Decreasing Midazolam Dose in Patients With Epilepsy Linked to Greater Need for Rescue Therapy

October 14, 2020

By Louise Gagnon

OTTAWA, Ontario -- October 13, 2020 -- Despite guidelines for elevated midazolam doses to decrease the use of rescue therapy in patients with status epilepticus, patients with the condition are typically administered lower doses of the benzodiazepine in urgent care, according to a study presented at the 2020 Virtual Meeting of the American Neurological Association (ANA).

“We need to treat [status epilepticus] in a certain way,” said Elan Guterman, MD, University of California San Francisco, San Francisco, California. “Getting the right treatment leads to better outcomes.”

The researchers conducted a cross-sectional analysis of adult patients with status epilepticus that were treated by an emergency medical services agency from January 2013 to January 2018. The objective of the study was to determine the rate of benzodiazepine use that is not evidence-based and the link between decreased benzodiazepine dose and outcomes, such as the need for rescue therapy.

They study involved 2,494 patients (mean age, 54 years; 46% women), of which 1,537 were given midazolam at any dose, 938 (99.5%) received a 5-mg dose, and 5 (0.5%) received a dose of >5 mg. A second dose of midazolam was necessary in 282 (18%) of the patients as rescue therapy.

The investigators observed that higher doses of midazolam were linked to lower odds of need for rescue therapy (odds ratio [OR] = 0.8; 95% confidence interval [CI], 0.7-0.9) and that the probability of needing rescue therapy was considerably lower in patients who received midazolam 10 mg than in those who received 1 mg (4.5% vs 32.3%).

Elevated doses of midazolam did not add to the burden for more respiratory support. Rather, they were linked to a decline in the need for respiratory support (OR = 0.9; 95% CI, 0.8-1.0).

“We found that getting a higher dose of benzodiazepines and preventing the recurrence of seizures is better than giving you a lower dose and putting you at risk for recurrent seizures,” said Dr. Guterman. “It is the recurrent seizures that are leading people to get intubated. Lower doses are not effective [in preventing recurrent seizures].”

The analysis showed no evidence of harm with higher doses of midazolam and that a future investigation to confirm these findings is the next step.

“We would like to replicate this in a larger population,” said Dr. Guterman.

[Presentation title: Prehospital Midazolam Use and Outcomes Among Patients With Out-of-Hospital Status Epilepticus. Abstract K-587]