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

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Abstract
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 (LT alpha+250) on the risk of prolonged mechanical ventilation after coronary artery bypass grafting. Prospective observational study. Tertiary care center. A total of 400 patients undergoing coronary artery bypass grafting were enrolled. 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. Patients with an AA genotype at the LT alpha+250 site and those without the LT alpha+250G/-308TNFG haplotype had a shorter duration of mechanical ventilation (11.5 vs. 27.8 hrs and 11.2 vs. 29.4 hrs; =.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 LT alpha+250 site and the LT alpha+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. The LT alpha+250 and LT alpha+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.