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Very-high-dose phenobarbital for refractory status epilepticus in children
T O Crawford1, W G Mitchell, L S Fishman
1Neurology Division, Childrens Hospital, Los Angeles, CA 90054-0700.
Insights
Very-high-dose phenobarbital effectively controlled refractory status epilepticus in 47 of 50 patients. This treatment approach demonstrated safety and efficacy, even with high serum levels, suggesting acute drug tolerance.
Area of Science:
- Neurology
- Clinical Pharmacology
Background:
- Refractory status epilepticus (RSE) presents significant morbidity and mortality risks.
- Current therapies for RSE have limitations.
Purpose of the Study:
- To evaluate the efficacy and safety of very-high-dose phenobarbital (VHDPB) for treating refractory status epilepticus.
- To determine if a maximum effective dose exists for VHDPB.
Main Methods:
- Retrospective analysis of 50 RSE cases treated with VHDPB.
- Dosage and serum levels were recorded without predetermined limits.
- Seizure control, respiratory drive, and hemodynamic stability were assessed.
Main Results:
- Seizures were controlled in 47 out of 50 patients (94%) with VHDPB.
- No maximum effective dose was identified; high serum levels (median 114 µg/ml) were achieved.
- Patients on mechanical ventilation often recovered respiratory drive, attributed to acute drug tolerance.
- Hypotension was infrequent and manageable.
Conclusions:
- Very-high-dose phenobarbital is an effective treatment for refractory status epilepticus.
- Acute drug tolerance may mitigate respiratory and hemodynamic side effects.
- VHDPB offers advantages over existing RSE therapies.
Abstract:
Status epilepticus refractory to initial anticonvulsant therapy is a serious condition with a high morbidity and mortality. We present 50 cases with refractory status epilepticus (RSE) treated with very-high-dose phenobarbital (VHDPB) without reference to a predetermined maximum level or dose. Maximum serum levels ranged from 70 to 344 micrograms/ml (median, 114 micrograms/ml). VHDPB controlled seizures in all cases where no limits were imposed upon maximum dose (47/50). We found no maximum dose beyond which further doses are likely to be ineffective. Forty patients were intubated prior to VHDPB, but recovered respiratory drive and could be removed from the ventilator despite very high serum levels. This is explained by acute drug tolerance. Hypotension was unusual, related to the highest levels, and easily controlled. VHDPB has many relative advantages over other therapies presently used for RSE.