Shorter Therapeutic Coma in Refractory Status Epilepticus May Be Safer, More Effective

Wolfgang Muhlhofer, MD, Assistant Professor UAB School of Medicine

Wolfgang Muhlhofer, MD

In a recent retrospective, observational cohort study, investigators concluded that a shorter, yet deeper therapeutic coma may be safer and more effective than the currently recommended therapeutic coma duration of 24 to 48 hours for refractory status epilepticus.

Researchers sought to examine the association between the duration of therapeutic coma and various outcomes like seizure recurrence, morbidity, and mortality in refractory status epilepticus and utilized clinical data to suggest an efficient and safe timeframe for the duration of therapeutic coma as treatment.

“Our study suggests that an initial trial of therapeutic coma with a duration of greater than 35 hours can be associated with an increased risk for seizure recurrence following the anesthetic wean. This cutoff lies within the currently recommended time window of 24-48 hours,” Wolfgang Muhlhofer, MD, assistant professor at the University of Alabama School of Medicine, and colleagues wrote.¹ “Furthermore, our study suggests that higher doses of anesthetic (ie, deeper therapeutic coma) are not only safe to use but also associated with fewer in-hospital complications and shorter duration of ventilation and total length of stay. Our findings suggest that clinicians should consider the duration and depth of therapeutic coma when managing patients with refractory status epilepticus and should try to expose the patient for the shortest time possible with an adequately deep therapeutic coma throughout the entire duration of treatment.”

The study included 182 adults who presented with refractory status epilepticus to the University of Alabama at Birmingham or the University of California at San Francisco Medical Center from 2010 to 2016. Study participants had to have failed treatment with at least 1 benzodiazepine and 1 intravenous antiseizure drug prior to intubation and treatment with either monotherapy or combination therapy of propofol, midazolam, pentobarbital, or ketamine. There were no major differences in baseline demographics, preadmission health status, and preadmission functional status between those with and without seizure recurrence; additionally, there were also no differences in underlying etiology, clinical details, initial treatment approach, and severity of refractory status epileptics defined by Status Epilepticus Severity Score (STESS) and Epidemiology-Based Mortality Score for Status Epilepticus (EMSE) scores. Investigators defined therapeutic coma as the time frame, in hours, from time point T₁ to T₂.

The primary outcome included the recurrence of seizure activity either on EEG or clinical presentation within 48 hours of initiation of anesthetic taper, while secondary outcomes focused on mortality and morbidity associated with the admission for treatment.

The study group with seizure recurrence was treated for a longer period during the first attempt of therapeutic coma than the nonrecurrence group (27.2 vs. 15.6 hours, P = .02). The duration of therapeutic coma was greatly associated with an increased number of in-hospital complications (P = .0002), showing a slight association with worse functional neurologic outcomes when discharged (P = .06). There was no substantial significant association between the duration of the first trial of therapeutic coma and mortality (P = .32). The duration of therapeutic coma was identified as an independent predictor of seizure recurrence with an optimal cutoff time at 35 hours. Higher doses of anesthetic use during the first trial of therapeutic coma were independently associated with fewer in-hospital complications (P = .003) and with a shorter duration of mechanical ventilation and total length of stay.¹

“Furthermore, a deeper coma appears to be an important factor for a decrease rate of in-hospital complications, shorter duration of ventilation, and total length of stay, but an association between coma depth and sustained seizure control after the first trial of therapeutic coma could not be established,” the investigators added.

The investigators recommend that clinicians try and expose this patient population to therapeutic coma for the shortest time possible, all while ensuring an adequate depth of coma.

This cohort study, according to investigators, cannot replace the need for a randomized clinical trial that will determine the safest and most efficient duration of therapeutic coma and will better characterize the short- and long-term functional and cognitive outcomes in those undergoing therapeutic coma as a treatment for refractory status epilepticus.

“Our findings suggest that clinicians should consider the duration and depth of therapeutic coma when managing patients with refractory status epilepticus and should try to expose the patient for the shortest time possible with an adequately deep therapeutic coma throughout the entire duration of treatment,” investigators concluded. “This retrospective analysis of the association between duration of therapeutic coma and seizure recurrence, mortality, and morbidity in patients with refractory status epilepticus treated with anesthetics (mainly propofol and midazolam) suggests that prolonged duration of therapeutic coma (>35 hours) was associated with increased risk for withdrawal seizures, prolonged length of hospital stay, and days spent on ventilation.”

REFERENCE

Muhlhofer WG, Layfield S, Lowenstein D, et al. Duration of therapeutic coma and outcome of refractory status epilepticus. Epilepsia. 2019;1—14. doi:10.1111/epi.14706.