Cefepime-Induced Encephalopathy in a High-Risk Patient With Renal Insufficiency and Cirrhosis.

Cefepime is a fourth-generation, cephalosporin antibiotic commonly used as a first-line empirical treatment in a wide range of bacterial infections. It is predominantly excreted renally; therefore, a reduction in kidney function allows for the accumulation of cefepime to potentially toxic levels. Here we present a case of cefepime-induced encephalopathy (CIE) in a 67 years old male patient with advanced-stage renal insufficiency and cirrhosis who was admitted to our hospital for altered mental status (AMS). The patient was initially treated for hepatic encephalopathy (HE) given an elevated ammonia level (105 µg/dL), which had significantly improved. He was also placed on intravenous (IV) cefepime for Pseudomonas bacteremia. Four days later, the patient became drowsy and confused. A detailed workup for secondary causes of AMS was performed however no significant acute abnormalities were detected. The ammonia level remained within the normal range. There was no acute intracranial pathology reported on a head computerized tomography (CT). Furthermore, an electroencephalograph (EEG) was obtained which showed generalized periodic discharge with a tri-phasic wave pattern suggesting non-convulsive status epilepticus (NCSE). CIE was suspected at that point and cefepime administration was stopped. Following cefepime discontinuation, there was a remarkable improvement in the patient's mental status for several days after cefepime discontinuation that supported the diagnosis of CIE in our patient. Although the exact pathophysiology is unclear, CIE should be suspected in elderly patients, patients with renal dysfunction, and critical illness. Meanwhile, liver dysfunction can be an additional risk factor for CIE as it increases the permeability of the blood-brain barrier (BBB), altered neurotransmission, and neuro-inflammation.

Hyperammonemia in patients receiving valproic acid in the hospital setting: A retrospective review.

INTRODUCTION: Valproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric conditions. The reported incidences of hyperammonemia induced by VPA use is variable. The purpose of this study is to evaluate the incidence of VPA-induced hyperammonemia in the general adult inpatient population. METHODS: Adult patients who received at least 1 dose of VPA and derivatives between June 1, 2017 to December 31, 2017 were included. Patients were excluded if they did not have VPA administered during their inpatient stay or if they had elevated ammonia levels (>33 µmol/L) prior to initiation of VPA. Patients with a confirmed diagnosis of liver cirrhosis were also excluded. The primary endpoint was the incidence of hyperammonemia. Secondary outcomes included symptoms of hyperammonemia, diagnosis of VPA-induced hyperammonemia, and treatment of VPA-induced hyperammonemia. RESULTS: A total of 162 patients were included in this study. A total of 33 (20.4%) patients were identified as having the primary outcome of hyperammonemia; 26 (16.0%) patients had symptoms of hyperammonemia, and 13 (8.0%) patients were diagnosed with VPA-induced hyperammonemia. Treatment modalities included administration of lactulose, levocarnitine, discontinuing VPA, or decreasing the VPA dose. DISCUSSION: The administration of VPA in the general adult inpatient population resulted in a 20.4% incidence of hyperammonemia, with a lower rate of diagnosed VPA-induced hyperammonemia. Clinicians should be encouraged to obtain ammonia levels in patients receiving VPA if symptoms of altered mental status or encephalopathy develop.