JAMA：静脉输注葡萄糖/胰岛素/钾可降低ACS死亡风险

3月27日，波士顿塔夫茨医学中心心血管健康服务研究中心科研人员在《美国医学会杂志》上在线发表的一项研究成果显示，对疑似急性冠状动脉综合征(ACS)患者补充葡萄糖、胰岛素和钾(GIK)可使住院前或住院期间发生心脏骤停或死亡的几率减半。

在这项前瞻性、双盲、随机研究中，波士顿塔夫茨医学中心心血管健康服务研究中心主任Harry P. Selker博士及其同事将911例疑似急性冠状动脉综合征的患者随机分成2组，一组(n=479)接受常规治疗，另一组(n=432)输注30%葡萄糖、50 IU胰岛素和80 mEq氯化钾，输注速率为1.5 ml/(kg·h)。所有患者在救护车上接受12导联心电图、急性心肌缺血-时间-非敏感预测仪(ACI-TIPI)和溶栓预测仪(TPI)检查。

患者至少具有以下其中一项：ACI-TIPI预测ACS的可能性至少为75%，TPI检出STEMI或根据地方急诊医疗方案检出STEMI。患者的平均年龄为63岁，1/3具有心肌梗死史。护理人员来自美国13个州的36个急诊医疗系统。

GIK组和安慰剂组患者住院前或住院期间发生心脏骤停或死亡的比例分别为4%和9%，差异显著。GIK组复合终点中单个组分的发生率也有低于安慰剂组的趋势，但差异不显著。

30 d时，GIK组和安慰剂组的死亡率分别为4%和6%，差异不显著。GIK组和安慰剂组的30 d心力衰竭死亡率或住院率也相似(6% vs. 8%)。在ST段抬高心肌梗死(STEMI)患者中，GIK可显著降低心脏骤停或住院前或住院期间死亡这一复合终点事件的发生率。与安慰剂相比，GIK使STEMI患者的该终点事件发生率显著降低60%[6% vs. 14；风险比(RR)=0.39]。GIK组和安慰剂组30 d进展至心肌梗死(主要终点)的发生率分别为49%和53%，差异不显著。

值得注意的是，亚组分析证实，与出现症状后至少1~6 h才接受GIK的患者[比值比(OR)=0.39]或出现症状后6 h以上才接受GIK治疗的患者(OR=1.18)相比，仅出现症状后1 h内接受GIK治疗者的心脏骤停或院内死亡率显著降低(OR=0.28)。

GIK组任意一次血糖＞300 mg/dl的患者比例显著高于安慰剂组(21% vs. 10%)。此外，GIK还增加糖尿病患者的血糖水平(44% vs. 29%)，但并未导致任何严重不良事件。研究者表示，尽管GIK不能预防梗死，但可显著减小梗死面积。（生物谷 bioon.com）

doi:10.1001/jama.2012.426
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Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes

Harry P. Selker，MD，MSPH； Joni R. Beshansky，RN，MPH； Patricia R. Sheehan，RN，MS，MPH； Joseph M. Massaro，PhD； John L. Griffith，PhD； Ralph B. D’Agostino，PhD； Robin Ruthazer，MPH； James M. Atkins，MD； Assaad J. Sayah，MD； Michael K. Levy，MD； Michael E. Richards，MD，MPA； Tom P. Aufderheide，MD； Darren A. Braude，MD，MPH； Ronald G. Pirrallo，MD，MHSA； Delanor D. Doyle，MD； Ralph J. Frascone，MD； Donald J. Kosiak，MD，MBA； James M. Leaming，MD； Carin M. Van Gelder，MD； Gert-Paul Walter，MD； Marvin A. Wayne，MD； Robert H. Woolard，MD； Lionel H. Opie，MD，DPhil； Charles E. Rackley，MD； Carl S. Apstein，MD； James E. Udelson，MD

Context Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration. Objective To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS). Design, Setting, and Participants Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS. Intervention Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) administered by paramedics in the out-of-hospital setting and continued for 12 hours. Main Outcome Measures The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation. Results There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) vs those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; P = .34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% (n = 28) with GIK vs 8.9% (n = 41) with placebo (P = .26). Conclusions Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality.