Phenobarbitone (Phenobarbital) Overdose

Overview

Mechanism of Toxicity

1. Potentiating GABA-A receptor activity → enhanced CNS inhibition
2. Blocking AMPA receptors (glutamate subtype) → further CNS depression

Clinical Presentation

Severity-dependent features:

Key vital sign abnormalities:

• Respiratory depression — occurs first, centrally mediated
• Hypotension — primarily from decreased vascular tone
• Hypothermia (30–36°C) — centrally mediated impairment of temperature regulation
• Pulse, pupil size, and nystagmus are variable

Complications:

• Early deaths: respiratory arrest, cardiovascular collapse
• Late deaths: acute lung injury, ventilator-acquired pneumonia, cerebral oedema, multiorgan failure
• Hypoglycaemia (from starvation during coma), pulmonary oedema, aspiration pneumonia
• Current mortality: 1–3%

The effects of phenobarbitone are potentiated by benzodiazepines and alcohol — always assess for co-ingestion.

Diagnosis

• Clinically based — serum levels do not reliably predict clinical severity and do not correlate with brain concentrations
• Serum barbiturate levels: useful to confirm diagnosis in an unresponsive/comatose patient
• Levels are unreliable in chronic barbiturate users (tolerance) and in renal/hepatic disease

Investigations:

• Blood glucose, electrolytes, full blood count, renal/liver function
• Arterial blood gas (if respiratory compromise)
• Urine toxicology screen (note: ibuprofen and naproxen can cause false positives — confirm with GC-MS if needed)
• Chest X-ray, ECG
• Serial serum phenobarbital levels during first 6 hours

Management

1. Airway & Supportive Care (First Priority)

• Assess mental status and airway immediately
• Intubate and ventilate in severe sedative-hypnotic overdose
• IV crystalloid fluids for hypotension (mainstay)
• Vasopressors (dopamine or norepinephrine) if fluid resuscitation fails
• Active rewarming for hypothermia with continuous core temperature monitoring

2. Activated Charcoal

• Single dose (50 g adult): give to cooperative, clinically stable patients presenting within 1 hour of ingestion
• Multidose activated charcoal (MDAC): recommended for life-threatening phenobarbital ingestion
  • Regimen: 50–100 g initial dose, then 12.5–25 g every 4 hours
  • Concurrent cathartics are not recommended
  • Monitor airway carefully to prevent aspiration
  • MDAC is superior to urinary alkalinisation for reducing serum levels

3. Urinary Alkalinisation

• Sodium bicarbonate enhances phenobarbital renal clearance 2–3 fold
• However, because baseline renal clearance of phenobarbital is already low (<3 mL/min), the impact on total body clearance is limited
• Not first-line — MDAC is preferred
• Not effective for shorter-acting barbiturates

4. Extracorporeal Treatment (ECTR)

• Coma with respiratory depression
• Hypotension not responding to vasopressors
• Failure of MDAC to reduce serum concentrations

• High-flux dialysers provide clearances at least equal to haemoperfusion
• ECTR is most beneficial if initiated within 24 hours of exposure
• ECTR is not useful for shorter-acting barbiturates

⚠️ Withdrawal risk: In chronic barbiturate users, rapidly lowering concentrations can precipitate barbiturate withdrawal at 48–72 hours (seizures, persistent delirium). Stop ECTR once levels reach the therapeutic range; reinitiate barbiturate therapy if needed.

Disposition

Withdrawal Syndrome (for context)