The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study

Despite the large body of evidence suggesting a beneficial role of fever in the host response, antipyretic therapy is commonly employed for febrile critically ill patients. Our objective was to evaluate the impact of antipyretic therapy strategies on the outcomes of critically ill patients.

Patients admitted to the Trauma Intensive Care Unit over a nine-month period were eligible for inclusion, except those with traumatic brain injury. Patients were randomized on day three of the ICU stay into aggressive or permissive groups. The aggressive group received acetaminophen 650 mg every 6 h for temperature of >38.5 degrees C and a cooling blanket was added for temperature of >39.5 degrees C. The permissive group received no treatment for temperature of >38.5 degrees C, but instead had treatment initiated at temperature of >40 degrees C, at which time acetaminophen and cooling blankets were used until temperature was <40 degrees C. Patient demographics, daily temperatures, systemic inflammatory response syndrome (SIRS) scores, multiple organ dysfunction syndrome (MODS) scores, and infections and complications were recorded.

Between December, 2002 and September, 2003, 572 patients were screened, of whom 82 met criteria for enrollment. Forty-four patients were randomized to the aggressive group and 38 patients were randomized to the permissive group for a total of 961 and 751 ICU days, respectively. There were 131 infections in the aggressive group and 85 infections in the permissive group (4 +/- 6 vs. 3 +/- 2 infections per patient, p = 0.26). There were seven deaths in the aggressive group and only one death in the permissive group (p = 0.06, Fisher Exact Test). The study was stopped after the first interim analysis due to the mortality difference, related to the issues of waiver of consent and the mandate for minimal risk.

Aggressively treating fever in critically ill patients may lead to a higher mortality rate.