Cefepime is Associated with Acute Encephalopathy in Critically Ill Patients: A Retrospective Case–Control Study

BACKGROUND: Acute encephalopathy (AE) is a common complication of critical illness and is associated with increased short and long-term mortality. In this study, we evaluated the role of cefepime in causing AE. METHODS: Retrospective case–control study involving consecutive patients enrolled in the intensive care units (ICUs) of Mayo Clinic Rochester, MN between July 1, 2004 and December 31, 2015. AE was defined by the presence of delirium or depressed level of consciousness in the absence of deep sedation. Controls were identified as patients not developing AE and were matched by propensity score for age, Charlson Comorbidity Index, 24-h Apache III score and invasive ventilation use. RESULTS: The total number of eligible ICU admissions during our study period was 152,999. AE was present in 57,726 (37.7%) with a median AE duration of 17 (interquartile range [IQR] 4.0–51.8) hours. We matched 14,645 cases with AE with the same number of controls. Cefepime was used in 1241 (4.2%) patients and its use was associated with greater incidence of AE [713 (4.9%) vs 528 (3.6%), p < 0.001] and duration [unit estimate 0.73; (95% CI 0.542–0.918)]. On multivariate analysis, cefepime was associated with an increased likelihood of AE after controlling for shock, midazolam infusion and acute kidney injury [OR 1.24 (95% CI 1.10–1.27)]. These associations were also present after controlling for prior chronic kidney disease. CONCLUSION: The use of cefepime is associated with increased likelihood and duration of AE. These associations are stronger among patients with impaired renal function, but can also occur in patients without renal impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-01035-w) contains supplementary material, which is available to authorized users.