Case Presentation: A 19-year-old male with past medical history of well-controlled juvenile myoclonic epilepsy was transferred from a community hospital for management of acute necrotizing pancreatitis. Upon arrival, he was severely hypovolemic and hypotensive, prompting aggressive intravenous fluid resuscitation and initiation of vasopressor therapy. He became obtunded, and was intubated for airway protection. Broad-spectrum antibiotics were started given his developing requirement of three vasopressors for undifferentiated shock. Initial workup to determine underlying etiology of the pancreatitis, including structural, infectious, and metabolic causes, was unrevealing. Given the lack of alternate causes identified in his workup, the underlying etiology was thought to be his valproic acid, which was discontinued on arrival, but has been known to sometime cause drug-induced pancreatitis. Despite supportive and antimicrobial therapies, he developed multi-organ dysfunction, beginning with acute renal failure requiring continuous renal replacement therapy, and later progressing to acute liver and pancreatic failure. His liver failure led to the development of significant coagulopathies, requiring administration of multiple blood products. His pancreatic insufficiency led to extremely labile blood glucose levels. He later developed acute abdominal compartment syndrome, which was managed conservatively with a peritoneal drain & nasogastric decompression. Despite his continued need for renal replacement therapy and blood products, he did begin to show signs of clinical improvement initially; however, he later abruptly re-developed shock refractory to vasopressors, prompting initiation of stress-dose corticosteroids, anti-fungal therapy, and intravenous albumin. Despite these measures, he unfortunately developed ventricular fibrillation, progressed to pulselessness despite attempted cardiopulmonary resuscitation, and he was declared deceased.
Discussion: Valproic acid is a broad-spectrum antiepileptic medication used for the treatment of various forms of epilepsy. Common adverse effects, including sedation, nausea, vomiting, alopecia, and/or weight gain, can be dose-dependent or idiosyncratic. Rarer side effects include hyperammonemic encephalopathy, hepatitis, and pancreatitis. There does not appear to be a dose-dependent association in cases of pancreatitis. The mechanism of injury is not well understood, with proposed hypotheses suggesting free radical toxicity to pancreatic parenchyma, and a concurrent depletion of superoxide dismutase, glutathione peroxidase, and catalase. The incidence of this phenomenon is more commonly seen in the pediatric and adolescent patient populations.
Conclusions: Understanding the less common etiologies of pancreatitis is important when triaging patients presenting with concern for the disease. Management of drug-induced pancreatitis requires withdrawal of the causative agent in addition to standard supportive care. Additionally, if the offending agent isn’t quickly identified and discontinued, continued exposure increases the risk of progression to necrotizing pancreatitis, which can be rapidly fatal. Physicians should counsel patients about the early signs and symptoms of pancreatitis, so that medical attention can be promptly sought if symptoms develop.