First‐line infusion therapies in refractory status epilepticus: A retrospective comparison of outcomes between midazolam and propofol in 7446 patients

OBJECTIVE: Refractory status epilepticus (RSE) is a medical emergency defined as "status epilepticus persisting despite administration of at least 2 appropriately selected and dosed parenteral medications including a benzodiazepine." Control of RSE is critical to avoid irreversible neuronal damage, with midazolam and propofol as the most commonly used agents. This study evaluates the effectiveness of midazolam versus propofol in preventing mortality and complications of RSE. METHODS: Patients from the TriNetX Research Network who received either midazolam or propofol monotherapy on the day of RSE onset were included. Outcomes were assessed at 30 days and maximal follow-up (≤20 years) using Cox proportional hazard models. Propensity score matching (1:1) controlled for demographics and 93 comorbidities from the Charlson Comorbidity Index. RESULTS: Among 117 736 patients with RSE, 5310 received midazolam and 2136 received propofol. Midazolam was associated with significantly decreased hazards of mortality at 30 days (HR = 0.509 [95% CI: 0.397, 0.653]) but not at maximal follow-up (HR = 0.922 [0.797, 1.067]). Midazolam was also associated with significantly reduced hazards of lactic acidosis (HR = 0.537 [0.427, 0.674]), rhabdomyolysis (HR = 0.295 [0.150, 0.578]), hypertriglyceridemia (HR = 0.316 [0.135, 0.740]), tracheostomy (HR = 0.633 [0.438, 0.916]), PEG placement (HR = 0.519 [0.371, 0.725]), and mechanical ventilation (HR = 0.313 [0.265, 0.370]). Among patients with a traumatic brain injury in the week prior to RSE, midazolam was associated with a significantly lower hazard of 30-day mortality (HR = 0.381 [0.136, 0.993]), while the hazards were not significantly changed in patients with CNS infections (HR = 1.150 [0.351, 3.768]) or cerebrovascular disease (HR = 0.656 [0.421, 1.025]) in the week prior to RSE onset. SIGNIFICANCE: Midazolam monotherapy for RSE was associated with decreased mortality and adverse effects compared to propofol monotherapy in the short term, but relatively equivalent in the long term. Prospective comparative trials are needed to ascertain superiority of either intervention in reducing morbidity and mortality in patients with RSE.