Buccal, Nasal Midazolam Most Cost-Effective for Pediatric Status Epilepticus

EEG brain waves
EEG brain waves
Rectal diazepam is currently the only FDA-approved treatment for pediatric status epilepticus.

Buccal and nasal midazolam are the most cost-effective, non-intravenous rescue medications for pediatric status epilepticus (SE), according to results of a cost-effectiveness analysis published in Epilepsia.

Pediatric SE is associated with cognitive, behavioral, and neurological impairments and an in-hospital mortality rate of up to 3%. Management focuses on early administration of anti-seizure medications that are typically given outside of the hospital. Currently, the only US Food and Drug Administration (FDA)-approved rescue medication in pediatric patients is rectal diazepam, though it is noted that this treatment “may be socially embarrassing in a non-private setting” and may present legal and privacy issues in school settings. Although nasal, buccal, and intramuscular midazolam and nasal lorazepam are also available, no studies have compared  the cost-effectiveness of nonintravenous SE rescue medications.

Ivan Sanchez Fernandez, MD, of Boston Children’s Hospital in Massachusetts, and colleagues sought to better understand the cost-effectiveness of nonintravenous rescue medications for pediatric status epilepticus. They conducted a decision analysis by comparing the effectiveness data obtained from literature to cost data obtained from market prices.

Overall, buccal midazolam was the most cost-effective rescue medication with, an incremental cost-effectiveness ratio (ICER) of $13.16 per seizure stopped. Nasal midazolam was the second most cost-effective option, with an ICER of $38.19 per seizure stopped.

Rectal diazepam, intramuscular midazolam, and nasal lorazepam were not more cost-effective at “any willingness to pay.” Notably, rectal diazepam would only become the most cost-effective if it cost $6 or less.

Further analysis demonstrated that buccal midazolam was more cost-effective at a willingness to pay from $14 to $41 per seizure stopped. Above $41 per seizure stopped, nasal midazolam was the more cost-effective option. At any willingness to pay, rectal diazepam was not cost-effective.  

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Nonintravenous midazolam and nasal lorazepam are approximately 30 to 50 times less expensive than rectal diazepam. Therefore, it would be difficult for rectal diazepam to be cost-effective when it is the more costly and less effective option.

The study had several limitations, including the fact that efficacy data was obtained from heterogenous patient populations from different countries, and subjective outcomes other than seizure cessations were not evaluated.

“For pediatric SE, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue medications in the United States,” the investigators concluded. “Rectal diazepam is not a cost effective alternative in the United States, and this conclusion remains extremely robust to wide variations of the input parameters.”


Sánchez Fernández I, Gaínza-Lein M, Loddenkemper T. Nonintravenous rescue medications for pediatric status epilepticus: A cost-effectiveness analysis. Epilepsia. 2017;58(8):1349-1359.