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在内毒素休克猪模型中,与碳酸氢钠和0.9%氯化钠相比,乳酸钠可改善肾微血管血栓形成:一项实验性随机开放标签对照研究。

Sodium lactate improves renal microvascular thrombosis compared to sodium bicarbonate and 0.9% NaCl in a porcine model of endotoxic shock: an experimental randomized open label controlled study.

作者信息

Duburcq Thibault, Durand Arthur, Tournoys Antoine, Gnemmi Viviane, Gmyr Valery, Pattou François, Jourdain Mercedes, Tamion Fabienne, Besnier Emmanuel, Préau Sebastien, Parmentier-Decrucq Erika, Mathieu Daniel, Poissy Julien, Favory Raphaël

机构信息

Centre de Réanimation - Rue Emile Laine, CHU de Lille - Hôpital R Salengro, 59037, Lille Cedex, France.

LIRIC Inserm U995 Glycation: From Inflammation to Aging, 59000, Lille, France.

出版信息

Ann Intensive Care. 2018 Feb 14;8(1):24. doi: 10.1186/s13613-018-0367-9.

Abstract

BACKGROUND

Sodium lactate seemed to improve fluid balance and avoid fluid overload. The objective of this study was to determine if these beneficial effects can be at least partly explained by an improvement in disseminated intravascular coagulation (DIC)-associated renal microvascular thrombosis.

METHODS

Ancillary work of an interventional randomized open label controlled experimental study. Fifteen female "Large White" pigs (2 months old) were challenged with intravenous infusion of E. coli endotoxin. Three groups of five animals were randomly assigned to receive different fluids: a treatment group received sodium lactate 11.2% (SL group); an isotonic control group received 0.9% NaCl (NC group); a hypertonic control group, with the same amount of osmoles and sodium than SL group, received sodium bicarbonate 8.4% (SB group). Glomerular filtration rate (GFR) markers, coagulation and inflammation parameters were measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn for histological study. Statistical analysis was performed with nonparametric tests and the Dunn correction for multiple comparisons. A p < 0.05 was considered significant.

RESULTS

The direct immunofluorescence study revealed that the percentage of capillary sections thrombosed in glomerulus were significantly lesser in SL group [5 (0-28) %] compared to NC [64 (43-79) %, p = 0.01] and SB [64 (43-79), p = 0.03] groups. Alterations in platelet count and fibrinogen level occurred earlier and were significantly more pronounced in both control groups compared to SL group (p < 0.05 at 210 and 300 min). The increase in thrombin-antithrombin complexes was significantly higher in NC [754 (367-945) μg/mL; p = 0.03] and SB [463 (249-592) μg/mL; p = 0.03] groups than in SL group [176 (37-265) μg/mL]. At the end of the experiment, creatinine clearance was significantly higher in SL group [55.46 (30.07-67.85) mL/min] compared to NC group [1.52 (0.17-27.67) mL/min, p = 0.03].

CONCLUSIONS

In this study, we report that sodium lactate improves DIC-associated renal microvascular thrombosis and preserves GFR. These findings could at least partly explain the better fluid balance observed with sodium lactate infusion.

摘要

背景

乳酸钠似乎可改善液体平衡并避免液体过载。本研究的目的是确定这些有益作用是否至少部分可通过弥散性血管内凝血(DIC)相关的肾微血管血栓形成的改善来解释。

方法

一项介入性随机开放标签对照实验研究的辅助工作。15只2月龄雌性“大白”猪接受静脉注射大肠杆菌内毒素的挑战。将三组,每组5只动物随机分配接受不同的液体:治疗组接受11.2%乳酸钠(SL组);等渗对照组接受0.9%氯化钠(NC组);高渗对照组接受8.4%碳酸氢钠(SB组),其渗透压和钠含量与SL组相同。在5小时内测量肾小球滤过率(GFR)标志物、凝血和炎症参数。安乐死后立即取出肾脏进行组织学研究。采用非参数检验和Dunn多重比较校正进行统计分析。p<0.05被认为具有统计学意义。

结果

直接免疫荧光研究显示,与NC组[64(43-79)%,p=0.01]和SB组[64(43-79),p=0.03]相比,SL组肾小球内血栓形成的毛细血管节段百分比显著更低[5(0-28)%]。与SL组相比,两个对照组血小板计数和纤维蛋白原水平的改变出现更早且更明显(在210和300分钟时p<0.05)。NC组[754(367-945)μg/mL;p=0.03]和SB组[463(249-592)μg/mL;p=0.03]凝血酶-抗凝血酶复合物的增加显著高于SL组[176(37-265)μg/mL]。实验结束时,SL组[55.46(30.07-67.85)mL/min]的肌酐清除率显著高于NC组[1.52(0.17-27.67)mL/min,p=0.03]。

结论

在本研究中,我们报告乳酸钠可改善DIC相关的肾微血管血栓形成并维持GFR。这些发现至少可以部分解释输注乳酸钠时观察到的更好的液体平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b21/5812960/8da3a6e85cca/13613_2018_367_Fig1_HTML.jpg

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