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 prostacyclin (PGI(2)) released after mesenteric traction during major abdominal surgery on perioperative endotoxemia and bacterial translocation. Design: Prospective, randomized, double-blind clinical study, Setting: Operating room and surgical intensive care unit in a university hospital. Patients: Fifty consecutive patients scheduled for major abdominal surgery (pancreas resection, abdominal aortic surgery). Interventions: Fifteen minutes before skin incision, either 400 mg of ibuprofen or a placebo equivalent were administered intra venously. Immediately after peritoneal incision, eventration and traction of the small bowel was intentionally performed in a uniform fashion. Measurements and Main Results: Baseline values were obtained before induction of anesthesia. Additional measurements, along with assessments of hemodynamics and gas exchange, 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 thromboxane B-2 (stable metabolites of PGI(2) and thromboxane A(2)) were determined by radioimmunoassay, Endotoxin was measured by limulus amebocyte lysate test, Mesenteric lymph nodes were sampled in 31 patients (ibuprofen n = 14, placebo n = 17) and sent for culture under sterile conditions. Transient hypotension and a marked increase of plasma 6-keto-prostaglandin F-1 alpha concentrations occurred up to 6 hrs after mesenteric traction in untreated patients with median peak concentrations (2243 vs. 72 ng/L [p < .0001, placebo vs, ibuprofen], observed 5 mins after mesenteric traction), Endotoxemia occurred in both study groups, However, after mesenteric traction, plasma endotoxin concentrations were significantly higher in the ibuprofen group, Median peak concentrations (0.12 vs. 0.27 EU/mL [p < .001, placebo vs, ibuprofen]) were observed 3 hrs after mesenteric traction. Gram-negative bacteria in mesenteric lymph nodes were detected exclusively in the ibuprofen group (n = 5, p < .01). Conclusions: In ibuprofen-pretreated patients, significantly 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 surgery, endogenous PGI(2) released in response to mesenteric traction may play a crucial role in maintaining splanchnic microcirculation and thus preserving gut mucosal barrier function.