How much refractory is ‘refractory status epilepticus’? A retrospective study of treatment strategies and clinical outcomes

Background and purpose: This study aimed to evaluate whether differences in clinical outcomes exist according to treatments received and seizure activity resolution in patients with refractory status epilepticus (RSE). Methods: Consecutive episodes of non-hypoxic status epilepticus (SE) in patients ≥ 14 years old were included. Episodes of RSE were stratified in: (i) SE persistent despite treatment with first‐line therapy with benzodiazepines and one second‐line treatment with antiseizure medications (ASMs), but responsive to successive treatments with ASMs (RSE-rASMs); (ii) SE persistent despite treatment with first‐line therapy with benzodiazepines and successive treatment with one or more second-line ASMs, but responsive to anesthetic drugs [RSE-rGA (general anesthesia)]. Study endpoints were mortality during hospitalization and worsening of modified Rankin Scale (mRS) at discharge. Results: Status epilepticus was responsive in 298 (54.1%), RSE-rASMs in 152 (27.6%), RSE-rGA in 46 (8.3%), and super-refractory (SRSE) in 55 (10.0%) out of 551 included cases. Death during hospitalization occurred in 98 (17.8%) and worsening of mRS at discharge in 287 (52.1%) cases. Multivariable analyses revealed increased odds of in-hospital mortality with RSE-rGA (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.27–7.35) and SRSE (OR 3.83, 95%. CI 1.73–8.47), and increased odds of worsening of mRS with RSE-rASMs (OR 2.06, 95% CI 1.28–3.31), RSE-rGA (OR 4.44, 95% CI 1.97–10.00), and SRSE (OR 13.81, 95% CI 5.34–35.67). Conclusions: In RSE, varying degrees of refractoriness may be defined and suit better the continuum spectrum of disease severity and the heterogeneity of SE burden and prognosis.