Sperber Jesper, Lipcsey Miklós, Larsson Anders, Larsson Anders, Sjölin Jan, Castegren Markus
Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
BMC Pulm Med. 2015 May 10;15:60. doi: 10.1186/s12890-015-0052-9.
Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome.
30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels.
TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb.
Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.
采用低潮气量（VT）和较高呼气末正压（PEEP）的保护性通气可降低全身炎症反应综合征期间机械通气的负面叠加效应。我们假设，在手术期间进行保护性通气会对内毒素诱导的脓毒症样综合征实验动物模型中的器官特异性免疫反应产生影响。
30头猪接受2小时开腹手术，之后以0.25微克×千克⁻¹×小时⁻¹的速度持续输注内毒素5小时。将导管插入颈动脉、肝静脉、门静脉和颈静脉球。动物被随机分为两个保护性通气组（每组n = 10）：一组在整个实验过程中采用6毫升×千克⁻¹的潮气量进行通气，而另一组在手术阶段采用10毫升×千克⁻¹的潮气量进行通气。两组在手术期间呼气末正压均为5厘米水柱，在内毒素输注开始时增加到10厘米水柱。对照组（n = 10）在整个实验过程中采用10毫升×千克⁻¹的潮气量和5厘米水柱的呼气末正压进行通气。在四个采样部位，我们a）同时比较细胞因子水平，b）研究在内毒素血症之前和期间启动保护性通气的效果，以及c）评估保护性通气对器官特异性细胞因子水平的影响。
肝静脉中肿瘤坏死因子-α（TNF-α）水平最高，动脉和颈静脉球中白细胞介素-6（IL-6）水平最高，动脉中白细胞介素-10（IL-10）水平最低。在内毒素血症之前和期间启动的保护性通气在器官特异性细胞因子水平上没有差异。与对照组相比，保护性通气导致肝静脉中TNF-α水平较低，而在动脉、门静脉或颈静脉球中未观察到显著差异。
在实验性脓毒症期间观察到各器官细胞因子输出存在差异。我们认为细胞因子水平对内毒素血症之前启动保护性通气没有影响。然而，在内毒素血症期间，保护性通气可减轻肝脏炎症细胞因子输出，从而减轻总的炎症负担。
