What is the role of lorazepam (Ativan) in the management of seizures?

Lorazepam in Seizure Management

First-Line Treatment for Active Seizures

Intravenous lorazepam is the most effective first-line treatment for generalized convulsive status epilepticus, with a 65% success rate compared to 44% for phenytoin alone, representing the highest quality evidence supporting lorazepam as superior initial therapy. 1

Dosing and Administration

Adults:

• Administer 4 mg IV slowly at 2 mg/min for ongoing seizures 1, 2
• May repeat once after 10-15 minutes if seizures persist (maximum total 8 mg) 1, 2
• If seizures stop after first dose, no additional lorazepam is required 1

Pediatrics:

• 0.1 mg/kg IV (maximum 4 mg per dose) for children aged 6-14 years 1, 3
• Can be repeated at least 1 minute apart, up to maximum 2 doses for convulsive status epilepticus 4

Critical Pre-Administration Requirements

Before administering lorazepam, ensure the following equipment is immediately available: 1, 2

• Equipment to maintain patent airway
• Bag-valve-mask ventilation capability
• Oxygen and suction
• Continuous cardiac monitoring and pulse oximetry 1

The most important risk is respiratory depression, which occurs in approximately 3-15% of patients depending on the study 2, 5. Airway patency must be assured and respiration monitored closely, with ventilatory support given as required 2.

When NOT to Give Lorazepam

Do not administer lorazepam if the seizure has already stopped on its own, as a single self-limiting seizure does not require acute benzodiazepine treatment 1. Simple febrile seizures do not require acute benzodiazepine treatment unless prolonged (>5 minutes) or recurrent 6.

Superiority Over Other Benzodiazepines

Lorazepam demonstrates 64.9% success rate and is statistically superior to phenytoin (p=0.002) in head-to-head comparison 1. Compared to diazepam, lorazepam controlled convulsions in 76% vs 51% of patients with a single dose, and significantly fewer patients required additional anticonvulsants 5.

The key pharmacokinetic advantage: Lorazepam has a much smaller volume of distribution of unbound drug compared to diazepam, resulting in an effective duration of action of several hours versus only 20-30 minutes for diazepam 7. This allows orderly administration of maintenance anticonvulsants after seizure control 7.

Escalation Protocol When Lorazepam Fails

If seizures persist after 2 doses of lorazepam (total 8 mg), immediately proceed to second-line agents: 1, 4

Second-Line Options (Choose One):

1. Valproate 20-30 mg/kg IV over 5-20 minutes

   • 88% efficacy with 0% hypotension risk (superior safety profile) 4, 6

2. Levetiracetam 30 mg/kg IV over 5 minutes

   • 68-73% efficacy with minimal cardiovascular effects 1, 4
   • Preferred in elderly patients or those with hypotension 6

3. Fosphenytoin 20 mg PE/kg IV at maximum 50 mg/min

   • 84% efficacy but 12% hypotension risk requiring continuous ECG and blood pressure monitoring 4, 6
   • Most widely available and traditional option 6

4. Phenobarbital 20 mg/kg IV over 10 minutes

   • 58.2% efficacy but higher risk of respiratory depression 4

Third-Line for Refractory Status Epilepticus:

If seizures continue despite benzodiazepines and one second-line agent, initiate continuous EEG monitoring and choose: 4

1. Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion

   • 80% efficacy with 30% hypotension risk 4

2. Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion

   • 73% efficacy, requires mechanical ventilation 4
   • Less hypotension than barbiturates (42% vs 77%) 4

3. Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion

   • 92% efficacy but 77% hypotension risk 4
   • Requires mean 14 days ventilation vs 4 days with propofol 4

Concurrent Management Priorities

While administering lorazepam, simultaneously: 1, 4

• Check fingerstick glucose immediately and treat hypoglycemia with 50 ml of 50% dextrose IV if present 1
• Search for reversible causes: hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, intracerebral hemorrhage, withdrawal syndromes 1, 4

Special Population Considerations

Elderly patients (>50 years):

• Consider lower doses due to increased sensitivity 1
• May have more profound and prolonged sedation 2
• Levetiracetam preferred as second-line due to minimal cardiovascular effects 6

Pediatric patients:

• Paradoxical excitation occurs in 10-30% of children under 8 years, characterized by tremors, agitation, euphoria, and hallucinations 2
• Benzyl alcohol preservative in lorazepam injection associated with "gasping syndrome" in neonates at doses >99 mg/kg/day 2
• Premature and low-birth-weight infants at higher risk for toxicity 2

Pregnancy:

• Lorazepam crosses placenta; animal studies show neuroapoptosis with prolonged exposure 2
• Not recommended during labor and delivery 2

Alternative Routes When IV Access Unavailable

Intranasal lorazepam 0.1 mg/kg (maximum 4 mg) is non-inferior to IV administration for termination of acute convulsive seizures, with 83.1% vs 80% efficacy 3. Rectal lorazepam showed 100% efficacy when venous access was not possible 5.

Intramuscular midazolam 0.2 mg/kg (maximum 6 mg) may be used if IV access is challenging, repeatable every 10-15 minutes 4.

Critical Pitfalls to Avoid

1. Never use neuromuscular blockers alone (e.g., rocuronium) as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 4

2. Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried 4

3. Do not administer flumazenil routinely as it reverses anticonvulsant effects and may precipitate seizure recurrence; reserve only for life-threatening respiratory compromise when mechanical ventilation unavailable 4

4. Avoid prophylactic anticonvulsants after stroke as they may harm neurological recovery; only treat active or recurrent seizures 1

5. Be alert to prolonged sedation especially with multiple doses, as sedative effects may add to post-ictal impairment of consciousness 2

6. Patients should not operate machinery or drive for 24-48 hours after receiving lorazepam until effects like drowsiness have subsided 2

Monitoring After Administration

• Continue monitoring for seizure recurrence 1
• Consider maintenance anticonvulsant only if recurrent seizures occur, not after single controlled seizure 1
• Maintain continuous vital sign monitoring, particularly respiratory status and blood pressure 4
• Consider EEG monitoring if seizures persist despite treatment to detect non-convulsive status epilepticus 1, 4