RCT Assessing Efficacy of Perioperative Hydrocortisone and Indomethacin Treatment in Reducing Major Complications after Whipple’s Pancreaticoduodenectomy

Abstract

Introduction: After Whipple’s Pancreaticoduodenectomy (PD), pancreatic anastomotic leak leading to postoperative pancreatic fistula (POPF), Post pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE) and Sepsis cause major morbidity. Hydrocortisone and indomethacin have been postulated to reduce post-operative pancreatitis and thus Pancreatic leak. This RCT compares their role in preventing major complications in high-risk patients, Methods: Between January 2018 to April 2019, 146 patients undergoing Whipple’s PD were randomized into 3 arms, intravenous (i.v) hydrocortisone, per rectal (PR) indomethacin, or placebo. Only high-risk patients (n= 105) with >40% of acini (a marker of the soft pancreas) based on the intraoperative frozen section were included. All patients received a total of 8 doses of i.v. treatment (8 hourly) and 6 doses of PR treatment (12 hourly). Primary end-points were major complications (Clavien–Dindo 2-5) Results: As compared to placebo The Hydrocortisone group, had significantly less major complications (14.3% vs 40.0%; P value = 0.003). Clinically significant POPF (8.6% vs 20%) and DGE (14.3% vs 22.9%) were lower. The Indomethacin group did not show decrease in major complications (37.2% vs 40%; p value = 1.00) except for DGE (14.3% vs 22.9%; p value = 0.001). Clinically significant POPF (17.1% vs 20%) and PPH (11.4% vs 14.3%) are not significantly lower in indomethacin group. No 30 day mortality in either group. Conclusion: This RCT shows that Hydrocortisone treatment is significantly better than Indomethacin in reducing the major postoperative complications in high-risk patients after Whipple’s PD.