Yende Sachin, Quasney Michael W, Tolley Elizabeth, Zhang Qing, Wunderink Richard G
Methodist Healthcare University Hospital, Memphis, TN, USA.
Crit Care Med. 2003 Jan;31(1):133-40. doi: 10.1097/00003246-200301000-00021.
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.
长时间机械通气是冠状动脉搭桥手术后常见的并发症。肿瘤坏死因子α是冠状动脉搭桥术后炎症级联反应中一种重要的促炎介质。我们试图研究肿瘤坏死因子基因启动子区域 -308 位点（TNF - 308）和淋巴毒素α基因内 +250 位点（LTα +250）的多态性对冠状动脉搭桥术后长时间机械通气风险的影响。
前瞻性观察研究。
三级医疗中心。
共纳入 400 例行冠状动脉搭桥手术的患者。
主要终点为拔管时间。次要终点为在 8、24 和 48 小时拔管的患者百分比；重症监护病房和住院时间；康复机构需求；以及 30 天死亡率。预先采集的血液用于基因分析。通过聚合酶链反应和限制性内切酶消化进行基因分型。
LTα +250 位点为 AA 基因型的患者以及无 LTα +250G/TNF - 308TNFG 单倍型的患者机械通气时间较短（分别为 11.5 小时对 27.8 小时和 11.2 小时对 29.4 小时；P 值分别为 0.039 和 0.01）。LTα +250 位点为 GA 或 GG 基因型以及 LTα +250G/TNF - 308G 单倍型的患者在 8、24 和 48 小时出现长时间机械通气的风险更高。这种基因型与机械通气时间之间的关联在接受传统冠状动脉搭桥手术的患者中比在接受非体外循环冠状动脉搭桥手术的患者中更为显著。通过贝叶斯分析，临床标准和基因型可依次用于预测长时间机械通气的风险。
LTα +250 和 LTα +250G/TNF - 308G 单倍型与冠状动脉搭桥术后长时间机械通气有关。术前基因筛查可能指导术中管理以减少术后并发症。
