Journal of hepatology | 2019
Perioperative Omega-3 fatty Acids Fails to Confer Protection in Liver Surgery. Results of a multicentric, double-blind, randomized controlled trial.
Abstract
OBJECTIVE\nTo investigate the perioperative use of Omega-3 polyunsaturated fatty acids (Ω3-FA) to reduce post-operative complications after liver surgery.\n\n\nSUMMARY BACKGROUND DATA\nIn a variety of animal models, Ω3-FA disclosed strong protective effects in alleviating hepatic ischemia/reperfusion injury and steatosis with enhancement of regeneration after major tissue loss. Given these benefits along with its safety profile, we hypothesized that perioperative administration of Ω3-FA in patients undergoing liver surgery may ameliorate the post-operative course.\n\n\nMETHODS\nA multi-centric, double-blind, randomized, placebo-controlled trial was designed to test whether two single intravenous infusions of OmegavenTM (Ω3-FA) vs. placebo may decrease morbidity. The primary endpoints were postoperative complications by severity (Clavien-Dindo classification) integrated in the Comprehensive Complication Index (CCI).\n\n\nRESULTS\nBetween July 2013 and July 2018, 261 patients (132 in the Omegaven and 129 in the placebo groups) were included in the trial from three centers. Most cases (87%, n=227) underwent open liver surgery and 56% (n=105) were major resections (≥3 segments). In an intention-to-treat analysis including the drop out cases, the mortality rate was 4% and 2% in the OmegavenTM and placebo groups (P=0.447; OR: 95%CI: 0.04-2.51), respectively. Any complications and major complications (Clavien-Dindo ≥3b) occurred in 46% vs. 43% (P=0.709) and 12% vs. 10% (P=0.69) in the Omegaven and placebo groups, respectively. The mean CCI was 17 (±23) vs.14 (±20) (P=0.417). An analysis excluding the drop-outs provided similar figures.\n\n\nCONCLUSIONS\nThe routine perioperative use of two single doses of intravenous Ω3-FA (100ml OmegavenTM) cannot be recommended in patients undergoing liver surgery (Grade A recommendation).\n\n\nLAY SUMMARY\nThis trial fails to detect an effect on the use of two single Omega-3 fatty acid infusions before and during liver surgery to reduce complications. Despite strong evidence of liver-directed anti-inflammatory and pro-regenerative action in various rodent models, this trial fails to confer liver protection with single Omega-3 fatty acid infusions and is therefore currently not recommended.