University of Illinois at Chicago College of Pharmacy, Drug Information Group, Chicago, IL, USA.
Cleveland Clinic Akron General, Akron, OH, USA.
J Intensive Care Med. 2020 Apr;35(4):327-337. doi: 10.1177/0885066618818460. Epub 2018 Dec 18.
Vasodilatory shock is the most common type of shock. Catecholamine vasopressors are the cornerstone of hemodynamic therapy but carry risks. Angiotensin II (AT) was recently approved, and other novel agents (selepressin and terlipressin) are under investigation and used outside the United States (terlipressin). We performed a systematic review to summarize the efficacy and safety of these novel vasopressors and to offer guidance on their appropriate use.
Systematic review of controlled trials.
Numerous databases were searched using terms related to , and . Twenty-one citations, including 16 prospective comparative trials and 5 post hoc analyses reporting effects of AT, selepressin, and terlipressin, were reviewed for data on outcomes related to hemodynamic measures, mortality, severity and duration of illness, concomitant vasopressor utilization, and adverse effects. Findings from eligible literature are described qualitatively using Cochrane methods.
Fourteen controlled trials were assessed after exclusion of 2 dated trials of a distinct AT formulation. Trials are limited for AT (n = 2) and selepressin (n = 1), while terlipressin was investigated in 11 small trials. Overall, the trials have an unclear risk of bias. Most report mean arterial pressure (MAP) as primary end point, and all indicate novel vasopressors increase MAP compared to placebo and to a similar degree as with catecholamine vasopressors. Mortality findings are preliminary, as they have been limited to specific subgroups in trials of terlipressin and post hoc analyses of one trial of AT. Trials reported safety concerns for each agent including thromboembolism with AT and ischemia with terlipressin/selepressin.
In this systematic review, controlled trials of novel vasopressors in treatment of vasodilatory shock were limited and of low quality. Angiotensin II, selepressin, and terlipressin appear to significantly increase MAP, but further study is required, particularly for selepressin, to determine their safety, efficacy, and role in treatment of vasodilatory shock.
血管舒张性休克是最常见的休克类型。儿茶酚胺血管加压素是血流动力学治疗的基石，但存在风险。血管紧张素 II（AT）最近获得批准，其他新型药物（selepressin 和 terlipressin）正在美国以外进行研究和使用（terlipressin）。我们进行了系统评价，以总结这些新型血管加压素的疗效和安全性，并就其合理使用提供指导。
对照试验的系统评价。
使用与血管舒张性休克相关的术语搜索了多个数据库。对 21 条引文进行了审查，其中包括 16 项前瞻性比较试验和 5 项事后分析报告 AT、selepressin 和 terlipressin 对血流动力学指标、死亡率、疾病严重程度和持续时间、同时使用血管加压素和不良反应的影响。使用 Cochrane 方法定性描述合格文献中的发现。
排除了 2 项不同 AT 制剂的陈旧试验后，评估了 14 项对照试验。AT（n = 2）和 selepressin（n = 1）的试验有限，而 terlipressin 则在 11 项小型试验中进行了研究。总体而言，这些试验存在不确定的偏倚风险。大多数报告平均动脉压（MAP）作为主要终点，并且所有试验都表明新型血管加压素与安慰剂相比可增加 MAP，与儿茶酚胺血管加压素的增加程度相似。由于仅在 terlipressin 试验的特定亚组和 AT 试验的一项事后分析中报告了死亡率发现，因此这些发现还不成熟。每个试验都报告了每个药物的安全性问题，包括 AT 血栓栓塞和 terlipressin/selepressin 缺血。
在本系统评价中，血管舒张性休克新型血管加压素治疗的对照试验有限且质量较低。血管紧张素 II、selepressin 和 terlipressin 似乎可显著增加 MAP，但需要进一步研究，特别是对于 selepressin，以确定其安全性、疗效以及在治疗血管舒张性休克中的作用。
