PERIOPERATIVE ENDOTOXEMIA AND BACTERIAL TRANSLOCATION DURING MAJOR ABDOMINAL-SURGERY - EVIDENCE FOR THE PROTECTIVE EFFECT OF ENDOGENOUS PROSTACYCLIN

Objective: To investigate the potential role of endogenous prostacycli n (PGI(2)) released after mesenteric traction during major abdominal s urgery on perioperative endotoxemia and bacterial translocation. Desig n: Prospective, randomized, double-blind clinical study, Setting: Oper ating room and surgical intensive care unit in a university hospital. Patients: Fifty consecutive patients scheduled for major abdominal sur gery (pancreas resection, abdominal aortic surgery). Interventions: Fi fteen minutes before skin incision, either 400 mg of ibuprofen or a pl acebo equivalent were administered intra venously. Immediately after p eritoneal incision, eventration and traction of the small bowel was in tentionally performed in a uniform fashion. Measurements and Main Resu lts: Baseline values were obtained before induction of anesthesia. Add itional measurements, along with assessments of hemodynamics and gas e xchange, were performed before incision of the peritoneum and at 5, 30 , and 45 mins and 3, 6, and 24 hrs after mesenteric traction, Arterial plasma concentrations of 6-keto-prostaglandin F-1 alpha and thromboxa ne B-2 (stable metabolites of PGI(2) and thromboxane A(2)) were determ ined by radioimmunoassay, Endotoxin was measured by limulus amebocyte lysate test, Mesenteric lymph nodes were sampled in 31 patients (ibupr ofen n = 14, placebo n = 17) and sent for culture under sterile condit ions. Transient hypotension and a marked increase of plasma 6-keto-pro staglandin F-1 alpha concentrations occurred up to 6 hrs after mesente ric traction in untreated patients with median peak concentrations (22 43 vs. 72 ng/L [p < .0001, placebo vs, ibuprofen], observed 5 mins aft er mesenteric traction), Endotoxemia occurred in both study groups, Ho wever, after mesenteric traction, plasma endotoxin concentrations were significantly higher in the ibuprofen group, Median peak concentratio ns (0.12 vs. 0.27 EU/mL [p < .001, placebo vs, ibuprofen]) were observ ed 3 hrs after mesenteric traction. Gram-negative bacteria in mesenter ic lymph nodes were detected exclusively in the ibuprofen group (n = 5 , p < .01). Conclusions: In ibuprofen-pretreated patients, significant ly higher endotoxin concentrations as well as bacterial translocation to mesenteric lymph nodes occurred, despite the absence of a transient decrease in mean arterial pressure that had been associated with PGI( 2) release. Therefore, we hypothesized that during major abdominal sur gery, endogenous PGI(2) released in response to mesenteric traction ma y play a crucial role in maintaining splanchnic microcirculation and t hus preserving gut mucosal barrier function.