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.

High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury. (From Pediatric Critical Care Medicine, March 2013 – Duggan)

Pediatric Critical Care Medicine. 2013 Mar;14(3):239-47. PMID: 23392360

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OBJECTIVES: To evaluate high-dose barbiturates as a second-tier therapy for pediatric refractory intracranial hypertension complicating severe traumatic brain injury.

DESIGN: This is a retrospective cohort study of children with refractory intracranial hypertension treated with high-dose barbiturates. SETTING: : A single center level I pediatric trauma from 2001 to 2010. PATIENTS: : Thirty-six children with refractory intracranial hypertension defined as intracranial pressure greater than 20 mm Hg despite standard management treated with high-dose barbiturates after severe traumatic brain injury.

INTERVENTIONS: High-dose barbiturates were administered for refractory intracranial hypertension for a minimum duration of 6 hours and monitored by continuous electroencephalography.

MEASUREMENTS AND MAIN RESULTS: Exposure was control of refractory intracranial hypertension defined as > 20 mm Hg within 6 hours after starting barbiturates. Pediatric cerebral performance category scores at hospital discharge and at 3 months (or longer) follow-up were the primary outcomes. Ten of 36 patients (28%) had control of refractory intracranial hypertension. Neither demographic nor injury characteristics were associated with refractory intracranial hypertension control. Children who responded received barbiturates significantly later after injury (76 vs. 29 median hours). Overall, 14 children died, 13 without control of intracranial pressure. Survival was more common in those who responded compared with those who did not respond to high-dose barbiturates, although this did not reach statistical significance (relative risk of death 0.2; 95% confidence interval; [0.03-1.3]). Of the 22 survivors, 19 had an acceptable survival (pediatric cerebral performance category less than 3) at 3 months or longer after injury; however, only three returned to normal function. Among survivors, control of refractory intracranial hypertension was associated with significantly better pediatric cerebral performance category scores and over two-fold likelihood of acceptable long-term outcome (relative risk 2.3; 95% confidence interval [1.4-4.0]) compared with uncontrolled refractory intracranial hypertension despite high-dose barbiturates.

CONCLUSIONS: Addition of high-dose barbiturates achieved control of refractory intracranial hypertension in almost 30% of treated children. Control of refractory intracranial hypertension was associated with increased likelihood of an acceptable long-term outcome.