RESUMO
INTRODUCTION: One of the advantages of partial Resuscitative Endovascular Balloon Occlusion of the Aorta (pREBOA) compared to the original model is the mitigation of reperfusion injury. The safety and efficacy of pREBOA have not been demonstrated in the setting of aeromedical evacuation. We hypothesized that the pREBOA would result in less ischemia-reperfusion injury after altitude exposure. METHODS: Twenty-four swine underwent femur fracture with hemorrhage for 20 min, followed by resuscitative endovascular balloon occlusion of the aorta (REBOA) deployment to Zone 1 and were randomized to pREBOA-PRO (Prytime Medical Devices Inc) full inflation, partial inflation, or sham inflation and then an altitude exposure of ground level or 8000 ft for 15 min. The primary endpoint was to examine if the balloon functioned at altitude. Our secondary endpoint was investigating evidence of ischemia-reperfusion by hemodynamic instability, electrolyte derangements, and acidosis. Comparisons were made by ANOVA. RESULTS: After deflation, the partially inflated group maintained a higher mean arterial pressure (MAP) compared to fully inflated group (P = 0.026). Full REBOA pigs were more tachycardic compared to sham pREBOA at ground (P < 0.001) and this was exacerbated at altitude (P < 0.001). Full REBOA pigs were more acidotic than sham and pREBOA at ground pigs (P = 0.0006 and P = 0.0002, respectively). Altitude increased the acidosis in full REBOA pigs, resulting in a greater base deficit (P < 0.0001), lactate (P < 0.0001), and IL-6 (P = 0.006). CONCLUSIONS: PREBOA resulted in less severe ischemia-reperfusion injury at both altitude and ground, while full balloon inflation at altitude exacerbated acidosis and ischemia-reperfusion injury. Efforts should therefore be made to utilize partial balloon occlusion when employing the REBOA catheter.
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Resgate Aéreo , Oclusão com Balão , Procedimentos Endovasculares , Traumatismo por Reperfusão , Choque Hemorrágico , Animais , Aorta , Oclusão com Balão/métodos , Modelos Animais de Doenças , Procedimentos Endovasculares/métodos , Ressuscitação/métodos , Choque Hemorrágico/terapia , SuínosRESUMO
INTRODUCTION: Traumatic brain injury (TBI) can lead to neurocognitive decline, in part due to phosphorylated tau (p-tau). Whether p-tau accumulation worsens in the setting of polytrauma remains unknown. Propranolol has shown clinical benefit in head injuries; however, the underlying mechanism is also unknown. We hypothesize that hemorrhagic shock would worsen p-tau accumulation but that propranolol would improve functional outcomes on behavioral studies. METHODS: A murine polytrauma model was developed to examine the accumulation of p-tau and whether it can be mitigated by early administration of propranolol. TBI was induced using a weight-drop model and hemorrhagic shock was achieved via controlled hemorrhage for 1 h. Mice were given intraperitoneal propranolol 4 mg/kg or saline control. The animals underwent behavioral testing at 30 d postinjury and were sacrificed for cerebral histological analysis. These studies were completed in male and female mice. RESULTS: TBI alone led to increased p-tau generation compared to sham on both immunohistochemistry and immunofluorescence (P < 0.05). The addition of hemorrhage led to greater accumulation of p-tau in the hippocampus (P < 0.007). In male mice, p-tau accumulation decreased with propranolol administration for both polytrauma and TBI alone (P < 0.0001). Male mice treated with propranolol also outperformed saline-control mice on the hippocampal-dependent behavioral assessment (P = 0.0013). These results were not replicated in female mice; the addition of hemorrhage did not increase p-tau accumulation and propranolol did not demonstrate a therapeutic effect. CONCLUSIONS: Polytrauma including TBI generates high levels of hippocampal p-tau, but propranolol may help prevent this accumulation to improve both neuropathological and functional outcomes in males.
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Lesões Encefálicas Traumáticas , Traumatismo Múltiplo , Choque Hemorrágico , Animais , Camundongos , Masculino , Feminino , Propranolol/farmacologia , Propranolol/uso terapêutico , Choque Hemorrágico/complicações , Choque Hemorrágico/tratamento farmacológico , Modelos Animais de DoençasRESUMO
INTRODUCTION: While the pillars of trauma resuscitation are surgical hemostasis and blood product administration, norepinephrine (NE) can be used as an adjunct. The goal of this study was to evaluate the relationship between the maximum dose of NE, timing of NE administration, and mortality in trauma patients. METHODS: Patients admitted between January 2013 and January 2021 treated with NE were reviewed. Univariate and multivariate logistic regression were used to assess whether maximum NE dose was independently associated with mortality. Optimal dosage rates for NE were determined via Youden Index. Subgroup analyses comparing those who received NE within versus after the first 24 h of admission were conducted. RESULTS: Three hundred fifty-first trauma patients were included, with 217 (62%) surviving. Patients who died received an average maximum dose of 16.7 mcg/min compared to 9.1 mcg/min in survivors (P = 0.0003). Mortality rate increased with dosage (P < 0.0001), with doses greater than 20 mcg/min having 79% mortality. Those who received NE within the first 24 h had an inflection point in mortality at 16 mcg/min (Youden = 0.45) (OR 1.06; 95% CI 1.03-1.10). For patients who received NE after the first 24 h, an inflection point in mortality was at 10 mcg/min (Youden = 0.34) (OR 1.09; 95% CI 1.04-1.14). CONCLUSIONS: Higher maximum doses of NE were associated with increased mortality. Patients initiated on NE more than 24 h into their admission displayed an inflection point at a lower dose than those initiated later. This suggests that trauma patients initiated on NE after 24 h from injury may have a dire prognosis.
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Norepinefrina , Vasoconstritores , Humanos , Norepinefrina/uso terapêutico , RessuscitaçãoRESUMO
INTRODUCTION: Early aeromedical evacuation after traumatic brain injury (TBI) has been associated with worse neurologic outcomes in murine studies and military populations. The goal of this study was to determine if commonly utilized medications, including allopurinol, propranolol, or tranexamic acid (TXA), could mitigate the secondary traumatic brain injury experienced during the hypobaric and hypoxic environment of aeromedical evacuation. METHODS: Porcine TBI was induced via controlled cortical injury. Twenty nonsurvival pigs were separated into four groups (n = 5 each): TBI+25 mL normal saline (NS), TBI+4 mg propranolol, TBI+100 mg allopurinol, and TBI+1g TXA. The pigs then underwent simulated AE to an altitude of 8000 ft for 4 h with an SpO2 of 82-85% and were sacrificed 4 h later. Hemodynamics, serum cytokines, and hippocampal p-tau accumulation were assessed. An additional survival cohort was partially completed with TBI/NS (n = 5), TBI/propranolol (n = 2) and TBI/allopurinol groups (n = 2) survived to postinjury day 7. RESULTS: There were no significant differences in hemodynamics, tissue oxygenation, cerebral blood flow, or physiologic markers between treatment groups and saline controls. Transient differences in IL-1b and IL-6 were noted but did not persist. Neurological Severity Score (NSS) was significantly lower in the TBI + allopurinol group on POD one compared to NS and propranolol groups. P-tau accumulation was decreased in the nonsurvival animals treated with allopurinol and TXA compared to the TBI/NS group. CONCLUSIONS: Allopurinol, propranolol, and TXA, following TBI, do not induce adverse changes in systemic or cerebral hemodynamics during or after a simulated postinjury flight. While transient changes were noted in systemic cytokines and p-tau accumulation, further investigation will be needed to determine any persistent neurological effects of injury, flight, and pharmacologic treatment.
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Resgate Aéreo , Lesões Encefálicas Traumáticas , Ácido Tranexâmico , Alopurinol , Animais , Lesões Encefálicas Traumáticas/complicações , Humanos , Interleucina-6 , Camundongos , Propranolol/farmacologia , Propranolol/uso terapêutico , Solução Salina , Suínos , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND: There is no consensus on what dose of norepinephrine corresponds with futility. The purpose of this study was to investigate the maximum infusion and cumulative doses of norepinephrine associated with survival for patients in medical and surgical intensive care units (MICU and SICU). MATERIALS AND METHODS: A retrospective review was conducted of 661 critically ill patients admitted to a large academic medical center who received norepinephrine. Univariate, multivariate, and area under the curve analyses with optimal cut offs for maximum infusion rate and cumulative dosage were determined by Youden Index. RESULTS: The population was 54.9% male, 75.8% white, and 58.7 ± 16.1 y old with 384 (69.8%) admitted to the MICU and 166 (30.2%) admitted to the SICU, including 38 trauma patients. Inflection points in mortality were seen at 18 mcg/min and 17.6 mg. The inflection point was higher in MICU patients at 21 mcg/min and lower in SICU patients at 11 mcg/min. MICU patients also had a higher maximum cumulative dosage of 30.7 mg, compared to 2.7 mg in SICU patients. In trauma patients, norepinephrine infusions up to 5 mcg/min were associated with a 41.7% mortality rate. CONCLUSION: A maximum rate of 18 mcg/min and cumulative dose of 17.6 mg were the inflection points for mortality risk in ICU patients, with SICU patients tolerating lower doses. In trauma patients, even low doses of norepinephrine were associated with higher mortality. These data suggest that MICU, SICU, and trauma patients differ in need for, response to, and outcome from escalating norepinephrine doses.
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Agonistas alfa-Adrenérgicos/administração & dosagem , Estado Terminal/terapia , Futilidade Médica , Norepinefrina/administração & dosagem , Ferimentos e Lesões/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Estudos Retrospectivos , Ferimentos e Lesões/tratamento farmacológicoRESUMO
INTRODUCTION: Thrombocytosis and leukocytosis are common after splenectomy. The potential effect of emergency surgery on these postoperative findings is unknown. We hypothesized that emergency splenectomy leads to a more profound and persistent hematologic change as compared to elective splenectomy. METHODS: A retrospective review was conducted of patients who underwent elective or trauma splenectomy. Records were queried for platelet (PLT) and white blood cell (WBC) count prior to splenectomy, on postoperative days 1-5, and at day 14, 1 month, 3 months, 6 months, and 1 year. Complications, including thromboembolic events, infection, need for repeat operation, and readmission within 30 days of discharge, were recorded. RESULTS: 463 patients were identified as being eligible for the study, with 173 patients in the elective cohort and 145 patients in each of the isolated trauma splenectomy and polytrauma cohorts. Both cohorts had peak thrombocytosis at week 2 postoperatively. However, polytrauma patients had a significantly higher peak platelet count (P < 0.01). The PLT:WBC ratio was lower in both trauma cohorts pre-operatively and postoperative day 1. Trauma splenectomy had a higher PLT:WBC ratio on days 2 and 3 whereas polytrauma had a lower ratio on days 4 and 5. Emergency cases had greater reoperation and infection rates, whereas elective cases were more likely to require readmission. Postoperative thromboembolic events were only higher in the polytrauma cohort. CONCLUSIONS: While trauma splenectomy resulted in more profound postoperative leukocytosis and thrombocytosis, there was no correlation with timing of infection or risk of thromboembolic events. These findings suggest that thrombocytosis and leukocytosis may be associated with thrombotic and infectious events but their presence alone does not indicate direct risks of concomitant infection or thrombosis.
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Esplenectomia , Trombocitose , Humanos , Contagem de Leucócitos , Contagem de Plaquetas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Esplenectomia/efeitos adversos , Trombocitose/complicações , Trombocitose/etiologiaRESUMO
BACKGROUND: Multimodal analgesia protocols have been implemented after elective surgery to reduce opioid use, however there is limited data on utility after polytrauma. Therefore, we investigated the impact of a multimodal analgesia protocol on inpatient and post-discharge outpatient opioid use after polytrauma. METHODS: A retrospective review of patients admitted to a Level I trauma center between September 2017-February 2018 (prior to multimodal protocol; "pre-cohort") and October 2018-April 2019 (after multimodal protocol; "post-cohort") was performed. An outpatient controlled substance registry was utilized to capture morphine milligram equivalents (MME) and gabapentin dispensed in the 6 mo after injury. RESULTS: 620 patients were included (295 pre-cohort, 325 post-cohort). Total inpatient MME decreased from 177.5 mg-130 mg (P= 0.01) between the cohorts. Daily inpatient MME decreased from 70.8 mg-44.7 mg (P< 0.01). Intravenous hydromorphone decreased from 2 mg in the pre-cohort to 1 mg in the post-cohort (P= 0.02). Inpatient oxycodone decreased from 45 mg-30 mg (P= 0.01). Concurrently, gabapentin increased from 0 mg-400 mg in the post-cohort (P< 0.01). Patients in the post-cohort were prescribed fewer MMEs than the pre-cohort at discharge (P< 0.05). However, the number of patients prescribed gabapentin increased from 6.1%-16% (P< 0.01). CONCLUSION: Implementation of an updated multimodal analgesia protocol decreased total MME, daily MME, hydromorphone, and oxycodone consumed while increasing gabapentin use. This suggests that while reducing opioid usage in-hospital is critical to reducing outpatient usage, multimodal pain protocols may lead to an increase in gabapentin prescriptions and utilization after discharge.
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Analgesia , Analgésicos Opioides , Assistência ao Convalescente , Analgesia/métodos , Analgésicos Opioides/uso terapêutico , Humanos , Pacientes Internados , Pacientes Ambulatoriais , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Alta do Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: There is interest in methods of measuring noninvasive intracranial pressure (ICP), including pupillometry, ultrasonographic transcranial Doppler (TCD), and optic nerve sheath diameter (ONSD), for diagnosing traumatic brain injury (TBI) in limited resource environments. Whether these technologies have diagnostic agreement is unknown. We hypothesized that ONSD, pupillometry, and TCD could both distinguish severe TBI and correlate with ICP. METHODS: A prospective study of 135 patients was conducted at a level 1 trauma center. Four test groups were established: nontrauma patients with ICP monitoring, trauma patients without TBI, trauma patients with mild TBI, and trauma patients with severe TBI with ICP monitoring. All patients underwent daily measurements of ONSD, pupillometry, and TCD with both CX50 Sonosite and the Spencer ST3 Yi Pencil probe. RESULTS: ONSD differed significantly in patients with severe TBI compared with patients with mild and no TBI, but did not correlate with ICP. Pupillometric constriction velocity, dilation velocity, and percent change in pupil diameter were significantly different in patients with severe TBI, but also did not correlate with ICP. TCD did not differ among TBI severities, but middle cerebral artery peak systolic velocity, middle cerebral artery flow velocity, and carotid flow velocity correlated with ICP. CONCLUSIONS: This is a novel study of four noninvasive tests to screen for severity of TBI and measure ICP. Our analysis indicates that no single device can do both. However, ONSD and pupillometry may be used as a supplementary screening tool for severe TBI, whereas TCD could be used to estimate and follow ICP in patients with severe TBI.
Assuntos
Lesões Encefálicas Traumáticas/diagnóstico , Pressão Intracraniana/fisiologia , Adulto , Idoso , Lesões Encefálicas Traumáticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/patologia , Estudos Prospectivos , Pupila , Triagem , Ultrassonografia Doppler Transcraniana , Adulto JovemRESUMO
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
INTRODUCTION: Negative pressure wound therapy (NPWT) is utilized early after soft tissue injury to promote tissue granulation and wound contraction. Early post-injury transfers via aeromedical evacuation (AE) to definitive care centers may actually induce wound bacterial proliferation. However, the effectiveness of NPWT or instillation NPWT in limiting bacterial proliferation during post-injury AE has not been studied. We hypothesized that instillation NPWT during simulated AE would decrease bacterial colonization within simple and complex soft tissue wounds. METHODS: The porcine models were anesthetized before any experiments. For the simple tissue wound model, two 4-cm dorsal wounds were created in 34.9 ± 0.6 kg pigs and were inoculated with Acinetobacter baumannii (AB) or Staphylococcus aureus 24 hours before a 4-hour simulated AE or ground control. During AE, animals were randomized to one of the five groups: wet-to-dry (WTD) dressing, NPWT, instillation NPWT with normal saline (NS-NPWT), instillation NPWT with Normosol-R® (NM-NPWT), and RX-4-NPWT with the RX-4 system. For the complex musculoskeletal wound, hind-limb wounds in the skin, subcutaneous tissue, peroneus tertius muscle, and tibia were created and inoculated with AB 24 hours before simulated AE with WTD or RX-4-NPWT dressings. Blood samples were collected at baseline, pre-flight, and 72 hours post-flight for inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor alpha. Wound biopsies were obtained at 24 hours and 72 hours post-flight, and the bacteria were quantified. Vital signs were measured continuously during simulated AE and at each wound reassessment. RESULTS: No significant differences in hemodynamics or serum cytokines were noted between ground or simulated flight groups or over time in either wound model. Simulated AE alone did not affect bacterial proliferation compared to ground controls. The simple tissue wound arm demonstrated a significant decrease in Staphylococcus aureus and AB colony-forming units at 72 hours after simulated AE using RX-4-NPWT. NS-NPWT during AE more effectively prevented bacterial proliferation than the WTD dressing. There was no difference in colony-forming units among the various treatment groups at the ground level. CONCLUSION: The hypoxic, hypobaric environment of AE did not independently affect the bacterial growth after simple tissue wound or complex musculoskeletal wound. RX-4-NPWT provided the most effective bacterial reduction following simulated AE, followed by NS-NPWT. Future research will be necessary to determine ideal instillation fluids, negative pressure settings, and dressing change frequency before and during AE.
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Resgate Aéreo , Tratamento de Ferimentos com Pressão Negativa , Lesões dos Tecidos Moles , Infecção dos Ferimentos , Animais , Suínos , Lesões dos Tecidos Moles/terapia , Citocinas , Bandagens , Infecção dos Ferimentos/prevenção & controleRESUMO
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.
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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: Administration of antifibrinolytic medications, including tranexamic acid (TXA), may reduce head injury-related mortality. The effect of these medications on post-traumatic brain injury (TBI) inflammatory response is unknown. The goal of this study was to investigate the role of available antifibrinolytic medications on both systemic and cerebral inflammation after TBI. METHODS: An established murine weight drop model was used to induce a moderate TBI. Mice were administered 1, 10, or 100 mg/kg of TXA, 400 mg/kg of aminocaproic acid (Amicar, Hospira, Lake Forest, IL), 100 kIU/kg of aprotonin, or equivalent volume of normal saline (NS) 10 minutes after recovery. Mice were euthanized at 1, 6, or 24 hours. Serum and cerebral tissue were analyzed for neuron-specific enolase and inflammatory cytokines. Hippocampal histology was evaluated at 30 days for phosphorylated tau accumulation. RESULTS: One hour after TBI, mice given TXA displayed decreased cerebral cytokine concentrations of tumor necrosis factor α (TNF-α) and, by 24 hours, displayed decreased concentrations of cerebral TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 compared with TBI-NS. However, serum concentrations of TNF-α and macrophage inflammatory protein 1α (MIP-1α) were significantly elevated from 1 to 24 hours in TBI-TXA groups compared with TBI-NS. The concentration of phosphorylated tau was significantly decreased in a dose-dependent manner in TBI-TXA groups compared with TBI-NS. By contrast, Amicar administration increased cerebral cytokine levels of IL-6 1 hour after TBI, with serum elevations noted in TNF-α, MIP-1α, and monocyte chemoattractant protein 1 at 24 hours compared with TBI-NS. Aprotonin administration increased serum TNF-α, IL-6, and MIP-1α from 1 to 24 hours without differences in cerebral cytokines compared with TBI-NS. CONCLUSION: Tranexamic acid administration may provide acute neuroinflammatory protection in a dose-dependent manner. Amicar administration may be detrimental after TBI with increased cerebral and systemic inflammatory effects. Aprotonin administration may increase systemic inflammation without significant contributions to neuroinflammation. While no antifibrinolytic medication improved systemic inflammation, these data suggest that TXA may provide the most beneficial inflammatory modulation after TBI.
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Antifibrinolíticos , Lesões Encefálicas Traumáticas , Ácido Tranexâmico , Ácido Aminocaproico/uso terapêutico , Animais , Antifibrinolíticos/farmacologia , Antifibrinolíticos/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Quimiocina CCL2 , Quimiocina CCL3 , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Interleucina-6 , Camundongos , Ácido Tranexâmico/farmacologia , Ácido Tranexâmico/uso terapêutico , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Blunt chest wall injury accounts for 15% of trauma admissions. Previous studies have shown that the number of rib fractures predicts inpatient opioid requirements, raising concerns for pharmacologic consequences, including hypotension, delirium, and opioid dependence. We hypothesized that intercostal injection of liposomal bupivacaine would reduce analgesia needs and improve spirometry metrics in trauma patients with rib fractures. METHODS: A prospective, double-blinded, randomized placebo-control study was conducted at a Level I trauma center as a Food and Drug Administration investigational new drug study. Enrollment criteria included patients 18 years or older admitted to the intensive care unit with blunt chest wall trauma who could not achieve greater than 50% goal inspiratory capacity. Patients were randomized to liposomal bupivacaine or saline injections in up to six intercostal spaces. Primary outcome was to examine pain scores and breakthrough pain medications for 96-hour duration. The secondary endpoint was to evaluate the effects of analgesia on pulmonary physiology. RESULTS: One hundred patients were enrolled, 50 per cohort, with similar demographics (Injury Severity Score, 17.9 bupivacaine 17.6 control) and comorbidities. Enrolled patients had a mean age of 60.5 years, and 47% were female. Rib fracture number, distribution, and targets for injection were similar between groups. While both groups displayed a decrease in opioid use over time, there was no change in mean daily pain scores. The bupivacaine group achieved higher incentive spirometry volumes over Days 1 and 2 (1095 mL, 1063 mL bupivacaine vs. 900 mL, 866 mL control). Hospital and intensive care unit lengths of stay were similar and there were no differences in postinjection pneumonia, use of epidural catheters or adverse events bet ween groups. CONCLUSION: While intercostal liposomal bupivacaine injection is a safe method for rib fracture-related analgesia, it was not effective in reducing pain scores, opioid requirements, or hospital length of stay. Bupivacaine injection transiently improved incentive spirometry volumes, but without a reduction in the development of pneumonia. LEVEL OF EVIDENCE: Therapeutic/care management, Level II.
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Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Manejo da Dor/métodos , Fraturas das Costelas/complicações , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Injeções , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Lipossomos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , EspirometriaRESUMO
INTRODUCTION: "Endotheliopathy of trauma" is recognized as endothelial dysfunction following traumatic injury leading to poor patient outcomes. Acute post-traumatic disruptions in endothelial cell function have been associated with profound physiologic, hemodynamic, and coagulation derangements. The goal of this study was to define the generation and extent of endotheliopathy in murine polytrauma models by evaluating the post-traumatic release of serum biomarkers of ongoing cellular injury. METHODS: Mice were randomized to undergo moderately severe concussive TBI by weight drop, 60-min hemorrhagic shock to MAP 25âmmHg with subsequent resuscitation with Lactated Ringer's, submandibular bleed (SMB), and/or midline laparotomy with rectus muscle crush. Mice were sacrificed at 1, 4, or 24âh for serum biomarker evaluation. RESULTS: Serum biomarkers revealed differential timing of elevation and injury-dependent release.At 24âh, soluble thrombomodulin was significantly elevated in combined TBIâ+âshockâ+âlap crush compared to untouched, and shock alone. Syndecan-1 levels were significantly elevated after shock 1 to 24âh compared to untouched cohorts with a significant elevation in TBIâ+âshockâ+âlap crush 24âh after injury compared to shock alone. UCHL-1 was significantly elevated in shock mice at 1 to 24âh post-injury compared to untouched mice. UCHL-1 was also significantly elevated in the TBIâ+âshock cohort 24âh after injury compared to shock alone. Hyaluronic acid release at 4âh was significantly elevated in shock alone compared to the untouched cohort with further elevations in TBIâ+âshockâ+âlap crush and TBIâ+âshock compared to shock alone at 24âh. Hyaluronic acid was also increased in lap crush and laparotomy only cohort compared to untouched mice 24âh after injury. CONCLUSIONS: A murine model of polytrauma including TBI, hemorrhagic shock, and laparotomy abdominal crush is a reliable method for evaluation of endotheliopathy secondary to trauma as indicated by differential changes in serum biomarkers.
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Traumatismo Múltiplo , Choque Hemorrágico , Animais , Biomarcadores , Ácido Hialurônico , Camundongos , Ressuscitação/métodosRESUMO
BACKGROUND: The goals of sedation in the critically ill surgical patient are to minimize pain, anxiety, and agitation without hindering cardiopulmonary function. One potential benefit of tracheostomy during endotracheal intubation is the reduction of sedation and analgesia; however, there are little data to support this supposition. We hypothesized that patients undergoing tracheostomy would have a rapid reduction in sedation and analgesia following tracheostomy. METHODS: A retrospective review of tracheostomies performed at a single Level I trauma center from January 2013 to June 2018 was completed. An evaluation of Glasgow Coma Scale, Richmond Agitation-Sedation Scale, and Confusion Assessment Method for the intensive care unit 72 hours pretracheostomy to 72 hours posttracheostomy was performed. The total daily dose of sedation, anxiolytic, and analgesic medications administered were recorded. Mixed-effects models were used to evaluate longitudinal drug does over time (hours). RESULTS: Four hundred sixty-eight patients included for analysis with a mean age of 58.8 ± 18.3 years. There was a significant decrease in propofol and fentanyl utilization from 24 hours pretracheostomy to 24 hours posttracheostomy in both dose and number of patients receiving these continuous intravenous medications. Similarly, total morphine milligram equivalents (MME) use and continuous midazolam significantly decreased from 24 hours pretracheostomy to 24 hours posttracheostomy. By contrast, intermittent enteral quetiapine and methadone administration increased after tracheostomy. Importantly, Richmond Agitation-Sedation Scale, Glasgow Coma Scale, and Confusion Assessment Method scoring were also significantly improved as early as 24 hours posttracheostomy. Total MME use was significantly elevated in patients younger than 65 years and in male patients pretracheostomy compared with female patients. Patients admitted to the medical intensive care unit had significantly higher MME use compared with those in the surgical intensive care unit pretracheostomy. CONCLUSION: Tracheostomy allows for a rapid and significant reduction in intravenous sedation and analgesia medication utilization. Posttracheostomy sedation can transition to intermittent enteral medications, potentially contributing to the observed improvements in postoperative mental status and agitation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.
Assuntos
Analgesia , Ansiolíticos , Propofol , Adulto , Idoso , Analgésicos , Endrin/análogos & derivados , Feminino , Fentanila , Humanos , Hipnóticos e Sedativos , Unidades de Terapia Intensiva , Masculino , Metadona , Midazolam , Pessoa de Meia-Idade , Derivados da Morfina , Dor , Fumarato de Quetiapina , Respiração Artificial , TraqueostomiaRESUMO
OBJECTIVE: There is considerable variability in surgeons' approach to write and obtain informed consent for surgery, particularly among resident trainees. We analyzed differences in procedures and complications described in documented surgical consents for cholecystectomy between residents and attendings. We hypothesized that attending consents would describe more comprehensive procedures and complications than those done by residents. DESIGN: This is a retrospective analysis of 334 patients who underwent cholecystectomy. Charts were queried for demographics, surgical approach, whether the consent was completed electronically, and which provider completed the consent. Specifically, consents were evaluated for inclusion of possible conversion to open procedure, intraoperative cholangiogram, bile duct injury, injury to nearby structures, reoperation, bile leak, as well as if the consent matched the actual procedure performed. SETTING: This study was conducted at an accredited general surgery training program at an academic tertiary care center in the Midwest. PARTICIPANTS: This was a review of 334 patients who underwent cholecystectomy over a 1 year period. RESULTS: Of all documented consents analyzed, 153 (47%) specifically included possible intraoperative cholangiogram, 156 (47%) included bile duct injury, 76 (23%) included injury to nearby structures, 22 (7%) included reoperation, and 62 (19%) included bile leak. In comparing residents and attendings, residents were more likely to consent for bile duct injury (pâ¯=â¯0.002), possible intraoperative cholangiogram (pâ¯=â¯0.0007), injury to nearby structures (p < 0.0001), reoperation (p < 0.0001), and bile leak (p < 0.0001). CONCLUSIONS: Significant variation exists between documentation between resident and attending cholecystectomy consents, with residents including more complications than attendings on their consent forms. These data suggest that experience alone does not predict content of written consents, particularly for common ambulatory procedures. Education regarding the purpose of informed consent and what should be included in one may lead to a reduction in variability between providers.
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Traumatismos Abdominais , Colecistectomia , Humanos , Estudos Retrospectivos , Consentimento Livre e Esclarecido , Gestão de Riscos , DocumentaçãoRESUMO
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.
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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
BACKGROUND: Surgical residencies have implemented boot-camps for early acquisition of basic technical skills for interns. However, educators worry that retention is poor. We hypothesized that a structured boot-camp curriculum would improve skills. METHODS: Interns underwent eight boot-camp sessions at the beginning of residency. Interns completed pre-, post-boot-camp, and end-of-year skills assessments, as well as post-boot camp and end-of-year porcine procedure labs. Proficiency was measured on a 5-point scale and by completion time. RESULTS: After boot-camp, interns improved all domains of knot-tying. Median time decreased for skin-closure (8.3 vs 9.9 min, p < 0.01), peg transfer (57 vs 87 s, p < 0.01), intracorporeal (178 vs 300 s, p < 0.01), and extracorporeal knot-tying (140 vs 259 s, p < 0.01). At the end-of-year assessment, interns exhibited retention of all skills and improved in knot-tying and central line skills. During the retention porcine lab, interns progressed basic but not complex skills. CONCLUSIONS: An eight-week boot-camp effectively improved technical skills among surgery interns. Interns retained all skills and improved upon techniques frequently practiced during intern year.
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Competência Clínica , Cirurgia Geral/educação , Internato e Residência , Procedimentos Cirúrgicos Operatórios/educação , Cateterismo Venoso Central , Avaliação Educacional , Feminino , Humanos , Internato e Residência/métodos , Internato e Residência/organização & administração , Laparoscopia/educação , Masculino , Retenção Psicológica , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/normas , Técnicas de Sutura/educação , Técnicas de Fechamento de Ferimentos/educaçãoRESUMO
The Boston Criteria and the Abbreviated Burn Severity Index are two widely accepted models for predicting mortality in burn patients. We aimed to elucidate whether these models are able to predict the risk of mortality in patients who sustain burns while smoking on home oxygen given their clinical fragility. We conducted a retrospective chart review of 48 patients admitted to our burn center from November 2013 to September 2017 who sustained a burn while smoking on home oxygen. Yearlong mortality was the primary outcome of the investigation; secondary outcomes included discharge to facility, length of stay, and need for tracheostomy. We calculated the expected mortality rate for each patient based on Boston Criteria and Abbreviated Burn Severity Index and compared the mortality rate observed in our cohort. Patients in our cohort suffered a 54% mortality rate within a year of injury, compared to a 23.5% mortality predicted by Boston Criteria, which was found to be statistically significant by chi-square analysis (P < .05). Abbreviated Burn Severity Index predicted mortality was 19.7%. While the absolute value of the difference in mortality was greater, this was not significant on chi-square analysis due to sample size. Our secondary outcomes revealed 42% discharge to facility, the average length of stay of 6.2 days, and 6.25% required tracheostomy. Patients whose burns are attributable to smoking on home oxygen may have an increased risk of mortality than prognostication models would suggest. This bears significant clinical impact, particularly regarding family and provider decision making in pursuing aggressive management.
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Queimaduras/mortalidade , Oxigenoterapia/efeitos adversos , Fumar/efeitos adversos , Idoso , Queimaduras/etiologia , Queimaduras/terapia , Feminino , Serviços de Assistência Domiciliar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
INTRODUCTION: Trauma patients may become hypoxic or iatrogenically hyperoxic in the early post-injury period. While both extremes of oxygenation may be harmful following injury, the mechanism has yet to be elucidated. We hypothesized that hypoxia or hyperoxia would induce changes in coagulation, creating a secondary insult exacerbating the primary injury. MATERIALS AND METHODS: Mice underwent traumatic brain injury (TBI) or sham and were subsequently exposed to room air or brief hypoxia (15% FiO2) then sacrificed at intervals. Another cohort of uninjured mice underwent more prolonged hypoxia (10% FiO2) or hyperoxia (60% FiO2). Platelet function was evaluated by ADP- or ASPi-induced impedance aggregometry and viscoelastic coagulation parameters were assessed with rotational thromboelastometry. RESULTS: In uninjured mice, ADP-induced platelet aggregation was acutely increased after prolonged hypoxia, but this difference did not persist at 6 h. Hypoxic and hyperoxic TBI mice had increased ADP induced platelet aggregation at 1 h compared to the normoxia group. TBI mice demonstrated an early increased platelet aggregation after hypoxia or hyperoxia. Viscoelastic coagulation parameters were similar between hypoxic, hyperoxic and room air groups at 1 h and 6 h. However, ROTEM clotting time and clot formation time were prolonged and maximal clot firmness were lower in sham TBI/hypoxia mice at 24 h. CONCLUSION: Post-TBI hypoxia and hyperoxia resulted in transiently increased platelet aggregation in response to ADP, without lasting effecting on platelet function or coagulation. Hypoxia also induced delayed hypocoagulability after platelet aggregation normalized. Brief changes in oxygenation may temporally affect coagulation and platelet aggregation, which could contribute to physiologic secondary injury after trauma.