Study Design Summary: Multicenter study in which 700 patients were split to either get 1g IV acetaminophen or not; to be eligible patients had to have a documented temperature ≥38°C with known or suspected infection. Primary outcome was ICU free days from randomization to day 28. End points were discharge from ICU, death, cessation of antimicrobial therapy or defervescence.
Notes: 30% of both the intervention and control group got open label acetaminophen, but physical cooling was given as rescue therapy if temperature rose above 39.5°C, rates of physical rescue cooling and NSAID use was similar in both groups. Tylenol only decreased peak temperatures by 0.25-0.4°C, which is constant with previous studies. The number of ICU free days did not differ significantly between the groups, neither did mortality at 28 or 90 days, ICU length of stay. There were higher rates of liver dysfunction in the placebo group actually.
There was shorter ICU LOS in acetaminophen group amongst survivors (3.5 vs 4.3 days) and longer LOS in acetaminophen group amongst the non-survivors (10.4 vs 4 days). Authors comment on this, “Our observation that ICU and hospital length of stay were longer with acetaminophen than with placebo among patients who died is consistent with the finding of a study in which physi- cal cooling to normothermia delayed death in mechanically ventilated patients with septic shock.4 These observations are also consistent with a recent retrospective cohort study in which a Cox proportional-hazards analysis showed that ICU patients who received acetaminophen had a significantly longer time to death than those who did not.”
The study outcomes table showed exactly no difference in the primary outcome or any of the secondary outcomes and 28 and 90 day death rates between the two groups.
Study Conclusion: Our findings suggest that acetaminophen has a modest clinical effect as an antipyretic in ICU patients with fever and probable infection but does not reduce ICU-free days in these patients. Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. There was no significant between-group differ- ence in 28-day mortality, 90-day mortality, or survival time to day 90.
Fusion Beat Bottom Line Impression: Tylenol for fever offers no benefit in the ICU. The observation of length of stay prolongation in non-survivors would need to be addressed specifically in a separate study that also takes into account time on antimicrobial therapy, which this study did not do, to provide specific recommendations.
I do think this observation of prolonged time to death is important and shouldn’t be overlooked but without data on time on antimicrobials it is a hypothesis generating observation only.
This study used 39.5°C as cut off for beginning rescue therapies which is appropriate based on previous studies, above this there is known deleterious effects of the fever.
A Fusion Beat 