What medications are used to induce a coma?

Medications Used to Induce Coma

The primary medications used to induce therapeutic coma are propofol, midazolam, pentobarbital/phenobarbital, and thiopentone, with propofol and benzodiazepines being the most commonly employed agents in ICU settings. 1

First-Line Agents for Therapeutic Coma

Propofol

• Propofol is the most frequently used agent for inducing deep sedation approaching coma, with a rapid onset of 1-2 minutes and short elimination half-life of 3-12 hours 1
• Loading dose: 5 μg/kg/min over 5 minutes (avoid in hemodynamically unstable patients) 1
• Maintenance infusion: 5-50 μg/kg/min, titrated to achieve burst suppression or desired sedation depth 1
• For medical coma induction (e.g., refractory intracranial hypertension), higher doses up to 50-70 mg/hour may be required after a 20 mg loading dose 2
• Critical adverse effects include hypotension (68% of patients experience >20% decrease in systolic blood pressure), respiratory depression, and propofol-related infusion syndrome at high doses 1, 3
• Propofol causes more cardiovascular depression than benzodiazepines but allows faster emergence from sedation 3

Midazolam

• Midazolam is a short-acting benzodiazepine with onset of 2-5 minutes and elimination half-life of 3-11 hours 1
• Loading dose: 0.01-0.05 mg/kg over several minutes 1
• Maintenance infusion: 0.02-0.1 mg/kg/hr for deep sedation 1
• For palliative sedation requiring coma-like states, doses of 1-20 mg/hour may be used 1
• Midazolam provides superior amnesia (100% vs 33% with propofol) and better maintenance of sedation, but causes more respiratory depression (45% vs 26% with propofol) 3
• Less cardiovascular depression than propofol during induction 3

Second-Line Agents for Refractory Cases

Barbiturates (Pentobarbital/Phenobarbital)

• Barbiturates are reserved primarily for inducing coma in refractory status epilepticus or severe intracranial hypertension unresponsive to other agents 1, 4
• Phenobarbital loading: 1-3 mg/kg subcutaneously or IV bolus, followed by infusion of 0.5 mg/kg/hour 2
• Major limitations include prolonged sedative effects, significant hemodynamic depression requiring invasive monitoring, and risk of propylene glycol toxicity at high doses 4, 5
• In pediatric refractory status epilepticus, high-dose phenobarbital coma achieved clinical seizure resolution in a median of 16 hours 6

Lorazepam

• Longer-acting benzodiazepine with onset of 15-20 minutes and half-life of 8-15 hours 1
• Loading dose: 0.02-0.04 mg/kg (≤2 mg) 1
• Maintenance: 0.02-0.06 mg/kg every 2-6 hours or 0.01-0.1 mg/kg/hr (≤10 mg/hr) 1
• Risk of propylene glycol-related acidosis and nephrotoxicity at high doses limits its use for prolonged coma induction 1

Clinical Context and Selection Algorithm

For Refractory Status Epilepticus

1. First attempt: Midazolam infusion (0.02-0.1 mg/kg/hr) 6
2. If midazolam fails: High-dose phenobarbital coma protocol 6
3. Alternative: Propofol infusion (requires careful monitoring for propofol infusion syndrome) 1, 4

For Refractory Intracranial Hypertension

1. Propofol is preferred due to rapid onset/offset allowing neurological assessments 1, 7
2. Administer as slow bolus of 20 mg every 10 seconds rather than rapid bolus to avoid significant hypotension and decreased cerebral perfusion pressure 8
3. Barbiturate coma reserved for cases refractory to propofol 4

For Cardiac Arrest with Targeted Temperature Management

• Deep sedation during induction phase using propofol or midazolam combined with fentanyl (25-300 μg/hour) 1
• Maintain moderate sedation during maintenance phase, titrated to minimum dose that suppresses shivering 1
• Reduce to light sedation during rewarming to allow neurological assessment 1

Critical Safety Considerations

All coma-inducing agents ablate sympathetic tone, resulting in vasodilation, hypotension, bradycardia, and potentially low cardiac output 1

• Propofol requires monitoring for hypertriglyceridemia, pancreatitis, and propofol infusion syndrome (especially at doses >5 mg/kg/hr for >48 hours) 1, 7
• Benzodiazepines at high doses risk propylene glycol toxicity (monitor for metabolic acidosis, acute kidney injury) 1, 5
• Barbiturate coma requires invasive hemodynamic monitoring and carries high risk of immunosuppression with nosocomial infections 4, 5
• Concomitant use of valproate with propofol increases propofol blood levels; reduce propofol dose by 25-50% 8
• In pediatric patients, fentanyl administered with propofol may cause serious bradycardia 8

Monitoring Requirements

• Continuous electroencephalography to titrate to burst suppression pattern (typically 80% burst suppression probability for medical coma) 9
• Invasive arterial blood pressure monitoring 4
• For propofol: Daily triglyceride levels, creatine kinase, lactate 1, 7
• For barbiturates: Serum drug levels, renal function, acid-base status 5
• Sedation scales are less relevant during coma induction; EEG burst suppression is the primary endpoint 9