Acetaminophen May Shorten ICU Stay For Some Patients

Dr. Paul Jeffrey Young MD Intensive Care Unit, Wellington Regional Hospital Wellington South, New ZealandMedicalResearch.com Interview with:
Dr. Paul Jeffrey Young MD
Intensive Care Unit, Wellington Regional Hospital
Wellington South, New Zealand

Medical Research: What is the background for this study? What are the main findings?

Response: Fever is a response to infection that is broadly conserved across many animal species and it seems reasonable to presume that the components of the immune response have adapted to function optimally in the physiological febrile range.  We have previously shown that among patients with fever and infection, increasing degrees of fever in the first 24 hours in ICU are generally associated with reducing mortality risk after adjusting for illness severity.  Although acetaminophen (paracetamol) is commonly used to treat fever in the ICU, there are no previous data to demonstrate the safety and efficacy of this practice.  The HEAT trial was designed by a group of ICU clinicians to test the hypothesis that treating fever with acetaminophen in critically ill patients with infections would worsen outcomes, or more specifically that it would reduce the number of days patients spent alive and free from requiring intensive care.

Medical Research: What are the main findings?

Response: The primary finding was that early administration of acetaminophen to treat fever did not alter the number of ICU-free days in adult ICU patients with infections.  The mortality rates of acetaminophen and placebo patients were similar.  Patients who received acetaminophen had lower body temperature than patients who received placebo and did not have significantly more adverse events.  Acetaminophen use was associated with a shorter ICU stay than placebo among survivors and a longer ICU stay among patients who died.

Medical Research: What should clinicians and patients take away from your report?

Response: For clinicians who choose to administer acetaminophen to ICU patients with infection and fever, our data provide evidence that this practice is probably not harmful and is likely to be well-tolerated.  Our study also suggests that the antipyretic effects of acetaminophen are likely to be relatively small.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Our observation that acetaminophen administration is associated with reduced ICU length of stay for patients who survive and increased length of stay for patients who die is potentially very important.  It is important to emphasise that this observation should be regarded as hypothesis-generating.  However, it raises the provocative possibility that acetaminophen might sped up recovery and delay death. A number of potential hypotheses follow.

Firstly, perhaps for critically ill patients who are supported beyond the limits of normal physiological homeostasis controlling temperature may actually be beneficial.  If this is the case then more aggressive control of temperature than was achieved with acetaminophen alone might improve outcomes.

Secondly, perhaps acetaminophen itself could be beneficial.  Acetaminophen has a range of properties beyond simply reducing body temperature.  For example, it has antioxidant effects.  In this study patients only received a median of around two days of study treatment.  It is possible that a more sustained course of treatment with acetaminophen might improve outcomes.

There is clearly a lot more work to be done in this area and this study is the first word on this topic not the last word.

Citation:

Acetaminophen for Fever in Critically Ill Patients with Suspected Infection

Paul Young, M.D., Manoj Saxena, M.D., Rinaldo Bellomo, M.D., Ross Freebairn, M.D., Naomi Hammond, R.N., M.P.H., Frank van Haren, M.D., Ph.D., Mark Holliday, B.Sc., Seton Henderson, M.D., Diane Mackle, M.N., Colin McArthur, M.D., Shay McGuinness, M.D., John Myburgh, M.D., Ph.D., Mark Weatherall, M.D., Steve Webb, M.D., Ph.D., and Richard Beasley, M.D., D.Sc. for the HEAT Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group

October 5, 2015DOI: 10.1056
NEJMoa1508375

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