Propofol in Status Epilepticus
Role and Positioning in Treatment Algorithm
Propofol is a third-line anesthetic agent reserved for refractory status epilepticus that has failed benzodiazepines and second-line anticonvulsants, administered as a 2 mg/kg IV bolus followed by 3-7 mg/kg/hour continuous infusion under continuous EEG monitoring with mandatory mechanical ventilation. 1
When to Use Propofol
Propofol should be initiated when:
- Status epilepticus persists despite adequate doses of benzodiazepines (first-line) 1
- A second-line agent (valproate, levetiracetam, fosphenytoin, or phenobarbital) has failed 1
- The patient requires intubation and mechanical ventilation 1
- Continuous EEG monitoring is available to guide therapy 1
Critical pitfall: Never skip directly to propofol without trying benzodiazepines and at least one second-line agent first. 1
Dosing Protocol
Initial Administration
- Loading dose: 2 mg/kg IV bolus 1, 2
- Maintenance infusion: 3-7 mg/kg/hour, titrated to EEG burst-suppression 1, 2
- Target: Maintain burst-suppression pattern on EEG for approximately 24 hours before attempting to wean 3
Efficacy Compared to Alternatives
Propofol demonstrates 73% seizure control efficacy in refractory status epilepticus, which is lower than pentobarbital (92%) but comparable to midazolam (80%). 1
Comparative advantages:
- Shorter mechanical ventilation time: 4 days versus 14 days with pentobarbital 1
- Lower hypotension risk: 42% versus 77% with pentobarbital 4, 1
- Rapid onset: Seizure termination in median 2.6 minutes 4
- Already familiar to intensivists for sedation in ventilated patients 1
Comparative disadvantages:
- Lower efficacy than pentobarbital (73% vs 92%) 1
- Higher hypotension risk than midazolam (42% vs 30%) 1
Critical Monitoring Requirements
Mandatory monitoring includes:
- Continuous EEG monitoring to guide titration and detect ongoing electrical seizures 1
- Continuous blood pressure monitoring due to 42% hypotension risk 1
- Mechanical ventilation with respiratory support (propofol requires this regardless of route) 1
- Cardiac monitoring for arrhythmias 5
Laboratory monitoring for propofol infusion syndrome:
- Creatine kinase for rhabdomyolysis 5
- Lactate levels for lactic acidosis 5
- Triglycerides for lipemia 5
- Liver enzymes 5
- Renal function 5
Propofol Infusion Syndrome: The Major Risk
Propofol infusion syndrome (PRIS) is a potentially fatal complication occurring with doses >4 mg/kg/hour for >48 hours, with a 66% mortality rate when it develops. 5
Clinical features of PRIS:
- Arrhythmias (100% of cases) 5
- Lactic acidosis (62% of cases) 5
- Rhabdomyolysis (42% of cases) 5
- Renal failure (38% of cases) 5
- Sudden unexplained cardiorespiratory arrest 6
Risk factors from clinical experience:
- High infusion rates (median peak 67 mcg/kg/min in one series) 6
- Prolonged duration (median 63 hours) 6
- Large cumulative doses (median 12,750 mg) 6
- 10% sudden cardiac arrest rate in refractory status epilepticus patients, with 2/3 being fatal 6
Prevention strategies:
- Limit infusion rate to <4 mg/kg/hour when possible 5
- Limit duration to <48 hours if feasible 5
- Consider combination therapy with other agents rather than escalating propofol dose 5
- Monitor for early signs and discontinue immediately if PRIS suspected 5
Clinical Context from FDA Data
The FDA label confirms propofol's effectiveness in status epilepticus refractory to standard anticonvulsant therapies, noting that sedation maintenance dosages for status epilepticus patients are generally higher than for other critically ill populations. 2
Practical Algorithm
- First-line: Benzodiazepines (lorazepam IV, midazolam IM/intranasal) 1
- Second-line: Valproate 20-30 mg/kg IV OR levetiracetam 30 mg/kg IV OR fosphenytoin 20 mg PE/kg IV 1
- Third-line (refractory): Choose based on clinical context:
Propofol is most appropriate for intubated patients who continue seizing, provided they do not exhibit significant hypotension. 1