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INTRODUCTION: hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. METHODS: examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. RESULTS: there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. CONCLUSION: the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.
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Biomarcadores , Ácido Láctico , Choque Hemorrágico , Humanos , Choque Hemorrágico/mortalidad , Choque Hemorrágico/sangre , Masculino , Femenino , Ácido Láctico/sangre , Adulto , Biomarcadores/sangre , Persona de Mediana Edad , Estudios de Cohortes , Unidades de Cuidados IntensivosRESUMEN
ABSTRACT: Purpose: To evaluate the dose-dependent effect of whole blood (WB) on the outcomes of civilian trauma patients with hemorrhagic shock. Methods: We performed a 2-year (2020-2021) retrospective analysis of the ACS-TQIP dataset. Adult (≥18) trauma patients with a shock index (SI) >1 who received at least 5 units of PRBC and one unit of WB within the first 4 h of admission were included. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications and hospital and intensive care unit length of stay. Results: A total of 830 trauma patients with a mean (SD) age of 38 (16) were identified. The median [IQR] 4-h WB and PRBC requirements were 2 [2-4] U and 10 [7-15] U, respectively, with a median WB:RBC ratio of 0.2 [0.1-0.3]. Every 0.1 increase in WB:RBC ratio was associated with decreased odds of 24-h mortality (aOR: 0.916, P = 0.035) and in-hospital mortality (aOR: 0.878, P < 0.001). Youden's index identified 0.25 (1 U of WB for every 4 U of PRBC) as the optimal WB:PRBC ratio to reduce 24-h mortality. High ratio (≥0.25) group had lower adjusted odds of 24-h mortality (aOR: 0.678, P = 0.021) and in-hospital mortality (aOR: 0.618, P < 0.001) compared to the low ratio group. Conclusions: A higher WB:PRBC ratio was associated with improved early and late mortality in trauma patients with hemorrhagic shock. Given the availability of WB in trauma centers across the United States, at least one unit of WB for every 4 units of packed red blood cells may be administered to improve the survival of hemorrhaging civilian trauma patients.
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Choque Hemorrágico , Heridas y Lesiones , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Heridas y Lesiones/sangre , Heridas y Lesiones/mortalidad , Choque Hemorrágico/terapia , Choque Hemorrágico/mortalidad , Choque Hemorrágico/sangre , Persona de Mediana Edad , Mortalidad Hospitalaria , Transfusión Sanguínea , EritrocitosRESUMEN
INTRODUCTION: Along with recent advances in analytical technologies, tricarboxylic acid-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock. For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with hemorrhagic shock. METHODS: Fifty-two male pigs (50 ± 5 kg) were randomized into two groups: group isolated fracture was subject to a standardized femur shaft fracture, and group polytrauma was subject to a femur fracture, followed by blunt chest trauma, liver laceration, and a pressure-controlled hemorrhagic shock for 60 minutes. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements of tissue perfusion. Longitudinal analyses were performed with linear mixed models, and Spearman's correlations were calculated. A p value of 0.05 was defined as threshold for statistical significance. RESULTS: From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant ( p < 0.001) twofold increase after hemorrhagic shock in group polytrauma that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess ( p = 0.005), but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery ( p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase ( p < 0.001, p < 0.001). CONCLUSION: Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in hemorrhagic shock. The more rapid normalization after resuscitation in comparison with acid base changes may warrant further investigation.
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Carnitina , Modelos Animales de Enfermedad , Lipidómica , Traumatismo Múltiple , Choque Hemorrágico , Animales , Choque Hemorrágico/sangre , Choque Hemorrágico/terapia , Traumatismo Múltiple/sangre , Traumatismo Múltiple/complicaciones , Masculino , Carnitina/análogos & derivados , Carnitina/sangre , Porcinos , Lipidómica/métodos , Resucitación/métodos , Fracturas del Fémur/sangre , Fracturas del Fémur/cirugía , Biomarcadores/sangre , Biomarcadores/metabolismoRESUMEN
INTRODUCTION: Whole blood resuscitation for hemorrhagic shock in trauma represents an opportunity to correct coagulopathy in trauma while also supplying red blood cells. The production of microvesicles in stored whole blood and their effect on its hemostatic parameters have not been described in previous literature. We hypothesized that microvesicles in aged stored whole blood are procoagulant and increase thrombin production via phosphatidylserine. METHODS: Whole blood was obtained from male C57BL/6 male mice and stored in anticoagulant solution for up to 10 days. At intervals, stored whole blood underwent examination with rotational thromboelastography, and platelet-poor plasma was prepared for analysis of thrombin generation. Microvesicles were prepared from 10-day-old whole blood aliquots and added to fresh whole blood or platelet-poor plasma to assess changes in coagulation and thrombin generation. Microvesicles were treated with recombinant mouse lactadherin prior to addition to plasma to inhibit phosphatidylserine's role in thrombin generation. RESULTS: Aged murine whole blood had decreased fibrin clot formation compared with fresh samples with decreased plasma fibrinogen levels. Thrombin generation in plasma from aged blood increased over time of storage. The addition of microvesicles to fresh plasma resulted in increased thrombin generation compared with controls. When phosphatidylserine on microvesicles was blocked with lactadherin, there was no difference in the endogenous thrombin potential, but the generation of thrombin was blunted with lower peak thrombin levels. CONCLUSION: Cold storage of murine whole blood results in decreased fibrinogen levels and fibrin clot formation. Aged whole blood demonstrates increased thrombin generation, and this is due in part to microvesicle production in stored whole blood. One mechanism by which microvesicles are procoagulant is by phosphatidylserine expression on their membranes.
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Conservación de la Sangre , Fibrinógeno , Ratones Endogámicos C57BL , Trombina , Animales , Trombina/metabolismo , Trombina/biosíntesis , Ratones , Masculino , Conservación de la Sangre/métodos , Fibrinógeno/metabolismo , Fibrinógeno/análisis , Fosfatidilserinas/metabolismo , Tromboelastografía , Coagulación Sanguínea/fisiología , Factores de Tiempo , Choque Hemorrágico/sangre , Choque Hemorrágico/terapia , Choque Hemorrágico/metabolismo , Resucitación/métodos , Micropartículas Derivadas de Células/metabolismoRESUMEN
BACKGROUND: Mesenchymal stromal cells (MSCs) express surface tissue factor (TF), which may affect hemostasis and detract from therapeutic outcomes of MSCs if administered intravenously. In this study, we determine a safe dose of MSCs for intravenous (IV) administration and further demonstrate the impact of IV-MSC on acute traumatic coagulopathy (ATC) in rats. METHODS: Tissue factor expression of rat bone marrow-derived mesenchymal stromal cell (BMSC) or adipose-derived mesenchymal stromal cell (AMSC) was detected by immunohistochemistry and enzyme-linked immunosorbent assay. The coagulation properties were measured in MSC-treated rat whole blood, and blood samples were collected from rats after IV administration of MSCs. Acute traumatic coagulopathy rats underwent polytrauma and 40% hemorrhage, followed by IV administration of 5 or 10 million/kg BMSCs (BMSC-5, BMSC-10), or vehicle at 1 hour after trauma. RESULTS: Rat MSCs expressed TF, and incubation of rat BMSCs or AMSCs with whole blood in vitro led to a significantly shortened clotting time. However, a dose-dependent prolongation of prothrombin time with reduction in platelet counts and fibrinogen was found in healthy rat treated with IV-MSCs. Bone marrow-derived mesenchymal stromal cells at 5 million/kg or less led to minimal effect on hemostasis. Mesenchymal stromal cells were not found in circulation but in the lungs after IV administration regardless of the dosage. Acute traumatic coagulopathy with prolonged prothrombin time was not significantly affected by 5 or 10 million/kg BMSCs. Intravenous administration of 10 million/kg BMSCs led to significantly lower fibrinogen and platelet counts, while significantly higher levels of lactate, wet/dry weight ratio, and leukocyte infiltration in the lung were present compared with BMSC-5 or vehicle. No differences were seen in immune or inflammatory profiles with BMSC treatment in ATC rats, at least in the acute timeframe. CONCLUSION: Intravenous administration of MSCs leads to a risk of coagulopathy associated with a dose-dependent reduction in platelet counts and fibrinogen and is incapable of restoring hemostasis of rats with ATC after polytrauma and hemorrhagic shock.
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Trastornos de la Coagulación Sanguínea/etiología , Trasplante de Células Madre Mesenquimatosas , Traumatismo Múltiple/sangre , Choque Hemorrágico/sangre , Tromboplastina/metabolismo , Administración Intravenosa , Animales , Pruebas de Coagulación Sanguínea , Modelos Animales de Enfermedad , Recuento de Plaquetas , RatasRESUMEN
BACKGROUND: Unlike recent advances in blood product resuscitation, intravenous crystalloid (IVF) use after intensive care unit (ICU) admission in hemorrhagic shock has received less attention and current recommendations are based on limited evidence. To address this knowledge gap, we aimed to determine associations between IVF administration during acute ICU resuscitation and outcomes. We hypothesized that larger IVF volumes are associated with worse outcomes. METHODS: We linked our trauma registry with electronic health record data (2012-2015) to identify adults with an initial lactate level of ≥4 mmol/L and documented lactate normalization (≤2 mmol/L), excluding those with isolated head Abbreviated Injury Scale score ≥3. We focused on the period from ICU admission to lactate normalization, analyzing duration, volume of IVF, and proportion of volume as 1-L boluses. We used linear regression to determine associations with ICU length of stay and duration of mechanical ventilation in survivors, and logistic regression to identify associations with acute kidney injury and home discharge while adjusting for important covariates. RESULTS: We included 337 subjects. Median time to lactate normalization was 15 hours (interquartile range, 7-25 hours), and median IVF volume was 3.7 L (interquartile range, 1.5-6.4 L). The fourfold difference between the upper and lower quartiles of both duration and volume remained after stratifying by injury severity. Hourly volumes tapered over time but persistently aggregated at 0.5 and 1 L, with 167 subjects receiving at least one 0.5-L bolus for 6 hours after ICU admission. Administration of larger volumes was associated with longer ICU length of stay and duration of mechanical ventilation, as well as acute kidney injury. CONCLUSION: There is substantial variation in volume administered during acute ICU resuscitation, both absolutely and temporally, despite accounting for injury severity. Administration of larger volumes during acute ICU resuscitation is associated with worse outcomes. There is an opportunity to improve outcomes by further investigating and standardizing this important phase of care. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.
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Soluciones Cristaloides/administración & dosificación , Fluidoterapia , Ácido Láctico , Choque Hemorrágico , Escala Resumida de Traumatismos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Adulto , Duración de la Terapia , Femenino , Fluidoterapia/efectos adversos , Fluidoterapia/métodos , Fluidoterapia/normas , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Ácido Láctico/análisis , Ácido Láctico/sangre , Tiempo de Internación , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Mejoramiento de la Calidad , Respiración Artificial/métodos , Respiración Artificial/estadística & datos numéricos , Resucitación/métodos , Choque Hemorrágico/sangre , Choque Hemorrágico/terapiaRESUMEN
OBJECTIVES: As thromboelastography (TEG) becomes the standard of care in patients with hemorrhagic shock (HS), an association between concomitant traumatic brain injury (TBI) and coagulopathy by TEG parameters is not well understood and is thus investigated. METHODS: Retrospective analysis of trauma registry data at a single level 1 trauma center of 772 patients admitted with head Abbreviated Injury Scale (AIS) score of 3 and TEG studies between 2014 and 2017. Patients were stratified to moderate-severe TBI by head AIS scores of 3 and 4 (435 patients) and critical TBI by head AIS score of 5 (328 patients). Hemorrhagic shock was defined by base deficit of 4 or shock index of 0.9. Statistical analysis with unpaired t tests compared patients with critical TBI with patients with moderate-severe TBI, and patients were grouped by presence or absence of HS. A comparison of TBI data with conventional coagulation studies was also evaluated. RESULTS: In the setting of HS, critical TBI versus moderate-severe TBI was associated with longer R time (p = 0.004), longer K time (p < 0.05), less acute angle (p = 0.001), and lower clot strength and stability (maximum amplitude [MA]) (p = 0.01). Worse TBI did not correlate with increased fibrinolysis by clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (p = 0.3). Prothrombin time and international normalized ratio failed to demonstrate more severe coagulopathy, while partial thromboplastin time was found to correlate with severity of TBI (p = 0.01). In patients with critical TBI, the presence of HS correlated with a statistically significant worsening of all parameters (p < 0.05) except for clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (LY-30). CONCLUSION: Thromboelastography demonstrates that, with and without hemorrhagic shock, critical TBI correlates with a significant worsening of traumatic coagulopathy in comparison with moderate/severe TBI. In HS, critical TBI correlates with impaired clot initiation, impaired clot kinetics, and impaired platelet-associated clot strength and stability versus parameters found in moderate-severe TBI. Hemorrhagic shock correlates with worse traumatic coagulopathy in all evaluated patient groups with TBI. Conventional coagulation studies underestimate TBI-associated coagulopathy. Traumatic brain injury-associated coagulopathy is not associated with fibrinolysis. LEVEL OF EVIDENCE: Prognostic/epidemiological, level IV; prognostic/epidemiological, level III.
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Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Choque Hemorrágico/sangre , Tromboelastografía , Escala Resumida de Traumatismos , Pruebas de Coagulación Sanguínea , Lesiones Traumáticas del Encéfalo/patología , Humanos , Puntaje de Gravedad del Traumatismo , Relación Normalizada Internacional , Modelos Logísticos , Estudios Retrospectivos , Choque Hemorrágico/etiología , Trombosis/sangre , Trombosis/etiología , Centros TraumatológicosRESUMEN
BACKGROUND: After severe trauma, the older host experiences more dysfunctional hematopoiesis of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs), and dysfunctional differentiation of circulating myeloid cells into effective innate immune cells. Our main objective was to compare BM HSPC microRNA (miR) responses of old and young mice in a clinically relevant model of severe trauma and shock. METHODS: C57BL/6 adult male mice aged 8 to 12 weeks (young) and 18 to 24 months (old) underwent multiple injuries and hemorrhagic shock (polytrauma [PT]) that engenders the equivalent of major trauma (Injury Severity Score, >15). Pseudomonas pneumonia (PNA) was induced in some young and old adult mice 24 hours after PT. MicroRNA expression patterns were determined from lineage-negative enriched BM HSPCs isolated from PT and PT-PNA mice at 24 and 48 hours postinjury, respectively. Genome-wide expression and pathway analyses were also performed on bronchoalveolar lavage (BAL) leukocytes from both mouse cohorts. RESULTS: MicroRNA expression significantly differed among all experimental conditions (p < 0.05), except for old-naive versus old-injured (PT or PT-PNA) mice, suggesting an inability of old mice to mount a robust early miR response to severe shock and injury. In addition, young adult mice had significantly more leukocytes obtained from their BAL, and there were greater numbers of polymorphonuclear cells compared with old mice (59.8% vs. 2.2%, p = 0.0069). Despite increased gene expression changes, BAL leukocytes from old mice demonstrated a more dysfunctional transcriptomic response to PT-PNA than young adult murine BAL leukocytes, as reflected in predicted upstream functional pathway analysis. CONCLUSION: The miR expression pattern in BM HSPCs after PT (+/-PNA) is dissimilar in old versus young adult mice. In the acute postinjury phase, old adult mice are unable to mount a robust miR HSPC response. Hematopoietic stem and progenitor cell miR expression in old PT mice reflects a diminished functional status and a blunted capacity for terminal differentiation of myeloid cells.
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Médula Ósea/patología , Hematopoyesis/genética , Células Madre Hematopoyéticas/fisiología , Traumatismo Múltiple/complicaciones , Choque Hemorrágico/inmunología , Factores de Edad , Envejecimiento/sangre , Envejecimiento/genética , Envejecimiento/inmunología , Animales , Médula Ósea/fisiología , Diferenciación Celular/inmunología , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/inmunología , Hematopoyesis/inmunología , Humanos , Inmunidad Innata , Masculino , Ratones , Ratones Endogámicos C57BL , Traumatismo Múltiple/sangre , Traumatismo Múltiple/inmunología , Choque Hemorrágico/sangre , Choque Hemorrágico/genética , Choque Hemorrágico/patologíaRESUMEN
INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.
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Transfusión Sanguínea , Hemorragia/terapia , Choque Hemorrágico/terapia , Heridas y Lesiones/terapia , Presión Sanguínea , Femenino , Hemorragia/sangre , Hemorragia/diagnóstico , Hemorragia/fisiopatología , Humanos , Lactatos/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Hemorrágico/sangre , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/fisiopatología , Triaje , Heridas y Lesiones/sangre , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/fisiopatologíaRESUMEN
Hemorrhage is a significant cause of death among military working dogs and in civilian canine trauma. While research specifically aimed at canine trauma is limited, many principles from human trauma resuscitation apply. Trauma with significant hemorrhage results in shock and inadequate oxygen delivery to tissues. This leads to aberrations in cellular metabolism, including anaerobic metabolism, decreased energy production, acidosis, cell swelling, and eventual cell death. Considering blood and endothelium as a single organ system, blood failure is a syndrome of endotheliopathy, coagulopathy, and platelet dysfunction. In severe cases following injury, blood failure develops and is induced by inadequate oxygen delivery in the presence of hemorrhage, tissue injury, and acute stress from trauma. Severe hemorrhagic shock is best treated with hemostatic resuscitation, wherein blood products are used to restore effective circulating volume and increase oxygen delivery to tissues without exacerbating blood failure. The principles of hemostatic resuscitation have been demonstrated in severely injured people and the authors propose an algorithm for applying this to canine patients. The use of plasma and whole blood to resuscitate severely injured canines while minimizing the use of crystalloids and colloids could prove instrumental in improving both mortality and morbidity. More work is needed to understand the canine patient that would benefit from hemostatic resuscitation, as well as to determine the optimal resuscitation strategy for these patients.
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Transfusión Sanguínea/veterinaria , Enfermedades de los Perros/terapia , Perros , Resucitación/veterinaria , Choque Hemorrágico/veterinaria , Heridas y Lesiones/veterinaria , Animales , Enfermedades de los Perros/sangre , Perros/sangre , Perros/fisiología , Hemostasis , Humanos , Choque Hemorrágico/sangre , Choque Hemorrágico/terapia , Perros de Trabajo/sangre , Perros de Trabajo/fisiología , Heridas y Lesiones/sangre , Heridas y Lesiones/terapiaRESUMEN
BACKGROUND: Low titer O+ whole blood (LTOWB) is being increasingly used for resuscitation of hemorrhagic shock in military and civilian settings. The objective of this study was to identify the impact of prehospital LTOWB on survival for patients in shock receiving prehospital LTOWB transfusion. STUDY DESIGN AND METHODS: A single institutional trauma registry was queried for patients undergoing prehospital transfusion between 2015 and 2019. Patients were stratified based on prehospital LTOWB transfusion (PHT) or no prehospital transfusion (NT). Outcomes measured included emergency department (ED), 6-h and hospital mortality, change in shock index (SI), and incidence of massive transfusion. Statistical analyses were performed. RESULTS: A total of 538 patients met inclusion criteria. Patients undergoing PHT had worse shock physiology (median SI 1.25 vs. 0.95, p < .001) with greater reversal of shock upon arrival (-0.28 vs. -0.002, p < .001). In a propensity-matched group of 214 patients with prehospital shock, 58 patients underwent PHT and 156 did not. Demographics were similar between the groups. Mean improvement in SI between scene and ED was greatest for patients in the PHT group with a lower trauma bay mortality (0% vs. 7%, p = .04). No survival benefit for patients in prehospital cardiac arrest receiving LTOWB was found (p > .05). DISCUSSION: This study demonstrated that trauma patients who received prehospital LTOWB transfusion had a greater improvement in SI and a reduction in early mortality. Patient with prehospital cardiac arrest did not have an improvement in survival. These findings support LTOWB use in the prehospital setting. Further multi-institutional prospective studies are needed.
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Transfusión Sanguínea , Resucitación , Choque Hemorrágico/terapia , Adulto , Transfusión Sanguínea/métodos , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Resucitación/métodos , Choque Hemorrágico/sangre , Choque Hemorrágico/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Prehospital plasma transfusion in trauma reduces mortality. However, the underlying mechanism remains unclear. Reduction in shock severity may play a role. Lactate correlates with physiologic shock severity and mortality after injury. Our objective was to determine if prehospital plasma reduces lactate and if this contributes to the mortality benefit of plasma. METHODS: Patients in the Prehospital Air Medical Plasma trial in the upper quartile of injury severity (Injury Severity Score, >30) were included to capture severe shock. Trial patients were randomized to prehospital plasma or standard care resuscitation (crystalloid ± packed red blood cells). Regression determined the associations between admission lactate, 30-day mortality, and plasma while adjusting for demographics, prehospital crystalloid, time, mechanism, and injury characteristics. Causal mediation analysis determined what proportion of the effect of plasma on mortality is mediated by lactate reduction. RESULTS: A total of 125 patients were included. The plasma group had a lower adjusted admission lactate than standard of care group (coefficient, -1.64; 95% confidence interval [CI], -2.96 to -0.31; p = 0.02). Plasma was associated with lower odds of 30-day mortality (odds ratio [OR], 0.27; 95% CI, 0.08-0.90; p = 0.03). When adding lactate to this model, the effect of plasma on 30-day mortality was no longer significant (OR, 0.36; 95% CI, 0.07-1.88; p = 0.23), while lactate was associated with mortality (OR, 1.74 per 1 mmol/L increase; 95% CI, 1.10-2.73; p = 0.01). Causal mediation demonstrated 35.1% of the total effect of plasma on 30-day mortality was mediated by the reduction in lactate among plasma patients. CONCLUSION: Prehospital plasma is associated with reduced 30-day mortality and lactate in severely injured patients. More than one third of the effect of plasma on mortality is mediated by a reduction in lactate. Thus, reducing the severity of hemorrhagic shock appears to be one mechanism of prehospital plasma benefit. Further study should elucidate other mechanisms and if a dose response exists. LEVEL OF EVIDENCE: Therapeutic, level II.
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Servicios Médicos de Urgencia , Ácido Láctico/sangre , Plasma , Resucitación/métodos , Choque Hemorrágico/mortalidad , Choque Hemorrágico/terapia , Adulto , Transfusión Sanguínea , Soluciones Cristaloides/administración & dosificación , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Choque Hemorrágico/sangre , Tasa de Supervivencia , Factores de Tiempo , Heridas y Lesiones/complicaciones , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapiaRESUMEN
OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is the most severe form of acute encephalopathy that progresses rapidly, often resulting in death or severe neurological sequelae. We report the case of a 4-year-old girl with HSES with shock and impaired consciousness. PATIENT AND METHODS: Blood test results showed hypercytokinemia, and the 4-year-old patient was immediately admitted to the intensive care unit. Within 4 h of symptom onset, she received mild brain hypothermia therapy with a target body temperature of 35°C. Methylprednisolone pulse, high dose immunoglobulin, and large doses of circulatory drugs were administered. RESULTS: After 72 h of brain hypothermia therapy, targeted temperature management with a target body temperature between 36°C and 37°C was continued for 96 h. The patient was diagnosed with HSES based on acute encephalopathy with shock, hypercytokinemia, low platelet count, coagulation disorder, renal damage, and intestinal bleeding. Magnetic resonance imaging results revealed no signs of any specific acute encephalopathy. She was discharged without neurological sequelae 28 days after symptom onset. CONCLUSIONS: Mild brain hypothermia therapy initiated in the early stages followed by targeted temperature management may be an effective way to improve neurological outcomes in children suffering from HSES.
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Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Encefalopatías/tratamiento farmacológico , Hipotermia Inducida , Hipotermia/tratamiento farmacológico , Inmunoglobulinas/uso terapéutico , Metilprednisolona/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Choque Hemorrágico/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Encefalopatías/sangre , Encefalopatías/diagnóstico , Preescolar , Femenino , Humanos , Hipotermia/sangre , Hipotermia/diagnóstico , Inmunoglobulinas/administración & dosificación , Unidades de Cuidados Intensivos , Imagen por Resonancia Magnética , Metilprednisolona/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificación , Choque Hemorrágico/sangre , Choque Hemorrágico/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Dabigatran is a direct oral anticoagulant thrombin inhibitor approved for stroke prophylaxis in patients with non-valvular atrial fibrillation and prophylaxis or treatment of venous thromboembolism. Since approval, there has been increasing concern regarding bleeding risk, predominantly in the elderly population and those with renal disease. We present a case of an 85-year-old female with an unknown medication history, shortness of breath and severe anemia due to an upper gastrointestinal bleed. Laboratory abnormalities were significant for INR 6.43 and serum creatinine 2.21 mg/dL. While in the emergency department the patient decompensated requiring intubation, aggressive crystalloid resuscitation, blood products and initiation of vasopressors. The inability to distinguish between warfarin- and dabigatran-induced coagulopathies paired with the lack of medical information complicated selection of the appropriate anticoagulation reversal agent. In an attempt to prevent a prothrombotic state, prothrombin complex concentrates (PCC) were held and reversal was accomplished with idarucizumab alone, although warfarin-induced coagulopathy remained a possibility. 30 min after administration, repeat PT/INR was 16.1 s and 1.55, respectively. It was later confirmed that the patient was on sole dabigatran therapy. This case highlights the potential for dabigatran to cause extreme elevation in PT/INR in patients with acute renal failure, which may mimic warfarin-induced coagulopathy. Further, it demonstrates significant, rapid correction of abnormal coagulation assays following administration of idarucizumab in a patient with severe INR elevation and suspected dabigatran use.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticoagulantes/uso terapéutico , Dabigatrán/antagonistas & inhibidores , Choque Hemorrágico/tratamiento farmacológico , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Servicio de Urgencia en Hospital , Femenino , Humanos , Relación Normalizada Internacional , Tiempo de Protrombina , Choque Hemorrágico/sangre , Choque Hemorrágico/complicacionesRESUMEN
INTRODUCTION: We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24âh after injury, independent of international normalized ratio (INR). METHODS: In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CAT+, CAT- but receiving some pRBC Tx, receiving no Tx within the first 24âh. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR. RESULTS: A total of 484 trauma pts were analyzed: injury severity scoreâ=â13 [7,22], ageâ=â48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT-, and 370 received no Tx. Risk factors for meeting CAT+: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2.27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type. CONCLUSIONS: Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.
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Transfusión Sanguínea , Transfusión de Eritrocitos , Choque Hemorrágico/sangre , Choque Hemorrágico/terapia , Trombina/análisis , Trombina/biosíntesis , Adulto , Transfusión de Eritrocitos/normas , Femenino , Humanos , Relación Normalizada Internacional , Cinética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Hemorrágico/etiología , Factores de Tiempo , Heridas y Lesiones/complicacionesRESUMEN
BACKGROUND: Hemorrhagic shock (HS) and trauma induce endothelial barrier compromise, inflammation, and aberrant clotting. We have shown that fresh human platelets (Plts) and Plt extracellular vesicles mitigate vascular leak in murine models of injury. Here, we investigate the potential of freeze-dried platelets (FDPlts) to attenuate pulmonary vascular permeability, decrease inflammation, and promote clotting in a murine model of HS. METHODS: Human FDPlts were characterized using in vitro assays of Plt marker expression, aggregation, coagulation, and endothelial cell permeability. An intravital model of vascular injury in the mouse cremaster muscle was used to assess the ability of FDPlts to incorporate into clots. Mouse groups subjected to controlled hemorrhage for 90 minutes were (1) lactated Ringer solution (LR), (2) FDPlts, (3) fresh human Plts, (4) murine whole blood (WB), and (5) shams (only instrumented). Hemorrhagic shock mouse endpoints included coagulation, pulmonary vascular permeability, and lung injury. RESULTS: Freeze-dried Plts expressed Plt-specific markers and retained functionality similar to fresh Plts. In in vitro assays of Plt aggregation, differences were noted. In vivo, FDPlts and Plts were found to incorporate into clots in postcapillary venules in the mouse cremaster muscle. Hemorrhagic shock mice resuscitated with LR displayed increased pulmonary vascular permeability compared with sham (sham, 686.6 ± 359.7; shock-LR, 2,637 ± 954.7; p = 0.001), and treatment with FDPlts or WB attenuated permeability compared with shock: shock-FDPlts, 1,328 ± 462.6 (p = 0.05), and shock-WB, 1,024 ± 370.5 (p = 0.0108). However, human Plts (Days 1-3) did not attenuate vascular leak in HS mice compared with shock-LR (shock-Plts, 3,601 ± 1,581; p = 0.33). CONCLUSION: FDPlts contribute to clot formation similar to fresh human Plts. FDPlts also attenuated vascular permeability in vitro and in vivo. Mouse WB resuscitation but not fresh human Plts attenuated vascular permeability after HS. These data suggest that the effect of FDPlts may be a suitable alternative to fresh Plts in modulating hemostasis and the endotheliopathy associated with injury.
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Plaquetas/fisiología , Permeabilidad Capilar/fisiología , Modelos Animales de Enfermedad , Células Endoteliales/fisiología , Liofilización , Hemostasis/fisiología , Pulmón/irrigación sanguínea , Transfusión de Plaquetas , Choque Hemorrágico/terapia , Trombosis/sangre , Animales , Humanos , Ratones , Choque Hemorrágico/sangreRESUMEN
Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1ß (IL-1ß), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.
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Biomarcadores/sangre , Trastornos de la Coagulación Sanguínea/sangre , Encefalopatías/sangre , Quimiocinas/sangre , Citocinas/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Choque Hemorrágico/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/terapia , Encefalopatías/diagnóstico , Encefalopatías/terapia , Quimiocina CCL2/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/terapia , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: During hemorrhagic shock and subsequent resuscitation, pathways reliant upon calcium such as platelet function, intrinsic and extrinsic hemostasis, and cardiac contractility are disrupted. The objective of this systematic review was to examine current literature for associations between pretransfusion, admission ionized hypocalcemia, and composite outcomes including mortality, blood transfusion requirements, and coagulopathy in adult trauma patients. METHODS: This review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We searched Ovid MEDLINE and grey literature from database inception till May 3, 2020. Case series and reports were excluded. Reference lists of appraised studies were also screened for articles that the aforementioned databases might not have captured. The Newcastle-Ottawa Scale was used to assess study quality. RESULTS: A total of 585 abstracts were screened through database searching and alternative sources. Six unique full-text studies were reviewed, of which three were excluded. Admission ionized hypocalcemia was present in up to 56.2% of the population in studies included in this review. Admission ionized hypocalcemia was also associated with increased mortality in all three studies, with increased blood transfusion requirements in two studies, and with coagulopathy in one study. CONCLUSION: Hypocalcemia is a common finding in shocked trauma patients. While an association between admission ionized hypocalcemia and mortality, blood transfusion requirements, and coagulopathy has been identified, further prospective trials are essential to corroborating this association. LEVEL OF EVIDENCE: Systematic review, level III.
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Calcio/metabolismo , Hipocalcemia , Choque Hemorrágico , Heridas y Lesiones , Coagulación Sanguínea/fisiología , Transfusión Sanguínea/métodos , Humanos , Hipocalcemia/sangre , Hipocalcemia/diagnóstico , Hipocalcemia/etiología , Pronóstico , Choque Hemorrágico/sangre , Choque Hemorrágico/etiología , Choque Hemorrágico/terapia , Heridas y Lesiones/sangre , Heridas y Lesiones/complicacionesRESUMEN
Immune dysfunction is an important factor driving mortality and adverse outcomes after trauma but remains poorly understood, especially at the cellular level. To deconvolute the trauma-induced immune response, we applied single-cell RNA sequencing to circulating and bone marrow mononuclear cells in injured mice and circulating mononuclear cells in trauma patients. In mice, the greatest changes in gene expression were seen in monocytes across both compartments. After systemic injury, the gene expression pattern of monocytes markedly deviated from steady state with corresponding changes in critical transcription factors, which can be traced back to myeloid progenitors. These changes were largely recapitulated in the human single-cell analysis. We generalized the major changes in human CD14+ monocytes into 6 signatures, which further defined 2 trauma patient subtypes (SG1 vs. SG2) identified in the whole-blood leukocyte transcriptome in the initial 12 hours after injury. Compared with SG2, SG1 patients exhibited delayed recovery, more severe organ dysfunction, and a higher incidence of infection and noninfectious complications. The 2 patient subtypes were also recapitulated in burn and sepsis patients, revealing a shared pattern of immune response across critical illness. Our data will be broadly useful to further explore the immune response to inflammatory diseases and critical illness.
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Heridas y Lesiones/genética , Heridas y Lesiones/inmunología , Adulto , Animales , Células de la Médula Ósea/inmunología , Quemaduras/sangre , Quemaduras/genética , Quemaduras/inmunología , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , RNA-Seq , Sepsis/sangre , Sepsis/genética , Sepsis/inmunología , Choque Hemorrágico/sangre , Choque Hemorrágico/genética , Choque Hemorrágico/inmunología , Análisis de la Célula Individual , Factores de Tiempo , Transcriptoma , Heridas y Lesiones/clasificación , Adulto JovenRESUMEN
BACKGROUND: Mechanisms underlying hemodynamic disturbance in hemorrhagic shock are not completely understood. Transient receptor potential vanilloid 1-expressing afferents are involved in hemorrhagic shock pathology, and transient receptor potential vanilloid 1 antagonist, capsazepine, acts on the central nervous system to improve mortality in a rat hemorrhagic shock model. In contrast, transient receptor potential vanilloid 1-positive efferents promote vasoactive reactions through the release of neuropeptides, including calcitonin gene-related peptides. This study aimed to investigate whether transient receptor potential vanilloid 1-positive peripheral sensory efferents are involved in hemodynamic responses after hemorrhagic shock. METHODS: Male rats underwent hemorrhagic shock (mean arterial pressure 30 mm Hg for 90 min, followed by resuscitation for 30 min) and received capsazepine (5 µM/kg) 30 min after shock induction. A separate cohort of rats subjected to hemorrhagic shock received hCGRP8-37 (300 µg/kg), a calcitonin gene-related peptide receptor antagonist, at 30, 60, or 90 minutes after shock induction. The 24-hour survival rate, mean arterial pressure, heart rate, arterial blood gas, and plasma calcitonin gene-related peptide levels were measured. Tissue blood flow and oxygenation both in the mesentery and skeletal muscle were also assessed. RESULTS: Capsazepine treatment prevented the hemorrhagic shock-induced increase in plasma calcitonin gene-related peptide levels, and hCGRP8-37 treatment improved the 24-h survival rates after hemorrhagic shock at a time-dependent manner. The hCGRP8-37- or capsazepine-treated rats exhibited tissue oxygenation and metabolic conditions comparable to those in control rats at the end of the experiment. CONCLUSION: Transient receptor potential vanilloid 1 plays a crucial role in hemodynamic responses to hemorrhagic shock, partly via calcitonin gene-related peptide release, involved in its peripheral sensory-efferent functions. The hCGRP8-37 appears to improve peripheral circulatory failure, which may be useful as adjunct treatment after hemorrhagic shock.