Refractory Status Epilepticus: Risk Factors and Analysis of Intubation in the Multicenter SENSE Registry

Abstract

Background and objectives: Refractory status epilepticus (RSE) bears significant morbidity and mortality. Therapy escalation and in some cases intubation are recommended. Most existing studies are retrospective and focus on intensive care units. We aimed to describe routine-care management and analyze determinants of RSE development and outcomes in a large multicenter cohort.

Methods: We performed post hoc analysis of an observational, cohort study, which prospectively registered all consecutive adults with SE at 9 centers from 3 central European countries. Only incident episodes were included. Ongoing SE despite 2 antiseizure medications was defined as RSE. Patients intubated during first-line or second-line treatments were excluded. Variables investigated included demographics, severity (Status Epilepticus Severity Score), etiology, and guideline-compliant treatment (defined as fixed minimum doses). Outcome parameters included survival and mRS at baseline, and discharge (good: 0-2, or absence of worsening compared with prehospitalization).

Results: Among 1,179 SE episodes from 1,049 adults, 996 patients were eligible (median age: 70 years, 52% female), of which 545 (54.7%) developed RSE. RSE was associated with higher baseline mRS (p < 0.001) and treatment deviation from guidelines (p < 0.001, OR 0.09; 95% CI 0.06-0.1). Good outcomes were observed in 52.7% of refractory patients, correlating with lower status epilepticus severity (p < 0.001), absence of acute etiology (p < 0.001, OR 0.5; 95% CI 0.3-0.7), adequate first-line benzodiazepine dose (p < 0.001, OR 2.5; 95% CI 1.6-4.0), shorter durations of SE and hospitalization (both p < 0.001), and lack of intubation (p < 0.001, OR 0.4; 95% CI 0.3-0.6). Most (71.7%) refractory patients were not intubated. Intubation was associated with younger age (p = 0.006), more severe consciousness disturbances (p < 0.001, OR 3.2; 95% CI 2.1-4.8), more severe SE types (p < 0.001), higher severity score (p = 0.009), acute etiologies (p = 0.01, OR 1.6; 95% CI 1.1-2.4), more antiseizure medications (p < 0.001), initial treatment after shorter latency (p = 0.01), worse outcomes (p < 0.001, OR 0.4; 95% CI 0.4-0.6), and longer hospitalizations (p < 0.001).

Discussion: Variables associated with RSE were identified, some potentially preventable. More than 70% of RSE were treated without intubation, suggesting that focal RSE without deep impairment of consciousness, in older patients, may be successfully treated outside ICUs.

Trial registration information: Original cohort study registered at the German Clinical Trials Register (DRKS00000725).