Drug-Induced Acute Pancreatitis: An Evidence-Based Classification (Revised).

INTRODUCTION: Drug induced acute pancreatitis is a difficult diagnosis for clinicians. We previously published an "Evidence-Based Classification System" on Drug-Induced Acute Pancreatitis widely used by clinicians to assist in the identification of drugs. Unfortunately, this prior analysis based only on published case reports has been misunderstood. The prior review did not include studies with higher evidentiary value, such as randomized trials, case-control studies, and/or pharmacoepidemiologic studies. The use of the prior classification system has led to many patients being inappropriately labeled as having drug-induced acute pancreatitis. We now propose a "Revised" Evidence- Based Classification System for the purpose of determining which drugs cause acute pancreatitis based on the Grading of Recommendations, Development, and Evaluation criteria. METHODS: A search of the English Language literature was performed to identify all case reports with medication and/or drug induced acute pancreatitis. We divided the drugs implicated as causing acute pancreatitis into four groups based on the quality of evidence as defined by GRADE quality parameters. RESULTS: Although 141 drugs were identified in the literature as causing acute pancreatitis, only 106 drugs published in the literature as causing acute pancreatitis were high quality case reports. Only 3 drugs had evidence as causing acute pancreatitis from randomized controlled clinical trials, including 6-mercaptopurine and azathioprine. DISCUSSION: The vast majority of drugs implicated as causing acute pancreatitis in the literature have low or very low quality of evidence supporting those claims.

Drug-induced acute pancreatitis: an evidence-based review.

The diagnosis of drug-induced acute pancreatitis often is difficult to establish. Although some medications have been shown to cause acute pancreatitis with a large body of evidence, including rechallenge, some medications have been attributed as a cause of acute pancreatitis merely by a single published case report in which the investigators found no other cause. In addition, some medications reported to have caused acute pancreatitis have obvious patterns of presentation, including the time from initiation to the development of disease (latency). There also appear to be patterns in the severity of disease. After reviewing the literature, we have classified drugs that have been reported to cause acute pancreatitis based on the published weight of evidence for each agent and the pattern of clinical presentation. Based on our analysis of the level of evidence, 4 classes of drugs could be identified. Class I drugs include medications in which at least 1 case report described a recurrence of acute pancreatitis with a rechallenge with the drug. Class II drugs include drugs in which there is a consistent latency in 75% or more of the reported cases. Class III drugs include drugs that had 2 or more case reports published, but neither a rechallenge nor a consistent latency period. Class IV drugs were similar to class III drugs, but only 1 case report had been published. Our analysis allows an evidence-based approach when suspecting a drug as causing acute pancreatitis.

Decreased mortality in acute pancreatitis related to early aggressive hydration.

OBJECTIVE: Early aggressive intravenous hydration is believed to prevent morbidity and mortality by preventing intravascular volume depletion and maintaining perfusion of the pancreas possibly preventing pancreatic necrosis. The following study was initiated to determine the relationship between the observed decrease in mortality and the role of early aggressive hydration. METHODS: A consecutive series of patients with acute pancreatitis from a single community hospital in 1998 were compared to a consecutive series of patients with acute pancreatitis from the same institution in 2008. RESULTS: Significantly more patients developed pancreatic necrosis; 26 (15%) of 173 patients in 1998 compared to 4 (4%) of 113 patients in 2008. The mean rate of hydration was significantly higher in 2008 compared with that in 1998 (P = 0.02). In 1998, hydration was provided at 184 mL/h during the first 6 hours and 188 mL/h during the first 12 hours compared with 284 mL/h during the first 6 hours and 221 mL/h during the first 12 hours in 2008. There was a significant decrease in mortality in 2008 compared with that in 1998 (3.5% vs 12%, P = 0.03). CONCLUSIONS: The decrease in mortality seen in patients with acute pancreatitis during the last decade may be related to the increased aggressive hydration preventing pancreatic necrosis.