Role of Octreotide in the Prevention of Postoperative Complications Following Pancreatic Resection Markus Btichler, MD, Helmut Friess, MD, Istvan Klempa, MD, Peter Hermanek, MD, Udo Sulkowski, MD, Heinz Becker, MD, Anton Schafmayer, MD, ho Baca, MD, Dietmar Lorenz, MD, Richard Meister, MD, Bernd Kremer, MD, Peter Wagner, MD, Jens Witte, MD, Ernst Ludwig Zurmayer, MD, Hans-Detlev Saeger, MD, Bernd Rieck, MD, Peter Dollinger, MD, Karl Glaser, MD, Reinhard Teichmann, MD, Jochen Konradt, MD, Wilhelm Gaus, Phn, Hans-Joachim Dennler, MD, Dieter Welzel, MD, Hans G. Beger, MD zyxwvutsrqpon Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associ- ated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exo- crine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, pla- cebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Pa- tients were stratified into a high-risk stratum (lim- ited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis) . Patients received octreotide (3 X 100 pg) or placebo subcutaneously for 7 days per- ioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resec- tion, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 pa- tients) and 55% in patients receiving placebo (67 of 121 patients) (p zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA <O.OOS) . In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreo- tide and in 46 of 71 (65%) patients given placebo (p KO.01) . Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (2 1 of 50 patients) in patients given placebo ( p = NS). A complete list of all affiliations appears on page 129. Requests for reprints should be addressed to Hans G. Beger, MD, FACS, Department of General Surgery, University of Ulm, Steinhoe- velstrasse 9, D-7900 Ulm, Germany. Presented at the 32nd Annual Meeting of the Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 20-22, 1991. The perioperative application of octreotide re- duces the occurrence of typical postoperative com- plications after pancreatic resection, particularly in patients with tumors. zyxwvutsrqponmlkjihgfedcbaZYXWVU T hough the mortality rate following pancreatic resec- tion has considerably improved in recent years, it remains between 3% and 10% [I-6]. Complications in- cluding medical and surgical morbidity occur in 30% to 40% of the patients [ 1,3,6-181. Major complications after pancreatic resection, some of which can be fatal, such as pancreatic fistula, intra-abdominal fluid collection, ab scess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. The concept of inhibiting exocrine pancreatic secre- tion to prevent postoperative complications was origi- nated in 1979 [ 191. In an open trial, a continuous intrave- nous infusion (250 pg/h) of somatostatin was administered to patients perioperatively after Whipple’s resection. The authors of the study reported a reduced complication rate. The human hormone somatostatin has been demonstrated to strongly inhibit basal and stimulat- ed exocrine pancreatic secretion [20-221. Recently, the synthetic somatostatin analogue, octreotide (SMS 201- 995), has become clinically available, and it is more po- tent in inhibiting pancreatic enzyme secretion [23,24] and has a much longer half-life [25,26] than does the native hormone. In a multicenter controlled and random- ized trial, we analyzed the value of the perioperative application (7 days) of octreotide in patients undergoing major elective pancreatic surgery. PATIENTS AND METHODS Between October 1989 and July 1990, 322 patients were recruited from 18 surgical departments in Germany (n = 17) and Austria (n = 1). The study was approved by the ethics committees of each of the participating hospi- tals. Patients with pancreatic or periampullary tumors and those suffering from chronic pancreatitis who were suitable for elective pancreatic surgery (resection) were enrolled in the study after giving written, informed con- sent. Patients were excluded who were undergoing emer- gency surgery of the pancreas (acute pancreatitis, pan- creatic trauma), total pancreatectomy, or pancreatic transplantation, or who were receiving only an elective pancreatic-cyst anastomosis. On the day before the oper- ation, the patients who satisfied the inclusion criteria were randomly assigned to receive a 7-day treatment of THE AMERICAN JOURNAL OF SURGERY VOLUME 163 JANUARY 1992 125