Dr Wolfgang MuhlhoferWolfgang Muhlhofer, MD
In a recent retrospective, observational cohort study investigators found 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.

The findings suggest that clinicians should consider the duration and depth of therapeutic coma when managing patients with refractory status epilepticus and should expose patients for the shortest time possible with an adequately deep therapeutic coma throughout the entire treatment duration.

Wolfgang Muhlhofer, MD, assistant professor at the University of Alabama School of Medicine, corresponding author, spoke with NeurologyLive in an interview, to further explain the results of this study and its clinical implications.

NeurologyLive: What are the results of this study? 

Wolfgang Muhlhofer, MD: The current management guidelines for treatment of refractory status epilepticus (RSE) are mainly based on expert opinion and suggest to intubate and maintain the patient in an artificially induced (therapeutic) coma for 24 and 48 hours. Yet to date, the duration of therapeutic coma has never been studied as an independent factor for successful treatment of RSE or its potential complications. In this retrospective, observational cohort study involving 182 patients with RSE treated with therapeutic coma we examined the association between duration of the first trial of therapeutic coma and the rate of seizure recurrence after the first weaning attempt of the anesthetic. Furthermore, we evaluated whether duration of therapeutic coma is independently associated with in-hospital complications, poor functional neurological outcome upon discharge or death.
Our study showed that prolonged duration of the first trial of therapeutic coma (27.2 versus 15.6 hours) is independently associated with an increased risk for seizure recurrence following the first weaning attempt. In fact, in this study cohort, almost half of the patients treated with therapeutic coma for longer than 35 hours had seizure recurrence, whereas 77% of the patients treated with a duration shorter than 35 hours remained seizure free after the anesthetic wean. Duration of therapeutic coma was not independently associated with poor functional neurologic outcome upon discharge, in-hospital complications or mortality. This raises the question whether prolonged duration of therapeutic coma is any better for sustained seizure control than shorter periods and whether prolonged therapeutic coma actually contributes to recurrence of seizure activity.

Was there anything you identified that was surprising or unexpected?

Interestingly we also found that higher doses of anesthetic utilized during the first trial of therapeutic coma, which typically results in a deeper therapeutic coma, was independently associated with significantly fewer in-hospital complications, shorter duration of mechanical ventilation and total length of stay. This is somewhat unexpected as most of the previous retrospective studies suggested an increased risk for in-hospital complications and an extended failure to wean from mechanical ventilation with higher doses of anesthetics. This might be in part related to the fact that our study cohort was primarily treated with propofol or midazolam rather than pentobarbital that had been more commonly used as the anesthetic of choice in older studies.  

What is the main takeaway for clinicians?

A shorter duration (<35 hours) yet deeper therapeutic coma as treatment for refractory status epilepticus might be as effective and safer than the currently recommended guideline of 24 to 48 hours. Clinicians should try to expose RSE patients to therapeutic coma for the shortest time possible while ensuring an adequate coma depth.

What recommendations do you have for future research as a result of this work?

In the future, EEG-based scores that help with prediction of seizure recurrence could be utilized to determine more patient- and etiology-specific time points for therapeutic coma, whereas quantitative analysis of the EEG signal could help the medical staff with titrating the anesthetic to an adequate coma depth. Finally, our cohort study cannot replace the longstanding need for a prospective, randomized clinical trial to determine the safest and most efficient duration of therapeutic coma and to better characterize the short- and long-term functional and cognitive outcomes in patients undergoing therapeutic coma as treatment for RSE.
Transcript edited for clarity.
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.