February 16, 2012
Auto-injectors Could Help Treat Prolonged Seizures
New research, published in the New England Journal of Medicine, finds that when a person is experiencing a prolonged seizure, quick medical intervention is critical, becoming harder to stop the seizure with each passing minute, placing the patient at risk of severe brain damage and death.
It is for this reason that paramedics are trained to administer anticonvulsive medications as soon as possible -- typically giving them intravenously before arriving at the hospital.
But according to findings in the new study, a major clinical trial has shown that using an auto-injector (similar to an EpiPen) to inject drugs into the thigh is just as safe and may be more effective.
The new research was conducted as part of the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), which included researchers from the University of Cincinnati and local paramedics studying status epilepticus (prolonged seizure lasting more than five minutes). The study was sponsored by the National Institutes of Health.
The researchers wanted to determine whether intramuscular injection was as safe and effective as giving medicine intravenously. The study compared how well delivery by each method stopped patients´ seizures by the time the ambulance arrived at the ER.
The trial involved 17 cities and 79 hospitals around the country, and involved 4,314 paramedics who treated 893 patients ranging from several months old to 103 between 2009 and 2011.
The researchers compared two medicines that are effective in controlling seizures: midazolam and lorazepam. Both are benzodiazepines, a class of sedating anticonvulsant drugs. Midazolam was a candidate for injection because it is rapidly absorbed from muscle. But lorazepam must be given by IV.
The study team found that 73 percent of patients in the midazolam group were seizure-free upon arrival at the hospital, compared to 63 percent of those who received the IV treatment. Patients also treated with midazolam were also less likely to require hospitalization than those receiving the lorazepam IV.
“Patients with status epilepticus can suffer severe consequences if seizures are not stopped quickly. This study establishes that rapid intramuscular injection of an anticonvulsant drug is safe and effective,” said Walter Koroshetz, MD, deputy director of the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH, which funded the study.
“This project is a great example of the importance of community-based emergency research and the combined strength of a city´s entire health care system, when we all work together,” said J. Claude Hemphill III, MD, MAS, who led the San Francisco part of the clinical trial. Hemphill is Chief of Neurology at SFGH and co-director of the UCSF Brain & Spinal Injury Center.
“It´s much easier to give intramuscular injections than have to start an IV,” said Hemphill. “Given the results of RAMPART, it is time for every emergency medical system in the United States to move toward intramuscular injection of midazolam as a first treatment to stop seizures in the pre-hospital setting.”
And auto-injectors may someday be available for use by epilepsy patients and their family members, but more research is currently needed, said the researchers. Because of the strong sedative effect of midazolam, on-site medical supervision is required for safety of the patient.
The RAMPART study was a unique form of clinical trial, eligible under the US Food and Drug Administration (FDA) requirement of “exception from informed consent.” The federal regulation was created to protect patients who are involved in research when consent is not possible because of their medical condition. RAMPART researchers held community consultation meetings prior to the study launch to get feedback.
AS investigators planned the trial, they learned that the US Defense Department and the Dept. of Health and Human Services were already working with a midazolam auto-injector and the study was an opportunity to confirm its effectiveness in patients with seizures.
“There was great synergy when we realized that RAMPART was studying a similar problem that was of concern to the chemical defense community. This led to a perfect collaboration between HHS and DoD,” said David Jett, PhD, program director for NIH CounterACT and NINDS. “The broader implication of RAMPART is that we now have critical information from studies in humans that a safe and effective tool may one day be available to enhance our public health preparedness. Auto-injectors provide a highly practical way to treat hundreds of people quickly during an emergency.”
“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 Robert Silbergleit, MD, of the University of Michigan in Ann Arbor, lead author of the paper.
“The use of the auto-injectors could further improve the excellent care our paramedics provide to their patients every day,” said Jason McMullan, MD, RAMPART co-investigator and assistant professor of clinical emergency medicine at UC. “While the auto-injectors are not yet commercially availability, this trial provides an opportunity to change the way that paramedics everywhere deliver time critical treatment for status epilepticus and improve the potential outcomes for our patients.”
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