引用

我们在2种不同给药方案诱导的实验性内毒素血症期间的健康男性志愿者中进行了一项前瞻性观察研究，并在败血症患者中进行了一项观察研究。数据来自19名18 - 35岁的健康、不吸烟的男性志愿者，其中11人加入了持续输注LPS的内毒素血症研究，8人加入了单次给药LPS的内毒素血症研究。所有受试者均提供书面知情同意，实验均符合赫尔辛基宣言和良好临床实践指南，并分别于2016年8月29日和2016年1月6日获得当地伦理委员会委员会Mensgebonden Onderwoek地区ArnhemNijmegen批准，文件编号为NL57410.091.16和NL53411.091.15。项目识别代码为:Clinicaltrials.gov NCT02922673用于持续输注LPS;Clinicaltrials.gov NCT02675868用于LPS单丸给药。受试者在纳入前进行筛选，并进行正常的体检、心电图和常规实验室检查。此外，包括10例感染性休克患者，年龄大于18岁。当地机构审查委员会放弃了对这些败血症患者的知情同意的需要。脓毒性休克由国际脓毒症定义会议[21]定义。脓毒症患者按照国际管理指南[22]进行治疗。 All sepsis patients received sedating medication and were mechanically ventilated to achieve normocapnia. Exclusion criteria were an irregular heart rhythm or an insufficient transtemporal bone window. EXPERIMENTAL HUMAN ENDOTOXEMIA Purified LPS (continuous infusion study: _Escherichia coli_ O:113, Lot no. 94332B4, List Biological Laboratories, Campbell, USA; bolus administration study: US Standard Reference Endotoxin _Escherichia coli_ O:113, Pharmaceutical Development Section of the National Institutes of Health, Bethesda, USA) was supplied as a lyophilized powder and dissolved in normal saline 0.9% as described previously [23,24]. For the continuous infusion study (c-LPS), a total of 4 ng/kg LPS was administered as a intravenous loading bolus of 1 ng/kg body weight at T = 0, followed by an intravenous infusion of 1 ng/kg/h for a period of 3 h [24]. For the bolus administration study (b-LPS), LPS was administered, as described previously, as an intravenous bolus injection at a dose of 2 ng/kg body weight in 1 min at T = 0 [23].