Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital. (Emrath)

Tasker RC, et al. Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital. Pediatr Crit Care Med. 2016 Oct;17(10):968-975.

OBJECTIVE: To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control.

DESIGN: Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent.

SETTING: Nine pediatric hospitals in the United States.

PATIENTS: In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment.

MAIN RESULTS: The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four “cycles” of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies.

CONCLUSIONS: Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.

Status epilepticus: impact of therapeutic coma on outcome. (Betters)

Marchi NA, Novy J, Faouzi M, et al. Status epilepticus: impact of therapeutic coma on outcome. Crit Care Med. 2015 May;43(5):1003-9.

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OBJECTIVES: Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome.

DESIGN: Retrospective assessment of a prospectively collected cohort.

SETTING: Academic hospital.

PATIENTS: Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013.

We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma.

CONCLUSIONS: This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus.