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
{"title":"Metabolomic assessment of low versus high volume resuscitation in a combined porcine model of severe burn and traumatic brain injury.","authors":"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","doi":"10.1097/SHK.0000000000002719","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002719","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
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.
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.