Abstract：
BACKGROUND: Sepsis-related mortality is decreasing over time after the introduction of \"Surviving Sepsis Campaign\" Guidelines in 2004. The last Guidelines version collects 93 recommendations, but several interventions supported by randomized evidence of mortality reduction are not included.
METHODS: We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies.
RESULTS: We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit.
CONCLUSIONS: Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.
METHODS: We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies.
RESULTS: We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit.
CONCLUSIONS: Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.
摘要：
背景：在2004年引入“存活脓毒症运动”指南后，与脓毒症相关的死亡率随着时间的推移而下降。上一个指南版本收集了93条建议，但不包括由死亡率降低的随机证据支持的几项干预措施.
方法：我们对所有报告脓毒症患者死亡率显著降低的随机对照试验进行了系统评价，并将已确定的研究与2021年脓毒症生存运动指南进行了比较，以突出差异。
结果：我们确定了83项影响脓毒症死亡率的随机对照试验（58项干预措施）。只有9/58的干预措施被纳入指南：乳酸测量和乳酸指导的血流动力学管理。降钙素原指导抗生素停药，平衡晶体作为首选流体，白蛋白输注,避免淀粉，去甲肾上腺素作为一线血管加压药,作为去甲肾上腺素的辅助血管加压素，中重度脓毒症相关急性呼吸窘迫综合征的神经肌肉阻滞剂，和皮质类固醇的使用。只有11/93指南的建议得到了具有死亡率差异的随机证据的支持。文献中具有生存益处的五种干预措施(维生素C，特利加压素,多粘菌素B,指南中建议避免使用自由输血策略和免疫球蛋白），虽然没有提到44项干预措施，包括三种干预措施(艾司洛尔，omega3和外部加温），至少进行了两项随机对照试验，并记录了生存获益。
结论：脓毒症患者死亡率差异的随机对照试验与最新的脓毒症生存运动指南之间存在一些差异。这种系统的审查可以帮助改进未来的指导方针，并可能指导对特定有希望的主题的研究。
方法：我们对所有报告脓毒症患者死亡率显著降低的随机对照试验进行了系统评价，并将已确定的研究与2021年脓毒症生存运动指南进行了比较，以突出差异。
结果：我们确定了83项影响脓毒症死亡率的随机对照试验（58项干预措施）。只有9/58的干预措施被纳入指南：乳酸测量和乳酸指导的血流动力学管理。降钙素原指导抗生素停药，平衡晶体作为首选流体，白蛋白输注,避免淀粉，去甲肾上腺素作为一线血管加压药,作为去甲肾上腺素的辅助血管加压素，中重度脓毒症相关急性呼吸窘迫综合征的神经肌肉阻滞剂，和皮质类固醇的使用。只有11/93指南的建议得到了具有死亡率差异的随机证据的支持。文献中具有生存益处的五种干预措施(维生素C，特利加压素,多粘菌素B,指南中建议避免使用自由输血策略和免疫球蛋白），虽然没有提到44项干预措施，包括三种干预措施(艾司洛尔，omega3和外部加温），至少进行了两项随机对照试验，并记录了生存获益。
结论：脓毒症患者死亡率差异的随机对照试验与最新的脓毒症生存运动指南之间存在一些差异。这种系统的审查可以帮助改进未来的指导方针，并可能指导对特定有希望的主题的研究。
