JAMA：非心脏手术围手术期使用β-受体阻滞剂或可降低患者死亡率

非心脏手术围手术期应用β-受体阻滞剂治疗的有效性仍存在争议。美国圣弗朗西斯科麻醉医学中心Martin J. London博士及其同事对此进行了深入研究，旨在明确非心脏手术早围手术期使用β-受体阻滞剂治疗与术后30天结局之间的关系。他们的研究发现，对于接受非心脏手术、非血管性手术的倾向性得分匹配的人群来说，围手术期使用β-受体阻滞剂可引起存在2项或更多项改良心脏风险指数因素的患者30天全因死亡率减少。这些发现支持将改良心脏风险指数因素的累积数目作为围手术期开始或连续给予β-受体阻滞剂治疗的决策指标。相关成果发表于2013年4月最新一期的JAMA在线版上。
这一回顾性队列分析评估了非心脏手术围手术期或术后β-受体阻滞剂治疗的效应，纳入样本包括2005年1月至2010年8月在104家VA医疗中心接受治疗的基于人群样本的136745例患者，并按倾向性得分1：1比例纳入对照受试者37805例。主要结局为30天全因死亡率及心脏事件发生率（心跳停止或Q波心肌梗死）。
结果显示，总共有55138例患者(40.3%)暴露于β-受体阻滞剂。与接受非血管手术的患者(95% CI, 37.1%-37.6%; P < .001)相比，接受血管手术的患者暴露率更高(95% CI, 65.9%-67.5%)，两者暴露率分别为37.4% VS 66.7%，病例基数分别为122 882例和13 863例。研究者发现，随着改良心危险指数因素的增多，暴露率就越高：无风险因素时β-受体阻滞剂暴露率为25.3% (95% CI, 24.9%-25.6%)，存在4项风险因素时暴露率则为71.3% (95% CI, 69.5%-73.2%)(P < .001)或更多。总死亡率为1.1% (95% CI, 1.1%-1.2%)，心脏事件死亡率为0.9% (95% CI, 0.8%-0.9%)。在倾向性得分匹配队列中，发现暴露与死亡率降低相关(相对危险值[RR], 0.73; 95% CI, 0.65-0.83; P < .001; 需治疗的病例数[NNT], 241; 95% CI, 173-397)。当就改良心危险指数因素的积累数目进行分层后分析得知，β-受体阻滞剂可引起存在2个危险因素(RR, 0.63 [95% CI, 0.50-0.80]; P < .001; NNT, 105 [95% CI, 69-212])，3个危险因素(RR, 0.54 [95% CI, 0.39-0.73]; P < .001; NNT, 41 [95% CI, 28-80])或4个危险因素或更多(RR, 0.40 [95% CI, 0.25-0.73]; P < .001; NNT, 18 [95% CI, 12-34])的患者的死亡率显著性降低。研究人员发现，这些关联仅限于接受非血管性手术的患者人群。β-受体阻滞剂暴露可引起非致命性Q波心肌梗死或心动停止发生率降低(RR, 0.67 [95% CI, 0.57-0.79]; P < .001; NNT, 339 [95% CI, 240-582])，同样仅限于接受非血管性手术患者人群。
冠心病及其高危患者进行非心脏手术时，围手术期心脏事件（如死亡、卒中、心肌梗死等）的危险性显著增加。其机制较为复杂，其中儿茶酚胺水平升高以及心动过速可能与不良心脏事件的发生具有密切关系。鉴于此，多数学者认为在围手术期为患者应用β-受体阻滞剂可对心血管系统起到有效保护作用。根据有限的研究证据，不久前ACC/AHA颁布的指南建议为接受非心脏手术的心血管高危患者围手术期应用β-受体阻滞剂，并将其静息心率控制在50-60次/分范围内。
对于接受非心脏手术的冠心病及其高危患者，由于围手术期的精神紧张、术中血容量的改变、麻醉及其他药物的应用等因素，可能显著增加心血管系统负担并提高心率以及交感神经系统兴奋水平，导致发生心脏事件的危险性增加。从病理生理机制而论，应用β-受体阻滞剂可能会对心血管系统具有保护作用。因此国外相关指南中推荐为此类患者在围手术期应用b-受体阻滞剂。
本研究得出的结论是：对于接受非心脏手术、非血管性手术的倾向性得分匹配的人群来说，围手术期使用β-受体阻滞剂可引起存在2项或更多项改良心脏风险指数因素的患者30天全因死亡率减少。这些发现支持将改良心脏风险指数因素的累积数目作为围手术期开始或连续给予β-受体阻滞剂治疗的决策指标。当然这一研究结果还需要进行多中心随机试验以对就风险因素分类为低危至中危的患者人群中予以证实。
与β受体相关的拓展阅读：

• ACE抑制剂与β受体阻滞剂或许可预防化疗导致的心脏毒性
• 对于高血压患者β受体阻滞剂可减少阿尔茨海默型脑损伤
• Medscape:何时使用β受体阻滞剂？
• β受体阻滞剂不影响慢性肾病死亡率
• SLEEP：褪黑素可改善高血压患者应用β受体阻滞剂相关失眠
• β受体阻断剂在COPD的治疗或使用不足
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Association of Perioperative β-Blockade With Mortality and Cardiovascular Morbidity Following Major Noncardiac Surgery
Importance 
The effectiveness of perioperative β-blockade in patients undergoing noncardiac surgery remains controversial.
Objective 
To determine the associations of early perioperative exposure to β-blockers with 30-day postoperative outcome in patients undergoing noncardiac surgery.
Design, Setting, and Patients 
A retrospective cohort analysis evaluating exposure to β-blockers on the day of or following major noncardiac surgery among a population-based sample of 136 745 patients who were 1:1 matched on propensity scores (37 805 matched pairs) treated at 104 VA medical centers from January 2005 through August 2010.
Main Outcomes and Measures 
All cause 30-day mortality and cardiac morbidity (cardiac arrest or Q-wave myocardial infarction).
Results 
Overall 55 138 patients (40.3%) were exposed to β-blockers. Exposure was higher in the 66.7% of 13 863 patients undergoing vascular surgery (95% CI, 65.9%-67.5%) than in the 37.4% of 122 882 patients undergoing nonvascular surgery (95% CI, 37.1%-37.6%; P < .001). Exposure increased as Revised Cardiac Risk Index factors increased, with 25.3% (95% CI, 24.9%-25.6%) of those with no risk vs 71.3% (95% CI, 69.5%-73.2%) of those with 4 risk factors or more exposed to β-blockers (P < .001). Death occurred among 1.1% (95% CI, 1.1%-1.2%) and cardiac morbidity occurred among 0.9% (95% CI, 0.8%-0.9%) of patients. In the propensity matched cohort, exposure was associated with lower mortality (relative risk [RR], 0.73; 95% CI, 0.65-0.83; P < .001; number need to treat [NNT], 241; 95% CI, 173-397). When stratified by cumulative numbers of Revised Cardiac Risk Index factors, β-blocker exposure was associated with significantly lower mortality among patients with 2 factors (RR, 0.63 [95% CI, 0.50-0.80]; P < .001; NNT, 105 [95% CI, 69-212]), 3 factors (RR, 0.54 [95% CI, 0.39-0.73]; P < .001; NNT, 41 [95% CI, 28-80]), or 4 factors or more (RR, 0.40 [95% CI, 0.25-0.73]; P < .001; NNT, 18 [95% CI, 12-34]). This association was limited to patients undergoing nonvascular surgery. β-Blocker exposure was also associated with a lower rate of nonfatal Q-wave infarction or cardiac arrest (RR, 0.67 [95% CI, 0.57-0.79]; P < .001; NNT, 339 [95% CI, 240-582]), again limited to patients undergoing nonvascular surgery.
Conclusions and Relevance 
Among propensity-matched patients undergoing noncardiac, nonvascular surgery, perioperative β-blocker exposure was associated with lower rates of 30-day all-cause mortality in patients with 2 or more Revised Cardiac Risk Index factors. Our findings support use of a cumulative number of Revised Cardiac Risk Index predictors in decision making regarding institution and continuation of perioperative β-blockade. A multicenter randomized trial involving patients at a low to intermediate risk by these factors would be of interest to validate these observational findings.