What is the recommended dosing of intranasal midazolam (IM) via a nasal atomization device (MAD) for a patient with a history of epilepsy experiencing an acute epileptic seizure?

Intranasal Midazolam Dosing via MAD for Acute Epileptic Seizures

Administer intranasal midazolam 5 mg (one spray per nostril, 2.5 mg each) for patients weighing less than 50 kg, or 10 mg (two sprays per nostril, 5 mg each) for patients weighing 50 kg or more, using a mucosal atomization device (MAD). 1, 2

Evidence-Based Dosing Protocol

Weight-Based Dosing Strategy

• For patients <50 kg: Administer 5 mg total (2.5 mg per nostril) intranasal midazolam via MAD 2
• For patients ≥50 kg: Administer 10 mg total (5 mg per nostril) intranasal midazolam via MAD 2
• The standard dose of 0.2 mg/kg has demonstrated equivalent efficacy to rectal diazepam 0.5 mg/kg, particularly in pediatric populations 3

Administration Technique

• Deliver the medication within 1-2 minutes of seizure onset for optimal efficacy 4
• Use proper atomization technique—poor delivery technique accounts for the majority of treatment failures 2
• If excessive head movement accompanies seizures, consider buccal administration as an alternative route 2
• Maximum single dose should not exceed 10 mg (5 mg per nostril) in the outpatient/emergency setting 2, 4

Clinical Efficacy and Timing

• Intranasal midazolam demonstrates 79 of 84 treatment episodes (94%) clinically effective when administered with proper technique 2
• The medication doubles the seizure-free timespan from a median of 5.0 hours without treatment to 10.67 hours after administration 4
• Patients receiving intranasal midazolam are 50% less likely to experience another seizure within 24 hours compared to no treatment 4
• Onset of action occurs within 1-2 minutes after intravenous administration, with peak effect at 3-4 minutes; intranasal absorption provides rapid systemic delivery 5

Safety Profile and Monitoring

• Common adverse effects include:

  • Nasal mucosal irritation in approximately 8% of cases 4
  • Prolonged sedation in 5.7% of cases 4
  • Respiratory depression occurs in approximately 1% of cases 3
  • Oxygen desaturation measured after 17% of seizures, though typically mild 4

• Critical monitoring requirements:

  • Have oxygen and airway equipment immediately available before administration 1
  • Monitor vital signs for at least 30 minutes following administration 2
  • Be prepared for respiratory support, as apnea can occur up to 30 minutes after the last dose 5
  • Risk of respiratory depression increases substantially when combined with opioids or other sedatives 5

Treatment Algorithm Context

When to Use Intranasal Midazolam

• First-line benzodiazepine when IV access is not immediately available 1
• Intranasal midazolam shows 97% relative efficacy compared to IV diazepam, making it an excellent pre-hospital or home treatment option 1
• Particularly valuable for patients with known epilepsy experiencing breakthrough seizures or seizure clusters 6, 7

Escalation if Ineffective

• If no response within 10 minutes, revert to standard rescue medication protocol (typically IV benzodiazepines) 2
• Consider retrial if initial failure was due to poor administration technique 2
• After benzodiazepine administration (any route), if seizures continue, escalate to second-line agents: valproate 20-30 mg/kg IV (88% efficacy), levetiracetam 30 mg/kg IV (68-73% efficacy), or fosphenytoin 20 mg PE/kg IV (84% efficacy) 1

Critical Pitfalls to Avoid

• Do not use intramuscular diazepam due to erratic absorption—intranasal or rectal routes are superior 1
• 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 is unavailable 1
• Do not attribute treatment failure to the medication without first assessing administration technique—three of five treatment failures in one study were due to improper delivery 2
• Do not delay treatment waiting for IV access in patients with active seizures—intranasal administration can be completed within 1-2 minutes 4

Advantages Over Alternative Routes

• More dignified and socially acceptable than rectal diazepam 2
• Can be administered by non-medical personnel, including family members and caregivers 7
• Faster administration time compared to establishing IV access 4
• Superior pharmacokinetic profile with rapid onset and appropriate duration of action 2
• No risk of thrombophlebitis associated with IV diazepam 5