CHAPTER 63

#### KEY POINTS

• Fever occurs in more than 50% of patients at some time during their ICU stay.

• Approximately 50% of fevers are due to noninfectious causes, such as drug fevers, surgical trauma, and central nervous system injury.

• A thoughtful evaluation of a fever may reduce costs and lessen the potential risk to the patient.

• Extreme elevations of temperature (>41.1°C) are most often not due to infectious etiologies.

• Heat stroke, serotonin syndrome, neuroleptic malignant syndrome, and malignant hyperthermia are life-threatening causes of hyperpyrexia that must be immediately recognized and treated in order to avoid multisystem organ failure and death.

• Although fever is associated with adverse outcomes in the ICU, there is no conclusive evidence to support the routine treatment of fever due to infection in non-brain-injured patients.

#### INTRODUCTION

Fever is a ubiquitous phenomenon in the intensive care unit.1 Although fever is a natural response to illness and injury, the occurrence of an elevated temperature in a critically ill patient frequently initiates both a gamut of unfocused diagnostic testing and multiple intravenous infusions of broad-spectrum antibiotics, often without a critical appraisal of the unique issues of the individual patient. This “one-size-fits-all” approach may not only add unnecessary costs, manpower, and interventions to patient care but may also expose patients to unnecessary risks. However, in selected patients, clinical pathways have the potential both to reduce costs and to improve the appropriateness of treatment, the latter of which may then lead to improved survival. A thorough understanding of the common etiologies of fever is critical to customizing the care of individual patients. In this chapter, we will review the physiology of temperature regulation, how to best measure temperature in the ICU, the epidemiology and the clinical impact of fever, the differential diagnosis of elevated body temperature, common infectious and noninfectious causes of fever, and general guidelines to evaluation and management in hopes to provide the reader with a rational approach to the febrile patient in the intensive care unit.

#### TEMPERATURE REGULATION AND MEASUREMENT

Healthy, nonfasting, resting adults, closely regulate sublingual temperature between 33.2°C and 38.1°C.2 There is normally a small normal diurnal variation in temperature of approximately 0.5°C, which nadirs around 6 am and peaks around 4 pm.3 This tight regulation occurs due to continual adjustment of thermogenic and cooling processes. Eating, exercise, and sleep deprivation increase body temperature while fasting reduces it.4 Technically fever refers to an increase in the natural set point for homeostatic temperature control while hyperthermia refers to an uncontrolled elevation of body temperature.

Thermoregulation resides within the hypothalamus.5 While countless exogenous and endogenous pyrogens have been identified, almost all have been shown to stimulate the release of proximal proinflammatory cytokines, such as IL-6, IL-8, IL-1β, and TNF, which subsequently induce the synthesis of prostaglandin E2 (PGE2) within the preoptic nucleus of the anterior hypothalamus (Fig. 63-1). Binding ...

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