When to switch to lorazepam (Ativan) in pediatric patients with seizures not responding to midazolam (Versed)?

When to Switch from Midazolam to Lorazepam in Pediatric Seizures

Lorazepam should be administered when a child's seizure has not responded to two properly dosed doses of midazolam within 10-15 minutes. This represents treatment failure of the initial benzodiazepine and requires prompt escalation to prevent progression to refractory status epilepticus.

Initial Treatment with Midazolam

Midazolam is commonly used as a first-line agent for seizure management in pediatric patients due to its:

• Rapid onset of action
• Multiple administration routes (IV, IM, buccal, intranasal)
• Favorable safety profile
• Effectiveness in achieving seizure cessation (with highest probability of success among benzodiazepines, SUCRA = 0.792) 1

The recommended dosing for midazolam in pediatric seizures is:

• IV/IO: 0.1 mg/kg (maximum 5 mg per dose)
• IM: 0.2 mg/kg (maximum 10 mg per dose)
• Intranasal/Buccal: 0.2-0.5 mg/kg

Criteria for Switching to Lorazepam

Switch to lorazepam when:

1. The patient has received 2 appropriate doses of midazolam with continued seizure activity
2. Seizure activity has persisted for 10-15 minutes despite midazolam administration
3. There are signs of respiratory depression from midazolam requiring intervention
4. The seizure initially responded to midazolam but quickly recurred

Lorazepam Administration

When switching to lorazepam, administer:

• IV/IO: 0.05-0.1 mg/kg (maximum 4 mg per dose) given slowly (2 mg/min) 2
• May repeat every 5 minutes to a maximum of 4 doses as needed 2

Lorazepam has several advantages in this setting:

• Longer duration of action than midazolam
• Potentially lower risk of respiratory depression (SUCRA = 0.4346) 1
• Efficacy rate of approximately 65% for status epilepticus 2

Important Considerations

1. Respiratory monitoring: Both benzodiazepines can cause respiratory depression. In a pediatric trial, 18% of patients treated with lorazepam required assisted ventilation 3.

2. Paradoxical excitation: This occurs in 10-30% of pediatric patients under 8 years of age and is characterized by tremors, agitation, euphoria, logorrhea, and brief visual hallucinations 3.

3. Benzyl alcohol content: Lorazepam injection contains benzyl alcohol as a preservative, which has been associated with serious adverse events in neonates and premature infants 3. Use with caution in very young infants.

4. Preparation for further escalation: If the seizure continues despite lorazepam, prepare for third-line agents such as levetiracetam (40 mg/kg IV, maximum 2,500 mg) or valproate (20-30 mg/kg IV) 2.

Special Situations

• Neonates: Use extreme caution with both midazolam and lorazepam due to increased risk of respiratory depression and sensitivity to benzyl alcohol preservatives 3.

• Prolonged seizures: If the seizure has already lasted >30 minutes before treatment, consider moving more quickly to third-line agents after initial benzodiazepine failure.

• Refractory status epilepticus: If seizures continue despite midazolam and lorazepam, consider levetiracetam, valproate, phenobarbital, or in extreme cases, anesthetic agents like propofol or ketamine 4.

By following this approach, you can optimize the management of pediatric seizures while minimizing risks associated with treatment delays or inappropriate medication use.