In a study in which Philadelphia's ethical objections forced local researchers to do their work in York County, scientists have found that an easier way to stop out-of-control seizures in an emergency worked at least as well as the more difficult recommended approach.
Researchers at 17 institutions, including the Hospital of the University of Pennsylvania and Temple University Hospital, compared giving antiseizure drugs either intravenously or intramuscularly to patients having prolonged seizures before they got to the hospital.
They found that giving a shot of midazolam (Versed) with an autoinjector was more likely to stop the seizures before arrival at the hospital than giving IV lorazepam (Ativan). Other outcome measures were similar. Both drugs are benzodiazepines, a kind of sedative.
According to the study, published Thursday in the New England Journal of Medicine, many emergency responders were already giving medicine by shots because it is faster and easier to do properly. That method, however, is off-label and had not been studied.
The new research found that 73.4 percent of patients were seizure-free when they arrived at the hospital after paramedics had given them the shots. That compared with 63 percent of patients who got the IV drug. Close to 450 patients got each treatment. In 42 cases, paramedics were unable to start the IV care.
The study involved people in "status epilepticus," in the midst of seizures that had lasted more than five minutes. Prolonged seizures can cause brain damage as well as breathing and heart problems and aspiration pneumonia, said Jill Baren, who directs emergency services for the University of Pennsylvania Health System and was in charge of Penn's part of this study.
Funding for the work was provided by the National Institutes of Health and the Department of Defense, both of which had an interest in developing treatments for seizures caused by chemical weapons. The Department of Defense supplied the autoinjectors, which are similar to EpiPens used by people who have serious allergic reactions.
Baren said Penn worked with York Hospital and its ambulance crews because Philadelphia's Department of Health, which said it feared lawsuits, would not allow emergency medical crews that work for the Fire Department to participate. Temple partnered with Narberth Ambulance, which took most of its patients to Lankenau Hospital, said Nina Gentile, an emergency physician who was Temple's lead investigator.
Baren said cities where all of the other research centers are based, including Detroit, Atlanta, New York, Baltimore and Minneapolis, allowed their paramedics to take part.
Penn had 30 patients in the study, which began in 2009, and Temple had eight. Gentile said Temple likely would have had many more if the city had cooperated. "Seizure is one of our more common neurological emergencies," she said.
The ethical dilemma stems from the fact that patients who are having such seizures cannot give informed consent to participate in a clinical trial. In situations like this, the government allows Institutional Review Boards (IRBs), groups that oversee research, to make exceptions to the consent rules. That makes it possible to investigate ways to improve care for patients in life-threatening situations.
The process requires consultation with community leaders. Baren said talks with seizure patients, their families, and Fire Department leaders went well, but researchers could not convince the Health Department's IRB after two years of negotiations. It had veto power because city employees would be involved.
Jeff Moran, a Health Department spokesman, said the IRB was "uncomfortable that the study required exemption from informed consent." He said the city's Risk Management Unit recommended against the study because of liability issues and the Law Department also recommended against approval.
Gentile described the study as one that had the "direct potential for benefit" for many patients and "very low risk for harm."
Baren said there had been no threats of suits in the study so far. "It was unfounded, the whole issue of legal retribution," she said.
Baren said Philadelphia residents would benefit from studies that bring more refined science to the first phases of treatment of trauma, septic shock, severe blood loss, stroke, heart attacks, and other medical emergencies. The government exception to informed consent rules, she said, was created to make such research possible.
Paramedics in York were very enthusiastic about participating in "cutting edge" research, Baren said. "I just think that it was sad that the medics here couldn't do that."