Metabolomic assessment of low versus high volume resuscitation in a combined porcine model of severe burn and traumatic brain injury.

IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE
SHOCK Pub Date : 2025-09-25 DOI:10.1097/SHK.0000000000002719
Linda M Schutzman, Sandra L Taylor, Oliver Fiehn, Timothy M Guenther, Marguerite W Spruce, Lindsay M Bach, Connor M Caples, Carl A Beyer, John K Grayson, Jeffrey R Fine, Frederick J Meyers, Tina L Palmieri, Ian E Brown
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引用次数: 0

Abstract

Background: Severe burns continue to be associated with significant morbidity and mortality despite advances in resuscitation techniques. Concomitant injury such as traumatic brain injury adds complexity to resuscitation paradigms as high volume fluid resuscitation together with high losses of plasma proteins may lead to poor outcomes with respect to traumatic brain injury and associated cerebral edema. Currently, "goal-directed" methods of resuscitation are utilized in which clinical end points guide fluid volume needs. Unfortunately, clinical changes often indicate that significant organ dysfunction has already occurred. In this targeted metabolomics study, we compare "aggressive" versus "restrictive" fluid resuscitation strategies to identify compounds indicative of injury progression.

Methods: A porcine model of combined brain injury and severe burns was utilized. Injured animals were randomized to receive either "aggressive" fluid resuscitation using the Parkland formula or "restrictive" resuscitation with the modified Brooke formula. Resuscitation was continued for 8 hours. Plasma and urine samples were collected for targeted analysis of oxylipins and steroids by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results: Sixty-nine serum and urinary oxylipins were identified. Significant elevations of 15 urinary oxylipins were noted in animals who received the restrictive resuscitation strategy. No significant differences in plasma oxylipins were found. Twenty-eight serum steroids and 29 urinary steroids were isolated. The concentrations of 3 serum steroids were significantly higher the "restricted" resuscitation group. No differences in urinary steroids were identified.

Conclusions: In this study, targeted metabolomics was used to identify plasma and urinary oxylipins and steroids in both the restrictive and aggressive resuscitation groups. Notably, significant elevations in 15 urinary oxylipins and 3 serum steroids were identified only in animals that were randomized to "restricted" resuscitation. These findings demonstrate detectable differences in lipid metabolites within 8 hours of severe injury, which may correlate with differences in inflammation and facilitate goal-directed resuscitation.

在猪严重烧伤和创伤性脑损伤联合模型中低容量与高容量复苏的代谢组学评估。
背景:尽管复苏技术有所进步,但严重烧伤仍然与显著的发病率和死亡率相关。伴随性损伤,如创伤性脑损伤,增加了复苏模式的复杂性,因为大容量液体复苏加上血浆蛋白的大量损失可能导致创伤性脑损伤和相关脑水肿的预后不良。目前,使用“目标导向”的复苏方法,其中临床终点指导液体量需求。不幸的是,临床变化往往表明明显的器官功能障碍已经发生。在这项有针对性的代谢组学研究中,我们比较了“积极”和“限制性”液体复苏策略,以确定指示损伤进展的化合物。方法:采用猪脑损伤合并严重烧伤模型。受伤的动物被随机分为两组,一组接受帕克兰配方的“积极”液体复苏,另一组接受改良布鲁克配方的“限制性”复苏。复苏持续8小时。收集血浆和尿液样本,采用超高效液相色谱-串联质谱(UPLC-MS/MS)对氧脂类和类固醇进行针对性分析。结果:共鉴定出69种血清和尿中氧化脂类。在接受限制性复苏策略的动物中,15种尿氧脂素显著升高。血浆中氧磷脂含量无显著差异。分离血清类固醇28例,尿液类固醇29例。“限制”复苏组血清3种甾体激素浓度均显著升高。尿类固醇没有发现差异。结论:在本研究中,靶向代谢组学用于鉴定限制性和积极复苏组的血浆和尿液中的氧脂素和类固醇。值得注意的是,只有在随机分配到“限制性”复苏组的动物中,才发现15种尿氧脂素和3种血清类固醇显著升高。这些发现表明,严重损伤后8小时内脂质代谢物可检测到差异,这可能与炎症差异有关,有助于目标导向复苏。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
SHOCK
SHOCK 医学-外科
CiteScore
6.20
自引率
3.20%
发文量
199
审稿时长
1 months
期刊介绍: SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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