Association Between Dose Escalation of Anesthetics and Outcomes in Patients With Refractory Status Epilepticus.

BACKGROUND AND OBJECTIVES: To investigate the association between dose escalation of continuously administered IV anesthetics and its duration with short-term outcomes in adult patients treated for refractory status epilepticus (RSE). METHODS: Clinical and electroencephalographic data of patients with RSE without hypoxic-ischemic encephalopathy who were treated with anesthetics at a Swiss academic medical center from 2011 to 2019 were assessed. The frequency of anesthetic dose escalation (i.e., dose increase) and its associations with in-hospital death or return to premorbid neurologic function were primary endpoints. Multivariable logistic regression analysis was performed to identify associations with endpoints. RESULTS: Among 111 patients with RSE, doses of anesthetics were escalated in 57%. Despite patients with dose escalation having a higher morbidity (lower Glasgow Coma Scale [GCS] score at status epilepticus [SE] onset, more presumably fatal etiologies, longer duration of SE and intensive care, more infections, and arterial hypotension) as compared with patients without, the primary endpoints did not differ between these groups in univariable analyses. Multivariable analyses revealed decreased odds for death with dose escalation (odds ratio 0.09, 95% CI 0.01-0.86), independent of initial GCS score, presumably fatal etiology, SE severity score, SE duration, and nonconvulsive SE with coma, with similar functional outcome among survivors compared with patients without dose escalation. DISCUSSION: Our study reveals that anesthetic dose escalation in adult patients with RSE is associated with decreased odds for death without increasing the proportion of surviving patients with worse neurofunctional state than before RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anesthetic dose escalation decreases the odds of death in patients with RSE.

Association Between Induced Burst Suppression and Clinical Outcomes in Patients With Refractory Status Epilepticus: A 9-Year Cohort Study.

BACKGROUND AND OBJECTIVES: To investigate the frequency of induced EEG burst suppression pattern during continuous IV anesthesia (IVAD) and associated outcomes in adult patients treated for refractory status epilepticus (RSE). METHODS: Patients with RSE treated with anesthetics at a Swiss academic care center from 2011 to 2019 were included. Clinical data and semiquantitative EEG analyses were assessed. Burst suppression was categorized as incomplete burst suppression (with ≥20% and <50% suppression proportion) or complete burst suppression (with ≥50% suppression proportion). The frequency of induced burst suppression and association of burst suppression with outcomes (persistent seizure termination, in-hospital survival, and return to premorbid neurologic function) were the endpoints. RESULTS: We identified 147 patients with RSE treated with IVAD. Among 102 patients without cerebral anoxia, incomplete burst suppression was achieved in 14 (14%) with a median of 23 hours (interquartile range [IQR] 1-29) and complete burst suppression was achieved in 21 (21%) with a median of 51 hours (IQR 16-104). Age, Charlson comorbidity index, RSE with motor symptoms, the Status Epilepticus Severity Score and arterial hypotension requiring vasopressors were identified as potential confounders in univariable comparisons between patients with and without any burst suppression. Multivariable analyses revealed no associations between any burst suppression and the predefined endpoints. However, among 45 patients with cerebral anoxia, induced burst suppression was associated with persistent seizure termination (72% without vs 29% with burst suppression, p = 0.004) and survival (50% vs 14% p = 0.005). DISCUSSION: In adult patients with RSE treated with IVAD, burst suppression with ≥50% suppression proportion was achieved in every fifth patient and not associated with persistent seizure termination, in-hospital survival, or return to premorbid neurologic function.

Balancing the risks and benefits of anesthetics in status epilepticus.

PURPOSE: According to international guidelines, status epilepticus refractory to first- and second-line antiseizure medication should be treated with anesthetics. Therefore, continuously delivered intravenous midazolam, propofol, or barbiturates are recommended as third-line therapy. While electroencephalographically (EEG)-controlled titration of anesthetics to seizure termination or to the emergence of an EEG burst-suppression pattern makes sense, evidence of the efficacy and tolerability of such third-line treatment is limited and concerns regarding the risks of anesthesia remain. The lack of treatment alternatives and persistent international discord reflecting contradictory results from some studies leave clinicians on their own when deciding to escalate treatment. In this conference-accompanying narrative review, we highlight the challenges of EEG-monitored third-line treatment and discuss recent studies that examined earlier administration of anesthetics. RESULTS: Based on the literature, maintaining continuous burst suppression is difficult despite the constant administration of anesthetics, and the evidence for burst suppression as an adequate surrogate target is limited by methodological shortcomings as acknowledged by international guidelines. In our Swiss cohort including 102 patients with refractory status epilepticus, burst suppression as defined by the American Clinical Neurophysiology Society's Critical Care EEG Terminology 2021 was established in only 21%. Besides case reports suggesting that rapid but short-termed anesthesia can be sufficient to permanently stop seizures, a study including 205 patients revealed that anesthesia as second-line treatment was associated with a shorter median duration of status epilepticus (0.5 versus 12.5 days, p < 0.001), median ICU (2 versus 5.5 days, p < 0.001) and hospital stay (8 versus 17 days, p < 0.001) with equal rates of complications when compared to anesthesia as third-line treatment. CONCLUSIONS: Recent investigations have led to important findings and new insights regarding the use of anesthetics in refractory status epilepticus. However, numerous methodological limitations and remaining questions need to be considered when it comes to the translation into clinical practice, and, in consequence, call for prospective randomized studies. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.