血浆复苏改善了盲肠结扎穿刺脓毒症大鼠模型的存活率。
Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis.
机构信息
Center for Translational Injury Research, University of Texas Health Science Center, Houston, Texas.
Department of Surgery, McGovern Medical School, University of Texas Health Science Center, Houston, Texas.
出版信息
Shock. 2018 Jan;49(1):53-61. doi: 10.1097/SHK.0000000000000918.
BACKGROUND
The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-h survival in a rat sepsis model.
METHODS
Adult male Sprague-Dawley rats (375-425 g) were subjected to 35% cecal ligation and puncture (CLP) (t = 0 h). Twenty-two hours post-CLP and prior to resuscitation (t = 22 h), animals were randomized to resuscitation with normal saline (NS, 10 cc/kg/h) or pooled rat fresh frozen plasma (FFP, 3.33 cc/kg/h). Resuscitation under general anesthesia proceeded for the next 6 h (t = 22 h to t = 28 h); lactate was checked every 2 h, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t = 22 h) and after resuscitation (t = 28 h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisher exact test was used to analyze the primary outcome of 48-h survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests.
RESULTS
Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but preresuscitation (t = 22 h) variables between FFP and NS animals were similar and significantly deranged compared with sham animals. FFP significantly increased 48-h survival compared to NS (n = 8 [57%] vs n = 2 [14%]), attenuated the post-resuscitation (t = 28 h) levels of epinephrine (mean 2.2 vs 7.0 ng/mL), norepinephrine, (3.8 vs 8.9 ng/mL), IL-6 (3.8 vs 18.7 ng/mL), and syndecan-1 (21.8 vs 31.0 ng/mL) (all P < 0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all P < 0.05).
CONCLUSION
Compared to crystalloid, plasma resuscitation increased 48-h survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.
背景
从晶体液复苏向血浆复苏的范式转变改善了创伤性失血性休克患者的预后，这部分归因于血浆介导的儿茶酚胺和炎症诱导的内皮损伤逆转，降低了血管通透性并减轻了器官损伤。由于败血症引起的内皮损伤与出血时相似，我们假设在败血症大鼠模型中，血浆复苏会增加 48 小时的存活率。
方法
成年雄性 Sprague-Dawley 大鼠（375-425g）接受 35%盲肠结扎和穿刺（CLP）（t=0h）。CLP 后 22 小时（t=22h）且在复苏之前，动物随机分为生理盐水（NS，10cc/kg/h）或大鼠新鲜冷冻血浆（FFP，3.33cc/kg/h）复苏。在全身麻醉下进行接下来的 6 小时复苏（t=22h 至 t=28h）；每 2 小时检查一次乳酸，根据乳酸清除率调整液体量。在复苏前（t=22h）和复苏后（t=28h）以及死亡或研究结束时获得血液样本。获得肺标本以计算湿重与干重比。Fisher 确切检验用于分析 48 小时存活率的主要结局。重复测量的方差分析用于分析 FFP 与 NS 复苏对血气、电解质、血尿素氮（BUN）、肌酐、白细胞介素（IL）-6、IL-10、儿茶酚胺和 syndecan-1（内皮损伤标志物）的影响。所有统计检验均使用双侧 alpha 水平<0.05。
结果
研究了 33 只动物：FFP 14 只，NS 14 只，假手术 5 只。FFP 和 NS 动物在 CLP 后但在预复苏时（t=22h）的变量与假手术动物相似，但与假手术动物相比明显紊乱。与 NS 相比，FFP 显著增加了 48 小时的存活率（n=8[57%] vs n=2[14%]），减轻了复苏后（t=28h）的肾上腺素（平均 2.2 与 7.0ng/mL）、去甲肾上腺素（3.8 与 8.9ng/mL）、IL-6（3.8 与 18.7ng/mL）和 syndecan-1（21.8 与 31.0ng/mL）的水平（均 P<0.05），改善了复苏后 PO2 与 FiO2 的比值（353 与 151），并降低了肺湿重与干重比（5.28 与 5.94）（均 P<0.05）。
结论
与晶体液相比，血浆复苏增加了败血症大鼠模型的 48 小时存活率，改善了肺功能并减少了肺水肿，并减轻了炎症、内皮损伤和儿茶酚胺的标志物。
Zotero 插件