Anti-seizure Drug Could Be Fatal, New Research Shows

New research presented at CHEST 2008, the 74th annual international scientific assembly of the American College of Chest Physicians (ACCP), shows that the use of propofol as an antiepileptic agent in patients with refractory status epilepticus (RSE), prolonged seizures that do not respond to initial treatment, was associated with significant mortality and morbidity.

RSE is a difficult clinical problem seen in patients with primary epilepsy and in those with other conditions such as trauma, tumors, and infections affecting the brain. Although propofol is used to treat patients with RSE, it is more commonly used for sedation during surgeries or other patient procedures but at a much lower dose and shorter duration than that used for the control of seizures.

“Patients with RSE treated with propofol are at high risk for propofol-related side effects because of the high propofol infusion rates and prolonged treatment duration necessary in these patients,” said Vivek Iyer, MD, Mayo Clinic, Rochester, MN. “However, it is well described that propofol toxicity can occur even with brief exposure to the drug.”

Dr. Iyer and his colleagues from Mayo Clinic reviewed 39 consecutive patients (median age of 54 years) from 1997 to 2007, who were admitted to the ICU with RSE, in order to examine the link between propofol use and related side effects, including propofol infusion syndrome (PRIS). PRIS is a usually fatal complication of propofol use that has been reported especially at high infusion rates for prolonged periods. For this study, PRIS was defined by the unexplained presence of at least one or more of the following: metabolic acidosis, rhabdomyolysis, bradycardia, and/or cardiac arrest.

Propofol was used in 32 (82 percent) of the patients (group A) for a median of 63 hours and a median peak infusion rate of 67 mcg/kg/min. Other agents, such as midazolam and pentobarbital, were used in the other seven (18 percent) patients (group B). Within group A, three patients had sudden unexplained cardiac arrest while on propofol infusions, resulting in two deaths, while no deaths occurred in group B. Median hospital stay (12 days) and ICU length of stay (9 days) did not differ between the two groups. The overall occurrence of PRIS was 30 percent of patients in group A (seven patients with bradycardia, three patients with sudden unexplained cardiac arrest) compared with less than 3 percent (one patient with bradycardia) in group B.

In light of the new data, Dr. Iyer advises that caution should be taken with the use of propofol to treat patients with RSE. “There are several other medications we can turn to in the case of uncontrolled seizures,” he said. “Alternative agents should first be tried for patients with RSE, and propofol should only be used after exhausting all other options.”

"With increasing awareness of the risks of propofol, physicians may become more cautious about using propofol for prolonged periods and at high doses,” James A. L. Mathers, Jr., MD, FCCP, President of the American College of Chest Physicians.