title: Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery.
abstract: This study investigated the relationship of the hepatosplanchnic production and uptake of inflammatory mediators, hepatosplanchnic perfusion, and outcome during major abdominal surgery to evaluate the hypothesis that regional production of inflammatory mediators precedes the development of hepatic dysfunction. This retrospective analysis of data and blood samples collected during a randomized controlled clinical trial included high-risk surgical patients undergoing major abdominal surgery in a 24-bed university-afilliated intensive care unit. Patients were divided into a subgroup that developed hepatic dysfunction (HD+) postoperatively and a subgroup without hepatic dysfunction (HD-). Hepatic vein and arterial plasma levels of IL-6, IL-8, s-E-selectin, s-ICAM-1, and the TNF-receptors 55 and 75 were measured, and the flux was calculated by multiplying the difference in hepatic vein minus arterial levels of the mediators by the hepatosplanchnic flow. Systemic (thermodilution) and total hepatosplanchnic blood flow (using indocyanine green [ICG]-dilution method) and gastric intramucosal pH (pHi) were assessed preoperatively, 4, 24, and 36 h postoperatively. Of a total of 26 patients, 6 patients developed hepatic dysfunction after their abdominal surgery (mean 6 days postoperatively). The number of sepsis-related deaths and postoperative days on the ventilator were significantly higher in this group. A higher production of IL-8, TNF-receptor-75 and 55 in the hepatosplanchnic area in the HD+ subgroups was found, which preceded the development of organ dysfunction (P = 0.04, P = 0.02, and P = 0.02, respectively). Moreover, the uptake of s-ICAM-1 was significantly increased in this subgroup. Furthermore, total hepatosplanchnic blood flow was significantly higher and pHi was significantly lower in the HD+ group, whereas global hemodynamic data were similar in the two subgroups. In conclusion, the development of postoperative organ dysfunction is preceded by an increased regional inflammatory response, indicated by an increased soluble TNF-receptor shedding and IL-8 production from the hepatosplanchnic area together with an increased uptake of s-ICAM-1. Moreover, an increased total hepatosplanchnic blood flow with intramucosal acidosis was associated with this regional inflammatory response.
authors.affiliation: Department of Surgery, University Hospital Maastricht, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Poeze
authors.forename: G
authors.initials: G
authors.lastname: Ramsay
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.forename: J W M
authors.initials: JW
authors.lastname: Greve
authors.forename: M
authors.initials: M
authors.lastname: Dentener
authors.forename: J
authors.initials: J
authors.lastname: Takala
mesh_terms: D000368:Aged; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008102:Liver Circulation; D017093:Liver Failure / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D012189:Retrospective Studies; D013152:Splanchnic Circulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators