The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock

Henning, Daniel J.; Carey, Jeremy R.; Oedorf, Kimie; Day, Danielle E.; Redfield, Colby; Huguenel, Colin J.; Roberts, Jonathan C.; Sánchez, León D.; Wolfe, Richard E.; Shapiro, Nathan I.

doi:10.1097/ccm.0000000000002311

Cited by 44 publications

(43 citation statements)

References 29 publications

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“… 34 Although body temperature can be an unreliable sign in sepsis, 34 sub-fever-range body temperature correlates with less-prompt treatment and much greater mortality in sepsis and septic shock. 35 , 36 For example, among intensive care unit-admitted patients with severe sepsis and septic shock, each 1°C reduction in body temperature was associated with a five percentage-point increase in in-hospital mortality rates, with patients in the highest and lowest temperature brackets having mortality rates of 9% and 50%, respectively. 36 Seen alongside our results, these findings suggest the hypothesis that lower patient temperatures in mornings could hinder management and perhaps worsen outcomes by delaying recognition of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Fever Incidence Is Much Lower in the Morning than the Evening: Boston and US National Triage Data

Harding¹,

Pompei

Bordonaro³

et al. 2020

WestJEM

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In this observational study, we evaluated time-of-day variation in the incidence of fever that is seen at triage. The observed incidence of fever could change greatly over the day because body temperatures generally rise and fall in a daily cycle, yet fever is identified using a temperature threshold that is unchanging, such as ≥38.0° Celsius (C) (≥100.4° Fahrenheit [F]). Methods: We analyzed 93,225 triage temperature measurements from a Boston emergency department (ED) (2009-2012) and 264,617 triage temperature measurements from the National Hospital Ambulatory Medical Care Survey (NHAMCS, 2002-2010), making this the largest study of body temperature since the mid-1800s. Boston data were investigated exploratorily, while NHAMCS was used to corroborate Boston findings and check whether they generalized. NHAMCS results are nationally representative of United States EDs. Analyses focused on adults. Results: In the Boston ED, the proportion of patients with triage temperatures in the fever range (≥38.0°C, ≥100.4°F) increased 2.5-fold from morning to evening (7:00-8:59 PM vs 7:00-8:59 AM: risk ratio [RR] 2.5, 95% confidence interval [CI], 2.0-3.3). Similar time-of-day changes were observed when investigating alternative definitions of fever: temperatures ≥39.0°C (≥102.2°F) and ≥40.0°C (≥104.0°F) increased 2.4-and 3.6-fold from morning to evening (7:00-8:59 PM vs 7:00-8:59 AM: RRs [95% CIs] 2.4 [1.5-4.3] and 3.6 [1.5-17.7], respectively). Analyses of adult NHAMCS patients provided confirmation, showing mostly similar increases for the same fever definitions and times of day (RRs [95% CIs] 1.8 [1.6-2.1], 1.9 [1.4-2.5], and 2.8 [0.8-9.3], respectively), including after adjusting for 12 potential confounders using multivariable regression (adjusted RRs [95% CIs] 1.8 [1.5-2.1], 1.8 [1.3-2.4], and 2.7 [0.8-9.2], respectively), in age-group analyses (18-64 vs 65+ years), and in several sensitivity analyses. The patterns observed for fever mirror the circadian rhythm of body temperature, which reaches its highest and lowest points at similar times. Conclusion: Fever incidence is lower at morning triages than at evening triages. High fevers are especially rare at morning triage and may warrant special consideration for this reason. Studies should examine whether fever-causing diseases are missed or underappreciated during mornings, especially for sepsis cases and during screenings for infectious disease outbreaks. The daily cycling of fever incidence may result from the circadian rhythm. [

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Section: Discussionmentioning

confidence: 99%

Fever Incidence Is Much Lower in the Morning than the Evening: Boston and US National Triage Data

Harding¹,

Pompei

Bordonaro³

et al. 2020

WestJEM

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“…Multiple studies have demonstrated that absence of fever is associated with higher morbidity and mortality in septic patients (4–8). Given the role of inflammation and immunity in the physiology of fever generation, immune dysfunction has been proposed as a potential link between failure to mount a fever and worse clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Fever is considered to be a hallmark of infection, yet over half of critically ill patients with severe sepsis do not exhibit a fever at the time of sepsis diagnosis (1–5). Several studies and a recent meta-analysis have shown that absence of fever is associated with higher morbidity and mortality in septic patients (5–8), but the reason for these worse outcomes is unknown. Failure to mount a fever may be representative of a more severely disrupted thermoregulatory response to infection and thus merely a reflection of increased disease severity.…”

Section: Introductionmentioning

confidence: 99%

Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis

Drewry

Ablordeppey

Murray

et al. 2018

Shock

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“…Sepsis is a syndrome with a broad clinical manifestation, defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) as “a life-threatening organ dysfunction caused by dysregulated host responses to infection” (1). Due to the numerous possible presentations, sepsis can be a difficult clinical condition to recognize, especially during the early stages if patients exhibit non-specific symptoms of being unwell (1–4) or if archetypal signs of infection are absent, e.g., in young infants, the elderly, and the immunocompromised (5–8). Signs which are highly suggestive of sepsis include (but are not limited to) acute confusion, hypotension, tachycardia, and tachypnoea, hypoxia, reduced urine production, a high blood lactate level and a non-blanching rash.…”

Section: Introductionmentioning

confidence: 99%

Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics

et al. 2019

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Sepsis has a complex pathophysiology in which both excessive and refractory inflammatory responses are hallmark features. Pro-inflammatory cytokine responses during the early stages are responsible for significant endothelial dysfunction, loss of endothelial integrity, and organ failure. In addition, it is now well-established that a substantial number of sepsis survivors experience ongoing immunological derangement and immunosuppression following a septic episode. The underpinning mechanisms of these phenomena are incompletely understood yet they contribute to a significant proportion of sepsis-associated mortality. Epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs, have an increasingly clear role in modulating inflammatory and other immunological processes. Recent evidence suggests epigenetic mechanisms are extensively perturbed as sepsis progresses, and particularly play a role in endothelial dysfunction and immunosuppression. Whilst therapeutic modulation of the epigenome is still in its infancy, there is substantial evidence from animal models that this approach could reap benefits. In this review, we summarize research elucidating the role of these mechanisms in several aspects of sepsis pathophysiology including tissue injury and immunosuppression. We also evaluate pre-clinical evidence for the use of “epi-therapies” in the treatment of poly-microbial sepsis.

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The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock

Abstract: In emergency department patients with septic shock, afebrile patients received lower rates of emergency department antibiotic administration, lower mean IV fluids volume, and suffered higher in-hospital mortality.

Cited by 44 publications

References 29 publications

Fever Incidence Is Much Lower in the Morning than the Evening: Boston and US National Triage Data

Fever Incidence Is Much Lower in the Morning than the Evening: Boston and US National Triage Data

Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis

Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics

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