Post-operative acute pancreatitis (POAP) is an early event following pancreatoduodenectomy (PD), which may play key role in post-operative pancreatic fistula (POPF). The aim of current study is efficacy of perioperative administration of indomethacin in preventing POAP.

Methods : Single-center, double-blind, RCT on consecutive patients undergoing PD, to receive either 100mg of indomethacin (IA) per-rectally at induction of anesthesia or standard care(CA). Primary endpoint was incidence of POAP in the two arms. POAP was defined as POD1 serum amylase levels >upper limit of normal. Secondary endpoints included incidence of POPF, delayed gastric emptying (DGE) & intra-abdominal abscesses, length of ICU & hospital stay.

Results : After exclusion 44 patients were randomized (IA = 21 vs CA = 23). The two arms were comparable for preoperative and intraoperative parameters. POAP was noted in 20 out of 44 (45.5%) with significantly lower incidence of POAP (60.9% vs 28.6%, p = 0.032) in IA. Median serum amylase, POD 1, 3 and 5 drain amylase and incidence of clinically relevant POPF (CR-POPF) were lower in IA (30.4% vs 14.3%, p = 0.18). The severity of delayed gastric emptying (DGE) was significantly lower in the IA (Grade B/C DGE 23.8% vs 47.8%, p = 0.023). Evaluation of risk factors for POAP, showed IA to confer an independent protective effect and increased risk with soft pancreas.

Conclusion : Per-rectal Indomethacin administration peri-operatively is effective in decreasing the incidence of POAP following pancreatoduodenectomy. It may have a role in decreasing the incidence and severity of POPF and DGE.