First Department of Intensive Care Medicine, University of Athens Medical School, Athens, Greece.
JAMA. 2013 Jul 17;310(3):270-9. doi: 10.1001/jama.2013.7832.
Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination.
To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility).
Patients received either vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methylprednisolone (40 mg) and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73).
Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2.
Follow-up was completed in all resuscitated patients. Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P = .005) and survival to hospital discharge with CPC score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; P = .02). Patients in the VSE group with postresuscitation shock vs corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; P = .02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the 2 groups.
Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status.
clinicaltrials.gov Identifier: NCT00729794.
重要性：初步数据显示，在心脏骤停患者中，与使用肾上腺素的血管加压素-皮质类固醇-肾上腺素（VSE）组合相比，使用血管加压素-肾上腺素进行心肺复苏（CPR）以及在 CPR 期间和之后给予皮质类固醇补充可以提高恢复自主循环和存活至出院的比例，并且出院时的神经系统功能良好（Cerebral Performance Category，CPC）评分为 1 或 2。
目的：确定在需要升压药的院内心脏骤停患者中，CPR 期间联合使用血管加压素和肾上腺素以及在 CPR 期间和之后给予皮质类固醇补充是否可以提高存活率，并且出院时的 CPC 评分为 1 或 2。
设计、地点和参与者：这是一项在 2008 年 9 月 1 日至 2010 年 10 月 1 日期间在希腊的 3 家三级护理中心（2400 张床位）进行的随机、双盲、安慰剂对照、平行组试验，共纳入 268 例符合复苏指南（从 364 例符合入选标准的患者中评估）需要使用肾上腺素的心脏骤停患者。
干预措施：患者随机分为 VSE 组（n=130）和对照组（n=138），VSE 组在随机分组后的前 5 个 CPR 循环中接受血管加压素（20 IU/CPR 循环）加肾上腺素（1 mg/CPR 循环；循环持续时间约 3 分钟），随后根据需要给予额外的肾上腺素；VSE 组患者在随机分组后的第一个 CPR 循环中接受甲泼尼龙（40 mg），对照组患者接受生理盐水安慰剂。复苏后休克采用氢化可的松应激剂量（最大每日 300 mg，持续 7 天，逐渐减量）治疗（VSE 组 n=76，对照组 n=73）。
主要结局和测量指标：20 分钟或更长时间的自主循环恢复（ROSC）和出院时 CPC 评分为 1 或 2 的存活率。
结果：所有复苏成功的患者均完成了随访。与对照组相比，VSE 组的 ROSC 概率更高（20 分钟或更长时间的患者：109/130[83.9%] vs 91/138[65.9%]；优势比[OR]，2.98；95%置信区间[CI]，1.39-6.40；P=0.005），且出院时的 CPC 评分为 1 或 2 的存活率更高（18/130[13.9%] vs 7/138[5.1%]；OR，3.28；95% CI，1.17-9.20；P=0.02）。与对照组相应患者相比，VSE 组中出现复苏后休克的患者的存活率更高（出院时 CPC 评分为 1 或 2 的患者：16/76[21.1%] vs 6/73[8.2%]；OR，3.74；95% CI，1.20-11.62；P=0.02），并且他们的血流动力学和中心静脉血氧饱和度得到改善，器官功能障碍更少。两组的不良事件发生率相似。
结论和相关性：在需要升压药的心脏骤停患者中，与肾上腺素/生理盐水安慰剂相比，CPR 期间联合使用血管加压素-肾上腺素和甲泼尼龙以及复苏后休克时给予氢化可的松应激剂量可以提高出院时的存活率和改善神经系统功能。
试验注册：clinicaltrials.gov 标识符：NCT00729794。
