What is the best initial intramuscular (IM) medication for an unprovoked seizure?

Intramuscular Midazolam for Unprovoked Seizures

For an unprovoked seizure requiring intramuscular treatment, midazolam 10 mg IM (or 0.2 mg/kg, maximum 6 mg per dose in pediatrics) is the best medication choice, as it demonstrates equivalent efficacy to intravenous lorazepam while being easier to administer when IV access is unavailable. 1

Why Midazolam IM is Preferred

• Midazolam is the only benzodiazepine that should be given intramuscularly due to its superior absorption profile compared to other benzodiazepines 2, 3
• A prehospital study demonstrated that 10 mg intramuscular midazolam was equivalent in efficacy to 4 mg intravenous lorazepam for status epilepticus in adults and children weighing greater than 40 kg 1
• Intramuscular midazolam showed 73.4% seizure cessation on arrival to the emergency department compared to 63.4% with IV lorazepam (p < 0.001 for superiority) 3
• Midazolam achieves rapid absorption via the IM route with 93-100% efficacy reported across studies, making it practical when IV access is not immediately available 2

Dosing Algorithm

Adults and Children >40 kg:

• 10 mg IM as a single dose 1
• May repeat every 10-15 minutes if seizures persist 1

Pediatric Patients:

• 0.2 mg/kg IM (maximum 6 mg per dose) 1
• May repeat every 10-15 minutes as needed 1

Why NOT Other IM Options

• Lorazepam IM is not preferred because therapeutic levels are not reached as quickly as with IV administration, though it may be used when IV ports are unavailable 4
• Diazepam IM is NOT recommended due to risk of tissue necrosis and erratic absorption 1, 2
• Phenytoin and valproate should NEVER be given intramuscularly despite having parenteral preparations 3

Critical Safety Considerations

• Be prepared to provide respiratory support as midazolam carries an increased risk of apnea, especially when combined with other sedative agents 1
• Monitor oxygen saturation continuously during and after administration 1
• Respiratory depression occurs in 0-18% of children treated with benzodiazepines, though no significant difference exists between agents 5
• Flumazenil may reverse respiratory depression but will also counteract anticonvulsant effects and may precipitate seizure recurrence 1

Important Context for Unprovoked Seizures

• Unprovoked seizures occur without acute precipitating factors and include remote symptomatic seizures (from insults >7 days prior) or idiopathic seizures 1
• This differs from provoked seizures which occur within 7 days of metabolic, toxic, or neurologic insults 1
• Antiepileptic drugs should not be routinely prescribed after a first unprovoked seizure - the IM benzodiazepine is for acute seizure termination only 6, 7

Common Pitfalls to Avoid

• Do not use diazepam IM - this is a critical error that can lead to tissue injury and unreliable absorption 1, 2
• Do not delay treatment waiting for IV access - IM midazolam is faster and equally effective when IV access is difficult 3
• Do not assume all benzodiazepines are equivalent for IM use - only midazolam has the pharmacokinetic properties suitable for reliable IM absorption 2, 3
• Do not forget that benzodiazepines are short-acting - midazolam has a duration of only 3-4 hours, so longer-acting anticonvulsants (phenytoin, fosphenytoin, or valproate) should follow if this represents status epilepticus or recurrent seizures 2, 8