Ritter Cristiane, Constantino Larissa, Michels Monique, Gonçalves Renata Casagrande, Fraga Cassiana, Damásio Danusa, Dal-Pizzol Felipe
Programa de Pós-Graduação em Ciências da Saúde, Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
Centro de Pesquisa, Hospital São José, Criciúma, SC, Brasil.
Rev Bras Ter Intensiva. 2020 Mar;32(1):108-114. doi: 10.5935/0103-507x.20200016. Epub 2020 May 8.
To examine the effectiveness of stratification to identify and target antioxidant therapy for animal models of lethal sepsis and in patients who develop sustained hypotension.
Rats were subjected to sepsis induced by cecal ligation and puncture. Animals were divided into two groups: those with high and low plasma levels of interleukin-6. Following stratification, N-acetylcysteine plus deferoxamine or saline was administered to animals starting 3 and 12 hours after surgery. N-Acetylcysteine plus deferoxamine or placebo was administered within 12 hours of meeting the inclusion criteria in hypotensive patients.
N-Acetylcysteine plus deferoxamine increased survival in the cecal ligation and puncture model when administered 3 and 12 hours after sepsis induction. When dividing animals that received antioxidants using plasma interleukin-6 levels, the protective effect was observed only in those animals with high IL-6 levels. The antioxidant effect of N-acetylcysteine + deferoxamine was similar in the two groups, but a significant decrease in plasma interleukin-6 levels was observed in the high-interleukin-6-level group. Compared with patients treated with antioxidants in the low-interleukin-6 subgroup, those in the high-interleukin-6 subgroup had a lower incidence of acute kidney injury but were not different in terms of acute kidney injury severity or intensive care unit mortality.
Targeting antioxidant therapy to a high inflammatory phenotype would select a responsive population.
研究分层对于确定致死性脓毒症动物模型以及发生持续性低血压患者的抗氧化治疗靶点并评估其有效性。
对大鼠进行盲肠结扎和穿刺诱导脓毒症。动物被分为两组：血浆白细胞介素-6水平高和低的组。分层后，在术后3小时和12小时开始对动物给予N-乙酰半胱氨酸加去铁胺或生理盐水。在低血压患者符合纳入标准后的12小时内给予N-乙酰半胱氨酸加去铁胺或安慰剂。
在脓毒症诱导后3小时和12小时给予N-乙酰半胱氨酸加去铁胺可提高盲肠结扎和穿刺模型的生存率。当根据血浆白细胞介素-6水平对接受抗氧化剂治疗的动物进行分组时，仅在白细胞介素-6水平高的动物中观察到保护作用。N-乙酰半胱氨酸+去铁胺在两组中的抗氧化作用相似，但在白细胞介素-6水平高的组中观察到血浆白细胞介素-6水平显著降低。与白细胞介素-6低亚组中接受抗氧化剂治疗的患者相比，白细胞介素-6高亚组中急性肾损伤的发生率较低，但在急性肾损伤严重程度或重症监护病房死亡率方面没有差异。
将抗氧化治疗靶向高炎症表型将筛选出有反应的人群。
