Diazepam for Status Epilepticus
Primary Recommendation
Diazepam is FDA-approved for status epilepticus but is NOT the preferred first-line benzodiazepine—lorazepam is superior with 65% efficacy compared to diazepam's 42.6% seizure termination rate. 1, 2
Evidence-Based Treatment Algorithm
First-Line Benzodiazepine Selection
Lorazepam 4 mg IV at 2 mg/min is the preferred first-line benzodiazepine for status epilepticus, demonstrating statistically superior efficacy over diazepam (59.1% vs 42.6% seizure termination, p<0.05) 1, 3
Lorazepam has a longer duration of action compared to diazepam, reducing the need for repeated dosing 3
If lorazepam is unavailable, diazepam 5-20 mg IV (for a 70 kg adult) can be used as an alternative benzodiazepine 4
When Diazepam May Be Considered
Non-IV routes: When IV access is difficult or unavailable, alternative benzodiazepines by non-IV routes are preferred over diazepam:
Buccal or intranasal midazolam is superior to rectal diazepam (RR = 1.54; 95% CI = 1.29 to 1.85) 5
Rectal diazepam 0.6-0.8 mg/kg can terminate status epilepticus in approximately 69% of cases (9 of 13 episodes) within an average of 4.4 minutes when IV access is not available 6
Non-IV midazolam is administered 2.46 minutes faster than diazepam on average 5
Special Circumstance: Continuous Infusion
Continuous IV diazepam infusion (titrated to 8 mg/hour) may be used for refractory status epilepticus when traditional second-line agents (phenytoin, phenobarbital) are contraindicated, such as in anticonvulsant hypersensitivity syndrome 7
This approach is fraught with pharmaceutical stability problems and should only be considered when standard therapies cannot be used 8
Critical Treatment Sequence
Step 1: Immediate Benzodiazepine Administration
- Administer lorazepam 4 mg IV at 2 mg/min (preferred) 3
- If lorazepam unavailable, give diazepam 5-20 mg IV 4
- May repeat once if seizures continue (maximum lorazepam 8 mg total) 3
- Have airway equipment, bag-valve-mask, oxygen, and suction immediately available before administration 3
Step 2: Simultaneous Actions
- Check fingerstick glucose and correct hypoglycemia with 50 ml of 50% dextrose IV if present 3
- Search for reversible causes: hypoglycemia, hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, hemorrhage, withdrawal syndromes 1, 3
Step 3: Second-Line Agents (If Seizures Persist After Adequate Benzodiazepines)
- Valproate 20-30 mg/kg IV over 5-20 minutes (88% efficacy, 0% hypotension risk—best safety profile) 1
- Levetiracetam 30 mg/kg IV over 5 minutes (68-73% efficacy, minimal cardiovascular effects) 1
- Fosphenytoin 20 mg PE/kg IV at max 50 mg/min (84% efficacy, but 12% hypotension risk requiring cardiac monitoring) 1, 9
- Phenobarbital 20 mg/kg IV over 10 minutes (58.2% efficacy, higher respiratory depression risk) 1
Step 4: Refractory Status Epilepticus (Failure of Benzodiazepines + One Second-Line Agent)
- Initiate continuous EEG monitoring 1
- Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion (80% efficacy, 30% hypotension risk) 1
- Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion (73% efficacy, requires mechanical ventilation) 1
- Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion (92% efficacy, but 77% hypotension risk) 1
Critical Pitfalls to Avoid
Never use diazepam as first-line when lorazepam is available—the efficacy difference is clinically significant 1, 3
Never skip directly to third-line anesthetic agents (propofol, pentobarbital) without trying benzodiazepines and at least one second-line agent 1
Never use neuromuscular blockers alone (e.g., rocuronium)—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1
Ensure respiratory support capability is immediately available, as respiratory depression occurs with all benzodiazepines regardless of route 1, 3