3 results
2200 The effect of antipyretics and fever on the mortality of mechanically ventilated patients
- Emily M. Evans, Rebecca J. Doctor, Brian M. Fuller, Richard S. Hotchkiss, Anne M. Drewry
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, pp. 30-31
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OBJECTIVES/SPECIFIC AIMS: (1) To evaluate clinical outcomes in mechanically ventilated patients with and without fever. We hypothesize that, after adjusting for confounding factors such as age and severity of illness: (a) In septic patients, fever will be associated with improved clinical outcomes. (b) In nonseptic patients, fever will be associated with worse clinical outcomes. (2) To examine the relationship between antipyretics and mortality in mechanically ventilated patients at risk for an acute lung injury. We hypothesize that antipyretics will have no effect on clinical outcomes in mechanically ventilated patients with and without sepsis. METHODS/STUDY POPULATION: This is a retrospective study of a “before and after” observational cohort of 1705 patients with acute initiation of mechanical ventilation in the Emergency Department from September 2009 to March 2016. Data were collected retrospectively on the first 72 hours of temperature and antipyretic medication from the EHR. Temperatures measurements were adjusted based on route of measurement. Patients intubated for cardiac arrest or brain injury were excluded from our primary analysis due to the known damage of hyperthermia in these subsets. Cox proportional hazard models and multivariable linear regression analyzed time-to-event and continuous outcomes, respectively. Predetermined patient demographics were entered into each multivariable model using backward and forward stepwise regression. Models were assessed for collinearity and residual plots were used to assure each model met assumptions. RESULTS/ANTICIPATED RESULTS: Antipyretic administration is currently undergoing analysis. Initial temperature results are reported here. In the overall group, presence of hypothermia or fever within 72 hours of intubation compared with normothermia conferred a hazard ratio (HR) of 1.95 (95% CI: 1.48–2.56) and 1.31 (95% CI: 0.97–1.78), respectively. Presence of hypothermia and fever reduced hospital free days by 3.29 (95% CI: 2.15–4.42) and 2.34 (95% CI: 1.21–3.46), respectively. In our subgroup analysis of patients with sepsis, HR for 28-day mortality 2.57 (95% CI: 1.68–3.93) for hypothermia. Fever had no effect on mortality (HR 1.11, 95% CI: 0.694–1.76). Both hypothermia and fever reduced hospital free days by 5.39 (95% CI: 4.33–7.54) and 3.98 (95% CI: 2.46–5.32) days, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: As expected, both hypothermia and fever increased 28-day mortality and decreased hospital free days. In our sepsis subgroup, hypothermia again resulted in higher mortality and fewer hospital free days, while fever did not have a survival benefit or cost, but reduced hospital free days. Antipyretic administration complicates these findings, as medication may mask fever or exert an effect on survival. Fever may also affect mechanically ventilated septic patients differently than septic patients not on mechanical ventilation. Continued analysis of this data including antipyretic administration, ventilator free days and progression to ARDS will address these questions.
2521 Use of forced air warming devices to induce fever-range hyperthermia in critically ill septic patients
- Anne M. Drewry, Enyo A. Ablordeppey, Marin H. Kollef, Richard S. Hotchkiss
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, p. 50
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OBJECTIVES/SPECIFIC AIMS: Afebrile septic patients are twice as likely to die and develop nosocomial infections as compared with those with fever; the reason for these differences is unknown. One hypothesis is that elevated temperatures directly boost immunity and inhibit microorganism growth. However, there is little data examining the clinical effects of warming septic patients. The goal of this study was to determine whether warming afebrile septic patients to fever-range hyperthermia with noninvasive forced air warmers is feasible and safe. METHODS/STUDY POPULATION: This is an ongoing randomized trial on afebrile mechanically ventilated patients with severe sepsis. The intervention consisted of 48 hours of external warming with a forced air warming device to a goal core temperature of 1.5°C higher than the lowest recorded temperature within the 24 hours preceding enrollment. Efficacy of the intervention and adverse event data (i.e., increases in heart rate and vasopressor doses) were collected. Clinical outcomes included 28-day mortality and acquisition of secondary infections. RESULTS/ANTICIPATED RESULTS: In total, 18 patients were randomized to the control and warming groups, respectively. Baseline characteristics (including demographics, comorbidities, and illness severity scores) were similar among the 2 groups, except the control group had more males (61% vs. 28%, p=0.04). Median (IQR) body temperature averaged over the 48-hour intervention period was higher in the warming group [38.2 (37.6, 38.6) vs. 37.1 (36.4, 37.4) °C, p<0.001). Patients in the warming group achieved core temperatures above their goal for a median of 37 (IQR 11, 45) hours during the 48-hour intervention period. There were no differences in heart rate or vasopressor dose changes or acquisition of secondary infections between the groups. Eight (44.4%) control patients and 3 (16.7%) warmed patients died by day 28 (p=0.07). DISCUSSION/SIGNIFICANCE OF IMPACT: Externally warming severe septic patients with forced air warming devices effectively raises core body temperature and is safe. Additional research will focus on cellular and immunological changes seen in warmed Versus control patients.
31 - Apoptotic Cell Death in Sepsis
- from Part II - Cell Death in Tissues and Organs
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- By Pavan Brahmamdam, Washington University School of Medicine, Jared T. Muenzer, Washington University School of Medicine, Richard S. Hotchkiss, Washington University School of Medicine, Jonathan E. McDunn, Washington University School of Medicine
- Edited by John C. Reed
- Douglas R. Green
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- Book:
- Apoptosis
- Published online:
- 07 September 2011
- Print publication:
- 22 August 2011, pp 363-371
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Summary
Introduction
More than 210,000 people die from sepsis in the United States each year, with an annual cost of more than 16 billion dollars. Despite continued advances in treatment and prevention, sepsis is a growing problem, with a significant mortality rate of 28% to 50%. In the past, death from sepsis was thought be due to uncontrolled inflammation, and as a result, numerous anti-inflammatory therapeutics were developed. Uncontrolled inflammation leading to death may be true in sepsis due to certain types of pathogens (e.g., Neisseria meningitides, Clostridium perfringens) and in these patients anti-inflammatory therapies may help. However, large-scale clinical trials of anti-inflammatory therapies in septic patients have failed to reduce patient mortality. Recent research into the host's immune response in sepsis has led to a fundamental change in the way clinicians and researchers think about this disease. After an initial hyper-inflammatory phase, septic patients may descend into a period of prolonged immune suppression, and it is during this period that the majority of patients die. Death usually occurs from multiorgan system failure brought on by the host's inability to clear the primary infection or from a second opportunistic or nosocomial infection. One important hallmark of sepsis is widespread cell death in multiple organ systems due to both apoptosis and necrosis. This chapter reviews the cell types that undergo apoptosis and necrosis, the known inciting factors and mechanisms of cell death, and the impact of sepsis-induced apoptosis on morbidity and mortality, especially focusing on the importance of the lymphocyte.