Impact of timing of continuous intravenous anesthetic drug treatment on outcome in refractory status epilepticus

Abstract

Background: Patients in refractory status epilepticus (RSE) may require treatment with continuous intravenous anesthetic drugs (cIVADs) for seizure control. The use of cIVADs, however, was recently associated with poor outcome in status epilepticus (SE), raising the question of whether cIVAD therapy should be delayed for attempts to halt seizures with repeated non-anesthetic antiepileptic drugs. In this study, we aimed to determine the impact of differences in therapeutic approaches on RSE outcome using timing of cIVAD therapy as a surrogate for treatment aggressiveness.

Methods: This was a retrospective cohort study over 14 years (n = 77) comparing patients with RSE treated with cIVADs within and after 48 h after RSE onset, and functional status at last follow-up was the primary outcome (good = return to premorbid baseline or modified Rankin Scale score of less than 3). Secondary outcomes included discharge functional status, in-hospital mortality, RSE termination, induction of burst suppression, use of thiopental, duration of RSE after initiation of cIVADs, duration of mechanical ventilation, and occurrence of super-refractory SE. Analysis was performed on the total cohort and on subgroups defined by RSE severity according to the Status Epilepticus Severity Score (STESS) and by the variables contained therein.

Results: Fifty-three (68.8%) patients received cIVADs within the first 48 h. Early cIVAD treatment was independently associated with good outcome (adjusted risk ratio [aRR] 3.175, 95% confidence interval [CI] 1.273-7.918; P = 0.013) as well as lower chance of both induction of burst suppression (aRR 0.661, 95% CI 0.507-0.861; P = 0.002) and use of thiopental (aRR 0.446, 95% CI 0.205-0.874; P = 0.043). RSE duration after cIVAD initiation was shorter in the early cIVAD cohort (hazard ratio 1.796, 95% CI 1.047-3.081; P = 0.033). Timing of cIVAD use did not impact the remaining secondary outcomes. Subgroup analysis revealed early cIVAD impact on the primary outcome to be driven by patients with STESS of less than 3.

Conclusions: Patients with RSE treated with cIVADs may benefit from early initiation of such therapy.

Keywords: Anesthetics; Continuous intravenous anesthetic drugs; Outcome; Refractory status epilepticus; Status Epilepticus Severity Score.

Fig. 1

Flowchart of study cohort. In total, 569 episodes were treated for status epilepticus (SE) in our institution between January 2001 and January 2015. Among those, 159 satisfied the criteria of refractory SE. In 83 episodes, patients received treatment with continuous intravenous anesthetic drugs (cIVADs). Seven recurrent episodes were excluded, leaving 77 patients for final analysis, of whom 53 received early cIVADs and 24 received late cIVADs. Primary and secondary study outcomes are depicted. Abbreviations: cIVAD continuous intravenous anesthetic drug, RSE refractory status epilepticus, SE status epilepticus, SRSE super-refractory status epilepticus

Fig. 2

Kaplan–Meier curves for a duration of mechanical ventilation and b duration of status epilepticus after initiation of continuous intravenous anesthetic drugs. Censored cases are depicted by plus (+) marks along the curves. Abbreviations: CI confidence interval, cIVAD continuous intravenous anesthetic drug, HR hazard ratio, RSE refractory status epilepticus

Fig. 3

Poisson regression was used to compare the influence of early continuous intravenous anesthetic drug (cIVAD) therapy in subgroups defined by overall STESS as well as variables included in the STESS. *Risk ratios (RRs) were adjusted for STESS (as a continuous variable) and a potentially fatal etiology. In the subgroups of patients with non-convulsive status epilepticus (NCSE) in coma, one outcome had zero observations and therefore adjusted RRs could not be calculated. Abbreviations: CI confidence interval, cIVAD continuous intravenous anesthetic drug, CPSE complex partial status epilepticus, GCSE generalized convulsive status epilepticus, STESS Status Epilepticus Severity Score