Backgrounds and Aims: Ulinastatin, a protease inhibitor, has proved to be effective for the prevention of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to assess the efficacy of prophylactic Ulinastatin administration for postoperative pancreatitis and pancreatic fistula following pancreaticoduodenectomy.
Method: Patients undergoing pancreaticoduodenectomy were randomized to receive Ulinastatin (300,000 U/day for 3 days) or placebo by intravenous infusion before and after the surgery. Serum pancreatic enzyme levels, drain amylase, and urine trypsinogen-2 were measured before and after the surgery. The primary end point was the incidence of postoperative pancreatitis and pancreatic fistula. The secondary objective was the occurrence of other postoperative complication. Hyperamylasemia was defined as serum amylase levels more than 3 times the upper limit of normal. Postoperative pancreatitis was defined as the elevation of urine trypsinogen-2 levels more than 80 ug/L. Pancreatic fistula was defined as drain output amylase levels greater than 3 times than the upper normal serum amylase value on or after postoperative day3 (according to the International Study Group Pancreatic Fistula definition).
Results: A total of 42 patients were enrolled (20 in the Ulinastatin group, 20 in the placebo group, 2 excluded). There were no difference between the two group regarding baseline characteristics, or details of operative procedures.Patient who received Ulinastatin did not present any side effects related to the medication. Nine (36%) patients in the placebo group and two (8%) patients in the Ulinastatin group developed hyperamylasemia at 24 hours after the surgery (P=0.030)Five (25%) patients in the placebo group but no patient (0%) in the Ulinastatin group developed postoperative pancreatitis. (P=0.047) Two patients (10%) in the placebo group and two patients (10%) in the Ulinastatin group developed postoperative pancreatic fistula.(N.S) All of the postoperative pancreatic fistula were grade A, and none of them required a change in management or adjustment in the clinical pathway. Other postoperative complications include one wound infection and one cerebral infarction in the placebo group, one enteritis and one mesenteric arterial thrombus in the Ulinastatin group.
Conclusions: Prophylactic administration of Ulinastatin decreased the level of serum amylase and the incidence of postoperative pancreatitis, but not the incidence of postoperative pancreatic fistula following pancreaticoduodenectomy.