(PHILADELPHIA) -- Injecting epilepsy patients with medication via an autoinjector -- similar to the EpiPens used to treat serious allergic reactions -- works more quickly to stop seizures than delivery of a drug via IV on board ambulances, according to a national study published today in the New England Journal of Medicine. Results of the trial, which included investigators from the Perelman School of Medicine at the University of Pennsylvania, also indicates that patients who receive the autoinjection are less likely to require hospitalization after treatment in emergency rooms.
The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) study provides a roadmap for improving and speeding treatment of status epilepticus -- severe seizure activity -- which causes 55,000 deaths each year.
"Status epilepticus is a life-threatening neurological emergency that requires immediate treatment, even before patients reach the hospital. With every minute the seizure continues, it becomes harder to stop, increasing the possibility of brain damage," said Jill Baren, MD, MBE, chair of the department of Emergency Medicine and principal investigator for the greater Philadelphia-Southern New Jersey Neurological Treatment Trials Network, which includes the community of York, PA, where the local portion of the study was performed. "This study establishes that rapid intramuscular injection of an anticonvulsant drug is safe and effective, and we believe this technique will ensure quicker, safer treatment of seizures by paramedics."
Starting an IV in a patient experiencing seizures can pose a challenge for paramedics -- as often as 20 percent of the time, first responders are unable to gain IV access, wasting precious minutes. Giving an intramuscular shot is easier, faster, and more reliable, especially in children, whose small bodies may make it even more difficult to obtain intravenous access. The study, which was carried out by paramedics for 33 EMS agencies across the country, compared how well two methods of drug delivery stopped patients' seizures by the time the ambulance arrived at the emergency department. The researchers found that 73 percent of patients who received an autoinjection of the anticonvulsant medication midazolam (also known as Versed) into their thigh muscle were seizure-free upon arrival at the hospital, compared to 63 percent of patients who received IV treatment with lorazepam (also known as Ativan). Patients treated with midazolam were also less likely to require hospitalization than those receiving IV lorazepam. Among those admitted, both groups had similarly low rates of recurrent seizures. Both drugs are benzodiazepines, a class of sedating anticonvulsant drugs, already known to be effective in controlling seizures.
The investigators said that while autoinjectors might someday be available for use by epilepsy patients and their family members, more research is required. Because of the strong sedative effect of midazolam, on-site medical supervision is now required for the safety of the patient. The pens are much easier to store on board ambulances, compared to IV drugs which require refrigeration and constant oversight to manage and discard expired doses.
The RAMPART study was conducted through the National Institute of Neurological Disorders and Stroke (NINDS) Neurological Emergencies Treatment Trials (NETT) network. The investigators studied 893 patients treated between 2009 and 2011, ranging in age from several months old to 103. The trial was conducted under federal Exception from Informed Consent regulations for emergency research, which protect patients who are involved in research for which advance consent is not possible because of their medical condition. To comply with these requirements, RAMPART investigators held community consultations in advance of the study to raise awareness, ensure transparency, and get input from residents in areas where the trial will be conducted.
"The success of this trial is an important step toward safely conducting research on other emergent conditions such as cardiac arrest, traumatic brain injury, stroke and sepsis," said Baren, who studies how to implement these regulations ethically within emergency research trials. "Studying treatments for patients who are unconscious and cannot understand the risks and benefits of various interventions is incredibly difficult. It requires precision and careful planning, but we have proven that these special trials can be conducted with rigor, in a way that both protects these especially vulnerable patients and answers important scientific questions which will ultimately benefit critically ill and injured patients."
The trial also represents an important synergy between academic medical investigators and the chemical defense community, which has a longstanding interest in research on the rapid treatment of nerve agent-induced seizures. The investigators say the study results provide critical information that autoinjectors could prove to be a valuable and highly practical way to treat hundreds of people quickly during a public health emergency such the 1995 sarin gas attacks in the Tokyo subway.