Higher doses of midazolam can reduce the need for rescue therapy without increasing the need for ventilatory assistance in patients with status epilepticus. This is evident from study results published in Neurology.
In this study, a team of researchers attempted to evaluate benzodiazepine use in patients with status epilepticus and the relationship between benzodiazepine dose and clinical outcomes.
To achieve this, they carried out a cross-sectional analysis of 2,494 patients with status epilepticus (mean age 54 years) who were treated by an EMS between 2013 and 2018. The study researchers obtained these patient and treatment data from EMS medical records. The primary outcome of the analysis was the need for rescue therapy, which was defined by treatment with a second dose of benzodiazepine. A secondary outcome was also the receipt of respiratory support. The only benzodiazepine used in these participants was midazolam.
The agency’s treatment protocol suggests either a single dose of 0.1 mg / kg to a maximum of 6 mg or a single dose of 5 mg for intranasal administration. However, national guidelines suggest that initial treatment with midazolam should be a single intramuscular dose of 10 mg.
A total of 1537 patients received midazolam at each dose, representing an administration rate of approximately 62 percent. None of the patients in this analysis received a dose or route of treatment recommended by national guidelines. About 18 percent of patients required rescue therapy with a second dose of midazolam. Of the 943 patients who received a midazolam dose of 5 mg or more, 99.5 percent received a 5 mg dose, while only 0.5 percent received a dose greater than 5 mg.
Higher doses of midazolam were associated with a lower likelihood of needing rescue treatment (odds ratio) [OR]0.8; 95% CI, 0.7-0.9). There was no association between the use of higher midazolam doses and an increased need for respiratory support (OR 1.0; 95% CI 0.9-1.0). The study’s researchers found evidence to support the hypothesis that higher doses of midazolam were associated with decreased need for respiratory support in a customized analysis (OR, 0.9; 95% CI, 0.8-1.0).
Limitations of this study were the use of “incomplete” preclinical medical records and the inability to validate whether a reduced need for rescue therapy actually represents a lack of recurrence.
The study’s researchers concluded that their results indicated that “a higher starting midazolam dose, even if the dose is lower than that recommended in national guidelines, is associated with an increased rate of successful seizure termination”.
Disclosure: Several authors of the study have stated that they are part of the pharmaceutical industry. For a full list of the authors’ information, see the original reference.
Guterman EL, Sanford JK, Betjemann JP et al. Pre-hospital use and results of midazolam in patients with epilepticus out of hospital. Neurology. 2020; 95 (24): 3203-320. 3212. doi: 10.1212 / WNL.0000000000010913