Objectives: The aim of this study was to study whether post-pancreaticoduodenectomy complications (PPDC) in high-risk patients can be reduced with hydrocortisone.
Background: Soft pancreas is a well-known risk factor for PPDC. Previously, we have shown that patients with >40% acini in the pancreatic transection line are most prone to PPDC. Recent studies have demonstrated that surgical trauma leads to inflammation of the pancreatic remnant, which precedes PPDC.
Methods: On the basis of power analysis, randomized controlled trial (RCT) (Clinicaltrials.gov NCT01460615), 155 patients (February 2011-May 2015) scheduled for pancreaticoduodenectomy were randomized to intravenous (i.v.) treatment with hydrocortisone 100 mg or placebo. All patients received the first dose at the induction of anesthesia. During the operation, the percentage of acini was calculated from pancreatic transection line frozen samples by a pathologist. As planned, only the high-risk patients with >40% acini (n = 62) continued in the study to receive in total 8 doses of randomization-based hydrocortisone/placebo every 8 hours. Primary endpoints were urine trypsinogen positive days and overall complications (Clavien-Dindo III-IV). Postoperative pancreatic fistulas (POPFs), postpancreatectomy hemorrhage (PPH), and delayed gastric emptying (DGE) were also graded.
Results: Hydrocortisone treatment did not alter trypsinogen release (2 or more positive days 46% vs 50%), but it significantly reduced overall complications compared with placebo in the high-risk patients (18% vs 41%; P < 0.05; Clavien-Dindo III-IV). Also, clinically significant POPF (11% vs 27%), PPH (14% vs 24%), and DGE (29% vs 44%) tended to be lower in the hydrocortisone group. Ninety-day mortality was zero.
Conclusions: This RCT shows that in high-risk patients, overall PPDC can be significantly reduced with hydrocortisone treatment. Inflammation may be an important mediator of PPDC.