Abstract：
BACKGROUND: Vasopressor administration at an appropriate time is crucial, but the optimal timing remains controversial.
OBJECTIVE: Does early vs late norepinephrine administration impact the prognosis of septic shock?
METHODS: Searches were conducted on PubMed, EMBASE, the Cochrane Library, and KMBASE. We included studies of adults with sepsis and categorized patients into an early and late norepinephrine group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the ICU, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume.
RESULTS: Twelve studies (four randomized controlled trials [RCTs] and eight observational studies) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early norepinephrine group and late norepinephrine group in RCTs (OR, 0.70; 95% CI, 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower IV fluid volumes, the early norepinephrine group showed significantly lower mortality than the late norepinephrine group (OR, 0.49; 95%, CI, 0.25-0.96). The early norepinephrine group demonstrated more mechanical ventilator-free days in observational studies (mean difference, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early norepinephrine group in the three RCTs that reported this outcome (OR, 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes.
CONCLUSIONS: Overall mortality did not differ significantly between early and late norepinephrine administration for septic shock. However, early norepinephrine administration seemed to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early norepinephrine use.
OBJECTIVE: Does early vs late norepinephrine administration impact the prognosis of septic shock?
METHODS: Searches were conducted on PubMed, EMBASE, the Cochrane Library, and KMBASE. We included studies of adults with sepsis and categorized patients into an early and late norepinephrine group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the ICU, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume.
RESULTS: Twelve studies (four randomized controlled trials [RCTs] and eight observational studies) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early norepinephrine group and late norepinephrine group in RCTs (OR, 0.70; 95% CI, 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower IV fluid volumes, the early norepinephrine group showed significantly lower mortality than the late norepinephrine group (OR, 0.49; 95%, CI, 0.25-0.96). The early norepinephrine group demonstrated more mechanical ventilator-free days in observational studies (mean difference, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early norepinephrine group in the three RCTs that reported this outcome (OR, 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes.
CONCLUSIONS: Overall mortality did not differ significantly between early and late norepinephrine administration for septic shock. However, early norepinephrine administration seemed to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early norepinephrine use.
摘要：
背景：在适当的时间给药血管升压药至关重要，但最佳时机仍存在争议。
目的：早期和晚期去甲肾上腺素（NE）给药是否影响感染性休克的预后？
方法：在PubMed上进行了搜索，EMBASE,Cochrane图书馆,KMBASE。我们纳入了成人脓毒症患者的研究，并根据特定时间点或去甲肾上腺素使用方案的差异将患者分为早期和晚期NE组。主要结果是总死亡率。次要结果包括重症监护病房的住院时间，天免费使用呼吸机，没有肾脏替代疗法的天数，天没有使用血管升压药，不良事件,和总流体体积。
结果：12项研究（4项随机对照试验[RCT]，8个观察性)，包括7,281例患者进行了分析。对于总死亡率，早期NE组和晚期NE组的RCT差异无统计学意义（比值比[OR]，0.70；95%置信区间[CI]，0.41-1.19)或观察性研究(OR，0.83；95%CI，0.54-1.29）。在两个没有限制性液体策略的RCT中，优先考虑血管加压药和降低静脉液体量，早期NE组的死亡率明显低于晚期NE组（OR0.49，95％，CI，0.25-0.96）。早期NE组在观察性研究中表现出更多的无机械呼吸机天数(MD，4.06；95%CI，2.82-5.30）。在报告该结果的三个RCT中，早期NE组的肺水肿发生率较低（OR0.43；95％CI，0.25-0.74）。在其他次要结果中没有发现差异。
结论：早期和晚期NE治疗脓毒性休克的总死亡率无显著差异。然而,早期NE给药似乎减少了肺水肿的发生率，在没有液体限制干预的研究中观察到死亡率改善，有利于早期使用NE。
目的：早期和晚期去甲肾上腺素（NE）给药是否影响感染性休克的预后？
方法：在PubMed上进行了搜索，EMBASE,Cochrane图书馆,KMBASE。我们纳入了成人脓毒症患者的研究，并根据特定时间点或去甲肾上腺素使用方案的差异将患者分为早期和晚期NE组。主要结果是总死亡率。次要结果包括重症监护病房的住院时间，天免费使用呼吸机，没有肾脏替代疗法的天数，天没有使用血管升压药，不良事件,和总流体体积。
结果：12项研究（4项随机对照试验[RCT]，8个观察性)，包括7,281例患者进行了分析。对于总死亡率，早期NE组和晚期NE组的RCT差异无统计学意义（比值比[OR]，0.70；95%置信区间[CI]，0.41-1.19)或观察性研究(OR，0.83；95%CI，0.54-1.29）。在两个没有限制性液体策略的RCT中，优先考虑血管加压药和降低静脉液体量，早期NE组的死亡率明显低于晚期NE组（OR0.49，95％，CI，0.25-0.96）。早期NE组在观察性研究中表现出更多的无机械呼吸机天数(MD，4.06；95%CI，2.82-5.30）。在报告该结果的三个RCT中，早期NE组的肺水肿发生率较低（OR0.43；95％CI，0.25-0.74）。在其他次要结果中没有发现差异。
结论：早期和晚期NE治疗脓毒性休克的总死亡率无显著差异。然而,早期NE给药似乎减少了肺水肿的发生率，在没有液体限制干预的研究中观察到死亡率改善，有利于早期使用NE。
