RESUMO
BACKGROUND: Noncompressible torso hemorrhage remains a leading cause of death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) placement may occur before transport; however, its efficacy has not been demonstrated at altitude. We hypothesized that changes in altitude would not result in blood pressure changes proximal to a deployed REBOA. METHODS: A simulation model for 7Fr guidewireless REBOA was used at altitudes up to 22,000 feet. Female pigs then underwent hemorrhagic shock to a mean arterial pressure (MAP) of 40 mm Hg. After hemorrhage, a REBOA catheter was deployed in the REBOA group and positioned but not inflated in the no-REBOA group. Animals underwent simulated aeromedical evacuation at 8000 ft or were left at ground level. After altitude exposure, the balloon was deflated, and the animals were observed. RESULTS: Taking the REBOA catheter to 22,000 ft in the simulation model resulted in a lower systolic blood pressure but a preserved MAP. In the porcine model, REBOA increased both systolic blood pressure and MAP compared with no-REBOA (P < 0.05) and was unaffected by altitude. No differences in postflight blood pressure, acidosis, or systemic inflammatory response were observed between ground and altitude REBOA groups. CONCLUSIONS: REBOA maintained MAP up to 22,000 feet in an inanimate model. In the porcine model, REBOA deployment improved MAP, and the balloon remained effective at altitude.
Assuntos
Medicina Aeroespacial , Altitude , Aorta , Oclusão com Balão , Choque Hemorrágico/terapia , Animais , Pressão Sanguínea , Procedimentos Endovasculares , Feminino , Distribuição Aleatória , SuínosRESUMO
BACKGROUND: Acute lung injury (ALI) is a frequent complication after severe trauma. Lung-protective ventilation strategies and damage control resuscitation have been proposed for the prevention of ALI; however, there are no clinical or laboratory parameters to predict who is at risk of developing ALI after trauma. In the present study, we explored pulmonary inflammatory markers as a potential predictor of ALI using a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Female swine were randomized to mechanical ventilation with low tidal volume (VT) (6 mL/kg) or high VT (12 mL/kg). After equilibration, animals underwent pressure-controlled hemorrhage (mean arterial pressure [MAP] 35 ± 5 mmHg) for 1 h, followed by resuscitation with fresh whole blood or Hextend. They were maintained at MAP of 50 ± 5 mmHg for 3 h in the postresuscitation phase. Bronchoalveolar lavage fluids were collected hourly and analyzed for inflammatory markers. Lung samples were taken, and porcine neutrophil antibody staining was used to evaluate the presence of neutrophils. ELISA evaluated serum porcine surfactant protein D levels. Sham animals were used as negative controls. RESULTS: Pigs that underwent hemorrhagic shock had higher heart rates, lower cardiac output, lower MAPs, and worse acidosis compared with sham at the early time points (P < 0.05 each). There were no significant differences in central venous pressure or pulmonary capillary wedge pressure between groups. Pulmonary neutrophil infiltration, as defined by neutrophil antibody staining on lung samples, was greater in the shock groups regardless of resuscitation fluid (P < 0.05 each). Bronchoalveolar lavage fluid neutrophil levels were not different between groups. There were no differences in levels of porcine surfactant protein D between groups at any time points, and the levels did not change over time in each respective group. CONCLUSIONS: Our study demonstrates the reproducibility of a porcine model of hemorrhagic shock that is consistent with physiologic changes in humans in hemorrhagic shock. Pulmonary neutrophil infiltration may serve as an early marker for ALI; however, the practicality of this finding has yet to be determined.
Assuntos
Lesão Pulmonar Aguda/diagnóstico , Neutrófilos/imunologia , Choque Hemorrágico/complicações , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/fisiopatologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Transfusão de Sangue , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Débito Cardíaco/imunologia , Modelos Animais de Doenças , Feminino , Frequência Cardíaca/imunologia , Humanos , Pulmão/citologia , Pulmão/imunologia , Pulmão/patologia , Infiltração de Neutrófilos , Valor Preditivo dos Testes , Prognóstico , Proteína D Associada a Surfactante Pulmonar/análise , Proteína D Associada a Surfactante Pulmonar/imunologia , Proteína D Associada a Surfactante Pulmonar/metabolismo , Reprodutibilidade dos Testes , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Ressuscitação/métodos , Choque Hemorrágico/imunologia , Choque Hemorrágico/terapia , Sus scrofa , Fatores de TempoRESUMO
BACKGROUND: Resuscitation strategies for combined traumatic brain injury (TBI) with haemorrhage in austere environments are not fully established. Our aim was to establish the effects of various saline concentrations in a murine model of combined TBI and haemorrhage, and identify an effective resuscitative strategy for the far-forward environment. METHODS: Male C57BL/6 mice underwent closed head injury and subjected to controlled haemorrhage to a systolic blood pressure of 25 mmHg via femoral artery cannulation for 60 min. Mice were resuscitated with a fixed volume bolus or variable volumes of fluid to achieve a systolic blood pressure goal of 80 mmHg with 0.9% saline, 3% saline, 0.1-mL bolus of 23.4% saline, or a 0.1-mL bolus of 23.4% saline followed by 0.9% saline (23.4+). RESULTS: 23.4% saline and 23.4+ resulted in higher mortality at 6 h compared to 0.9% saline. Use of 3% saline required less volume to achieve targeted resuscitation, did not affect survival, and did not exacerbate post-traumatic inflammation. While 23.4+ resuscitation utilized lower volume, it resulted in hypernatremia, azotemia, and elevated systemic pro-inflammatory cytokines. All groups except 3% saline demonstrated progression of neuron damage, with cerebral oedema highest with 0.9% saline. CONCLUSIONS: 3% saline demonstrated favourable balance of survival, blood pressure restoration, minimization of inflammation, and prevention of ongoing neurologic injury without contributing to significant physiologic derangements. 23.4% saline administration may not be appropriate in the setting of concomitant hypotension.
Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Ressuscitação/métodos , Solução Salina/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrólitos/sangue , Hemodinâmica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Taxa de SobrevidaRESUMO
BACKGROUND: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight. METHODS: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes. RESULTS: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1ß was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR. CONCLUSION: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.
Assuntos
Resgate Aéreo , Transfusão de Sangue/métodos , Lesões Encefálicas Traumáticas , Soluções Cristaloides , Ressuscitação/métodos , Lactato de Ringer , Choque Hemorrágico , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/terapia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Soluções Cristaloides/administração & dosagem , Soluções Cristaloides/efeitos adversos , Modelos Animais de Doenças , Pressão Intracraniana/efeitos dos fármacos , Pressão Intracraniana/fisiologia , Traumatismo Múltiplo/fisiopatologia , Traumatismo Múltiplo/terapia , Monitorização Neurofisiológica/métodos , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Lactato de Ringer/administração & dosagem , Lactato de Ringer/efeitos adversos , Choque Hemorrágico/complicações , Choque Hemorrágico/fisiopatologia , Choque Hemorrágico/terapia , Suínos , Resultado do TratamentoRESUMO
BACKGROUND: Traumatic brain injury (TBI) is common in civilians and military personnel. No potential therapeutics have been evaluated to prevent secondary injury induced by the hypobaric hypoxia (HH) environment integral to postinjury aeromedical evacuation (AE). We examined the role of allopurinol, propranolol, adenosine/lidocaine/magnesium (ALM), or amitriptyline administration prior to simulated flight following murine TBI. METHODS: Mice underwent TBI and were given allopurinol, propranolol, amitriptyline, or ALM prior to simulated AE or normobaric normoxia (NN) control. Heart rate (HR), respiratory rate, and oxygen saturation (Spo2) were recorded throughout simulated AE. Mice were sacrificed at 24 hours, 7 days, or 30 days. Serum and cerebral cytokines were assessed by enzyme-linked immunosorbent assay. Motor function testing was performed with Rotarod ambulation. Immunohistochemistry was conducted to examine phosphorylated tau (p-tau) accumulation in the hippocampus at 30 days. RESULTS: While all treatments improved oxygen saturation, propranolol, amitriptyline, and allopurinol improved AE-induced tachycardia. At 24 hours, both propranolol and amitriptyline reduced tumor necrosis factor alpha levels while allopurinol and ALM reduced tumor necrosis factor alpha levels only in NN mice. Propranolol, amitriptyline, and ALM demonstrated lower serum monocyte chemoattractant protein-1 7 days after AE. Both amitriptyline and allopurinol improved Rotarod times for AE mice while only allopurinol improved Rotarod times for NN mice. Propranolol was able to reduce p-tau accumulation under both HH and NN conditions while ALM only reduced p-tau in hypobaric hypoxic conditions. CONCLUSION: Propranolol lowered post-TBI HR with reduced proinflammatory effects, including p-tau reduction. Amitriptyline-induced lower post-TBI HR and improved functional outcomes without affecting inflammatory response. Allopurinol did not affect vital signs but improved late post-TBI systemic inflammation and functional outcomes. Adenosine/lidocaine/magnesium provided no short-term improvements but reduced p-tau accumulation at 30 days in the HH cohort. Allopurinol may be the best of the four treatments to help prevent short-term functional deficits while propranolol may address long-term effects. LEVEL OF EVIDENCE: Basic science article.
Assuntos
Resgate Aéreo , Lesões Encefálicas Traumáticas/terapia , Serviços Médicos de Emergência/métodos , Adenosina/uso terapêutico , Alopurinol/uso terapêutico , Amitriptilina/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Química Encefálica , Lesões Encefálicas Traumáticas/patologia , Citocinas/análise , Citocinas/sangue , Modelos Animais de Doenças , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Propranolol/uso terapêutico , Teste de Desempenho do Rota-RodRESUMO
INTRODUCTION: Combined burn injury and hemorrhagic shock are a common cause of injury in wounded warfighters. Current protocols for resuscitation for isolated burn injury and isolated hemorrhagic shock are well defined, but the optimal strategy for combined injury is not fully established. Direct peritoneal resuscitation (DPR) has been shown to improve survival in rats after hemorrhagic shock, but its role in a combined burn/hemorrhage injury is unknown. We hypothesized that DPR would improve survival in mice subjected to combined burn injury and hemorrhage. MATERIALS AND METHODS: Male C57/BL6J mice aged 8 weeks were subjected to a 7-second 30% total body surface area scald in a 90°C water bath. Following the scald, mice received DPR with 1.5 mL normal saline or 1.5 mL peritoneal dialysis solution (Delflex). Control mice received no peritoneal solution. Mice underwent a controlled hemorrhage shock via femoral artery cannulation to a systolic blood pressure of 25 mm Hg for 30 minutes. Mice were then resuscitated to a target blood pressure with either lactated Ringer's (LR) or a 1:1 ratio of packed red blood cells (pRBCs) and fresh frozen plasma (FFP). Mice were observed for 24 hours following injury. RESULTS: Median survival time for mice with no DPR was 1.47 hours in combination with intravascular LR resuscitation and 2.08 hours with 1:1 pRBC:FFP. Median survival time significantly improved with the addition of intraperitoneal normal saline or Delflex. Mice that received DPR followed by 1:1 pRBC:FFP required less intravascular volume than mice that received DPR with LR, pRBC:FFP alone, and LR alone. Intraperitoneal Delflex was associated with higher levels of tumor necrosis factor alpha and macrophage inflammatory protein 1 alpha and lower levels of interleukin 10 and intestinal fatty acid binding protein. Intraperitoneal normal saline resulted in less lung injury 1 hour postresuscitation, but increased to similar severity of Delflex at 4 hours. CONCLUSIONS: After a combined burn injury and hemorrhage, DPR leads to increased survival in mice. Survival was similar with the use of normal saline or Delflex. DPR with normal saline reduced the inflammatory response seen with Delflex and delayed the progression of acute lung injury. DPR may be a valuable strategy in the treatment of patients with combined burn injury and hemorrhage.
Assuntos
Queimaduras , Ressuscitação , Choque Hemorrágico , Animais , Queimaduras/complicações , Queimaduras/terapia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/complicações , Choque Hemorrágico/terapiaRESUMO
INTRODUCTION: Intrathoracic pressure regulation (ITPR) can be utilized to enhance venous return and cardiac preload by inducing negative end expiratory pressure in mechanically ventilated patients. Previous preclinical studies have shown increased mean arterial pressure (MAP) and decreased intracranial pressure (ICP) with use of an ITPR device. The aim of this study was to evaluate the hemodynamic and respiratory effects of ITPR in a porcine polytrauma model of hemorrhagic shock and acute lung injury (ALI). METHODS: Swine were anesthetized and underwent a combination of sham, hemorrhage, and/or lung injury. The experimental groups included: no injury with and without ITPR (ITPR, Sham), hemorrhage with and without ITPR (ITPR/Hem, Hem), and hemorrhage and ALI with and without ITPR (ITPR/Hem/ALI, Hem/ALI). The ITPR device was initiated at a setting of -3 cmH2O and incrementally decreased by 3 cmH2O after 30 minutes on each setting, with 15 minutes allowed for recovery between settings, to a nadir of -12 cmH2O. Histopathological analysis of the lungs was scored by blinded, independent reviewers. Of note, all animals were chemically paralyzed for the experiments to suppress gasping at ITPR pressures below -6 cmH2O. RESULTS: Adequate shock was induced in the hemorrhage model, with the MAP being decreased in the Hem and ITPR/Hem group compared with Sham and ITPR/Sham, respectively, at all time points (Hem 54.2 ± 6.5 mmHg vs. 88.0 ± 13.9 mmHg, p < 0.01, -12 cmH2O; ITPR/Hem 59.5 ± 14.4 mmHg vs. 86.7 ± 12.1 mmHg, p < 0.01, -12 cmH2O). In addition, the PaO2/FIO2 ratio was appropriately decreased in Hem/ALI compared with Sham and Hem groups (231.6 ± 152.5 vs. 502.0 ± 24.6 (Sham) p < 0.05 vs. 463.6 ± 10.2, (Hem) p < 0.01, -12 cmH2O). Heart rate was consistently higher in the ITPR/Hem/ALI group compared with the Hem/ALI group (255 ± 26 bpm vs. 150.6 ± 62.3 bpm, -12 cmH2O) and higher in the ITPR/Hem group compared with Hem. Respiratory rate (adjusted to maintain pH) was also higher in the ITPR/Hem/ALI group compared with Hem/ALI at -9 and - 12 cmH2O (32.8 ± 3.0 breaths per minute (bpm) vs. 26.8 ± 3.6 bpm, -12 cmH2O) and higher in the ITPR/Hem group compared with Hem at -6, -9, and - 12 cmH2O. Lung compliance and end expiratory lung volume (EELV) were both consistently decreased in all three ITPR groups compared with their controls. Histopathologic severity of lung injury was worse in the ITPR and ALI groups compared with their respective injured controls or Sham. CONCLUSION: In this swine polytrauma model, we demonstrated successful establishment of hemorrhage and combined hemorrhage/ALI models. While ITPR did not demonstrate a benefit for MAP or ICP, our data demonstrate that the ITPR device induced tachycardia with associated increase in cardiac output, as well as tachypnea with decreased lung compliance, EELV, PaO2/FIO2 ratio, and worse histopathologic lung injury. Therefore, implementation of the ITPR device in the setting of polytrauma may compromise pulmonary function without significant hemodynamic improvement.
Assuntos
Lesão Pulmonar Aguda , Lesão Pulmonar Aguda/complicações , Animais , Pressão Sanguínea , Débito Cardíaco , Frequência Cardíaca , Pulmão , Complacência Pulmonar , SuínosRESUMO
INTRODUCTION: Acute hemorrhage remains the leading cause of death in potentially survivable injuries. The use of topical hemostatic agents has increased over the last two decades with the evolution of damage control surgery. By 2008, the military widely adopted Combat Gauze as the hemostatic dressing of choice for compressible hemorrhage. The goal of this study was to compare the performance of a novel fibrin sealant patch to Combat Gauze in two clinically relevant models of hemorrhage. MATERIALS AND METHODS: Yorkshire swine underwent unilateral femoral artery puncture or a grade V liver laceration with timed free bleeding then received either the fibrin patch or Combat Gauze packing with 3 minutes of standardized pressure. Animals were then resuscitated to maintain a mean arterial pressure of 60 mmHg for 4 hours. Hemostasis, blood loss, resuscitation volume, survival, vessel patency, and hematologic parameters were evaluated. RESULTS: Hemostasis was equivalent in both groups after hepatic and vascular injury. Survival was 80% in the fibrin patch vascular injury group and 100% in all other groups. Hematologic parameters were not significantly different between treatment groups. Femoral artery patency was 80% in both groups after vascular injury. With simulated ambulation after vessel injury, 60% of the Combat Gauze group and 80% of the fibrin patch group remained hemostatic (p > 0.05). In simulated re-exploration with packing removal, all animals rebled after hemostatic product removal. CONCLUSION: There was no significant difference in hemostasis between a novel fibrin patch and Combat Gauze after extremity arterial or hepatic injury. This novel fibrin patch may have a clinical advantage over the Combat Gauze, as it can be left in the body, thereby limiting the potential need for reoperation.