Clinical and demographic factors associated with antipyretic use in gram-negative severe sepsis and septic shock

Abstract

Background: Antipyretic therapy is commonly prescribed for patients with infection, but studies of its impact on clinical outcomes have yielded mixed results. No data exist to characterize the use of antipyretic medications in patients with severe sepsis or septic shock.

Objective: To identify clinical and demographic factors associated with antipyretic medication administration in severe sepsis and septic shock.

Methods: This single-center, retrospective, cohort study assessed febrile patients (temperature ≥ 38.3 °C) with gram-negative severe sepsis or septic shock at an 1111-bed academic medical center between January 2002 and February 2008. Patients were excluded if they had liver disease, acute brain injury, or allergy to acetaminophen. Generalized estimating equations were used to estimate the effect of clinical factors on treatment of patients with antipyretic medications.

Results: Although 76% of patients in this febrile cohort (n = 241) were prescribed an antipyretic agent, only 42% received antipyretic therapy; 95% of the doses were acetaminophen. Variables associated with antipyretic treatment were maximum body temperature (OR 2.11, 95% CI 1.53 to 2.89), time after sepsis diagnosis (OR 0.88, 95% CI 0.82 to 0.95), surgery during hospitalization (OR 0.49, 95% CI 0.31 to 0.80), death within 36 hours (OR 0.35, 95% CI 0.15 to 0.85), and mechanical ventilation (OR 0.58, 95% CI 0.34 to 0.98). Severity of illness factors, demographic factors, and patient treatment location did not predict who would receive antipyretic therapy.

Conclusions: Most febrile episodes in patients with gram-negative severe sepsis or septic shock were not treated with antipyretic medications. Further studies are needed to demonstrate the effect of antipyretics on clinically relevant outcomes in severe sepsis and septic shock.

Figure 1. Patient flow diagram

Figure 2. Proportion of patients treated with antipyretic medication by fever threshold

The rate of treatment with antipyretic medications depends on the clinician’s definition of fever. Although fever is defined as 38.3°C, practitioners may have different treatment thresholds. The graph shows the rate of antipyretic treatment based on treatment threshold (95% confidence interval), including all febrile time periods (n = 673). Each patient may be represented in more than one time period.

Figure 3. Patients treated with antipyretic medication by time since diagnosis of severe sepsis or septic shock

The rate of treatment with antipyretic medications varies based on the time since diagnosis with infection. As the time increases, the rate of therapy falls over the first 32 hours, then rises again. White bars represent the rate of treatment, and black bars represent the portion of the cohort that is febrile (95% confidence interval). All time periods (n = 2169) are included in this analysis, and each patient may be represented in more than one time period.