, hepatic encephalopathy and brainstem lesions.

• Airway protection, oxygen and ventilation as needed; there is no specific antidote, and flumazenil and naloxone do not reverse barbiturates.
• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a significant ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness without a protected airway, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Long acting agents (phenobarbital): multiple dose activated charcoal 50 g orally or via nasogastric tube every 4 hours (children 1 g/kg, maximum 50 g) for up to 24 hours. Monitor bowel sounds, abdominal distension and aspiration. Avoid with unprotected airway, ileus, obstruction or recent bowel surgery; no renal or hepatic adjustment.
• Urinary alkalinisation for phenobarbital: sodium bicarbonate 8.4% 1 to 2 mmol/kg (1 to 2 mL/kg) intravenously, then an infusion of 150 mmol in 1 litre of 5% glucose at 250 mL/hour, titrated to urine pH 7.5 to 8.5. Maximum serum pH 7.55 and sodium 150 mmol/L. Monitor urine pH, potassium (replace to over 4.0 mmol/L), calcium, sodium and pH. Avoid in heart failure with fluid overload and renal failure.
• Hypotension: intravenous fluids, then noradrenaline 0.05 micrograms/kg/minute intravenously, titrated to a mean arterial pressure of 65 mmHg or higher. Maximum 1 microgram/kg/minute. Give by central line; monitor blood pressure, extravasation and arrhythmia.
• Haemodialysis or haemoperfusion for severe long acting barbiturate poisoning with prolonged coma, shock, apnoea or a level over 100 mg/L.
• Active rewarming for hypothermia; pressure area care; bladder catheterisation; treat aspiration pneumonia.
• Brainstem death testing only after toxic causes are excluded, with drug levels falling.
• Psychiatric assessment in intentional ingestion.

Monitoring. Conscious level, ventilation, blood pressure, temperature, urine output and levels in long acting poisoning.

Referral and escalation. Poisons information centre; intensive care for all with reduced consciousness; nephrology for dialysis.

Special groups. Children: dose by weight. Chronic users: expect withdrawal seizures after recovery.