去甲肾上腺素给药时机对脓毒性休克患者预后的影响：一项前瞻性队列研究

Journal of intensive medicine Pub Date : 2024-11-29 DOI:10.1016/j.jointm.2024.10.002

Yuting Li, Deyou Zhang, Hongxiang Li, Youquan Wang, Dong Zhang

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引用次数: 0

摘要

脓毒症和脓毒性休克是世界范围内的主要卫生保健问题，与大量死亡率相关。脓毒性休克患者早期给予去甲肾上腺素可提高生存率，但脓毒性休克到开始使用去甲肾上腺素的时间存在争议。本研究探讨了成人脓毒性休克患者初始去甲肾上腺素给药时间与临床结果之间的关系。方法本前瞻性队列研究于2021年9月至2022年6月在某三级综合医院重症监护病房（ICU）进行。根据脓毒性休克发生至首次应用去甲肾上腺素的时间是否为1 h，将所有入组患者分为早期和晚期去甲肾上腺素组。主要终点为28天死亡率。次要结局包括ICU住院时间（LOS）、医院LOS、达到平均动脉压(MAP)≥65 mmHg的时间、24小时输注量、6小时Lac清除率、机械通气天数和持续肾脏替代治疗（CRRT）比率。采用多变量logistic回归分析评价28天死亡率的独立危险因素。结果本研究共纳入120例患者，其中去甲肾上腺素早期组42例（占35.0%），晚期组78例（占65.0%）。早期组28天死亡率低于晚期组（28.6%比47.4%，P=0.045）。早期组达到MAP≥65 mmHg的中位时间短于晚期组（1.0 h比1.5 h， P=0.010）。早期组24小时静脉内液量中位数低于晚期组（40.7%比14.9%，P=0.030）。早期组6小时乳酸清除率中位数高于晚期组（40.7% vs. 14.9%， P=0.009）。ICU LOS （P=0.748）、医院LOS （P=0.369）、机械通气时间（P=0.128）、CRRT比值（P=0.637）早、晚两组比较差异均无统计学意义。28天死亡率的独立危险因素包括男性（优势比[OR]=3.288, 95%可信区间[CI]: 1.236 ~ 8.745, P = 0.017）、开始使用去甲肾上腺素1小时的时间（OR=4.564, 95% CI: 1.382 ~ 15.079, P = 0.013）、达到MAP≥65 mmHg的时间（OR=1.800, 95% CI: 1.171 ~ 2.767, P = 0.007）。结论甲肾上腺素起始≤1 h与感染性休克患者28天死亡率降低相关。早期给药去甲肾上腺素也与达到MAP≥65 mmHg所需时间较短、24小时静脉输液量较低和6小时Lac清除率较高相关。男性，达到MAP≥65 mmHg的时间和去甲肾上腺素起始时间1 h是28天死亡率的独立危险因素。中国临床试验注册号：ChiCTR2100044071。

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Effect of timing of norepinephrine administration on prognosis of patients with septic shock: A prospective cohort study

Background

Sepsis and septic shock are major healthcare problems worldwide, associated with substantial mortality. Early administration of norepinephrine in septic shock patients has been associated with an increased survival rate, but the timing from septic shock to norepinephrine initiation is controversial. This study examined the associations between the timing of initial norepinephrine administration and clinical outcomes in adult patients with septic shock.

Methods

This prospective cohort study was conducted from September 2021 to June 2022 in an intensive care unit (ICU) of a tertiary general hospital. All enrolled patients were divided into early and late norepinephrine groups according to whether the time from the onset of septic shock to the first application of norepinephrine was >1 h. The primary outcome was 28-day mortality. Secondary outcomes included ICU length of stay (LOS), hospital LOS, time to achieve a mean arterial pressure (MAP) ≥65 mmHg, 24-hour infusion volume, 6-hour Lac clearance, mechanical ventilation days, and continuous renal replacement therapy (CRRT )ratio. Multivariable logistic regression analysis was used to evaluate the independent risk factors for 28-day mortality.

Results

This study enrolled 120 patients, including 42 patients (35.0%) and 78 patients (65.0%) in the early and late norepinephrine groups, respectively. The 28-day mortality was lower in the early group than in the late group (28.6% vs. 47.4%, P=0.045). The median time to achieve MAP ≥65 mmHg was shorter in the early group than in the late group (1.0 h vs. 1.5 h, P=0.010). The median 24-hour intravenous fluids volume in the early group was lower than that in the late group (40.7% vs. 14.9%, P=0.030). The median 6-hour lactate (Lac) clearance rate in the early group was higher than that in the late group (40.7% vs. 14.9%, P=0.009). There were no significant differences between early and late groups by ICU LOS (P=0.748), hospital LOS (P=0.369), mechanical ventilation time (P=0.128), and CRRT ratio (P=0.637). The independent risk factors for 28-day mortality included being male (odds ratio [OR]=3.288, 95% confidence interval [CI]: 1.236 to 8.745, P = 0.017), time to norepinephrine initiation >1 h (OR=4.564, 95% CI: 1.382 to 15.079, P = 0.013), and time to achieve MAP ≥65 mmHg (OR=1.800, 95% CI: 1.171 to 2.767, P = 0.007).

Conclusions

Norepinephrine initiation ≤1 h is associated with lower 28-day mortality in patients with septic shock. Early norepinephrine administration is also associated with a shorter time to achieve MAP ≥65 mmHg, lower 24-hour intravenous fluids volume, and higher 6-hour Lac clearance rate. Being male, time to achieve MAP ≥65 mmHg, and norepinephrine initiation >1 h are independent risk factors for 28-day mortality.

Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR2100044071.

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