Plasma ammonia concentration after L-asparaginase therapy in 27 dogs with high-grade lymphoma or leukemia.

OBJECTIVES: To establish the occurrence of increased plasma ammonia concentration after L-asparaginase (L-asp) administration in dogs with high-grade lymphoma or leukemia; to identify risk factors for the development of hyperammonemia after L-asp administration; and to determine occurrence of adverse events related to hyperammonemia. DESIGN: Prospective case controlled study of sequentially enrolled dogs between May 2011 and March 2012. SETTING: A university veterinary teaching hospital. ANIMALS: Twenty-seven dogs with high-grade lymphoma or leukemia. INTERVENTIONS: All dogs received L-asp intramuscularly at a median dose of 400 IU/kg. MEASUREMENTS AND MAIN RESULTS: Plasma ammonia concentrations were measured at baseline, 16 hours, and 48 hours after L-asp therapy. Clinicopathological abnormalities were assessed to determine risk factors for the development of hyperammonemia. Adverse events following L-asp were recorded. Median plasma ammonia concentrations at baseline, 16 hours, and 48 hours were 26 µmol/L (44 µg/dL), 98 µmol/L (166.9 µg/dL), and 67 µmol/L (114 µg/dL), respectively. Median plasma ammonia concentrations at 16 and 48 hours after administration were significantly increased compared to baseline. Six dogs had adverse events following L-asp administration. No significant clinical signs were noted that could clearly be attributed to hyperammonemia. No risk factors for developing hyperammonemia were identified; however, there was a positive correlation between the development of hyperammonemia at 16- and 48-hour time points. CONCLUSIONS: Subclinical hyperammonemia in dogs with lymphoma or leukemia after L-asp administration appears to be common. No risk factors were identified for the development of hyperammonemia after L-asp treatment, and severe adverse events were rare.

Acute hyperammonemia after L-asparaginase administration in a dog.

OBJECTIVE: To describe a previously unreported and potentially fatal complication of L-asparaginase (L-asp) administration in a dog. CASE SUMMARY: A 7-year-old, 6.6 kg, female spayed Beagle presented with a 1-week history of progressive inappetance and lethargy. Diagnostic tests identified the presence of stage Vb lymphoma and liver dysfunction. The dog was treated with L-asp at 400 IU/kg, corticosteroids, and IV fluids. Within 12 hours the dog became depressed, vomited, and developed abdominal pain. Within 24 hours, the dog's mentation progressed from obtunded to comatose; subsequently the dog developed a "decerebrate posture." Blood ammonia concentrations exceeded 1,000 µmol/L (1,700 µg/dL). Treatment with broad-spectrum antimicrobials, lactulose enemas, and continuous renal replacement therapy were initiated without response and the dog suffered cardiopulmonary arrest. NEW OR UNIQUE INFORMATION PROVIDED: The purpose of this report is to describe the development of severe hyperammonemia after L-asp therapy in a dog, which has not been previously reported in the literature. Given the rapid progression and fatal outcome observed in this case, early recognition may be crucial for management and treatment of this complication.