Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy.
Crit Care. 2013 Nov 7;17(6):R264
Authors: Fugate JE, Kalimullah EA, Hocker SE, Clark SL, Wijdicks EF, Rabinstein AA
INTRODUCTION: Cefepime, a broad spectrum antibiotic, is commonly prescribed in intensive care units (ICU) and may be an overlooked cause of neurologic symptoms such as encephalopathy, myoclonus, seizures, and coma. We aimed to characterize cefepime neurotoxicity in the ICU.
METHODS: We performed a retrospective study of adult ICU patients treated with intravenous cefepime for at least 3 days between January 1st, 2009 and December 31st, 2011. The primary outcome was the development of cefepime neurotoxicity, with the likelihood of causality ascribed via a modified Delphi method.
RESULTS: This study included 100 patients. The mean age was 65.8 years (+/- 12.7 years). The median daily average dose of cefepime was 2.5 (IQR 2.0-3.5) grams. The median treatment duration was 6 (IQR 4--10) days. Renal failure in any form was present in 84 patients. Chronic kidney disease affected 40 patients, and 77 had acute kidney injury. Cefepime neurotoxicity occurred in 15 patients. Of these, 7 were considered definite cases, 3 probable, and 5 possible. Neurotoxic symptoms included impaired consciousness (n=13), myoclonus (n=11), disorientation (n=6), and nonconvulsive status epilepticus (n=1). The dose of cefepime was appropriately adjusted for renal clearance in 64 patients (75.3%) without cefepime neurotoxicity and 4 patients (28.6%) with neurotoxicity (P=0.001). Chronic kidney disease was present in 30 patients (35.3%) without neurotoxicity and in 10 (66.7%) of those with neurotoxicity (P=0.04).
CONCLUSIONS: Critically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Myoclonus and impaired consciousness are the predominant clinical manifestations. Neurotoxic symptoms occur more often when the cefepime dose is not adjusted for renal function, but can still occur despite those modifications.
PMID: 24200036 [PubMed - as supplied by publisher]