Association of tumor necrosis factor gene polymorphisms and prolonged mechanical ventilation after coronary artery bypass surgery

Objective: Prolonged mechanical ventilation is a common complication after coronary artery bypass graft surgery. Tumor necrosis factor alpha is an important proinflammatory mediator in the post-coronary artery bypass graft inflammatory cascade. We attempted to study the effect of polymorphisms at the -308 site in the promoter region of the tumor necrosis factor gene (TNF-308) and the +250 site within the lymphotoxin-alpha gene (LTalpha+250) on the risk of prolonged mechanical ventilation after coronary artery bypass grafting. Design: Prospective observational study. Setting: Tertiary care center. Patients: A total of 400 patients undergoing coronary artery bypass grafting were enrolled. Measurements: The primary end point was time to extubate. Secondary end points were the percentages of patients extubated at 8, 24, and 48 hrs; the length of intensive care unit and hospital stay; the need for a rehabilitation facility; and 30-day mortality. Precollected blood was used for gene analysis. Genotyping was performed by polymerase chain reaction and restriction enzyme digestion. Main Results: Patients with an AA genotype at the LTalpha+250 site and those without the LTalpha+250G/-308TNFG haplotype had a shorter duration of mechanical ventilation (11.5 vs. 27.8 hrs and 11.2 vs. 29.4 hrs; p = .039 and .01, respectively). The risk of prolonged mechanical ventilation at 8, 24, and 48 hrs was higher for patients with a GA or GG genotype at the LTalpha+250 site and the LTalpha+250G/TNF-308G haplotype. This association between genotype and duration of mechanical ventilation was more dramatic in patients undergoing conventional coronary artery bypass grafting than in those undergoing off-pump coronary artery bypass grafting. With Bayesian analysis, clinical criteria and genotype can be used sequentially to predict the risk of prolonged mechanical ventilation. Conclusions. The LTalpha+250 and LTalpha+250G/TNF-308G haplotypes are associated with prolonged mechanical ventilation after coronary artery bypass graft. Preoperative genetic screening may guide intraoperative management to reduce postoperative complications.