Treatment of Fever After Stroke

Conflicting Evidence

Sylwia E. Wrotek, Ph.D.; Wieslaw E. Kozak, Ph.D.; David C. Hess, M.D.; Susan C. Fagan, Pharm.D.

Disclosures

Pharmacotherapy. 2011;31(11):1085-1091. 

In This Article

Abstract and Introduction

Abstract

Approximately 50% of patients hospitalized for stroke develop fever. In fact, experimental evidence suggests that high body temperature is significantly correlated to initial stroke severity, lesion size, mortality, and neurologic outcome. Fever occurring after stroke is associated with poor outcomes. We investigated the etiology of fever after stroke and present evidence evaluating the efficacy and safety of interventions used to treat stroke-associated fever. Oral antipyretics are only marginally effective in lowering elevated body temperature in this population and may have unintended adverse consequences. Nonpharmacologic approaches to cooling have been more effective in achieving normothermia, but whether stroke outcomes can be improved remains unclear. We recommend using body temperature as a biomarker and a catalyst for aggressive investigation for an infectious etiology. Care must be taken not to exceed the new standard of a maximum acetaminophen dose of 3 g/day to avoid patient harm.

Introduction

In a healthy human, the normal core body temperature is 37°C and is tightly controlled by the thermoregulatory center in the hypothalamus. Effective thermoregulatory defenses, which can be grouped into autonomic and behavioral responses, make body temperature difficult to disrupt. For a thorough review of this topic, the reader is referred to a previously published article.[1] Sometimes, however, thermoregulatory control is impaired by serious illness. Between 40% and 61% of patients who experience stroke develop fever, and those patients with fever are far more likely to die within the first 10 days after a stroke than those with lower temperatures.[2,3] Clinical data support that body temperature higher than 37.5°C significantly correlates with poor outcomes.[2,4–7] This was confirmed in two separate meta-analyses that showed that high body temperature after stroke is associated with significantly higher morbidity and mortality rates compared with normothermic patients, independent of the origin of the temperature elevation.[8,9]

There are two distinct causes of high body temperature: fever and hyperthermia. Very often, authors use the terms fever and hyperthermia interchangeably. However, it is important to make the distinction between them, because the origin and influence of these syndromes are different.[10] Hyperthermia represents a failure in thermoregulation in which there is uncontrolled heat production (e.g., during exercise), poor heat dissipation (e.g., wearing protective clothing in a hot and humid environment), or an external heat load (e.g., sunbathing or sauna) that does not involve a thermoregulatory set point.[11] Hyperthermia represents an unregulated rise in body temperature in which microbial products and pyrogenic cytokines are not directly involved and against which standard antipyretics are ineffective. Fever, however, is a complex reaction to pyrogens that not only causes the body's thermoregulatory set point to rise, but also simultaneously stimulates an acute-phase reaction and activates numerous metabolic, endocrinologic, and immunologic systems and behaviors.[12,13] It is likely that most cases of elevated body temperature after stroke are due to fever, not hyperthermia.

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