Using Autoinjectors to Treat Seizures

The National Institutes of Health
From NIH Research Matters (NIH)

February 27, 2012

Drug delivery into muscle using an autoinjector-akin to the EpiPen used to treat serious allergic reactions-can be a fast, effective way to stop prolonged epileptic seizures. The finding provides a safe tool to treat people quickly during an emergency.

Epilepsy is a brain disorder in which nerve cells in the brain sometimes signal abnormally. When the normal pattern of neuronal activity becomes disturbed, it can lead to convulsions and muscle spasms. Status epilepticus is a prolonged seizure lasting longer than 5 minutes. This potentially life-threatening emergency causes 55,000 deaths each year.

Anticonvulsant drugs are typically delivered intravenously (IV) as a first-line treatment for status epilepticus. But starting an IV in a patient having a seizure can be challenging and waste precious time. Giving an intramuscular shot is easier, faster and more reliable.

A team of researchers led by Dr. Robert Silbergleit of the University of Michigan in Ann Arbor sought to determine whether an intramuscular injection, which quickly delivers anticonvulsant medicine into a patient's thigh muscle, is as safe and effective as giving medicine directly into a vein. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) compared how well delivery by each method stopped patients' seizures by the time the ambulance arrived at the emergency department. The research was funded primarily by NIH's National Institute of Neurological Disorders and Stroke (NINDS).

The study compared 2 medications proven effective at controlling seizures, both from the benzodiazapine class of sedating anticonvulsant drugs. Lorazepam, which must be given by IV, is the current standard of care. Midazolam, which is rapidly absorbed from muscle, was delivered by injection. The trial involved more than 79 hospitals, 33 emergency medical services agencies, more than 4,000 paramedics and almost 900 patients ranging in age from several months to 103 years old.

In the February 16, 2012, issue of the New England Journal of Medicine, the researchers reported that 73% of patients in the group receiving midazolam were seizure-free upon arrival at the hospital, compared to 63% who received IV treatment with lorazepam. 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.

"Few other areas of medicine are as time-dependent as injury to the brain," Silbergleit says. "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."

These results also have implications for public health preparedness. The trial shows that autoinjectors can provide a practical way to treat hundreds of people quickly during a widespread emergency, such as a chemical or biological attack.