Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Department of Emergency Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Shock. 2020 Jan;53(1):50-57. doi: 10.1097/SHK.0000000000001345.
Patients with septic shock in whom norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP.
The PubMed, EMBASE, and Cochrane Central Register databases were searched from the database inception until October 18, 2018. Studies were limited to adult patients with septic shock who received concomitant NE and VP treatment, that included different orders of vasopressor discontinuation. The primary outcome was the incidence of hypotension. Overall mortality, ICU mortality, and length of stay (LOS) in the ICU were secondary outcomes. Sensitivity and subgroup analyses as well as trial sequential analysis were performed.
One prospective randomized controlled trial and seven retrospective cohort studies were included in present meta-analysis. Compared with discontinuing VP first, the incidence of hypotension was significantly lower when NE was discontinued first (odds ratio, OR 0.3, 95% confidence interval, CI 0.10 to 0.86, P = 0.02; I = 91%). No significant difference was detected in either overall mortality (OR 1.28, 95% CI 0.77 to 2.10, P = 0.34) or ICU mortality (OR 0.99, 95% CI 0.74 to 1.34, P = 0.96) between these two groups. Furthermore, ICU LOS was also evaluated in five studies, and no statistical significance was observed between the two groups with different orders in weaning vasopressors (mean difference 1.35, 95% CI -2.05 to 4.74, P = 0.44). The subgroup analyses suggested a significant association between hypotension and the practice of discontinuing VP first specifically in patients with a low usage rate of corticosteroids (odds ratio, OR 0.18, 95% confidence interval, CI 0.04 to 0.78, P = 0.02). The trial sequential analysis indicated a lack of sufficient evidence to draw conclusions from the current results (required information size = 11 821).
In adults with septic shock treated with concomitant VP and NE therapy, discontinuing VP first may lead to a higher incidence of hypotension but is not associated with mortality or ICU LOS. Further prospective studies with larger sample sizes are warranted.
对于需要升压治疗的脓毒性休克患者，若去甲肾上腺素（NE）升压效果不佳，需联合使用血管加压素（VP）。然而，目前的指南并没有建议临床医生在患者脓毒性休克开始缓解时，首先停用哪种血管活性药物。此外，对于接受 NE 和 VP 联合治疗的脓毒性休克患者，如何停用血管加压剂，目前的数据存在争议，尚无定论。
从数据库建立到 2018 年 10 月 18 日，检索了 PubMed、EMBASE 和 Cochrane 中央注册数据库。研究对象为接受 NE 和 VP 联合治疗的脓毒性休克成年患者，包括不同的血管加压剂停药顺序。主要结局为低血压的发生率。总体死亡率、重症监护病房（ICU）死亡率和 ICU 住院时间（LOS）为次要结局。进行了敏感性和亚组分析以及试验序贯分析。
本次荟萃分析纳入了 1 项前瞻性随机对照试验和 7 项回顾性队列研究。与首先停用 VP 相比，首先停用 NE 时低血压的发生率显著降低（比值比，OR 0.3，95%置信区间，CI 0.10 至 0.86，P=0.02；I²=91%）。两组间总体死亡率（OR 1.28，95%CI 0.77 至 2.10，P=0.34）或 ICU 死亡率（OR 0.99，95%CI 0.74 至 1.34，P=0.96）无显著差异。此外，在 5 项研究中还评估了 ICU LOS，两组在撤机时不同的血管加压剂顺序之间也没有统计学意义（平均差异 1.35，95%CI -2.05 至 4.74，P=0.44）。亚组分析表明，在皮质激素使用率较低的患者中，首先停用 VP 与低血压之间存在显著关联（比值比，OR 0.18，95%置信区间，CI 0.04 至 0.78，P=0.02）。试验序贯分析表明，目前的结果缺乏足够的证据得出结论（需要的信息量大小为 11 821）。
在接受 VP 和 NE 联合治疗的脓毒性休克成人患者中，首先停用 VP 可能会导致更高的低血压发生率，但与死亡率或 ICU LOS 无关。需要进行更大样本量的前瞻性研究。
