Epidemiology

Fever is a common presenting complaint in both pediatric and adult (aged 18-65 years) emergency department (ED) patients. Patients often confuse fever with a disease process itself, rather than a sign of an illness. Morbidity and mortality rates from febrile illnesses vary dramatically with age. Younger adults with fever usually have benign self-limited disease, with less than 1% mortality. The challenge in this group is to identify the rare meningitis or septic conditions when confronted with a predominance of self-limited viral and focal bacterial diseases. Patients older than 65 years, or those with chronic disease who have fever, represent a group at high risk for serious disease. Morbidity and mortality rates in this group are significant. From 70 to 90% are hospitalized, and 7 to 9% die within 1 month of admission.¹ Infection is the most common cause of fever in these patients, and most of these infections are bacterial in nature. Three body systems—the respiratory tract, the urinary tract, and the skin and soft tissue—are the target for more than 80% of these infections.^1,2 The relative mortality and morbidity for any given infection are much higher in the geriatric population. For example, elders are at 5 to 10 times greater risk for urinary tract infections and 15 to 20 times for appendicitis.^1,3 Even viral illnesses that are generally not fatal, such as influenza, can be highly lethal in elder persons.

Pathophysiology

Body temperature is normally controlled within a narrow range by the preoptic area of the hypothalamus. This range is usually 36.0 to 37.8° C (96.8-100.0° F). There is a circadian rhythm within this range, with lower temperatures in the morning and higher temperatures in the late afternoon. Fever occurs when this normal range is reset to a higher value. Fever is defined by the Centers for Disease Control and Prevention as a core temperature greater than 37.8° C in the absence of fever-reducing medication. Fever should not be confused with hyperthermia. Hyperthermia is an elevation of the temperature related to the inability of the body to dissipate heat. Most cases of temperatures higher than 41.0° C (105.8° F) are a result of hyperthermia, but febrile illness also is considered.

In the anterior hypothalamus, neurons directly sense the blood temperature. Temperature is subsequently controlled by a combination of vasomotor changes, shivering, changes in metabolic heat production, and behavioral changes.

Fever may be produced by a number of endogenous and exogenous substances referred to as pyrogens. Endogenous pyrogens include a variety of cytokines released by leukocytes in response to infectious and inflammatory and neoplastic processes. Exogenous pyrogens include a large number of bacterial and viral products and toxins. Toxins induce fever by stimulating cells of the immune system to release endogenous pyrogens. These cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor, and interferon, travel to the hypothalamus and induce the production of prostaglandin E₂ (PGE₂).

PGE₂ raises the set point of the temperature range by a combination of effects, including peripheral vasoconstriction, increased metabolic heat production, shivering, and behavioral changes that conserve heat. Fever is maintained as long as the levels of endogenous pyrogens and PGE₂ are high. Cyclooxygenase inhibitors, such as aspirin, decrease fever by blocking the production of PGE₂. Age, malnutrition, and chronic disease may also blunt the febrile response.

Moderate elevations of the body temperature may serve to aid the host defense by increasing chemotaxis, decreasing microbial replication, and improving lymphocyte function. Elevated temperatures directly inhibit the growth of certain bacteria and viruses.⁴

Fever also results in certain increased physiologic costs to the host, including increased oxygen consumption, metabolic demands, protein breakdown, and gluconeogenesis. These costs are particularly problematic in elders, who typically have a smaller margin of reserve for any given body system. It is well established that the ability to develop fever in elders is somewhat impaired. Older individuals also are known to have lower baseline temperatures than younger adults.⁵ It has not been shown that treatment of fever with antipyretics has a beneficial effect on outcome or prevents complications; however, treatment to reduce the fever makes febrile patients more comfortable.⁴

The initial step in the process of fever is the resetting of the thermostatic set point in the hypothalamus to a higher temperature while actual body temperature remains normal. This mismatch of the thermostat with the “sensed” body temperature causes the patient to feel chilled (chills). If the chills are reported to a caregiver and the temperature is taken, it is usually found to be normal or minimally elevated. To the examiner’s touch, the patient’s skin temperature will feel normal. The patient remains chilled until the body temperature rises to near the (elevated) hypothalamic set point. At this point, the patient feels euthermic (but may feel fatigued or ill), but to the caregiver the skin temperature or thermometer reading is now elevated. The sequence of chills followed by febrile illness is the basis of the (incorrect) popular belief that getting chilled leads to infection (classically pneumonia). When the thermostatic set point is reduced to normal, the patient suddenly feels hot and sweats until the body temperature falls to match the (now normal) set point.

Differential Considerations

The complete differential diagnosis for the patient in the ED with fever is extensive. The major infectious and noninfectious causes are summarized in Table 12-1 and Box 12-1, respectively. The vast majority of serious causes are infectious in origin. Immediate threats to life are from decompensated shock (usually septic), respiratory failure (related to shock or pneumonia), or central nervous system infection (meningitis). Some critical noninfectious causes of fever also exist (see Box 12-1), but these are relatively rare and frequently do not occur with fever as the primary symptom.

A primary medical decision in acute febrile illness is based on assessment of patient stability (Fig. 12-1). Patients with life-threatening signs and symptoms, including significant alterations in mental status, respiratory distress, and cardiovascular instability, may require rapid, vigorous treatment. Prompt airway management and initiation of monitoring, intravenous access, fluid resuscitation, supplemental oxygen, and respiratory support are often necessary despite incomplete information concerning the cause of the fever. Sustained temperatures above 41.0° C are rare but can be damaging to neural tissue and require rapid cooling (e.g., misting, fans, cooling blankets).