No effect of preoperative selective gut decontamination on endotoxemia and cytokine activation during cardiopulmonary bypass: A randomized, placebo-controlled study

Background: Cardiopulmonary bypass predisposes the splanchnic region to inadequate perfusion and increases in gut permeability. Related to these changes, circulating endotoxin has been shown to rise during cardiac surgery, and may contribute to cytokine activation, high oxygen consumption, and fever (post-perfusion syndrome). To a large extent, free endotoxin in the gut is a product of the proliferation of aerobic Gram-negative bacteria and may be reduced by nonabsorbable antibiotics. Objective: To evaluate the effect of preoperative selective gut decontamination (SGD) on the incidence of endotoxemia and cytokine activation in patients undergoing open heart surgery. Design: Prospective, randomized, placebo-controlled double-blind trial. Setting: Tertiary-care university teaching hospital. Intervention: Preoperative administration for 5 to 7 days of oral nonabsorbable antibiotics (polymyxin B and neomycin) vs. placebo. The efficacy of SGD was assessed by culture of rectal swabs. Patients: Forty-four patients (median age 65 yrs, 29 males) were included in a pilot study to establish the sampling points of perioperative measurements. Seventy-eight consecutive patients (median age 65 yrs, 55 males) were enrolled for the prospective study; of these, 51 were randomly allocated to take SGD (n = 24) or placebo (n = 27); 27 were included in a control group (no medication). Measurements and Results: SGD but not placebo effectively reduced the number of rectal swabs that grew aerobic Gram-negative bacteria (27% vs. 93%, respectively; p < .001). SGD did not affect the occurrence of perioperative endotoxemia, nor did it reduce the tumor necrosis factor-alpha, interleukin-10, or interleukin-6 concentrations (p > .20), as determined before surgery, upon aorta declamping, 30 mins into reperfusion, or 2 hrs after surgery. Also, SGD did not alter the incidence of postoperative fever or clinical outcome measures such as duration of artificial ventilation and intensive care unit and hospital stay. Conclusion: SGD effectively reduces the aerobic Gram-negative bowel flora in cardiac surgery patients but fails to affect the incidence of perioperative endotoxemia and cytokine activation during cardiopulmonary bypass and the occurrence of a postperfusion syndrome.