Can a propofol infusion be started simultaneously with a midazolam (Benzodiazepine) infusion in the management of status epilepticus?

Propofol and Midazolam Infusions in Status Epilepticus

Yes, propofol infusion can be started simultaneously with midazolam infusion in refractory status epilepticus, as this combination has been shown to be rapidly effective for seizure control without increased adverse effects compared to single-agent therapy. 1

Treatment Algorithm for Status Epilepticus

1. First-line treatment: Benzodiazepines (lorazepam preferred)

   • Lorazepam 0.05 mg/kg IV (max 4 mg) - success rate ~65% 2
   • If IV access unavailable: rectal diazepam or nasal/buccal midazolam 3

2. Second-line treatment: Anti-epileptic drugs

   • Options include levetiracetam, valproate, or fosphenytoin 2
   • All have similar efficacy (approximately 45-47%) 2

3. Refractory status epilepticus: When seizures continue after benzodiazepines and a second anticonvulsant

   • Midazolam infusion:

     • Loading dose 0.15-0.20 mg/kg
     • Continuous infusion starting at 1 mg/kg per min
     • Increase by 1 mg/kg per min every 15 min (maximum: 5 mg/kg per min) until seizures stop 4

   • Propofol infusion:

     • Loading dose 50-75 mg/kg over 10-60 min
     • Infusion: 0.50-0.75 mg/kg per min 4
     • Monitor blood pressure and ECG continuously

Evidence for Combination Therapy

The Management of Refractory Status Epilepticus International Cohort Study (MORSE CODe) found that propofol and midazolam are equally effective in controlling refractory status epilepticus 1. When used as single agents, approximately 26% of patients initially treated with midazolam and 35% with propofol required the addition of a second anesthetic agent 1.

Continuous intravenous midazolam and propofol (alone or in combination) are rapidly effective for refractory status epilepticus 3. A structured review by Claassen et al. found that both agents are effective, though pentobarbital had fewer treatment failures (8%) compared to propofol (27%) and midazolam (20%) 4.

Important Monitoring and Precautions

1. Respiratory monitoring:

   • Increased incidence of apnea when midazolam is combined with other sedative agents 4
   • Be prepared to provide respiratory support regardless of route of administration
   • Monitor oxygen saturation continuously

2. Hemodynamic monitoring:

   • Propofol may cause hypotension, ventricular arrhythmias, and angina 4
   • Monitor blood pressure and ECG continuously
   • Maintain intravascular volume
   • Longer propofol infusion times reduce the risk of hypotension

3. EEG monitoring:

   • Prolonged EEG monitoring is associated with fewer days requiring continuous intravenous anticonvulsant medications 1
   • EEG monitoring helps detect breakthrough seizures and guide therapy

Practical Considerations

• Flumazenil may be administered to reverse life-threatening respiratory depression caused by benzodiazepines like midazolam; however, it will also reverse the anticonvulsant effects and may precipitate seizures 4

• When using propofol, longer infusion times (10-60 minutes for loading dose) reduce the risk of hypotension 4

• Breakthrough and withdrawal seizures are associated with an increased number of days requiring continuous intravenous anticonvulsant medications 1

Conclusion from Evidence

The evidence supports using propofol and midazolam together in refractory status epilepticus. The MORSE CODe study specifically noted that continuous intravenous midazolam and propofol in combination are rapidly effective for refractory status epilepticus 1. This combination approach is particularly useful when single-agent therapy fails to control seizures.