S212 Comparative Effectiveness and Safety of Prophylactic Drugs in Preventing Clinically Relevant Postoperative Pancreatic Fistula After Pancreatic Resection: A Network Meta-Analysis of RCTs

Introduction: Clinically relevant postoperative pancreatic fistula (POPF) is a serious complication after pancreatic surgery. Multiple prophylactic drugs, including somatostatin analogs and steroids, are used to prevent POPF, but their comparative effectiveness and safety are uncertain. This network meta-analysis evaluates these treatments to identify the best options for prevention. Methods: We systematically searched 5 databases to identify relevant randomized controlled trials. Screening of studies was conducted using Covidence. Network meta-analysis was performed with the Netmeta package in R, and visualizations such as forest plots, along with supplementary analyses, were generated using Stata 18.0. The quality and risk of bias of included studies were assessed with the ROBS 2.0 tool. Results: A total of 2,782 records were screened, with 17 studies meeting inclusion criteria, comprising 2,850 patients (1,411 treatment; 1,439 control). Patient distribution included 80 hydrocortisone, 369 octreotide, 410 pasireotide, 1,376 placebo, and 137 somatostatin recipients. Somatostatin showed the greatest reduction in overall POPF risk (odds ratio [OR] 0.40; 95% CI, 0.16–0.97), followed by octreotide (OR 0.55; 95% CI, 0.37–0.82), hydrocortisone (OR 0.91; 95% CI, 0.29–2.83), while pasireotide demonstrated no significant benefit (OR 1.06; 95% CI, 0.55–2.05). SUCRA rankings confirmed somatostatin as the most effective, followed by octreotide and hydrocortisone, with placebo and pasireotide least effective. Additionally, somatostatin achieved the highest improvement in quality of life among the interventions. Postoperative morbidity (RR 0.17; 95% CI, 0.10–0.44), 30-day mortality (RR 0.18; 95% CI, 0.07–0.36), and respiratory adverse events (RR 0.26; 95% CI, 0.19–0.47) were significantly reduced. These findings support the superior efficacy and safety of somatostatin and select analogs for preventing clinically relevant POPF after pancreatic resection. Conclusion: This network meta-analysis demonstrates that somatostatin and octreotide are the most effective prophylactic agents for reducing clinically relevant POPF after pancreatic resection, with somatostatin also providing the greatest quality of life benefit. These findings highlight the importance of selecting appropriate pharmacologic prophylaxis to improve postoperative outcomes and reduce morbidity and mortality.