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J Crit Care. 2013 Jun;28(3):296-302. doi: 10.1016/j.jcrc.2012.08.015. Epub 2012 Oct 24.

Assessment of the safety and feasibility of administering antipyretic therapy in critically ill adults: a pilot randomized clinical trial.

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Department of Critical Care Medicine, University of Calgary, and Alberta Health Services, Calgary, Alberta, Canada.



To assess the safety and feasibility of treating critically ill adults with different fever control strategies.


This was a pilot, open-label clinical trial (, number NCT01173367) that randomized febrile patients to an aggressive or permissive fever control strategy. For the aggressive and permissive groups, antipyretic therapy (acetaminophen, physical cooling) was administered when the temperature was ≥ 38.3°C and ≥ 40.0°C respectively. The primary outcome was 28-day mortality.


Two hundred patients experienced a fever (31% of the originally projected estimate), among which 26 were randomized to the aggressive (n = 14) or permissive (n = 12) arm. The aggressive group received a greater dose of acetaminophen (2275 mg vs 0 mg, P = .0001), and more frequently received physical cooling than patients in the permissive group (57% vs 8%, P = .01). The mean daily temperature was lower in the aggressive group (37.8°C vs 38.0°C, P = .02). There was no difference in the primary outcome (21% vs 17%, P = 1.0) or in any safety outcome between the treatment groups.


This study demonstrated the safety and feasibility of administering antipyretic therapy in critically ill adults. The key finding was a lower than expected incidence of fever.

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