RESUMO
BACKGROUND: Hypertonic saline (23.4%, HTS) bolus administration is common practice for refractory intracranial hypertension, but its effects on coagulation are unknown. We hypothesize that 23.4% HTS in whole blood results in progressive impairment of coagulation in vitro and in vivo in a murine model of traumatic brain injury (TBI). STUDY DESIGN: For the in vitro study, whole blood was collected from 10 healthy volunteers, and citrated native thrombelastography was performed with normal saline (0.9%, NS) and 23.4% HTS in serial dilutions (2.5%, 5%, and 10%). For the in vivo experiment, we assessed the effects of 23.4% HTS bolus vs NS on serial thrombelastography and tail-bleeding times in a TBI murine model (n = 10 rats with TBI and 10 controls). RESULTS: For the in vitro work, clinically relevant concentrations of HTS (2.5% dilution) shortened time to clot formation and increased clot strength (maximum amplitude) compared with control and NS. With higher HTS dosing (5% and 10% blood dilution), there was progressive prolongation of time to clot formation, decreased angle, and decreased maximum amplitude. In the in vivo study, there was no significant difference in thrombelastography measurements or tail-bleeding times after bolus administration of 23.4% HTS compared with NS at 2.5% blood volume. CONCLUSIONS: At clinically relevant dilutions of HTS, there is a paradoxical shortening of time to clot formation and increase in clot strength in vitro and no significant effects in a murine TBI model. However, with excess dilution, caution should be exercised when using serial HTS boluses in TBI patients at risk for trauma-induced coagulopathy.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Hipertensão Intracraniana/sangue , Hipertensão Intracraniana/tratamento farmacológico , Solução Salina Hipertônica/farmacologia , Solução Salina Hipertônica/uso terapêutico , Animais , Lesões Encefálicas Traumáticas/complicações , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão Intracraniana/etiologia , Masculino , Ratos Sprague-Dawley , Autorrelato , Tromboelastografia , Fatores de TempoRESUMO
BACKGROUND: Understanding the molecular mechanisms in perturbation of the metabolome following ischaemia and reperfusion is critical in developing novel therapeutic strategies to prevent the sequelae of post-injury shock. While the metabolic substrates fueling these alterations have been defined, the relative contribution of specific organs to the systemic metabolic reprogramming secondary to ischaemic or haemorrhagic hypoxia remains unclear. MATERIALS AND METHODS: A porcine model of selected organ ischaemia was employed to investigate the relative contribution of liver, kidney, spleen and small bowel ischaemia/reperfusion to the plasma metabolic phenotype, as gleaned through ultra-high performance liquid chromatography-mass spectrometry-based metabolomics. RESULTS: Liver ischaemia/reperfusion promotes glycaemia, with increases in circulating carboxylic acid anions and purine oxidation metabolites, suggesting that this organ is the dominant contributor to the accumulation of these metabolites in response to ischaemic hypoxia. Succinate, in particular, accumulates selectively in response to the hepatic ischemia, with levels 6.5 times spleen, 8.2 times small bowel, and 6 times renal levels. Similar trends, but lower fold-change increase in comparison to baseline values, were observed upon ischaemia/reperfusion of kidney, spleen and small bowel. DISCUSSION: These observations suggest that the liver may play a critical role in mediating the accumulation of the same metabolites in response to haemorrhagic hypoxia, especially with respect to succinate, a metabolite that has been increasingly implicated in the coagulopathy and pro-inflammatory sequelae of ischaemic and haemorrhagic shock.
Assuntos
Fígado/metabolismo , Metaboloma , Traumatismo por Reperfusão/metabolismo , Animais , Fígado/patologia , Masculino , Oxirredução , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Ácido Succínico/sangue , Ácido Succínico/metabolismo , SuínosRESUMO
BACKGROUND: Resuscitation guided by thrombelastography improves survival after injury. If bleeding is rapid, however, or if no thrombelastography data are available, the optimal strategy remains controversial. Our current practice gives fresh frozen plasma and red blood cells (1:2) empirically in patients with life-threatening hemorrhage, with subsequent administration based on rapid thrombelastography. We identified patients at risk of massive transfusion at 1 hour, examined their initial rapid thrombelastography, and used this value to provide empiric recommendations about transfusions. METHODS: Massive transfusion was defined as >4 units of red blood cells in the first hour. Patients managed by a trauma activation (2014-2017) had an admission rapid thrombelastography analyzed to determine what proportion met thresholds for administration of cryoprecipitate or platelets. RESULTS: Overall, 35 patients received >4 units of red blood cells in the first hour. Based on the admission rapid thrombelastography, 37% met criteria for both platelets and cryoprecipitate, 35% for either platelets or cryoprecipitate and 29% for neither. Kaplan-Meier analysis showed a significant delay in the administration of cryoprecipitate and platelets compared to fresh frozen plasma. CONCLUSION: Patients who require >4 units of red blood cells within the first hour should receive cryoprecipitate and platelets if thrombelastography results are not available. Point-of-care devices are needed for optimal care of trauma-induced-coagulopathy, but these data offer guidance in their absence.
Assuntos
Transfusão de Sangue/estatística & dados numéricos , Hemorragia/mortalidade , Adulto , Transfusão de Sangue/métodos , Estudos de Coortes , Colorado/epidemiologia , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Tromboelastografia , Ferimentos e Lesões/complicaçõesRESUMO
BACKGROUND: Thrombelastography platelet mapping is a useful assay to assess antiplatelet therapy. Inhibited response to the adenosine diphosphate receptor on platelets occurs early after injury, but recent work suggests this alteration occurs even with minor trauma. However, the utility of thrombelastography platelet mapping, specifically the percent of adenosine diphosphate receptor inhibition, in predicting outcomes and guiding platelet transfusion in trauma-induced coagulopathy remains unknown We assessed the role of percent of adenosine diphosphate-inhibition in predicting survival, requirement for massive transfusion or platelet transfusion in patients at risk for trauma-induced coagulopathy. METHODS: Thrombelastography platelet mapping was assessed in 303 trauma activation patients from 2014-2016 and in 89 healthy volunteers. Percent of adenosine diphosphate-inhibition is presented as median and interquartile range. We compared the area under the receiver operating characteristic curve of percent of adenosine diphosphate-inhibition, platelet count, and rapid thrombelastography maximum amplitude for in-hospital mortality, massive transfusion (>10 red blood cells or death/6 hours), and platelet transfusion (>0 platelet units or death/6 hour). RESULTS: Overall, 35 (11.5%) patient died, 27 (8.9%) required massive transfusion and 46, platelet transfusions (15.2%). Median percent of adenosine diphosphate-inhibition was 42.5% (interquartile range: 22.4-69.1%), compared with 4.3 % (interquartile range: 0-13.5%) in healthy volunteers (P < .0001). Patients that died, had a massive transfusion, or platelet transfusion had higher percent of adenosine diphosphate-inhibition than those that did not (P < .05 for all). However, percent of adenosine diphosphate-inhibition did not add significantly to the predictive performance of maximum amplitude or platelet count for any of the 3 outcomes, after adjustment for confounders. Subgroup analyses by severe traumatic brain injury, severe injury and requirement of red blood cells showed similar results. CONCLUSION: Adenosine diphosphate receptor inhibition did not add predictive value to predicting mortality, massive transfusion, or platelet transfusion. Thus, the role of thrombelastography platelet mapping as a solitary tool to guide platelet transfusions in trauma requires continued refinement.