What is a suitable alternative to lorazepam (Ativan) for acute epilepsy management in adults and children?

Acute Epilepsy Management When Lorazepam is Not Available

When lorazepam is unavailable, intravenous diazepam should be administered as the first-line benzodiazepine alternative, or if IV access is not available, use buccal/intranasal midazolam or rectal diazepam. 1

First-Line Alternatives Based on IV Access

If IV Access is Available:

• Administer IV diazepam as the alternative benzodiazepine when lorazepam is not available 1
• While lorazepam is preferred over diazepam (65% vs 56% success rate), diazepam remains an effective first-line option when lorazepam is unavailable 2
• Dose: Standard benzodiazepine dosing protocols apply, with continuous monitoring for respiratory depression 1

If IV Access is NOT Available:

• Buccal midazolam 0.2 mg/kg is highly effective and preferred due to ease of administration 3, 4
• Intranasal midazolam 0.2 mg/kg demonstrates equivalent efficacy to IV diazepam (98% relative efficacy) with rapid onset 2
• Rectal diazepam 0.5 mg/kg should be administered if buccal/intranasal routes are not feasible 1
• Intramuscular midazolam may be considered when rectal diazepam is not possible due to medical or social reasons, showing similar efficacy to IV diazepam (97% relative efficacy) 1, 2

Critical Advantage of Non-IV Routes

• Intranasal lorazepam (if available) is non-inferior to IV lorazepam, with 80% vs 83.1% seizure cessation rates within 10 minutes 5
• Non-IV benzodiazepines avoid delays associated with establishing IV access, which can undermine the time advantage of IV administration 2, 4
• Buccal and intranasal routes achieve similar seizure cessation rates as IV routes while enabling earlier pre-hospital intervention 4, 6

Second-Line Agents (If Seizures Continue After Benzodiazepines)

Proceed immediately to second-line anticonvulsants if seizures persist after adequate benzodiazepine dosing:

Preferred Second-Line Options:

• Valproate 20-30 mg/kg IV over 5-20 minutes: 88% efficacy with 0% hypotension risk—superior safety profile compared to phenytoin 2, 7
• Levetiracetam 30 mg/kg IV over 5 minutes (maximum 2500-3000 mg): 68-73% efficacy with minimal cardiovascular effects and no cardiac monitoring required 2, 7
• Fosphenytoin 20 mg PE/kg IV at maximum 50 mg/min: 84% efficacy but 12% hypotension risk requiring continuous ECG and blood pressure monitoring 2, 7
• Phenobarbital 20 mg/kg IV over 10 minutes: 58.2% efficacy as initial second-line agent, but higher risk of respiratory depression 2

Refractory Status Epilepticus (If Second-Line Fails)

If seizures continue despite benzodiazepines and one second-line agent, initiate anesthetic therapy with continuous EEG monitoring:

• Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion (80% efficacy, 30% hypotension risk) 2
• Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion (73% efficacy, 42% hypotension risk, requires mechanical ventilation) 2, 7
• Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion (92% efficacy but 77% hypotension risk) 2

Critical Monitoring and Safety Considerations

• Respiratory depression occurs in 0-18% of cases across all benzodiazepine routes—have airway equipment, bag-valve-mask, and oxygen immediately available 4, 6
• Lorazepam causes significantly less respiratory depression than diazepam (RR 0.72,95% CI 0.55-0.93), but when lorazepam is unavailable, this risk must be accepted with diazepam 4
• Simultaneously search for and treat reversible causes: hypoglycemia, hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, and withdrawal syndromes 2, 7
• Administer 50 mL of 50% dextrose IV immediately if hypoglycemia is present 8

Common Pitfalls to Avoid

• Never skip benzodiazepines and go directly to second-line agents—benzodiazepines remain first-line even when lorazepam is unavailable 2, 9
• Do not use intramuscular diazepam due to erratic absorption—use rectal route instead if IM administration is being considered 1
• Do not delay treatment to establish IV access if non-IV benzodiazepines are available—buccal/intranasal routes achieve equivalent efficacy 4, 5
• Avoid neuromuscular blockers alone as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 2