White Kyle C, Costa-Pinto Rahul, Blank Sebastiaan, Whebell Stephen, Quick Lachlan, Luke Stephen, Attokaran Antony G, Garrett Peter, Ramanan Mahesh, Tabah Alexis, Shekar Kiran, Laupland Kevin B, Kumar Aashish, McCullough James, Udy Andrew, Eastwood Glenn, Bellomo Rinaldo, Chaba Anis
Department of Intensive Care Unit, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Brisbane, QLD, 4102, Australia.
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Crit Care. 2025 May 12;29(1):188. doi: 10.1186/s13054-025-05401-y.
In septic shock, the optimal timing of adjunctive vasopressin initiation shock is unknown. We aimed to assess the effect of its early initiation for patients with septic shock.
We conducted a multicenter target trial emulation to estimate the intensive care unit (ICU) mortality effect of early (≤ 6 h) adjunctive vasopressin compared with usual care. Eligible patients had septic shock diagnosed within 6 h of ICU admission. The primary outcome of this study was 30-day ICU mortality. Subgroup analyses were conducted to test the interaction of early vasopressin start with peak norepinephrine-equivalent dose (NED) at 6 h, APACHE score, peak lactate at 6 h and invasive mechanical ventilation. Secondary outcomes were the impact of delayed vasopressin introduction on 30-day ICU mortality and effect of NED at vasopressin start on 30-day ICU mortality. We used the parametric g-formula to emulate a target trial.
Overall, 3,105 patients fulfilled the inclusion criteria. Mean age was 62 years and mean APACHE III score was 83. In the first six hours of vasopressor therapy, 1,864 (60%) patients were invasively ventilated. Estimated 30-day ICU mortality was 19.34% (95%CI, 17.0 to 21.68) in the no vasopressin group and 18.45% (95%CI, 16.26 to 20.63) in the early vasopressin group; relative risk 0.95 (95%CI, 0.93 to 0.98). The estimated 30-day ICU mortality effect of starting vasopressin was particularly strong at lower norepinephrine doses (< 0.25 µg.kg.min) and significant at lower norepinephrine doses than recommended by the Surviving Sepsis Campaign Guidelines. Vasopressin administration progressively increased over the study period, from 35.2% (95%CI, 30.0 to 40.5) in 2015 to 45.1% (95%CI, 40.7 to 49.6) in 2021 (ß = + 1.3% per year; 95%CI, + 0.46 to + 2.16, p = 0.011). Patients had progressively lower norepinephrine equivalent dose (ß = - 0.05 µg.kg.min per year; 95%CI, - 0.09 to - 0.002, p = 0.038) and lower total SOFA score (ß = - 0.1 point per year; 95%CI, - 0.18 to - 0.07, p < 0.001) at vasopressin start.
In this emulation of a hypothetical target trial, patients with septic shock benefited from early vasopressin administration. These findings can help design prospective randomised-control trials of early adjunctive vasopressin use in septic shock.
在感染性休克中，辅助使用血管加压素的最佳起始时机尚不清楚。我们旨在评估早期使用血管加压素对感染性休克患者的影响。
我们进行了一项多中心目标试验模拟，以评估早期（≤6小时）辅助使用血管加压素与常规治疗相比对重症监护病房（ICU）死亡率的影响。符合条件的患者在入住ICU后6小时内被诊断为感染性休克。本研究的主要结局是30天ICU死亡率。进行亚组分析以检验早期血管加压素起始与6小时时去甲肾上腺素等效剂量峰值（NED）、急性生理与慢性健康状况评分系统（APACHE）评分、6小时时乳酸峰值以及有创机械通气之间的相互作用。次要结局是延迟使用血管加压素对30天ICU死亡率的影响以及血管加压素起始时NED对30天ICU死亡率的影响。我们使用参数化g公式来模拟目标试验。
总体而言，3105例患者符合纳入标准。平均年龄为62岁，平均APACHE III评分为83分。在血管升压药治疗的前6小时内，1864例（60%）患者接受了有创通气。无血管加压素组的估计30天ICU死亡率为19.34%（95%置信区间，17.0至21.68），早期血管加压素组为18.45%（95%置信区间，16.26至20.63）；相对风险为0.95（95%置信区间，0.93至0.98）。在去甲肾上腺素剂量较低（<0.25μg·kg·min）时，起始血管加压素对估计的30天ICU死亡率的影响尤为显著，且在低于《拯救脓毒症运动指南》推荐剂量的去甲肾上腺素剂量下也具有显著意义。在研究期间，血管加压素的使用逐渐增加，从2015年的35.2%（95%置信区间，30.0至40.5）增至2021年的45.1%（95%置信区间，40.7至49.6）（每年增加1.3%；95%置信区间，0.46至2.16，p = 0.011）。在开始使用血管加压素时，患者的去甲肾上腺素等效剂量逐渐降低（每年降低0.05μg·kg·min；95%置信区间，-0.09至-0.002，p = 0.038），总序贯器官衰竭评估（SOFA）评分也逐渐降低（每年降低0.1分；95%置信区间，-0.18至-0.07，p < 0.001）。
在这项对假设目标试验的模拟中，感染性休克患者从早期使用血管加压素中获益。这些发现有助于设计关于在感染性休克中早期辅助使用血管加压素的前瞻性随机对照试验。
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