The likelihood of brain damage is reduced if seizures are stopped quickly – preferably within 30 minutes of onset, and many paramedic units already administer benzodiazepines, bolstered by anecdotal evidence that they are effective in stopping seizures before reaching the hospital, the researches note. But benzodiazepines can cause some people to stop breathing, breathe too shallowly or can cause cardiac complications, and emergency medical vehicles lack the full range of support measures available in hospitals to respond to these events.
The new study is the first to systematically examine the benefits of early administration of modest doses of benzodiazepines by paramedics and determine if the benefits clearly outweigh potential serious side effects.
The findings are published in the August 30 issue of The New England Journal of Medicine. Lead author is Brian Alldredge, PharmD, UCSF professor of clinical pharmacy and clinical professor of neurology.
The study is based on 205 patients diagnosed with “status epilepticus,” continuous or repeated seizures lasting at least five minutes without recovery of consciousness. About half the people in the study had seizures as a result of epilepsy, and about half experienced seizures from other causes, such as alcohol abuse, adverse drug reactions, stroke or head trauma, Alldredge said.
Those who received the anti-seizure drugs in the ambulance were far more likely to be free of seizures by the time they reached the hospital than were those who remained unmedicated en route, the researchers found.
Although diazepam --also know as Valium -- is currently the drug of choice used by paramedics to treat someone with a prolonged seizure, lorazepam, a related drug also in the benzodiazepine class, was found to be at least as effective and possibly more so, the study found. While 43 percent of those given five-to-ten-milligram diazepam injections were seizure-free upon arrival at the hospital, almost 60 percent of those given comparable doses of lorazepam were free of their seizures. The differences between the two drugs, while striking, were not found to be statistically significant because of the relatively small number of people in the study. By contrast with the two drug-treated groups, only 21 percent of the unmedicated group were seizure free by the time they reached the hospital.
“This study will reassure many EMS systems that treatment with benzodizepines is both safe and effective,” Alldredge said. “It suggests too that lorazepam is likely to be a better choice than diazepam. Lorazepam is not as stable as diazepam in warm climates, so in hot areas, it might be necessary to install refrigeration units on ambulances.”
In future studies Alldredge intends to explore the effectiveness of other forms of intervention, such as increased doses of the drugs, since many of the patients were still experiencing seizures when they arrived at the hospital. He also wants to include studies of other drug delivery routes, such as intramuscular injections, which are easier to administer than intravenous injections.
Senior author on the study is Daniel H. Lowenstein, MD, dean of medical education at Harvard Medical School who was a UCSF professor of neurology when the study was undertaken.
Co- authors are Alan Gelb, MD, UCSF clinical professor of medicine and chief of the emergency services at San Francisco General Hospital Medical Center (SFGHMC); S. Marshal Isaacs, MD, UCSF associate clinical professor of medicine; and Nelda O’Neil, RN, MSN, UCSF clinical nurse, both also in SFGHMC emergency services.
Other researchers are Megan D. Corry, EMT-P, Emergency Medical Services, San Francisco Fire Department; Faith Allen, MD, staff research associate in neurology, UCSF; John M Neuhaus, PhD and Mark R. Segal, PhD, both UCSF professors of epidemiology and biostatistics; and Mildred D. Gottwald, PharmD, assistant clinical professor of pharmacy, UCSF; and SueKay Ulrich, RN, of the Carondelet Health Network in Tucson, Arizona.
Isaacs is also medical director of the Emergency Medical Services Division of the San Francisco Fire Department.
The study was funded by the National Institute of Neurological Disorders and Stroke.
Journal
New England Journal of Medicine