Seizure treatment en route to hospital safe and effective, study shows

By Wallace Ravven

Potentially life threatening seizures can be safely treated by paramedics using
injections of Valium or similar benzodiazepine drugs en route to the hospital,
rather than waiting for hospital staff to administer the drugs, according to a
new study led by researchers at the University of California, San Francisco.

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

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 also holds posts in the Department of Surgery at UCSF and the Emergency
Medical Services Division of the San Francisco Fire Department.
The study was funded by the National Institute of Neurological Disorders and