Date: November 11th, 2017

Reference: Sundén-Cullberg et al. Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU. Critical Care Medicine 2017.

Guest Skeptic: Jesse Spurr works as a Nurse Educator in the Emergency Department at Redcliffe Hospital in Australia. Outside his family and work, Jesse pours energy into his professional hobbies: healthcare simulation podcast Simulcast, nursing practice development blog and podcast Injectable Orange and faculty and team member of The Teaching Coop. Jesse classes himself a lifelong student of teaching, learning, health and human performance.

Case: You are working night shift in the emergency department. Two patients present to the front desk in close succession, brought in by concerned family members. Both are similarly hypotensive and tachypnoeic,drowsy but orientated, with hot, reddened and increasingly painful cellulitis. Following the triage sepsis pathway, recently amended to use qSOFA. The nurse triages both to beds in the acute/resuscitation area of the department. Each patient is seen quickly and has initial vital signs and blood samples obtained. One patient has a temperature of 38.3C and the other 35.5C. Being a night shift, staff resources are tight. How do you allocate resources wisely?

Background:  If you work in emergency medicine, you are probably aware of the continuous debate about fever. Is it harmful? Is it helpful? Should it be treated?

There are two opposing schools of thought about the value of fever in infection. One side argues that fever causes an increased metabolic stress than might be detrimental to already sick patients. The other side points out that fever is a natural immune response designed to fight infection. So, eliminating this natural line of defense could make sick patients even sicker.

Dr. Anthony Crocco

Dr. Anthony Crocco

We have covered fever before on the SGEM in pediatric patients. There was the great episode on pediatric fever fear with PedEM Super Hero Anthony Crocco (SGEM#95).  We also did a RANThony on pediatric fever fear that you can watch on YouTube.

The American Academy of Pediatrics Guides say: fever, in and of itself, is not known to endanger a generally healthy child.  In contrast, fever may actually be of benefit; thus, the real goal of antipyretic therapy is not simply to normalize body temperature but to improve the overall comfort and well-being of the child.

There were three questions covered in that pediatric fever fear episode:

  1. Should parent’s combine/alternate acetaminophen and ibuprofen?
    • Parents and caregivers should focus on patient comfort instead of normalizing a temperature in febrile children. Alternating therapy may be beneficial for comfort, but more research is required to address this specific question.
  2. Will treating the fever make the child sicker, longer?
    • Probably not. Antipyretics should be used to improve comfort during an illness.
  3. Will treating with antipyretics prevent a febrile seizure?
    • Antipyretics appear to offer no significant improvement in the recurrence rates of febrile seizures in children.

When looking at fever in adult patients in the intensive care unit (ICU), we did an episode with Justin Morgenstern from First10EM. The question in SGEM#146 was does regular administration of intravenous acetaminophen in febrile ICU patients being treated for a known or suspected infection impact the number of ICU-free days?

  • The routine use of IV acetaminophen for the treatment of fever in ICU patients thought to be due to infection cannot be recommended at this time.

Clinical Question: Does patient body temperature in the emergency department predict survival of adult patients with severe sepsis and septic shock admitted to the intensive care unit?

Reference: Sundén-Cullberg et al. Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU. Critical Care Medicine 2017.

  • Population: Adult patients (age > 17 years) with documented diagnosis of severe sepsis or septic shock admitted to one of 30 Swedish intensive care units within 24 hours after presentation to the emergency department.
  • Intervention: None
  • Comparison: Four stratified groups of body temperatures (<37C, 37C-38.29C, 38.3C-39.49C and >39.49C).
  • Primary Outcome: In hospital mortality

Authors Conclusions: Contrary to common perceptions and current guidelines for care of critically ill septic patients, increased body temperature in the emergency department was strongly associated with lower mortality and shorter hospital stays in patients with severe sepsis or septic shock subsequently admitted to the ICU.” 

checklistQuality Checklist for Observational Study:

  1. Do you believe the results? Yes
  2. How precise are the results? Very precise
  3. Was the follow up of subjects complete enough? Yes
  4. Have the authors identified all-important confounding factors? Unsure
  5. Was the outcome accurately measured to minimize bias? Yes
  6. Was the exposure accurately measured to minimize bias? Unsure
  7. Was the cohort recruited in an acceptable way? Yes
  8. Did the authors use an appropriate method to answer their question? Yes
  9. Did the study address a clearly focused issue? Yes
  10. Can the results be applied to the local population? Unsure
  11. Do the results of this study fit with other available evidence? Unsure.

Key Results: A total of 2,225 patients were included in the main analysis. The median age was 68 and 56% were male.

Primary Outcome: In hospital mortality was inversely correlated with body temperature.

For each one degree, increase in body temperature there was an observed 5% decrease in mortality.

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  1. Observational Study: We can only conclude associations and not causation due to the nature of this study. Lack of mounting a fever could just be a surrogate marker of frailty. In addition, different temperature groups had different primary focus of infection and different organisms identified. Those with fevers also were treated more aggressively. They tried to adjust for these different factors but some unmeasured cofounder could be responsible for the observed inverse correlation between body temperature and mortality.
  1. Measurement Error and Antipyretics: There was a lack of a uniform way to measure body temperature (Tympanic, Oral, Rectal). This could have resulted in could measurement errors. Information about antipyretics or immune-modifying drugs prior to arrival to emergency department was also lacking. This is important as our many emergency medical services still routinely give antipyretics for fever and common community perception is still to take antipyretics for high temperature.
  1. Treatment: This study does not provide information on whether or not antipyretics should be given to septic or septic shock patients in the intensive care unit. We mentioned in the background information the study of using IV acetaminophen in the ICU did not result in benefit.
  1. Severity Score: They did not calculate a severity score like SOFA. This makes it difficult to adjust for disease severity. However, they did adjust for age, sex, underlying comorbidity, vital signs, preliminary focus of infection and sepsis bundle achievement and the inverse correlation between body temperature and mortality remained. And pragmatically, the information required for SOFA would not available immediately to the emergency physician or nurse.
  1. Missing Data: A large proportion of patients in this study had missing data. Only 58% of patients had complete information on all variables. Nine percent did not even have a body temperature documented. Missing values were more prevalent in patients without fever (i.e. lower quality of care) – while potentially biasing the quantitative prognostic accuracy, this actually confirms the need to pay greater attention to the quality of care and documentation for the afebrile septic patient.

Comment on Authors Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusion.

SGEM Bottom Line: We should pay greater attention to patients presenting with features of severe sepsis and septic shock that do not have fever in the emergency department as they have an associated high mortality rate.

Case Resolution: The senior physician and two nurses attended to the initial treatment of the patient without a fever. He required rapid fluid administration and treatment with empirical antibiotics and initiation of vasopressor via peripheral cannula until a central line could be placed. The intensive care unit was involved early and facilitated transfer.

The gentleman with a fever received further assessment via the remaining nurse and a junior resident, responded to 30ml/kg of intravenous crystalloid, empirical antibiotics and was safely admitted under internal medicine to the ward in the early hours of the morning.

Clinical Application: It is difficult to say what to do with this observational data. The clinical application may be to augment the triage of patients presenting with characteristics of severe sepsis or septic shock, flagging those without fever as having a greater risk of poor outcome and allocating resources/prioritizing accordingly. This could reframe the common perception that fever is a marker of acuity in sepsis.

Jesse and Archie

Jesse and Archie

What do I tell My Patients?

  • Patient Without Fever: You are very sick with serious skin infection. However, you do not seem to have the natural response of a fever and this makes us more concerned. We would like to treat you very rapidly and there will be a lot activity in getting antibiotics, blood tests, giving you fluids and quite possibly medications to raise your blood pressure. We will be monitoring you very closely and will very likely get the Intensive Care team to come and see you.
  • Patient with a Fever: You are very sick with a serious skin infection. Your body seems to be fighting it with a fever. Lowering your body temperature has not shown to save lives but it could make you feel better. The most important things right now are to get you intravenous antibiotics, intravenous fluids and admit you to hospital.

Keener Kontest: Last weeks’ winner was Mateusz Szmidt from Liverpool, England. He knew oncologist use dexamethasone to treat cancer patients’ vomiting and also to increase their appetite.

FOAM logoListen to the SGEM podcast on iTunes to hear this weeks’ keener question. If you know the answer, then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Other FOAMed:

  • ScanCrit– Is Fever the Normal Temperature of Sepsis?
  • REBEL EM– Is Fever the New Hotness in Sepsis?

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

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