Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial
Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial
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DOI：
10.1001/jama.2019.20833
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发表时间：
2020-01-21
影响因子：
120.7
通讯作者：
Laclautre, Lise
中科院分区：
文献类型：
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作者：
Futier, Emmanuel;Garot, Matthias;Laclautre, Lise
重要性目前尚不清楚使用含有羟乙基淀粉（HES）的胶体溶液来纠正高危外科患者的血管内缺陷是否有效或安全。目的评价HES 130/0.4与0.9%生理盐水相比用于血管内容量扩张对腹部大手术后死亡率和术后并发症的影响。2016年2月至2018年7月在法国20家大学医院接受腹部大手术的775例术后肾损伤风险增加的成人患者的平行组、随机临床试验;最终随访时间为2018年10月。干预患者随机接受含6%羟乙基淀粉130/0.4（稀释于0.9%生理盐水中）的液体（n= 10）。389）或0.9%生理盐水单独（n=386）在250-mL推注中使用个体化血流动力学算法在手术期间和术后第一天长达24小时，定义为在第二天上午7：59结束。次要结果包括术后14天内预定义的术后并发症、重症监护室和住院时间以及术后28天和90天的全因死亡率。结果在入组的826例患者中（平均年龄68 [SD，7]岁; 91例女性[12%]），775例（94%）完成了试验。HES组389例患者中有139例（36%）发生主要结局，生理盐水组386例患者中有125例（32%）发生主要结局（差异，3.3% [95% CI，-3.3%至10.0%];相对风险，1.10 [95% CI，0.91-1.34]; P = 0.33）。在报告的12个预先规定的次要结局中，11个显示无显著差异，但在第1天给予的研究液体中位体积方面存在统计学显著差异：1250毫升（四分位距，750-2000 mL），1500 mL（四分位距，750-2150 mL）（中位数差异，250 mL [95% CI，83-417 mL]; P = .006）。术后28天，HES组和生理盐水组分别有4.1%和2.3%的患者死亡（差异，1.8% [95%CI，-0.7%至4.3%];相对危险度，1.76 [95%CI，0.79-3.94]; P = .17）。结论和相关性在接受腹部大手术的术后肾损伤风险患者中，与0.9%生理盐水相比，使用羟乙基淀粉进行容量替代治疗在术后14天内死亡或严重术后并发症的复合结局方面没有显著差异。这些结果不支持在此类患者中使用羟乙基淀粉进行容量替代治疗。
IMPORTANCE It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe.OBJECTIVE To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery.DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018.INTERVENTIONS Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n=389) or 0.9% saline alone (n=386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day.MAIN OUTCOMES AND MEASURES The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90.RESULTS Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17).CONCLUSIONS AND RELEVANCE Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients.