Oxaliplatin-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Pancreatic Cancer: A Case Report

Abstract

Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX) chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m²) and oxaliplatin (100 mg/m²) on day 1, repeated every 2 weeks. The second cycle of GEMOX was administered as planned. However, he appeared to have difficulties with daily activities. Two days later, he visited the emergency room complaining of drowsiness. On examination, the patient had a Glasgow Coma Scale (GCS) score of 14 (E4V4M6), and asterixis was not present. Blood examination revealed a serum ammonia level of 202 µg/dL. The levels of serum hepatic enzymes were only mildly elevated, and the hemoglobin level was typical for this patient. Computed tomography, magnetic resonance imaging, lumbar puncture test, and blood culture showed no abnormality. Based on these results, he was diagnosed with oxaliplatin-induced hyperammonemia. One day after hospitalization, GCS score had significantly decreased to 6 (E1V1M4). His consciousness disorder improved after administration of a nutritional supplement containing a high concentration of branched-chain amino acids for 5 days, and the level of serum ammonia improved to 79 µg/dL. He stated that he could not remember the episode. The findings of this case suggest the importance of examining serum ammonia levels in patients receiving an oxaliplatin-containing regimen who develop disordered consciousness.

Drug-induced hyperammonaemia

“…The exact mechanism however remains unclear but may be related to negative effects on the Krebs cycle impacting the proximal urea cycle. Values of ammonia of up to 200 µmol/L have been recorded comfortably above the treatment threshold (see the Treatment section) 54 55…”

“…Combination therapy of VPA plus other AEDs (such as phenytoin, phenobarbital, carbamazepine and/or topiramate, zonisamide) has also been shown to be associated with increased risk of HA 55 56. While the mechanisms for HA are clear in some, others remain uncertain and so clinicians should be aware of the increased risk of HA in combination therapy particularly in those with symptoms associated with HA 58 59…”

Chemotherapy in a Breast Cancer Patient Heterozygous Carrier of Ornithine Transcarbamylase Deficiency

“…Several published cases show acquired hyperammonemia emulating UCD without a proven genetic alteration but induced by chemotherapy drugs. Several are associated with chemotherapy drugs and steroids in patients with hepatic and hematologic malignancies undergoing intensive cytoreductive treatment or bone marrow transplantation [11][12][13][14][15][16][17][18][19]. Causes are multifactorial, but catabolic state induced by chemotherapeutic agents that overwhelm the capacity of the urea cycle is possibly one of the main milestones.…”