Phenobarbital in super‐refractory status epilepticus (<scp>PIRATE</scp>): A retrospective, multicenter analysis
Stefan Kunst, Mikel Rojo, Moritz L. Schmidbauer, Johann Pelz, Annekatrin Mueller, Jens Minnerup, Lennart Meyer, Dominik Madžar, Caroline Reindl, Marie Madlener, Michael P. Malter, Bernhard Neumann, Konstantinos Dimitriadis, for the IGNITE Study Group
Abstract
OBJECTIVE: Super-refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE. METHODS: This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model. RESULTS: Ninety-one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per μg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0-1.2, p < .01). The median length of treatment in the NICU was 33.7 [23.2-56.6] days across groups. Clinical complications occurred in 89% (n = 81) of patients and included ICU-acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in-hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In-hospital mortality was significantly higher in patients in whom seizure control could not be achieved. SIGNIFICANCE: We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long-term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value.