Kotani Yuki, Belletti Alessandro, D'Amico Filippo, Bonaccorso Alessandra, Wieruszewski Patrick M, Fujii Tomoko, Khanna Ashish K, Landoni Giovanni, Bellomo Rinaldo
Department of Intensive Care Medicine, Kameda Medical Center, 929 Higashi-Cho, Kamogawa, 296-8602, Japan.
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Crit Care. 2024 Dec 30;28(1):439. doi: 10.1186/s13054-024-05212-7.
Excessive exposure to adrenergic vasopressors may be harmful. Non-adrenergic vasopressors may spare adrenergic agents and potentially improve outcomes. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of non-adrenergic vasopressors in adult patients receiving vasopressor therapy for vasodilatory shock or perioperative vasoplegia.
We searched PubMed, Embase, and Cochrane Library for RCTs comparing non-adrenergic vasopressors with adrenergic vasopressors alone or placebo in critically ill or perioperative patients. Each eligible study was categorized into septic shock, cardiac surgery, or non-cardiac surgery. Non-adrenergic vasopressors included vasopressin, terlipressin, selepressin, angiotensin II, methylene blue, and hydroxocobalamin. The primary outcome was mortality at longest follow-up. We conducted a random-effects meta-analysis. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CRD42024505039).
Among 51 eligible RCTs totaling 5715 patients, the predominant population was septic shock in 30 studies, cardiac surgery in 11 studies, and non-cardiac surgery in 10 studies. Cochrane risk-of-bias tool for randomized trials version 2 identified 17 studies as low risk of bias. In septic shock, mortality was significantly lower in the non-adrenergic group (960/2232 [43%] vs. 898/1890 [48%]; risk ratio [RR], 0.92; 95% confidence interval [95% CI], 0.86-0.97; P = 0.03; I = 0%), with none of the individual non-adrenergic vasopressors showing significant survival benefits. No significant mortality difference was observed in patients undergoing cardiac surgery (34/410 [8.3%] vs. 47/412 [11%]; RR, 0.82; 95% CI, 0.55-1.22; P = 0.32; I = 12%) or those undergoing non-cardiac surgery (9/388 [2.3%] vs. 18/383 [4.7%]; RR, 0.66; 95% CI, 0.31-1.41; P = 0.28; I = 0%).
Administration of non-adrenergic vasopressors was significantly associated with reduced mortality in patients with septic shock. However, no single agent achieved statistical significance in separate analyses. Although the pooled effects of non-adrenergic vasopressors on survival did not reach statistical significance in patients undergoing cardiac or non-cardiac surgery, the confidence intervals included the possibility of both no effect and a clinically important benefit from non-adrenergic agents. These findings justify the conduct of further RCTs comparing non-adrenergic vasopressors to usual care based on noradrenaline alone.
过度使用肾上腺素能血管升压药可能有害。非肾上腺素能血管升压药可能减少肾上腺素能药物的使用，并有可能改善预后。我们旨在对随机对照试验（RCT）进行系统评价和荟萃分析，以评估非肾上腺素能血管升压药在接受血管升压药治疗的血管舒张性休克或围手术期血管麻痹成年患者中的疗效。
我们检索了PubMed、Embase和Cochrane图书馆，查找在危重症或围手术期患者中比较非肾上腺素能血管升压药与单独使用肾上腺素能血管升压药或安慰剂的RCT。每项符合条件的研究被分为脓毒性休克、心脏手术或非心脏手术。非肾上腺素能血管升压药包括血管加压素、特利加压素、塞雷加压素、血管紧张素II、亚甲蓝和羟钴胺素。主要结局是最长随访期的死亡率。我们进行了随机效应荟萃分析。我们在PROSPERO国际前瞻性系统评价注册库（CRD42024505039）中注册了研究方案。
在总计5715例患者的51项符合条件的RCT中，主要人群为30项研究中的脓毒性休克、11项研究中的心脏手术和10项研究中的非心脏手术。随机试验的Cochrane偏倚风险工具第2版将17项研究确定为低偏倚风险。在脓毒性休克中，非肾上腺素能组的死亡率显著较低（960/2232 [43%] 对898/1890 [48%]；风险比 [RR]，0.92；95% 置信区间 [95% CI]，0.86 - 0.97；P = 0.03；I = 0%），没有一种单独的非肾上腺素能血管升压药显示出显著的生存获益。在接受心脏手术的患者中未观察到显著的死亡率差异（34/410 [8.3%] 对47/412 [11%]；RR，0.82；95% CI，0.55 - 1.22；P = 0.32；I = 12%），在接受非心脏手术的患者中也未观察到显著差异（9/388 [2.3%] 对18/383 [4.7%]；RR，0.66；95% CI，0.31 - 1.41；P = 0.28；I = 0%）。
使用非肾上腺素能血管升压药与脓毒性休克患者死亡率降低显著相关。然而，在单独分析中没有单一药物达到统计学显著性。尽管非肾上腺素能血管升压药对生存的综合效应在接受心脏或非心脏手术的患者中未达到统计学显著性，但置信区间包括了无效应和非肾上腺素能药物具有临床重要获益的可能性。这些发现证明有必要进行进一步的RCT，比较非肾上腺素能血管升压药与仅基于去甲肾上腺素的常规治疗。
