Written by Peter Liu
Spoon Feed
Antipyretic therapy in febrile patients has not been shown to improve death or serious adverse events.
For fever, focus on the treating the underlying cause
For the internist, it is ingrained in our psyche to look beyond superficial vital sign derangements and to the underlying causes. For example, we avoid suppressing sinus tachycardia reflexively. When given the opportunity, we differentiate shock syndromes prior to ordering fluids, diuretics, or pressors. Similarly, for fevers, we generally find the underlying cause rather than suppressing the temperature itself. The HEAT trial is one of several RCTs that informs this practice. This multicenter double-blind RCT studied whether the effects of intravenous acetaminophen affected the number of ICU-free days in 700 critically ill patients with fever and suspected infection. Patients received either 1g acetaminophen or placebo every 6 hours. The median ICU-free days were 23 (IQR, 13–25) with acetaminophen and 22 (IQR, 12–25) with placebo (absolute difference 0 days; 96.2%CI 0 to 1; P=0.07). 90-day mortality was similar (15.9% vs. 16.6%; RR 0.96; 95%CI 0.66–1.39; P=0.84). The findings from the HEAT Trial mirror meta-analyses on antipyretic therapy for febrile patients, which concluded no mortality benefit nor prevention of serious adverse events with antipyretic therapy. On the flip side, results from these studies generally show that routine antipyretic therapy, such as acetaminophen therapy, is quite safe.
Of note, external cooling in the ICU setting remains slightly more controversial. In part, this is due to a positive RCT on external cooling in septic shock (mortality benefit noted). These findings have not clearly been reproduced, though there are ongoing trials (SEPSISCOOL II).
How does this change my practice?
Due to limited evidence to suggest a clear benefit to antipyretic therapy, I generally order these therapies for symptomatic benefit for most patients with fever. In cases such as hyperpyrexia (e.g. severe elevations in temperature over 41.5°C), traumatic brain injury with fever, or severely elevated intracranial pressure with fever, I generally favor antipyretic therapy, since this tends to be the standard of care, though RCT-level evidence is lacking even in these settings.
Source
Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med. 2015 Dec 3;373(23):2215-24. doi: 10.1056/NEJMoa1508375. Epub 2015 Oct 5. PMID: 26436473
