Abstract
IntroductionCefepime, 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.MethodsWe performed a retrospective study of adult ICU patients treated with intravenous cefepime for at least 3 days between January 1, 2009 and December 31, 2011. The primary outcome was the development of cefepime neurotoxicity, with the likelihood of causality ascribed via a modified Delphi method.ResultsThis 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 to 3.5) grams. The median treatment duration was 6 (IQR 4 to 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, seven were considered definite cases, three probable, and five 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 four 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).ConclusionsCritically 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.
Highlights
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
To identify our cohort of interest, we entered these results into our electronic Mayo Medical Record Retrieval System and searched the clinical notes for diagnoses of ‘renal failure, kidney injury, renal insufficiency, kidney disease, renal disease, tubular necrosis, end-stage renal disease (ESRD), acute tubular necrosis (ATN), chronic kidney disease (CKD), acute kidney injury (AKI), chronic renal insufficiency (CRI), or acute renal failure (ARF)’ during the same time period
The likelihood of causality was ascribed via a modified Delphi method; in order for symptoms to be attributed to cefepime neurotoxicity, the following criteria had to be met: 1) neurologic symptoms consisting of encephalopathy, including decreased level of alertness, myoclonus, seizures, or any combination of these, 2) no alternative cause for neurological deterioration, 3) clear temporal relationship between neurologic symptoms and cefepime administration
Summary
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. The terms ‘encephalopathy’ or ‘delirium’ generically describe cerebral dysfunction of some type, but most of the time they are used to characterize patients with a change in attention, perception and memory. These neurological manifestations are very poorly understood considering their high prevalence in the ICU [13,14]. Given the pervasiveness of confounding causes of encephalopathy (for example infection, postoperative state, electrolyte disturbances, hypoglycemia, uremia, shock, alcohol withdrawal, pain, hypercapnia, hypoxemia), elucidating the cause of ‘altered mental status’ or ‘failure to awaken’ in a patient in the ICU can be challenging. We have noted that cefepime neurotoxicity may be a underappreciated phenomenon in ICUs [16]
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