Fever is often observed in patients with documented infection, and we know from personal experience that fever makes you feel like ass, so we take motrin and tylenol to feel better, but what does this mean for our patients. Our we fighting evolution here?

Egi et al performed a prospective observational study on the association of body temperature and antipyretic treatments with mortality in critically ill patients with and without sepsis, excluding patients with neurologic injury (we know fever is bad when you have a neurologic insult). 

Here is what they found:

1. Why is this topic important?

It is almost reflexive to give febrile patients tylenol or Motrin for fever control. We know that fever creates tachycardia, and is uncomfortable for patients. However, fever is a natural response and multiple studies have demonstrated an increase in heat shock proteins, and a more robust microbicidal activity in patients with fever when compared to patients with euthermia or hypothermia. However, patients who are not infected may also have fever as part of an inflammatory cascade, and this could be detrimental. In this study Egi et al examined the associated between mortality and the treatment of fever in both septic and non-septic patients who were admitted to the intensive care unit with fever. 

2. What does the study attempt to show?

The study attempts to identify associations between fever and outcomes in septic and non-septic patients who were treated with pharmocologic agents like tylenol and Motrin or cooling blankets after being admitted to the intensive care unit. 

3. What were the findings?

1,425 consectuctive adult critically ill patients WITHOUT neurologic injury requiring > 48 hours in the intensive care unit were admitted in 25 ICU's. Every 4 hours body temperature was recorded and antipyretic treatment was monitored until ICU discharge or 28 days after ICU admission, whichever occurred first. Patients were divided into septic and non-septic patients, and the maximum body temperature and use of antipyretic treatment were assessed separately to mortality. 

Treatment with non-steroidal anti-inflammatory drugs (NSAID's) or acetaminophen INDEPENDENTLY increased 28-day mortality for SEPTIC patients (OR:  NSAID's 2.61 p = 0.028 and OR Acetaminophen 2.05 p =0.01), but did not change mortality for non-septic patients (NSAIDs 0.22 P =0.15, Acetaminophen 0.58 P =0.63). Application of physical cooling methods did not associate with mortality in any group. 

Since this is an observational study only association and not causality can be inferred, but this is strong food for thought regarding the aggressive treatment of fever with antipyretics in patients with suspected sepsis. To reiterate the point that fever is a response to stimulate the body's innate immune activity through the production of heat shock proteins and inflammatory mediators that stimulate bactericidal activity of leukocytes. Although fever is associated with increased volume loss, and increased metabolic demand, intravenous fluids, antibiotics, cooling blankets may be a more suitable alternative to antipyresis in the sicker cohort of patients (septic going to the ICU, not febrile kids in the PEC). 

5. Is this an area of controversy?

Since many physicians regard fever as an evil that must be treated, and some won't ever discharge a patient home until the fever has broken I would say yes. Although there are some adverse effects to fever (as previously mentioned and febrile seizures due to rate of rise in children), there advantages to a billion years of evolution. Maybe our bodies have it right. 

6. Major limitations of the study?

The study is observational, and in the ICU patients could be treated with antipyretics at the attending physicians discretion. Maybe sicker patients got tylenol and Motrin (although multivariate analysis should have accounted for this variability). Either way a randomized placebo controlled trial would be necessary to draw practice changing conclusions. 

In summary fever is a common occurrence in septic patients, and this study demonstrated an associated with increased mortality when treating septic patients in the intensive care unit with tylenol and motrin for fever control. This suggests fever may be a host response and suppression of the febrile response might worsen outcomes in septic ICU patients.