News UMCB Physician Contributes to Seizure Study in New England Journal

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University Medical Center Brackenridge emergency physician Dr. T.J. Milling was a leader in a study group publishing a research paper that validates an easier, faster and more reliable treatment to stop seizures in patients transported by ambulance to hospital emergency rooms.

The study was selected to be published Feb. 16 in The New England Journal of Medicine, one of the world's top medical publications.

Of the 893 patients participating in this national study, about 10 percent were Central Texans.


"This was an important study that will greatly improve care for patients with seizures. But more importantly, it really showcased what Austin is capable of in biomedical research. The support we received from our world class EMS (emergency medical services) system, City Council, Commissioners Court and many other corners was amazing. Clinical research and academic medicine really is Austin's next big thing," said Dr. Milling, a leader in increasing medical research being conducted at UMC Brackenridge and elsewhere within Seton Healthcare Family.

Status epilepticus, a prolonged seizure lasting longer than five minutes, is life-threatening emergency, causing 55,000 deaths annually in the U.S. Delivering medication to stop it as soon as possible can save lives, keep patients from being hospitalized and improve patient outcomes.

Dr. Milling helped lead a study called RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial), which was led by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH). Between 2009 and mid-2011, RAMPART involved more than 79 hospitals, 33 EMS agencies, more than 4,000 paramedics and patients ranging in age from several months to 103 years old. The network of investigators that designed and carried out the trial was established by NINDS to conduct clinical trials on a variety of acute conditions affecting the brain, such as stroke and traumatic brain injury.


Currently, an effective anticonvulsant medicine called lorazepam is delivered intravenously to halt seizures in patients being transported by ambulance to hospitals. RAMPART compared it to an intramuscular injection of another effective anticonvulsant medicine, called midazolam. Midazolam can be rapidly absorbed from muscle, but lorazepam must be given by IV. A midazolam injection into the thigh muscle is easier for a paramedic to deliver than lorazepam via IV when a patient is in the throes of a seizure in a moving ambulance.

The study - the first of its kind - compared how well delivery by each method stopped patients' seizures by the time ambulances arrived at hospital ERs. The results show that 73 percent of patients in the midazolam injection group were seizure-free upon arrival at the hospital, compared to 63 percent of patients medicated via IV by lorazepam.

"This study establishes that rapid intramuscular injection of an anticonvulsant drug is safe and effective," said Dr. Walter Koroshetz, NINDS deputy director.

Paramedics in RAMPART used study boxes with a time-stamped voice recorder, designed by NINDS' Neurological Emergencies Treatment Trials (NETT) network. This tool allowed paramedics to make quick decisions, indicate the time treatment began and the time each patient's convulsions stopped, all without having to interrupt patient care to record data. The goal was to control seizures within 10 minutes without having to deliver a second dose of medicine. Prolonged status epilepticus can last for hours and sometimes is controlled only with general anesthesia.

"The City of Austin/Travis County EMS System was pleased to collaborate with local hospitals on the RAMPART study. Our active participation in this study allowed our EMS providers to contribute to the body of science associated with pre-hospital medicine. Most importantly, this type of clinical research allows us to use an evidence-based approach to define effective treatments for patients with potentially life-threatening conditions," said Dr. Paul R. Hinchey, medical director, City of Austin/Travis County EMS System.

"Few other areas of medicine are as time-dependent as injury to the brain. In epilepsy, even a few minutes can be important. With every minute the seizure continues, it becomes harder to stop. RAMPART offers first responders an important treatment tool that will have a meaningful impact on the lives of many people with epilepsy," said Dr. Robert Silbergleit of the University of Michigan in Ann Arbor and first author of the New England Journal paper.

RAMPART was conducted through the NINDS' NETT network and was managed in Central Texas by Hospital Physicians in Clinical Research, PLLC (HPCR), the research arm of a large, multi-specialty physician group focused on emergency and critical care. HPCR works closely with the Seton Healthcare Family.

Additional funding was provided by the NIH Countermeasures Against Chemical Threats (NIH CounterACT) program and the Biomedical Advanced Research and Development Authority (BARDA). The Department of Defense's Chemical Biological Medical Systems (CBMS) Joint Project Management Office provided the midazolam autoinjectors for the trial under a Memorandum of Agreement with NINDS.

NIH CounterACT, BARDA and CBMS are responsible for enhancing the U.S. government's development of medical countermeasures to natural and intentional public health threats. The chemical defense community has a longstanding interest in research on the rapid treatment of nerve agent-induced seizures.

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