Department of Intensive Care Medicine, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.
Crit Care Med. 2012 Oct;40(10):2841-9. doi: 10.1097/CCM.0b013e31825b916b.
Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability.
Prospective, randomized, controlled experimental study.
Experimental laboratory in a university hospital.
Thirty-two anesthetized and mechanically ventilated pigs.
Pigs were randomly assigned (n=8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48-hr period of protocolized resuscitation started 6 (ΔT-6 hrs), 12 (ΔT-12 hrs), or 24 (ΔT-24 hrs) hrs later. The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction.
Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-α prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1±0.5 mL/kg/hr, 2.8±0.7 mL/kg/hr, and 3.2±1.5 mL/kg/hr, respectively, for groups ΔT-6 hrs, ΔT-12 hrs, and ΔT-24 hrs; p<.01) and norepinephrine requirements during the 48-hr resuscitation protocol (0.02±0.04 μg/kg/min, 0.06±0.09 μg/kg/min, and 0.13±0.15 µg/kg/min; p=.059), decreased maximal brain mitochondrial complex II respiration (p=.048), and tended to increase mortality (p=.08). Muscle tissue adenosine triphosphate decreased in all groups (p<.01), with lowest values at the end in groups ΔT-12 hrs and ΔT-24 hrs.
Increasing the delay between sepsis initiation and resuscitation increases disease severity, need for resuscitation, and sepsis-associated brain mitochondrial dysfunction. Our results support the concept of a critical window of opportunity in sepsis resuscitation.
脓毒症的早期治疗可能改善预后。本研究旨在评估复苏开始延迟如何影响脓毒症的严重程度以及实现血流动力学稳定所需的治疗。
前瞻性、随机、对照的实验研究。
大学医院的实验实验室。
32 头麻醉和机械通气的猪。
猪被随机分配（每组 8 头）至非脓毒症对照组或三组中的一组，其中诱导粪性腹膜炎（腹腔内注入 2 g/kg 自体粪便），并在 6 小时（ΔT-6 小时）、12 小时（ΔT-12 小时）或 24 小时（ΔT-24 小时）后开始 48 小时的方案化复苏。本研究旨在评估复苏开始延迟对疾病严重程度、复苏需求以及脓毒症相关器官和线粒体功能障碍的影响。
任何复苏开始的延迟都与复苏前低血容量的进行性迹象以及白细胞介素-6 和肿瘤坏死因子-α 血浆水平的升高有关。延迟复苏增加了累积净液体平衡（分别为 2.1±0.5 毫升/公斤/小时、2.8±0.7 毫升/公斤/小时和 3.2±1.5 毫升/公斤/小时，对于 ΔT-6 小时、ΔT-12 小时和 ΔT-24 小时组；p<.01）和 48 小时复苏方案期间去甲肾上腺素的需求（0.02±0.04 微克/公斤/分钟、0.06±0.09 微克/公斤/分钟和 0.13±0.15 微克/公斤/分钟；p=.059），降低了最大脑线粒体复合物 II 呼吸（p=.048），并倾向于增加死亡率（p=.08）。所有组的肌肉组织三磷酸腺苷均减少（p<.01），在 ΔT-12 小时和 ΔT-24 小时组结束时最低。
增加脓毒症发作与复苏之间的延迟时间会增加疾病的严重程度、复苏的需求以及与脓毒症相关的脑线粒体功能障碍。我们的结果支持脓毒症复苏存在关键机会窗的概念。
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