Acetaminophen for Febrile ICU Patients with Probable Infection

Research Highilghts

      Many patients in communities and hospitals present fever as a symptom. Especially for those in the ICU (Intensive Care Unit), fever can be a sign of infection. Lowering temperatures in febrile patients helps lower physiological stress and discomfort for those who that are already sick. Though treating fever in those with an infection is common practice, recent studies have shown that fevers may actually be beneficial to these patients. Various studies has shown that a fever may inhibit the grow the grow of pathogens, strengthen immune-cell function, and enhance antimicrobial drug activity. Observational studies have shown that there is a lower risk of death associated with high early fever in ICU patients with infections.  ICU clinicians are left not knowing if administering acetaminophen will help or hurt their patients’ chance of survival.

            A study in New Zealand and Australia aimed to provide evidence showing that acetaminophen is ultimately harmful to ICU patients with probably infection. During the study, patients were either given 5% dextrose in water or 1 gram of acetaminophen intravenously every 6 hours. The dextrose acted as a placebo. The patients were all at least 16 years of age and, within 12 hours of enrollment, had a temperature of 100.40 F. The patients were assigned acetaminophen or dextrose randomly and with a ration of 1:1. Patients were given the drug of 28 days after enrolment unless they had been discharged, their fever had been resolved, their antimicrobial therapy had be been stopped, or the patient had died. Physical cooling intervention was administered in any patient’s temperature reached 103.10F.

The outcomes were measured by ICU-free days within a 28 day time period starting from administration of a dextrose or acetaminophen. The number of days was calculated by subtracting the number of days spent in the ICU from 28. Patients who died were assigned zero days. Secondary outcomes were measured within a 90 day period. This included all-cause mortality, ICU stay-length and hospital stay-length, days free from support in the ICU, days free from varying therapies, and hospital-free days.

Between February 2013 and January 2014, 690 patients were enrolled in the study through 23 different ICUs in New Zealand and Australia. 346 of the patients were given acetaminophen, while 344 received the dextrose placebo. Originally 700 patients enrolled in the trial, but 10 patients withdrew consent. Ultimately, patients that received the acetaminophen had lower means for average daily temperatures and daily peak temperatures. The primary outcome did not show a significant difference between the two groups, with an average of 23 ICU-free days for acetaminophen patients and 22 days for placebo patients. The secondary outcomes also did not show any significant differences. The trial concluded that acetaminophen early administration in ICU patients with fever and infection did not yield any more or less ICU-free days than those that did not receive acetaminophen. There was also no difference in 28-day and 90-day mortality, nor adverse effects. 

NEJMoa1508375

Lena Chatterjee is the 2015-2016 Research Highlights Editor.