Original Investigation | August 2, 2016Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic ShockThe VANISH Randomized Clinical TrialAnthony C. Gordon, Alexina J. Mason, Neeraja Thirunavukkarasu, et al. for the VANISH InvestigatorsJAMA. 2016;316(5):509-518.doi:10.1001/jama.2016.10485.Importance 背景Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. 去甲肾上腺素目前是感染性休克首选的升压药物；然而，也有建议早期使用血管加压素。 Objective 目的To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. 比较早期使用血管加压素或去甲肾上腺素对感染性休克患者肾功能衰竭的影响。 Design, Setting, and Participants 设计，场景及研究人群A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. 2013年2月至2015年5月，在英国18个成人综合ICU中进行的一项析因(2 x 2)、双盲、随机临床试验，入选患者为液体复苏后仍需升压药物治疗的成年感染性休克患者，且休克发生不超过6小时。 Interventions 干预措施Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n?=?101), vasopressin and placebo (n?=?104), norepinephrine and hydrocortisone (n?=?101), or norepinephrine and placebo (n?=?103). 患者被随机分为血管加压素（调整剂量不超过0.06 U/min）及氢化可的松(n = 101)，血管加压素和安慰剂(n = 104)，去甲肾上腺素及氢化可的松(n = 101)，或去甲肾上腺素和安慰剂(n = 103)。 Main Outcomes and Measures 主要终点指标The primary outcome was kidney failure–free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. 主要预后指标为随机分组后28天内无肾功能衰竭天数，定义为 (1) 从未发生肾功能衰竭的患者比例；(2) 未存活患者和（或）发生肾功能衰竭患者中位存活且无肾功能衰竭天数。肾脏替代治疗比例、病死率及严重不良反应为次要预后指标。 Results 结果A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, ?2.3% [95% CI, ?13.0% to 8.5%]). The median number of kidney failure–free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to –24) in the vasopressin group and 13 days (IQR, 1 to –25) in the norepinephrine group (difference, ?4 days [95% CI, ?11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, ?9.9% [95% CI, ?19.3% to ?0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, ?3.3% to 8.2%]). 研究共入选409名患者（中位年龄66岁，男性58.2%），诊断休克到开始用药的中位时间为3.5小时。血管加压素组165名患者中94名(57.0%)存活且未发生肾功能衰竭，去甲肾上腺素组157名患者中93名(59.2%)存活且未发生肾功能衰竭 （差异，?2.3% [95% CI, ?13.0% to 8.5%]）。血管加压素组死亡和（或）肾功能衰竭患者无肾功能衰竭中位天数为9天（四分位区间[IQR], 1 to –24），去甲肾上腺素组为13 天 (IQR, 1 to –25) （差异，?4 天 [95% CI, ?11 to 5]）。与去甲肾上腺素组相比，血管加压素组更少患者使用肾脏替代治疗（25.4% vs 35.3%；差异?9.9% [95% CI, ?19.3% to ?0.6%]）。两组间病死率无显著差异。血管加压素组205名患者中22名(10.7%)出现严重不良反应，去甲肾上腺素组204名患者中17名(8.3%)发生严重不良反应（差异，2.5% [95% CI, ?3.3% to 8.2%]）。 Conclusions and Relevance 结论与意义Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure–free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. 在成年感染性患者中，与使用去甲肾上腺素相比，早期使用血管加压素不能改善无肾功能衰竭天数。尽管这些发现不支持在这种情况下使用血管加压素替代去甲肾上腺素作为初始治疗药物，但可信区间提示血管加压素可能具有重要的临床获益，需要更大样本的临床试验进行评价。 Trial Registrationclinicaltrials.gov Identifier: ISRCTN 20769191  |
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