A closer look at therapeutic coma for refractory status epilepticus

As many as 30%-40% of status epilepticus cases fail to respond to the standard treatment of antiepileptic medications and benzodiazepines. As a result, up to 44% of cases can progress to refractory status epilepticus (RSE), the second most common neurological emergency in the US, and require more extreme treatments be employed, such as medically induced coma, or “therapeutic coma.”

“These emergencies require prompt and effective treatment. The longer status epilepticus is going on, the higher the chances of brain damage or the body’s being unable to compensate for the trauma, leading to other complications like cardiac arrest or kidney or heart failure. There’s a lot of risk associated with this condition,” said Wolfgang Muhlhofer, MD, assistant professor of neurology, University of Alabama at Birmingham Epilepsy Center, Birmingham, Alabama.

“The idea is to hit the reboot button on the brain, sedating the brain to a stage where there is no seizure activity and the patient is in a deep coma,” he added. “Let the brain get some rest and have some time to reorganize itself.”

Although experts agree that therapeutic coma is the proper treatment forRSE, it has yet to be elucidated how long patients should be kept in this state. Importantly, the longer a patient is maintained in a therapeutic coma, the higher the risk of complications.

Dr. Muhlhofer specifically researches RSE and plans to conduct a randomized clinical trial that examines this condition in a more systematic fashion. The trial will assess different durations of therapeutic coma, as well as seizure control and other health outcomes. The hope is that these efforts will contribute evidence-based data that guide the length of medically induced coma in patients with RSE.

In particular, he’s interested in complications of medically induced coma, including urinary tract infections, iatrogenic pneumonia, pulmonary and embolism, and stroke. He is also interested in examining whether patients placed in such comas are discharged with disability.

“Do patients slip back into seizing the moment you take away the medications? The second question is whether there are issues during the hospital stay. Are there any complications right after their discharge? Up to a year after?” queried Dr. Muhlhofer. He has already performed a preliminary analysis involving 42 patients from the University of California, San Francisco, plus an additional 100 patients from the University of Alabama at Birmingham (UAB).

At UAB, the investigator have harnessed the power of i2b2 (Informatics for Integrating Biology and the Bedside), a National Institutes of Health-funded National Center for Biomedical Computing based within Partners HealthCare. i2b2 was developed as a scalable informatics framework designed for translational research. This novel application allows UAB researchers to access de-identified patient data, to double their current sample size and help formulate preliminary analysis. Moreover, Dr. Muhlhofer has used i2b2 to gauge sample sizes needed for future investigations.

“I think it’s a very intuitive way of using different filters and criteria to narrow down a patient population, especially for creating preliminary data sets for applications. It’s an excellent tool, and they’re also continuously developing it, improving it and making it more user-friendly, trying to simplify it and make it more intuitive. I think i2b2 will continue to be a very beneficial tool,” said Dr. Muhlhofer. “Hopefully this is the springboard to something bigger, and to clarifying questions on a topic that’s very controversial in the field right now,” he reflected.

With this research, investigators are looking to help solidify clinical standards for what the best treatment plans for RSE patients are.