Low drain fluid amylase predicts absence of pancreatic fistula following pancreatectomy.

INTRODUCTION: Improvements in the ability to predict pancreatic fistula could enhance patient outcomes. Previous studies demonstrate that drain fluid amylase on postoperative day 1 (DFA1) is predictive of pancreatic fistula. We sought to assess the accuracy of DFA1 and to identify a reliable DFA1 threshold under which pancreatic fistula is ruled out. METHODS: Patients undergoing pancreatic resection from November 1, 2011 to December 31, 2012 were selected from the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project database. Pancreatic fistula was defined as drainage of amylase-rich fluid with drain continuation >7 days, percutaneous drainage, or reoperation for a pancreatic fluid collection. Univariate and multi-variable regression models were utilized to identify factors predictive of pancreatic fistula. RESULTS: DFA1 was recorded in 536 of 2,805 patients who underwent pancreatic resection, including pancreaticoduodenectomy (n = 380), distal pancreatectomy (n = 140), and enucleation (n = 16). Pancreatic fistula occurred in 92/536 (17.2%) patients. DFA1, increased body mass index, small pancreatic duct size, and soft texture were associated with fistula (p < 0.05). A DFA1 cutoff value of <90 U/L demonstrated the highest negative predictive value of 98.2%. Receiver operating characteristic (ROC) curve confirmed the predictive relationship of DFA1 and pancreatic fistula. CONCLUSION: Low DFA1 predicts the absence of a pancreatic fistula. In patients with DFA1 < 90 U/L, early drain removal is advisable.

Impurities in a morphine sulfate drug product identified as 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine.

Stability testing of morphine sulfate formulated with nonpareil sugar seeds (consisting of sucrose and starch) and fumaric acid revealed the formation of the three impurities 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine. 5-(Hydroxymethyl)-2-furfural was isolated via semipreparative HPLC utilizing volatile mobile phase constituents and was identified by analysis of its HRMS and NMR spectra. 10-Hydroxymorphine and 10-oxomorphine were obtained via semipreparative HPLC and subsequent removal of ion-pair reagents using an anion exchange resin, or by solid phase extraction, and identified by spectroscopic analysis followed by comparison with authentic materials. 5-(Hydroxymethyl)-2-furfural is a degradation product of hexose sugars, and its formation in the presence of morphine sulfate formulated with fumaric acid suggests that caution should be exercised when including nonpareil seeds in formulations that contain acidic drug salts and/or acid excipients. The preliminary results of tests on the interaction of acidic salts of some other drugs with nonpareil seeds are presented.