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Abstract：
BACKGROUND: As per the latest Surviving Sepsis Campaign guidelines, fluid resuscitation should be guided by repeated measurements of blood lactate levels until normalization. Nevertheless, raised lactate levels should be interpreted in the clinical context, as there may be other causes of elevated lactate levels. Thus, it may not be the best tool for real-time assessment of the effect of hemodynamic resuscitation, and exploring alternative resuscitation targets should be an essential research priority in sepsis.
OBJECTIVE: To compare the 28-d mortality in two clinical patterns of septic shock: hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion context.
METHODS: This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context (Group 1, n = 95) and patients with hyperlactatemia in a non-hypoperfusion context (Group 2, n = 40). Hypoperfusion context was defined by a central venous saturation less than 70%, central venous-arterial PCO2 gradient [P(cv-a)CO2] ≥ 6 mmHg, and capillary refilling time (CRT) ≥ 4 s. The patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h, 3 h, and 6 h. All-cause 28-d mortality and all other secondary objective parameters were observed at specified intervals. Nominal categorical data were compared using the χ2 or Fisher\'s exact test. Non-normally distributed continuous variables were compared using the Mann-Whitney U test. Receiver operating characteristic curve analysis with the Youden index determined the cutoff values of lactate, CRT, and metabolic perfusion parameters to predict the 28-d all-cause mortality. A P value of < 0.05 was considered significant.
RESULTS: Patient demographics, comorbidities, baseline laboratory, vital parameters, source of infection, baseline lactate levels, and lactate clearance at 3 h and 6 h, Sequential Organ Failure scores, need for invasive mechanical ventilation, days on mechanical ventilation, and renal replacement therapy-free days within 28 d, duration of intensive care unit stay, and hospital stay were comparable between the two groups. The stratification of patients into hypoperfusion and non-hypoperfusion context did not result in a significantly different 28-d mortality (24% vs 15%, respectively; P = 0.234). However, the patients within the hypoperfusion context with high P(cv-a)CO2 and CRT (P = 0.022) at baseline had significantly higher mortality than Group 2. The norepinephrine dose was higher in Group 1 but did not achieve statistical significance with a P > 0.05 at all measured intervals. Group 1 had a higher proportion of patients requiring vasopressin and the mean vasopressor-free days out of the total 28 d were lower in patients with hypoperfusion (18.88 ± 9.04 vs 21.08 ± 8.76; P = 0.011). The mean lactate levels and lactate clearance at 3 h and 6 h, CRT, P(cv-a)CO2 at 0 h, 3 h, and 6 h were found to be associated with 28-d mortality in patients with septic shock, with lactate levels at 6 h having the best predictive value (area under the curve lactate at 6 h: 0.845).
CONCLUSIONS: Septic shock patients fulfilling the hypoperfusion and non-hypoperfusion context exhibited similar 28-d all-cause hospital mortality, although patients with hypoperfusion displayed a more severe circulatory dysfunction. Lactate levels at 6 h had a better predictive value in predicting 28-d mortality than other parameters. Persistently high P(cv-a)CO2 (> 6 mmHg) or increased CRT (> 4 s) at 3 h and 6 h during early resuscitation can be a valuable additional aid for prognostication of septic shock patients.
OBJECTIVE: To compare the 28-d mortality in two clinical patterns of septic shock: hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion context.
METHODS: This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context (Group 1, n = 95) and patients with hyperlactatemia in a non-hypoperfusion context (Group 2, n = 40). Hypoperfusion context was defined by a central venous saturation less than 70%, central venous-arterial PCO2 gradient [P(cv-a)CO2] ≥ 6 mmHg, and capillary refilling time (CRT) ≥ 4 s. The patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h, 3 h, and 6 h. All-cause 28-d mortality and all other secondary objective parameters were observed at specified intervals. Nominal categorical data were compared using the χ2 or Fisher\'s exact test. Non-normally distributed continuous variables were compared using the Mann-Whitney U test. Receiver operating characteristic curve analysis with the Youden index determined the cutoff values of lactate, CRT, and metabolic perfusion parameters to predict the 28-d all-cause mortality. A P value of < 0.05 was considered significant.
RESULTS: Patient demographics, comorbidities, baseline laboratory, vital parameters, source of infection, baseline lactate levels, and lactate clearance at 3 h and 6 h, Sequential Organ Failure scores, need for invasive mechanical ventilation, days on mechanical ventilation, and renal replacement therapy-free days within 28 d, duration of intensive care unit stay, and hospital stay were comparable between the two groups. The stratification of patients into hypoperfusion and non-hypoperfusion context did not result in a significantly different 28-d mortality (24% vs 15%, respectively; P = 0.234). However, the patients within the hypoperfusion context with high P(cv-a)CO2 and CRT (P = 0.022) at baseline had significantly higher mortality than Group 2. The norepinephrine dose was higher in Group 1 but did not achieve statistical significance with a P > 0.05 at all measured intervals. Group 1 had a higher proportion of patients requiring vasopressin and the mean vasopressor-free days out of the total 28 d were lower in patients with hypoperfusion (18.88 ± 9.04 vs 21.08 ± 8.76; P = 0.011). The mean lactate levels and lactate clearance at 3 h and 6 h, CRT, P(cv-a)CO2 at 0 h, 3 h, and 6 h were found to be associated with 28-d mortality in patients with septic shock, with lactate levels at 6 h having the best predictive value (area under the curve lactate at 6 h: 0.845).
CONCLUSIONS: Septic shock patients fulfilling the hypoperfusion and non-hypoperfusion context exhibited similar 28-d all-cause hospital mortality, although patients with hypoperfusion displayed a more severe circulatory dysfunction. Lactate levels at 6 h had a better predictive value in predicting 28-d mortality than other parameters. Persistently high P(cv-a)CO2 (> 6 mmHg) or increased CRT (> 4 s) at 3 h and 6 h during early resuscitation can be a valuable additional aid for prognostication of septic shock patients.
摘要：
背景：根据最新的败血症生存运动指南，液体复苏应通过反复测量血乳酸水平来指导,直至恢复正常.然而，乳酸水平升高应在临床背景下进行解释，因为可能有其他原因导致乳酸水平升高。因此，它可能不是实时评估血流动力学复苏效果的最佳工具，探索替代复苏目标应该是脓毒症的重要研究重点。
目的：比较两种临床类型感染性休克的28天死亡率：低灌注的高乳酸血症患者和无低灌注的高乳酸血症患者。
方法：这项前瞻性观察性比较研究对135例符合脓毒症-3定义的感染性休克成年患者进行了比较，比较了低灌注环境中的高乳酸血症患者（第1组，n=95）和非低灌注环境中的高乳酸血症患者（第2组，n=40）。低灌注背景由中心静脉饱和度低于70%定义。中心静脉-动脉PCO2梯度[P(cv-a)CO2]≥6mmHg，和毛细血管再充盈时间（CRT）≥4s。每隔0h观察患者的各种宏观和微观血流动力学参数，3h,和6小时。在指定的时间间隔观察全因28天死亡率和所有其他次要目标参数。使用χ2或Fisher精确检验比较标称分类数据。使用Mann-WhitneyU检验比较非正态分布连续变量。用Youden指数进行受试者工作特征曲线分析，确定乳酸的截止值，CRT,和代谢灌注参数来预测28d全因死亡率。<0.05的P值被认为是显著的。
结果：患者人口统计，合并症,基线实验室，重要参数，感染源,基线乳酸水平，和乳酸清除率在3小时和6小时，序贯器官衰竭评分,需要有创机械通气，机械通气的天数，和28d内无肾脏替代治疗日，重症监护病房的住院时间，两组之间的住院时间相当。将患者分层为低灌注和非低灌注的背景并没有导致显著不同的28天死亡率(24%vs15%,分别为；P=0.234)。然而,在低灌注背景下,基线时高P(cv-a)CO2和CRT(P=0.022)的患者死亡率显著高于第2组.第1组的去甲肾上腺素剂量较高，但在所有测量间隔均未达到统计学意义，P>0.05。第1组需要加压素的患者比例较高，而灌注不足的患者在28d中的平均无血管加压素天数较低（18.88±9.04vs21.08±8.76；P=0.011）。3h和6h的平均乳酸水平和乳酸清除率，CRT,P(cv-a)CO2在0h时，3h,发现6小时与感染性休克患者的28天死亡率相关，6h时的乳酸水平具有最佳预测价值（6h时乳酸曲线下面积：0.845）。
结论：符合低灌注和非低灌注背景的脓毒性休克患者表现出相似的28天全因住院死亡率，尽管低灌注患者表现出更严重的循环功能障碍。与其他参数相比，6h时的乳酸水平在预测28d死亡率方面具有更好的预测价值。在早期复苏期间，在3h和6h持续升高P（cv-a）CO2（>6mmHg）或增加CRT（>4s）可能是预测感染性休克患者的有价值的额外帮助。
目的：比较两种临床类型感染性休克的28天死亡率：低灌注的高乳酸血症患者和无低灌注的高乳酸血症患者。
方法：这项前瞻性观察性比较研究对135例符合脓毒症-3定义的感染性休克成年患者进行了比较，比较了低灌注环境中的高乳酸血症患者（第1组，n=95）和非低灌注环境中的高乳酸血症患者（第2组，n=40）。低灌注背景由中心静脉饱和度低于70%定义。中心静脉-动脉PCO2梯度[P(cv-a)CO2]≥6mmHg，和毛细血管再充盈时间（CRT）≥4s。每隔0h观察患者的各种宏观和微观血流动力学参数，3h,和6小时。在指定的时间间隔观察全因28天死亡率和所有其他次要目标参数。使用χ2或Fisher精确检验比较标称分类数据。使用Mann-WhitneyU检验比较非正态分布连续变量。用Youden指数进行受试者工作特征曲线分析，确定乳酸的截止值，CRT,和代谢灌注参数来预测28d全因死亡率。<0.05的P值被认为是显著的。
结果：患者人口统计，合并症,基线实验室，重要参数，感染源,基线乳酸水平，和乳酸清除率在3小时和6小时，序贯器官衰竭评分,需要有创机械通气，机械通气的天数，和28d内无肾脏替代治疗日，重症监护病房的住院时间，两组之间的住院时间相当。将患者分层为低灌注和非低灌注的背景并没有导致显著不同的28天死亡率(24%vs15%,分别为；P=0.234)。然而,在低灌注背景下,基线时高P(cv-a)CO2和CRT(P=0.022)的患者死亡率显著高于第2组.第1组的去甲肾上腺素剂量较高，但在所有测量间隔均未达到统计学意义，P>0.05。第1组需要加压素的患者比例较高，而灌注不足的患者在28d中的平均无血管加压素天数较低（18.88±9.04vs21.08±8.76；P=0.011）。3h和6h的平均乳酸水平和乳酸清除率，CRT,P(cv-a)CO2在0h时，3h,发现6小时与感染性休克患者的28天死亡率相关，6h时的乳酸水平具有最佳预测价值（6h时乳酸曲线下面积：0.845）。
结论：符合低灌注和非低灌注背景的脓毒性休克患者表现出相似的28天全因住院死亡率，尽管低灌注患者表现出更严重的循环功能障碍。与其他参数相比，6h时的乳酸水平在预测28d死亡率方面具有更好的预测价值。在早期复苏期间，在3h和6h持续升高P（cv-a）CO2（>6mmHg）或增加CRT（>4s）可能是预测感染性休克患者的有价值的额外帮助。
