Treatment of Status Epilepticus

Katherine Lemming, PharmD

Disclosures

Pediatr Pharm. 2018;24(2) 

In This Article

Initial Therapy Phase: 5 -20 Minutes

The initial therapy phase begins when the duration of the seizure lasts at least five minutes. The recommended initial therapy choice is a benzodiazepine (Table 1). Benzodiazepines bind to a stereospecific benzodiazepine binding site (between then α and γ subunits) on postsynaptic GABAA neurons leading to an increase in frequency of channel opening and inhibition of neurotransmission. Intramuscular (IM) midazolam (0.2 mg/kg/dose, maximum single dose: 6 mg), intravenous (IV) lorazepam (0.1 mg/kg/dose, maximum single dose: 4 mg), or intravenous diazepam (0.1–0.3 mg/kg/dose, maximum single dose: 10 mg) are the preferred benzodiazepines. If none of these options are available, intravenous phenobarbital (15 mg/kg/dose, single dose), rectal diazepam (0.2–0.5 mg/kg/dose, maximum single dose: 20 mg) or intranasal or buccal midazolam can be considered. The most common adverse events associated with benzodiazepine use include sedation, hypotension, and respiratory depression.

Available Pediatric Literature

Chamberlain and colleagues evaluated the efficacy and safety of lorazepam compared to diazepam for the treatment of pediatric status epilepticus.[2] Two-hundred and seventy-three patients, aged 3 months to younger than 18 years were included in the trial. Patients received either IV diazepam 0.2 mg/kg or IV lorazepam 0.1 mg/kg, with half this dose repeated at 5 minutes if necessary. The primary outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. There was no statistically significant difference between the two groups with 72.1% in the diazepam group and 72.9% in the lorazepam group having met the primary outcome. The authors concluded that there was no evidence to support the preferential use of lorazepam.

The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) was a double-blind randomized trial comparing IM midazolam to IV lorazepam.[3] Eight hundred and ninety-three patients, including 120 children, were randomized to receive either IM midazolam dose via auto-injector or IV lorazepam administered prior to emergency department arrival. The primary efficacy endpoint, absence of seizures at the time of arrival to the emergency department, was achieved in 73% of subjects in the IM midazolam group compared with 63% in the IV lorazepam group (P < 0.001 for non-inferiority and superiority). IM midazolam was shown to have a shorter time to administration (1.2 versus 4.8 minutes); however, onset after administration favored IV administration (1.6 versus 3.3 minutes).

Arya and colleagues performed a non-inferiority, randomized, open-label study comparing the efficacy and safety of intranasal versus IV lorazepam in children aged 6 to 14 years presenting with acute seizures.[4] Patients were randomized to receive either IV or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). For the primary outcome of clinical seizure remission within 10 minutes of drug administration, there was no statistically significant difference between the IV and intranasal groups at 80% versus 83.1%, respectively. The authors concluded that intranasal administration is an acceptable alternative to IV administration of lorazepam.

Moretti and colleagues conducted a retrospective review evaluating the differences in terms of immediate management and subsequent outcome when comparing the use of rectal diazepam versus buccal midazolam.[5] A total of 33 children were included in the subgroup analysis with 17 and 16 who received effective administration of rectal diazepam and buccal midazolam, respectively, for the treatment of a subsequent seizure. Seizure duration was significantly shorter (10.3 versus 48.4 minutes, p = 0.004) and risk of status epilepticus was decreased (1 versus 11, p = 0.0008) in those who received buccal midazolam. Admission rate was not statistically significantly different between the two subgroups (8 versus 2 patients, p = 0.06). Buccal midazolam may offer some advantages over rectal diazepam; however, further studies are necessary to confirm these results.

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