NASHVILLE — Almost half of the patients in the intensive care unit received medications for off-label indications, with little or no supporting evidence for that use, according to a retrospective review.
Patients received a mean of six approved and five nonapproved medications. Three drug classes accounted for most of the off-label orders: endocrine/metabolic, respiratory, and gastrointestinal. The most frequently prescribed off-label drugs were regular insulin for hyperglycemia; fentanyl for analgesia in critically ill, mechanically ventilated patients; and esomeprazole for the prophylaxis of stress ulcers.
“The use of off-label medications for critically ill patients is very common, and there appears to be a correlation between how sick the patients are and how many off-label drugs they receive,” Ishaq Lat, Pharm.D., said at the annual congress of the Society of Critical Care Medicine. “We extrapolate a lot of what we do in the ICU from other areas of medical treatment, without a great deal of evidence in this patient population.”
Dr. Lat, a pharmacist at the University of Chicago Medical Center, and his colleagues, reviewed all the medication orders in 37 U.S. intensive care units during the same 24-hour period. The study captured data on 414 patients, for whom 4,535 medications were ordered. Of these, 1,805 (40%) were for an off-label use.
Most medications given off label had little evidence supporting their use, Dr. Lat said in an interview. “When the off-label medication orders were evaluated by level of evidence and strength of recommendation, 829 (46%) had grade C or no evidence, and 718 (40%) had a grade 3 or indeterminate rating.”
The analysis found an association between the increasing severity of illness and the use of off-label medications. Patients who received off-label drugs had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sepsis-Related Organ Failure) scores than did those who did not receive these drugs.
Off-label use varied significantly with the type of ICU, Dr. Lat noted. Cardiothoracic, surgical, trauma, and bone marrow transplant units had more off-label than on-label medication usages. Medical, coronary, and neurologic ICUs used more on-label medications, he added.
The high rate of off-label prescribing in ICUs may reflect a lack of adequate pharmaceutical research in critically ill patients, Dr. Lat said. “It's very difficult to perform drug studies on patients who are this sick, and there is not much funding available for these studies. So, we're applying what we know from other areas of medicine… without much good evidence.”
A follow-up study will explore the possible relationship between off-label prescribing in the ICU and patient outcomes, he added.