Bottom Line Up Top: There doesn’t appear to be a morbidity or mortality benefit to treating fever in sepsis and fever may have a protective effect. Only treat fever if it causes the patient distress.
Clinical Scenario: A 45-year-old woman presents with cough and shortness of breath. Vitals are BP 114/42, HR 138, T 102.1, Sat 93% on RA. The patient is alert and oriented and has no other complaints. X-ray reveals a right lower lobe consolidation. You order antibiotics, an initial fluid bolus as well as blood cultures. The nurse asks if you want to give the patient acetaminophen for her fever.
What Your Gut Says: Order the acetaminophen. Fever is bad and should be treated. The patient will feel better and numbers will look better.
What The Evidence Says:
Antipyretics are commonly given to patients with fever suspected to be caused by an infection in both at home and in the hospital setting. There are, however, opposing theories to the utility of decreasing fever in these situations. One side argues that fever places “additional physiological stress on patients,” who are already ill (Young 2015). Removing this source of increased metabolic demand would allow the body to allocate additional resources to fighting infection, respiratory function etc. On the other hand, fever may serve as a protective role by enhancing immune cell function and inhibiting pathogen growth and spread (Young 2015). From an evolutionary standpoint, fever, which entails a significant cost to the host, likely evolved and persists because it benefits the host.
There is scant high-quality data investigating the metabolic costs versus the physiologic benefits of fever or the benefits of antipyretics versus their toxicologic cost. A large observational study of > 2000 patients found an association with fever at presentation and ICU survival for patients with severe sepsis or septic shock (Sunden-Culberg 2017). This may suggest a protective mechanism for fever. It may also be that it is easier to recognize patients with sepsis if they have a fever and early recognition and treatment of sepsis has shown improved outcomes.
A small RCT of 200 patients with septic shock using external cooling found that patients who were cooled had lower vasopressor requirements and a lower 14-day mortality rate. Importantly, all of the patients in this study had septic shock requiring vasopressors and mechanical ventilation. It is unclear if this data can be applied to a less sick cohort of patients.
The HEAT trial represents the highest quality evidence on the topic (Young 2015). This double-blind RCT randomized > 700 ICU patients with suspected infection to IV acetaminophen or placebo and found no difference in ICU-free days up to 28 days after study entry. Additionally, there was no difference in mortality rates between the groups.
Bottom Line: Fever does not always need to be treated in patients with suspected infection. Limited data shows that it’s reasonable to give antipyretics to patients in whom the fever is causing distress but it is similarly reasonable to withhold it in patients who are not distressed.
Read More
REBEL EM: The HEAT Trial: Acetaminophen for Fever?
The Bottom Line: HEAT Trial – Acetaminophen for Fever in critically Ill Patients with Suspected Infection
The SGEM: SGEM #146 – The Heat is On – IV Acetaminophen for Fever in the ICU
References
Young, P et al. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. NEJM 2015; 373(23): 2215-24. PMID: 26436473
Schortgen F et al. Fever control using external cooling in septic shock: a randomized controlled trial. Am J Resp Crit Care Med 2012; 185(10): 1088-1095. PMID: 22366046
Sunden-Culberg J et al. Fever in the Emergency Department predicts survival of patients with severe sepsis and septic shock admitted to the ICU. Crit Care Med 2017; 45(4): 591-9. PMID: 28141683
