吸入性损伤和烧伤所致急性呼吸窘迫综合征和多器官衰竭的辅助治疗对靶器官损害及组织学损伤严重程度的影响。
Effects of adjunct treatments on end-organ damage and histological injury severity in acute respiratory distress syndrome and multiorgan failure caused by smoke inhalation injury and burns.
机构信息
The Geneva Foundation, Tacoma WA, United States; United States Army Institute of Surgical Research, JBSA-Ft. Sam Houston, TX, United States.
United States Army Institute of Surgical Research, JBSA-Ft. Sam Houston, TX, United States.
出版信息
Burns. 2019 Dec;45(8):1765-1774. doi: 10.1016/j.burns.2019.07.020. Epub 2019 Aug 2.
BACKGROUND
We investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as adjunctive treatments for acute respiratory distress syndrome (ARDS) due to inhalation injury and burns. We hypothesized that these interventions decrease histological end-organ damage.
METHODS
Anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, then critical care for 72h. The following groups were studied: CTR (no injury, n = 4), ICTR (injured untreated, n = 10), Allo (injured treated with allogenic MSC, n = 10), Auto (injured treated with autologous MSC, n = 10), Hemo (injured and treated with the Hemolung low flow ECLS system, n = 9), and Nova (injured and treated with the NovaLung low flow ECLS system, n = 8). Histology scores from lung, kidneys, liver, and jejunum were calculated. Data are presented as means±SEM.
RESULTS
Survival at 72h was 100% in CTR; 40% in ICTR; 50% in Allo; 90% in Auto; 33% in Hemo; 63% in Nova. ARDS developed in 0/10 CTR; 10/10 ICTR; 8/9 Hemo; 5/8 Nova; 9/10 Allo; 6/10 Auto. Diffuse alveolar damage (DAD) was present in all injured groups. MSC groups had significantly lower DAD scores than ICTR animals (Allo 26.6 ± 3.4 and Auto 18.9 ± 1.5 vs. ICTR 46.8 ± 2.1, p < 0.001). MSC groups also had lower DAD scores than ECLS animals (Allo vs. Nova, p < 0.05, Allo vs. Hemo p < 0.001, Auto vs. Nova p < 0.001, Auto vs. Hemo, p < 0.001). Kidney injury ICTR (p < 0.05) and Hemo (p < 0.01) were higher than in CTR. By logistic regression, a PaO-to-FiO ratio (PFR) < 300 was a function of the DAD score: logit (PFR < 300) = 0.84 + 0.072*DAD Score, odds ratio 1.074 (1.007, 1.147, p < 0.05) with a ROC AUC of 0.76, p < 0.001.
CONCLUSION
Treatment with Auto MSC followed by Allo and then Nova were most effective in mitigating ARDS and MOF severity in this model. Further studies will elucidate the role of combination therapies of MSC and ECLS as comprehensive treatments for ARDS and MOF.
背景
我们研究了间充质干细胞（MSC）或低流量体外生命支持（ECLS）作为吸入性损伤和烧伤引起的急性呼吸窘迫综合征（ARDS）辅助治疗的效果。我们假设这些干预措施可以减少组织学终末器官损伤。
方法
麻醉雌性猪接受烟雾吸入性损伤和 40%总体表面积烧伤，然后进行 72 小时的重症监护。研究了以下组：对照组（无损伤，n=4），ICT 组（损伤未治疗，n=10），Allo 组（损伤用同种异体 MSC 治疗，n=10），Auto 组（损伤用自体 MSC 治疗，n=10），Hemo 组（损伤并接受 Hemolung 低流量 ECLS 系统治疗，n=9）和 Nova 组（损伤并接受 NovaLung 低流量 ECLS 系统治疗，n=8）。计算肺、肾、肝和空肠的组织学评分。数据以平均值±SEM 表示。
结果
72 小时存活率为 100%在 CTR；40%在 ICTR；50%在 Allo；90%在 Auto；33%在 Hemo；63%在 Nova。ARDS 在 0/10 CTR 中发展；10/10 ICTR；8/9 Hemo；5/8 Nova；9/10 Allo；6/10 Auto。所有受伤组均出现弥漫性肺泡损伤（DAD）。MSC 组的 DAD 评分明显低于 ICTR 动物（Allo 为 26.6±3.4，Auto 为 18.9±1.5，与 ICTR 相比，46.8±2.1，p<0.001）。MSC 组的 DAD 评分也低于 ECLS 动物（Allo 与 Nova 相比，p<0.05，Allo 与 Hemo 相比，p<0.001，Auto 与 Nova 相比，p<0.001，Auto 与 Hemo 相比，p<0.001）。肾损伤 ICTR（p<0.05）和 Hemo（p<0.01）高于 CTR。通过逻辑回归，PaO-to-FiO 比（PFR）<300 是 DAD 评分的函数：logit（PFR<300）=0.84+0.072*DAD 评分，优势比 1.074（1.007，1.147，p<0.05），ROC AUC 为 0.76，p<0.001。
结论
在该模型中，Auto MSC 治疗后再进行 Allo 和 Nova 治疗，对减轻 ARDS 和 MOF 严重程度最有效。进一步的研究将阐明 MSC 和 ECLS 的联合治疗作为 ARDS 和 MOF 综合治疗的作用。
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