Int J Surg：去甲肾上腺素-苯肾上腺素与去甲肾上腺素-血管加压素在感染性休克中的临床结局比较：一项回顾性队列研究

Abstract

Purpose: This study aims to compare the clinical outcomes of norepinephrine combined with phenylephrine (NE-PE) versus norepinephrine combined with vasopressin (NE-VP) in patients with septic shock.

目的：本研究旨在比较感染性休克患者中去甲肾上腺素联合苯肾上腺素（NE-PE）与去甲肾上腺素联合血管加压素（NE-VP）的临床结局。

Materials and methods: This retrospective cohort study included septic shock patients identified from the Medical Information Mart for Intensive Care (MIMIC-IV; 2008-2019) and the eICU Collaborative Research Database (eICU-CRD). Within the MIMIC-IV cohort, propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) were carried out to balance baseline characteristics between groups, with outcomes compared across the crude, PSM, and IPTW cohorts. Multivariable logistic regression was further employed for subgroup analyses to assess the association between NE-VP versus NE-PE and in-hospital mortality. The observed association was subsequently validated using the external eICU-CRD cohort. Interaction and marginal effects were evaluated within the MIMIC-IV cohort to determine whether Shock Index modified the treatment effect of NE-VP versus NE-PE on in-hospital mortality.

材料与方法：本项回顾性队列研究纳入了来自重症监护医学信息数据库（MIMIC-IV，2008-2019）和eICU协作研究数据库（eICU-CRD）的感染性休克患者。在MIMIC-IV队列中，采用倾向评分匹配（PSM）和稳定逆概率治疗加权（IPTW）以平衡两组间的基线特征，并在原始队列、PSM队列及IPTW队列中比较临床结局。进一步采用多变量logistic回归分析进行亚组分析，评估NE-VP与NE-PE对院内死亡率的影响，并在外部eICU-CRD队列中验证该关联。此外，在MIMIC-IV队列中评估交互作用和边际效应，以确定休克指数（Shock Index）是否影响NE-VP与NE-PE对院内死亡率的治疗效果。

Results: The MIMIC-IV cohort comprised 753 patients (NE-PE: 238; NE-VP: 515), with an eICU-CRD validation cohort of 313 (NE-PE: 67; NE-VP: 246). After 1:1 PSM (336 patients; 168 pairs) and stabilized IPTW (weighted n = 724.7), both methods effectively reduced selection bias. Consistently across PSM/IPTW cohorts, the NE-PE group exhibited a shorter duration of dual vasopressor therapy and a lower in-hospital mortality rate. Multivariable regression analysis within the MIMIC-IV cohort confirmed reduced in-hospital mortality for NE-PE versus NE-VP, a finding further validated in the eICU-CRD cohort. Subgroup analyses with interaction testing within the MIMIC-IV cohort revealed that the mortality reduction associated with NE-PE was particularly pronounced in patients aged < 65 years and in those without hypertension. Marginal effect analysis further indicated that higher Shock Index values amplified the mortality risk associated with NE-VP versus NE-PE.

结果：MIMIC-IV队列共纳入753例患者（NE-PE组238例，NE-VP组515例），eICU-CRD验证队列313例（NE-PE组67例，NE-VP组246例）。经1:1 PSM（336例，168对）和稳定IPTW（加权n=724.7）后，两种方法均有效减少选择偏倚。在PSM和IPTW队列中，NE-PE组的双血管加压药治疗时间更短，且院内死亡率更低。MIMIC-IV队列的多变量回归分析证实，NE-PE组的院内死亡率低于NE-VP组，该结果在eICU-CRD队列中进一步得到验证。亚组分析与交互作用检验显示，NE-PE的死亡风险降低效应在年龄<65岁及无高血压患者中尤为显著。边际效应分析进一步表明，较高的休克指数会加剧NE-VP相较于NE-PE的死亡风险。

Conclusion: In septic shock patients, NE-PE may be associated with reduced in-hospital mortality compared to NE-VP, especially among patients aged <65 years or those without hypertension. The Shock Index may serve as a valuable indicator for selecting a secondary vasopressor during vasopressor escalation. 

结论：在感染性休克患者中，与NE-VP相比，NE-PE可能与更低的院内死亡率相关，尤其在年龄<65岁或无高血压的患者中。休克指数或可作为血管加压药物升级时选择二线血管加压药的参考指标。