We found the unadjusted mortality was as high as 66% in patients with MAXICU < 36.5��C. This finding may also support the argument that fever is naturally protective. For sensitive analysis to scientific assay avoid the bias of hypothermia (defined as lowest body temperature < 35.0��C.), we performed further multivariate analysis and found a similar association of the use of pharmacological antipyretic with mortality. Fourth, any combination of the above factors might also apply.There is limited information on the effect of antipyretics on patient outcomes and there are no recommendations for antipyretic treatments for febrile patients with or without infectious diseases [2,4]. One study of trauma patients was abandoned early with the 82nd patient on instruction of a safety monitoring board.

This study reported the trend toward increased risk of infection and death in patients when acetaminophen and physical cooling were aggressively used [30]. Additionally, two studies reported that short-term therapy with ibuprofen in patients with sepsis did not influence mortality [31,32]. To our knowledge, this study is the first multicenter examination of the epidemiology and outcome associations of antipyretic treatments [33]. While the clinical benefits and risk of antipyretic treatments can only be properly assessed in a randomized controlled trial; until such time, our findings do have some practical implications.ConclusionsIn conclusion, the association with mortality of fever and type of antipyretic treatment was different between patients with and without sepsis at admission to ICU.

For non-septic patients, MAXICU �� 39.5��C was associated with 28-day mortality. Meanwhile, for septic patients, administration of NSAIDs and acetaminophen was independently associated with increased mortality. Since many ICU patients are or become febrile and antipyretic treatments are common, further studies now appear desirable to confirm or refute our observations.Key messages? The association of fever with mortality was different for patients with and without sepsis at admission to ICU.? For patients without sepsis, MAXICU �� 39.5��C was associated with 28-day mortality.? The association of pharmacological antipyretic treatments with mortality was different for patients with and without sepsis at admission of ICU.? For patients without sepsis, administration of NSAIDs and acetaminophen was independently associated with increased mortality.

AbbreviationsAPACHE: Acute Physiology and Chronic Health Evaluation; ICU: intensive care unit; MAXICU: maximum body temperature during ICU stay; NSAIDs: non-steroidal anti-inflammatory drugs; STROBE: Strengthening the Reporting of Observational Studies in Epidemiology.Competing interestsAll principal investigators have no financial competing interests to disclose. There are no conflicts Entinostat of interest to disclose related to this investigation.Writing committee (contributions)Korea: Younsuck Koh, M.D.