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Fever in ICU Review

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Fever in ICU Review Fever in the ICU* Paul E. Marik, MD, FCCP Fever is a common problem in ICU patients. The presence of fever frequently results in the performance of diagnostic tests and procedures that significantly increase medical costs and expose the patient to unnecessary invasive diagnostic procedures and the inappropriate use of antibiotics. ICU patients frequently have multiple infectious and noninfectious causes of fever, necessitating a systematic and comprehensive diagnostic approach. Pneumonia, sinusitis, and blood stream infection are the most common infectious causes of fever. The urinary tract is unimportant in most ICU patients as a primary source of infection. Fever is a basic evolutionary response to infection, is an important host defense mechanism and, in the majority of patients, does not require treatment in itself. This article reviews the common infectious and noninfectious causes of fever in ICU patients and outlines a rational approach to the management of this problem. (CHEST 2000; 117:855–869) Key words: cytokines; fever; ICU; sinusitis; urinary tract infection; ventilator-associated pneumonia Abbreviations: CDC ϭ Centers for Disease Control and Prevention; CFU ϭ colony-forming units; ELISA ϭ enzyme- linked immunosorbent assay; IL ϭ interleukin; TNF ϭ tumor necrosis factor; UTI ϭ urinary tract infection; VAP ϭ ventilator-associated pneumonia ever is a common problem in ICU patients. The primarily involved in the development of fever in- F presence of fever frequently results in the per- clude interleukin (IL) 1, IL-6, and tumor necrosis formance of diagnostic tests and procedures that factor (TNF)-␣.2–13 The interaction between these significantly increase medical costs and expose the cytokines is complex, with each being able to up- patient to unnecessary invasive diagnostic proce- regulate and down-regulate their own expression as dures and the inappropriate use of antibiotics. The well as that of the other cytokines. These cytokines main diagnostic dilemma is to exclude noninfectious bind to their own specific receptors located in close causes of fever and then to determine the site and proximity to the preoptic region of the anterior hypothalamus.2,3 Here, the cytokine receptor inter- For editorial comment see page 627 action activates phospholipase A2, resulting in the liberation of plasma membrane arachidonic acid as likely pathogens of those with infections. ICU pa- substrate for the cyclo-oxygenase pathway. Some tients frequently have multiple infectious and non- cytokines appear to increase cyclo-oxygenase expres- infectious causes of fever,1 necessitating a systematic sion directly, leading to liberation of prostaglandin and comprehensive diagnostic approach. This article E2. This small lipid mediator diffuses across the reviews the common infectious and noninfectious blood brain barrier, where it acts to decrease the rate causes of fever in ICU patients and outlines a of firing of preoptic warm-sensitive neurons, leading rational approach to the management of these pa- to activation of responses designed to decrease heat tients. loss and increase heat production.2,14 In a small proportion of hospitalized patients, hyperthermia may result from increased sympathetic activity with Pathogenesis of Fever increased heat production. Cytokines released by monocytic cells play a cen- tral role in the genesis of fever. The cytokines Significance of Fever Fever appears to be a preserved evolutionary * From the Department of Internal Medicine, Section of Critical 15–20 Care, Washington Hospital Center, Washington, DC. response within the animal kingdom. With few Manuscript received May 11, 1999; revision accepted October exceptions, reptiles, amphibians, and fish, as well as 25, 1999. several invertebrate species, have been shown to Correspondence to: Paul E. Marik, MD, Department of Internal Medicine, Washington Hospital Center, 110 Irving St NW, manifest fever in response to challenge with micro- Washington, DC 20010-2975; e-mail: [email protected] organism.15–19 Increased body temperature has been CHEST / 117/3/MARCH, 2000 855 shown to enhance the resistance of animals to infec- nary artery is considered the optimal site for core tion.21,22 Although fever has some harmful effects, temperature measurement; however, this method fever appears to be an adaptive response that has requires placement of a pulmonary artery cathe- evolved to help rid the host of invading pathogens. ter.40–42 Infrared ear thermometry has been demon- Temperature elevation has been shown to enhance strated to provide values that are a few tenths of a several parameters of immune function, including degree below temperatures in the pulmonary artery antibody production, T-cell activation, production of and brain.43–46 Rectal temperatures obtained with a cytokines, and enhanced neutrophil and macrophage mercury thermometer or electronic probe are often function.23–26 Furthermore, some pathogens such as a few tenths of a degree higher than core tempera- Streptococcus pneumoniae are inhibited by febrile ture.40–42 Rectal temperatures are perceived by pa- temperatures.27 tients as unpleasant and intrusive. Furthermore, It has long been known that increasing body access to the rectum may be limited by patient temperature is associated with improved outcome position, with an associated risk of rectal trauma. from infectious diseases. The preantibiotic era pro- Oral measurements are influenced by events such as vides abundant, although uncontrolled data, on the eating and drinking and the presence of respiratory deliberate use of elevated body temperature to treat devices delivering warmed gases.43 Axillary measure- infections. The beneficial effects of hot baths and ments substantially underestimate core temperature malarial fevers in syphilis were noted as early as the and lack reproducibility.43 Body temperature is 15th century.28 In mammalian models, increasing therefore most accurately measured by an intravas- body temperature results in enhanced resistance to cular thermistor, but measurement by infrared ear infection.29–32 In a retrospective analysis of 218 thermometry or with an electronic probe in the patients with Gram-negative bacteremia, Bryant and rectum is an acceptable alternative.47 Normal body colleagues33 reported a positive correlation between temperature is generally considered to be 37.0°C maximum temperature on the day of bacteremia and (98.6°F) with a circadian variation of between 0.5 to survival. Similarly, Weinstein and colleagues34 re- 1.0°C.2,14 The definition of fever is arbitrary and ported that a temperature Ͼ 38°C increased survival depends on the purpose for which it is defined. The in patients with spontaneous bacterial peritonitis. Society of Critical Care Medicine practice parame- Dorn and colleagues35 reported that children with ters define fever in the ICU as a temperature chickenpox who were treated with acetaminophen Ͼ 38.3°C (Ն 101°F).47 Unless the patient has other had a longer time to crusting of lesions than when features of an infectious process, only a temperature treated with placebo. Ͼ 38.3°C (Ն 101°F) warrants further investigation. An elevated body temperature may, however, also be associated with a number of deleterious effects, Fever Patterns most notably an increase in cardiac output, oxygen consumption, carbon dioxide production, and energy Attempts to derive reliable and consistent clues expenditure.36 Oxygen consumption increases by from evaluation of a patient’s fever pattern is fraught approximately 10% per degree Celsius.36 These with uncertainly and not likely to be helpful diagnos- changes may be poorly tolerated in patients with tically.2,14,48 Most patients have remittent or inter- limited cardiorespiratory reserve. In patients who mittent fever that, when due to infection, usually have suffered a cerebrovascular accident or trau- follow a diurnal variation.48 Sustained fevers have matic head injury, moderate elevations of brain been reported in patients with Gram-negative pneu- temperature may markedly worsen the resulting monia or CNS damage.48 The appearance of fever at injury.37 Maternal fever has been suggested to be a different time points in the course of a patient’s cause of fetal malformations or spontaneous abor- illness may however provide some diagnostic clues. tions.38,39 However, this association has not been Fevers that arise Ͼ 48 h after institution of mechan- rigorously tested. ical ventilation may be secondary to a developing pneumonia.49,50 Fevers that arise 5 to 7 days postop- eratively may be related to abscess formation.51 Definitions and Measurement of Fever Fevers that arise 10 to 14 days postinstitution anti- biotics for intra-abdominal abscess may be due to Accurate and reproducible measurement of body fungal infections.52–54 temperature is important in detecting disease and in monitoring patients with an elevated temperature. A Causes of Fever in the ICU variety of methods are used to measure body tem- perature, combining different sites, instruments, and As outlined above, any disease process that results techniques. The mixed venous blood in the pulmo- in the release of the proinflammatory cytokines IL-1, 856 Reviews IL-6, and TNF-␣ will result in the development of be considered in ICU patients are listed in Table fever. While infections are the commonest cause of 1.1,55,66–68 For reasons that are not entirely clear, fever in ICU patients, many noninfectious inflamma- most noninfectious disorders usually do not lead to a tory conditions cause the release of
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