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Hypothermia for Neuroprotection in Convulsive Status Epilepticus
Hypothermia for Neuroprotection in Convulsive Status Epilepticus
Legriel S, Lemiale V, Schenck M, et al. N Engl J Med. 2016;375:2457-2467.
Study Question: Does therapeutic hypothermia (TH) increase the chance of a favorable neurologic outcome compared to standard care in status epilepticus?
Study Description: This multicenter, open-label, parallel-group, randomized controlled trial included 268 patients in French ICUs with convulsive status epilepticus (> 5 minutes of seizure activity or > 2 seizures without return to baseline), admitted for < 8 hours and mechanically ventilated. In the hypothermia group, patients were lowered to a core body temperature of 32 to 34°C as quickly as possible and were maintained at this target temperature for 24 hours. The primary outcome was proportion of patients with Glasgow Outcome Scale (GOS) of 5 (minimal to no neurologic deficit).
Results: Patient populations were similar between the TH (n = 138) and control (n = 130) groups, with a rate of refractory status epilepticus of 23% in the TH group and 27% in the control group. The primary outcome of favorable neurologic outcome was not significant, with 49% of patients in the TH group and 43% of patients in the control group achieving a GOS = 5 (OR 1.22, 95% CI 0.75-1.99, p = 0.43).
Conclusion(s): Therapeutic hypothermia does not lead to improved neurologic outcomes in patients with status epilepticus.
Perspective: Listed in the 2012 Neurocritical Care guidelines for status epilepticus as an “emerging therapy”, data linking its use to improved outcomes has been lacking. This was the first major, well-designed trial to compare TH to standard care in this patient population. It did not demonstrate a significant change in any outcome measure other than the incidence of progression to EEG-confirmed status epilepticus. This study had multiple limitations, including a lack of standardization of patient care outside of the TH protocol, low enrollment of patients with refractory status epilepticus, a strict definition of good outcome and dichotomization of an ordinal variable (GOS). Based on this study, therapeutic hypothermia should not be routinely used in status epilepticus. Further studies are needed to determine if a sub-population in status epilepticus may benefit.