Does perioperative hydrocortisone or indomethacin improve pancreatoduodenectomy outcomes? A triple arm, randomized placebo-controlled trial

Backgrounds/Aims: This trial evaluated whether anti-inflammatory agents hydrocortisone (H) and indomethacin (I) could reduce major complications after pancreatoduodenectomy (PD). Methods: Between June 2018 and June 2020, 105 patients undergoing PD with>40% of acini on the intraoperative frozen section were randomized into three groups (35 patients per group): 1) intravenous H 100 mg 8 hourly, 2) rectal I suppository 100 mg 12 hourly, and 3) placebo (P) from postoperative day (POD) 0–2. Participants, investigators, and outcome assessors were blinded. The primary outcome was major complications (Clavien–Dindo grades 3–5). Secondary outcomes were overall complications (Clavien–Dindo grades 1–5), Clinically relevant postoperative pancreatic fistula (CR-POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), surgical site infections (SSI), length of stay, POD-3 serum amylase, readmission rate, and mortality. Results: Major complications were comparable (8.6%, 5.7%, and 8.6% in groups H, I, and P, respectively). However, overall complications were significantly lower in group H than in group P (45.7% vs. 80.0%, p=0.006). CR-POPF (14.3% vs. 25.7%, p=0.371), PPH (8.6% vs. 14.3%, p=0.710), DGE (8.6% vs. 22.9%, p=0.188), and SSI (14.3% vs. 25.7%, p=0.371) were comparable between groups H and P. Major complications and overall complications in group I were 5.7% and 60.0%, respectively, which were comparable to those in groups P and H. CR-POPF rates in groups H, I, and P were 14.3%, 17.1%, and 25.7%, respectively, which was comparable. Conclusions: H and I did not decrease major complications in PD.