Authors :
Presenting Author: Isaac Thorman, ScM – NYMC
Patricia McGoldrick, NP, MPA, MSN, FAES – Boston Children's Health Physicians; Westchester Medical Center Health Network
Ariel Sacknovitz, MS – New York Medical College
Steven M Wolf, MD – Westchester Medical Center, Hawthorne, NY, United States
Carrie Muh, MD – Maria Fareri Children’s Hospital and Westchester Medical Center
Stephan Mayer, MD – Westchester Medical Center
Michael Schubert, PhD – NYMC
Richard Wang, BS – New York Medical College
Rationale: Refractory status epilepticus (RSE) is a medical emergency defined as “status epilepticus persisting despite administration of at least two appropriately selected and dosed parenteral medications, including a benzodiazepine.” Control of RSE is critical to avoid irreversible neuronal damage, with midazolam and propofol the most commonly used agents. This study evaluates the effectiveness of midazolam compared to propofol in preventing mortality and complications of RSE.
Methods: All 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. Patients were censured at the end of their medical record. Propensity score matching (1:1) controlled for demographics and 93 comorbidities from the Charlson Comorbidity Index.
Results:
Among 117,736 patients with RSE, 5,310 received midazolam and 2,136 received propofol. After matching, 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]). Midazolam was associated with a significant decrease in the hazard of 30-day mortality in RSE in patients with focal/partial symptomatic epilepsy with complex/partial seizures (HR=0.550 [0.378, 0.799]). However, midazolam was not associated with significantly changed hazards of 30-day mortality in RSE in focal/partial idiopathic epilepsy with localized onset (HR=0.142 [0.018, 1.157)], focal/partial symptomatic epilepsy with simple/partial seizures (HR=0.690 [0.378, 1.258]), general idiopathic epilepsy (HR=0.582 [0.275, 1.232]), and other generalized epilepsy (HR=0.757 [0.434, 1.287]). Among patients with a traumatic brain injury in the week prior to RSE onset, 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.
Conclusions:
: Midazolam monotherapy for RSE was associated with decreased mortality and adverse effects compared to propofol monotherapy in the short term, but was relatively equivalent in the long term. These findings support the 2012 Neurocritical Care Society Guidelines, which recommend midazolam over propofol as treatment for RSE. Prospective comparative trials are needed to ascertain the superiority of either intervention in reducing morbidity and mortality in patients with RSE.
Funding:
This research received no funding from any agencies in the public, commercial, or not-for-profit sectors.