Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial.
Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial.
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DOI：
10.1097/ccm.0000000000003004
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发表时间：
2018-05
影响因子：
8.8
通讯作者：
Rosengart MR
中科院分区：
文献类型：
--
作者：
Lewis AJ;Griepentrog JE;Zhang X;Angus DC;Seymour CW;Rosengart MR
脓毒症是由宿主对感染的反应失调引起的急性器官功能障碍，构成了严重的公共卫生负担。目前的管理包括早期发现，开始使用抗生素和液体，以及必要的源头控制。虽然观察数据表明，即使延迟几个小时开始使用抗生素或静脉输液也与生存有关，但这些发现是有争议的。没有人类的随机数据，先前的动物研究研究从实验操作开始，而不是从脓毒症的临床特征开始。使用最近开发的小鼠盲肠结扎和穿孔（CLP）模型，精确监测生理恶化，我们假设在多微生物脓毒症的生理恶化的临床相关点，在第一次推注的液体复苏中，或在第一次推注的抗生素的增量每小时延迟，或两者的组合将缩短生存。随机实验动物实验。大学基础科学实验室雄性C57 BL/6 J、雌性C57 BL/6 J、年龄（40-50周）雄性C57 BL/6 J和BALB/C小鼠小鼠（n=200）进行生物遥测增强CLP，并在满足急性生理恶化的验证标准后随机分组。给药组包括单剂量亚胺培南/西司汀、单次推注30 mL/kg液体复苏或两者联合。在符合恶化标准时、延迟2小时后或延迟4小时后分配小鼠接受治疗。在我们的模型中，抗生素治疗开始的每小时延迟导致生存期逐渐缩短（p<0.001）。添加液体复苏无法挽救动物，这些动物在符合入组标准后4小时接受治疗。全身炎症增加，宿主生理学随着抗生素的每小时延迟而日益紊乱。我们的结论是，抗生素治疗是高度时间敏感性，并应努力提供这种关键的治疗，尽可能早的败血症，也许延伸到医院外的第一个医疗接触点。
Sepsis, the acute organ dysfunction caused by a dysregulated host response to infection, poses a serious public health burden. Current management includes early detection, initiation of antibiotics and fluids, and source control as necessary. Although observational data suggest that delays of even a few hours in the initiation of antibiotics or intravenous fluids is associated with survival, these findings are controversial. There are no randomized data in humans, and prior animal studies studied time from experimental manipulation, not from the onset of clinical features of sepsis. Using a recently developed murine cecal ligation and puncture (CLP) model that precisely monitors physiologic deterioration, we hypothesize that incremental hourly delays in the first dose of antibiotics, in the first bolus of fluid resuscitation, or a combination of the two at a clinically relevant point of physiologic deterioration during polymicrobial sepsis will shorten survival. Randomized laboratory animal experimental trial. University basic science laboratory Male C57BL/6J, female C57BL/6J, aged (40–50 weeks) male C57BL/6J, and BALB/C mice Mice (n=200) underwent biotelemetry-enhanced CLP and were randomized after meeting validated criteria for acute physiologic deterioration. Treatment groups consisted of a single dose of imipenem/cilastin, a single bolus of 30 mL/kg fluid resuscitation, or a combination of the two. Mice were allocated to receive treatment at the time of meeting deterioration criteria, after a 2-hour delay, or after a 4-hour delay. Hourly delays in the initiation of antibiotic therapy led to progressively shortened survival in our model (p<0.001). The addition of fluid resuscitation was unable to rescue animals, which received treatment four hours after meeting enrollment criteria. Systemic inflammation was increased and host physiology was increasingly deranged with hourly delays to antibiotics. We conclude that antibiotic therapy is highly time-sensitive, and efforts should be made to deliver this critical therapy as early as possible in sepsis, perhaps extending into the first point of medical contact outside the hospital.