Intensive Care and Anesthesiology Laboratory, Research and Education Institute, Hospital Sírio-Libanês, São Paulo, Brazil.
Shock. 2011 Dec;36(6):604-12. doi: 10.1097/SHK.0b013e3182336aa4.
The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO(2))-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO(2)-driven resuscitation including fluids, norepinephrine and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress during a clinically resembling experimental model of septic shock. Eighteen anesthetized and catheterized pigs (35-45 kg) were submitted to peritonitis by fecal inoculation (0.75 g/kg). After hypotension, antibiotics were administered, and the animals were randomized to two groups: control (n = 9), with hemodynamic support aiming central venous pressure 8 to 12 mmHg, urinary output 0.5 mL/kg per hour, and mean arterial pressure greater than 65 mmHg; and SvO(2) (n = 9), with the goals above, plus SvO(2) greater than 65%. The interventions lasted 12 h, and lactated Ringer's and norepinephrine (both groups) and dobutamine (SvO(2) group) were administered. Inflammatory response was evaluated by plasma concentration of cytokines, neutrophil CD14 expression, oxidant generation, and apoptosis. Oxidative stress was evaluated by plasma and myocardial nitrate concentrations, myocardial and vascular NADP(H) oxidase activity, myocardial glutathione content, and nitrotyrosine expression. Mixed venous oxygen saturation-driven resuscitation was associated with improved systolic index, oxygen delivery, and diuresis. Sepsis induced in both groups a significant increase on IL-6 concentrations and plasma nitrate concentrations and a persistent decrease in neutrophil CD14 expression. Apoptosis rate and neutrophil oxidant generation were not different between groups. Treatment strategies did not significantly modify oxidative stress parameters. Thus, an approach aiming SvO(2) during sepsis improves hemodynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects associated with this strategy may be related to other mechanisms.
混合静脉血氧饱和度指导复苏对脓毒症有益影响的发病机制尚不清楚。我们的目的是评估包括液体、去甲肾上腺素和多巴酚丁胺在内的 SvO2 驱动复苏算法对脓毒性休克类似临床模型中血流动力学、炎症反应和心血管氧化应激的影响。18 只麻醉和置管的猪（35-45kg）通过粪便接种（0.75g/kg）发生腹膜炎。低血压后，给予抗生素，并将动物随机分为两组：对照组（n=9），以中心静脉压 8-12mmHg、尿量 0.5ml/kg/小时和平均动脉压大于 65mmHg 为目标进行血流动力学支持；和 SvO2 组（n=9），以上述目标为目标，外加 SvO2 大于 65%。干预持续 12 小时，给予乳酸林格氏液和去甲肾上腺素（两组）和多巴酚丁胺（SvO2 组）。通过细胞因子、中性粒细胞 CD14 表达、氧化产物和细胞凋亡的血浆浓度评估炎症反应。通过血浆和心肌硝酸盐浓度、心肌和血管 NADP（H）氧化酶活性、心肌谷胱甘肽含量和硝基酪氨酸表达评估氧化应激。混合静脉血氧饱和度驱动复苏与改善收缩指数、氧输送和利尿有关。两组脓毒症均导致 IL-6 浓度和血浆硝酸盐浓度显著增加，中性粒细胞 CD14 表达持续降低。细胞凋亡率和中性粒细胞氧化产物生成在两组之间没有差异。治疗策略并未显著改变氧化应激参数。因此，在脓毒症期间采用 SvO2 指导的治疗方法可改善血流动力学，而对炎症反应和氧化应激没有任何显著影响。这种策略的有益效果可能与其他机制有关。
