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1.
Medicine (Baltimore) ; 100(12): e25143, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761680

RESUMO

BACKGROUND: Whether to use limited fluid resuscitation (LFR) in patients with hemorrhagic shock or septic shock remains controversial. This research was aimed to assess the pros and cons of utilizing LFR in hemorrhagic shock or septic shock patients. METHODS: PubMed, Cochrane Library, Embase, Web of science, CNKI, VIP, and Wan Fang database searches included for articles published before December 15, 2020. Randomized controlled trials of LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients were selected. RESULT: This meta-analysis including 28 randomized controlled trials (RCTs) and registered 3288 patients. The 7 of 27 RCTs were the patients with septic shock. Others were traumatic hemorrhagic shock patients. Comparing LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients, the summary odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.42-0.60, P < .00001) for mortality, 0.46 (95% CI 0.31-0.70, P = .0002) for multiple organ dysfunction syndrome (MODS), 0.35 (95% CI 0.25-0.47) for acute respiratory distress syndrome (ARDS), and 0.33 (95% CI 0.20-0.56) for disseminated intravascular coagulation (DIC). CONCLUSION: Limited fluid resuscitation is the benefit of both traumatic hemorrhagic shock patients and septic shock patients.


Assuntos
Hidratação/mortalidade , Ressuscitação/mortalidade , Choque Hemorrágico/terapia , Choque Séptico/terapia , Choque Traumático/terapia , Hidratação/métodos , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , /mortalidade , Ressuscitação/métodos , Choque Hemorrágico/complicações , Choque Hemorrágico/mortalidade , Choque Séptico/complicações , Choque Séptico/mortalidade , Choque Traumático/complicações , Choque Traumático/mortalidade , Resultado do Tratamento
2.
J Trauma Acute Care Surg ; 89(4): 792-800, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32590558

RESUMO

BACKGROUND: Whole blood is optimal for resuscitation of traumatic hemorrhage. Walking Blood Banks provide fresh whole blood (FWB) where conventional blood components or stored, tested whole blood are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the coronavirus disease 2019 pandemic. We conducted a systematic review and meta-analysis of the available evidence to inform practice. METHODS: Standard systematic review methodology was used to obtain studies that reported the delivery of FWB (PROSPERO registry CRD42019153849). Studies that only reported whole blood from conventional blood banking were excluded. For outcomes, odds ratios (ORs) and 95% confidence interval (CI) were calculated using random-effects modeling because of high risk of heterogeneity. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. RESULTS: Twenty-seven studies published from 2006 to 2020 reported >10,000 U of FWB for >3,000 patients (precise values not available for all studies). Evidence for studies was "low" or "very low" except for one study, which was "moderate" in quality. Fresh whole blood patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for eight studies that compared these (OR, 1.00 [95% CI, 0.65-1.55]; p = 0.61). However, the highest quality study (matched groups for physiological and injury characteristics) reported an adjusted OR of 0.27 (95% CI, 0.13-0.58) for mortality for the FWB group (p < 0.01). CONCLUSION: Thousands of units of FWB from Walking Blood Banks have been transfused in patients following life-threatening hemorrhage. Survival is equivalent for FWB resuscitation when compared with non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas Walking Blood Banks may be an attractive resilience measure, caution is still advised. Walking Blood Banks should be subject to prospective evaluation to optimize care and inform policy. LEVEL OF EVIDENCE: Systematic/therapeutic, level 3.


Assuntos
Bancos de Sangue , Transfusão de Sangue/métodos , Ressuscitação/métodos , Choque Hemorrágico/terapia , Choque Traumático/terapia , Humanos , Índice de Gravidade de Doença , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Traumático/complicações , Choque Traumático/diagnóstico , Choque Traumático/mortalidade , Análise de Sobrevida , Resultado do Tratamento
3.
J Trauma Acute Care Surg ; 88(5): 588-596, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32317575

RESUMO

BACKGROUND: Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. METHODS: We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less. RESULTS: Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index). CONCLUSION: Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy. LEVEL OF EVIDENCE: Therapeutic, level II.


Assuntos
Transfusão de Componentes Sanguíneos/efeitos adversos , Cálcio/administração & dosagem , Serviços Médicos de Emergência/normas , Hipocalcemia/prevenção & controle , Ressuscitação/efeitos adversos , Choque Hemorrágico/terapia , Choque Traumático/terapia , Adulto , Transfusão de Componentes Sanguíneos/normas , Cálcio/sangue , Soluções Cristaloides/administração & dosagem , Serviços Médicos de Emergência/métodos , Feminino , Humanos , Hipocalcemia/sangue , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Plasma , Guias de Prática Clínica como Assunto , Ressuscitação/métodos , Ressuscitação/normas , Choque Hemorrágico/sangue , Choque Hemorrágico/mortalidade , Choque Traumático/sangue , Choque Traumático/mortalidade , Resultado do Tratamento
4.
J Trauma Acute Care Surg ; 88(5): 597-606, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32317576

RESUMO

BACKGROUND: Hemodynamically unstable pelvic fractures often require a multi-modal approach including both operative and endovascular management. While an important adjunct in hemorrhage control, time to angioembolization even at the most advanced trauma centers may take hours. Extraperitoneal packing (EPP) is a fast and effective procedure that can immediately address pelvic hemorrhage from the retroperitoneal space in severe pelvic injuries. The aim of this study was to evaluate the efficacy of early EPP, looking at 24 hours and overall mortality, and the hemodynamic impact of EPP in unstable blunt pelvic trauma. METHODS: All trauma patients admitted to an urban Level I trauma center were evaluated from 2002 to 2018 in a retrospective single-center comparative study. Inclusion criteria were patients 14 years or older who sustained blunt trauma with pelvic fractures and hemodynamic instability. Exclusion criteria were a concomitant head injury (Abbreviated Injury Scale >3) and patients who underwent resuscitative thoracotomy. The patient population was divided into two groups: an EPP group and a no-EPP group. Propensity score matching was used to adjust for differences in baseline characteristics in the two groups: a one-to-one matched analysis using nearest-neighbor matching was performed based on the estimated propensity score of each patient. RESULTS: Two hundred forty-four patients presented hemodynamically unstable, with a pelvic fracture (180 no-EPP, 64 EPP). With propensity score matching, 37 patients in each group were analyzed. Survival within the first 24 hours was significantly improved in the EPP group (81.1% vs. 59.5%, p = 0.042) and we registered similar results in overall survival rate (78.4% EPP group vs. 56.8% no-EPP group, p = 0.047). Those patients who underwent early EPP (n = 64) were associated with a significant improvement in hemodynamic stability, with a pre-EPP mean arterial pressure of 49.9 mm Hg and post-EPP mean arterial pressure of 70.1 mm Hg (p < 0.01). CONCLUSION: Extraperitoneal pelvic packing is an effective procedure that can be performed immediately, even within the trauma bay, to improve hemodynamic stability and overall survival in patients who sustain severe blunt pelvic trauma. The early use of EPP can be lifesaving. LEVEL OF EVIDENCE: Therapeutic, Level III.


Assuntos
Fraturas Ósseas/complicações , Hemostasia Cirúrgica/métodos , Ossos Pélvicos/lesões , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ferimentos não Penetrantes/complicações , Adulto , Feminino , Fraturas Ósseas/mortalidade , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Pelve/cirurgia , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Taxa de Sobrevida , Centros de Traumatologia/estatística & dados numéricos , Resultado do Tratamento , Ferimentos não Penetrantes/mortalidade , Adulto Jovem
5.
J Surg Res ; 252: 139-146, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278968

RESUMO

BACKGROUND: Age and massive transfusion are predictors of mortality after trauma. We hypothesized that increasing age and high-volume transfusion would result in progressively elevated mortality rates and that a transfusion "ceiling" would define futility. METHODS: The Trauma Quality Improvement Program (TQIP) database was queried for 2013-2016 records and our level I trauma registry was reviewed from 2013 to 2018. Demographic, mortality, and blood transfusion data were collected. Patients were grouped by decade of life and by packed red blood cell (pRBC) transfusion requirement (zero units, 1-3 units, or ≥4 units) within 4 h of admission. RESULTS: TQIP analysis demonstrated an in-hospital mortality risk that increased linearly with age, to an odds ratio of 10.1 in ≥80 y old (P < 0.01). Mortality rates were significantly higher in older adults (P < 0.01) and those with more pRBCs transfused. In massively transfused patients, the transfusion "ceiling" was dependent on age. Owing to the lack granularity in the TQIP database, 230 patients from our institution who received ≥4 units of pRBCs within 4 h of admission were reviewed. On arrival, younger patients had significantly higher heart rates and more severe derangements in lactate levels, base deficits, and pH compared with older patients. There were no differences among age groups in injury severity score, systolic blood pressure, or mortality. CONCLUSIONS: In massively transfused patients, mortality increased with age. However, a significant proportion of older adults were successfully resuscitated. Therefore, age alone should not be considered a contraindication to high-volume transfusion. Traditional physiologic and laboratory criteria indicative of hemorrhagic shock may have reduced reliability with increasing age, and thus providers must have a heightened suspicion for hemorrhage in the elderly. Early transfusion requirements can be combined with age to establish prognosis to define futility to help counsel families regarding mortality after traumatic injury.


Assuntos
Transfusão de Eritrócitos/normas , Futilidade Médica , Ressuscitação/normas , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Adulto , Fatores Etários , Idoso , Tomada de Decisão Clínica/métodos , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Sistema de Registros/estatística & dados numéricos , Ressuscitação/métodos , Ressuscitação/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Centros de Traumatologia/normas , Centros de Traumatologia/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade
6.
Updates Surg ; 72(2): 527-536, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130669

RESUMO

EndoVascular and Hybrid Trauma Management (EVTM) has been recently introduced in the treatment of severe pelvic ring injuries. This multimodal method of hemorrhage management counts on several strategies such as the REBOA (resuscitative endovascular balloon occlusion of the aorta). Few data exist on the use of REBOA in patients with a severely injured pelvic ring. The ABO (aortic balloon occlusion) Trauma Registry is designed to capture data for all trauma patients in hemorrhagic shock where management includes REBOA placement. Among all patients included in the ABO registry, 72 patients presented with severe pelvic injuries and were the population under exam. 66.7% were male. Mean and median ISS were respectively 43 and 41 (SD ± 13). Isolated pelvic injuries were observed in 12 patients (16.7%). Blunt trauma occurred in 68 patients (94.4%), penetrating in 2 (2.8%) and combined in 2 (2.8%). Type of injury: fall from height in 15 patients (23.1%), traffic accident in 49 patients (75.4%), and unspecified impact in 1 patient (1.5%). Femoral access was gained pre-hospital in 1 patient, in emergency room in 43, in operating room in 12 and in angio-suite in 16. REBOA was positioned in zone 1 in 59 patients (81,9%), in zone 2 in 1 (1,4%) and in zone 3 in 12 (16,7%). Aortic occlusion was partial/periodical in 35 patients (48,6%) and total occlusion in 37 patients (51,4%). REBOA associated morbidity rate: 11.1%. Overall mortality rate was 54.2% and early mortality rate (≤ 24 h) was 44.4%. In the univariate analysis, factors related to early mortality (≤ 24 h) are lower pH values (p = 0.03), higher base deficit (p = 0.021), longer INR (p = 0.012), minor increase in systolic blood pressure after the REBOA inflation (p = 0.03) and total aortic occlusion (p = 0.008). None of these values resulted significant in the multivariate analysis. In severe hemodynamically unstable pelvic trauma management, REBOA is a viable option when utilized in experienced centers as a bridge to other treatments; its use might be, however, accompanied with severe-to-lethal complications.


Assuntos
Aorta , Arteriopatias Oclusivas/terapia , Oclusão com Balão/métodos , Pelve/lesões , Sistema de Registros , Choque Hemorrágico/terapia , Adolescente , Adulto , Arteriopatias Oclusivas/etiologia , Oclusão com Balão/efeitos adversos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Sístole , Índices de Gravidade do Trauma , Adulto Jovem
7.
West J Emerg Med ; 21(2): 217-225, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32191179

RESUMO

INTRODUCTION: Patients with trauma-induced coagulopathies may benefit from the use of antifibrinolytic agents, such as tranexamic acid (TXA). This study evaluated the safety and efficacy of TXA in civilian adults hospitalized with traumatic hemorrhagic shock. METHODS: Patients who sustained blunt or penetrating trauma with signs of hemorrhagic shock from June 2014 through July 2018 were considered for TXA treatment. A retrospective control group was formed from patients seen in the same past five years who were not administered TXA and matched based on age, gender, Injury Severity Score (ISS), and mechanism of injury (blunt vs penetrating trauma). The primary outcome of this study was mortality measured at 24 hours, 48 hours, and 28 days. Secondary outcomes included total blood products transfused, hospital length of stay (LOS), intensive care unit LOS, and adverse events. We conducted three pre-specified subgroup analyses to assess outcomes of patients, including (1) those who were severely injured (ISS >15), (2) those who sustained significant blood loss (≥10 units of total blood products transfused), and (3) those who sustained blunt vs penetrating trauma. RESULTS: Propensity matching yielded two cohorts: the hospital TXA group (n = 280) and a control group (n = 280). The hospital TXA group had statistically lower mortality at 28 days (1.1% vs 5%, odds ratio [OR] [0.21], (95% confidence interval [CI], 0.06, 0.72)) and used fewer units of blood products (median = 4 units, interquartile range (IQR) = [1, 10] vs median=7 units, IQR = [2, 12.5] for the hospital TXA and control groups, respectively, (95% CI for the difference in median, -3 to -1). There were no statistically significant differences between groups with regard to 24-hour mortality (1.1% vs 1.1%, OR = 1, 95% CI, 0.20, 5.00), 48-hour mortality (1.1% vs 1.4%, OR [0.74], 95% CI, 0.17, 3.37), hospital LOS (median= 9 days, IQR = (5, 16) vs median =12 days IQR = (6, 22.5) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-5 to 0)), and incidence of thromboembolic events (eg, deep vein thrombosis, pulmonary embolism) during hospital stay (0.7% vs 0.7% for the hospital TXA and control group, respectively, OR [1], 95% CI, 0.14 to 7.15). We conducted subgroup analyses on patients with ISS>15, patients transfused with ≥10 units of blood products, and blunt vs penetrating trauma. The results indicated lower 28-day mortality for ISS>15 (1.8% vs 7.1%, OR [0.23], 95% CI, 0.06 to 0.81) and blunt trauma (0.6% vs 6.3%, OR [0.09], 95% CI, 0.01 to 0.75); fewer units of blood products for penetrating trauma (median = 2 units, IQR = (1, 8) vs median = 8 units, IQR = (5, 15) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-6 to -3)), and ISS>15 (median = 7 units, IQR = (2, 14) vs median = 8.5 units, IQR = (4, 16) for the hospital TXA and control groups, respectively, 95% CI for the difference in median, -3 to 0). CONCLUSION: The current study demonstrates a statistically significant reduction in mortality after TXA administration at 28 days, but not at 24 and 48 hours, in patients with traumatic hemorrhagic shock.


Assuntos
Ressuscitação/métodos , Choque Hemorrágico , Ácido Tranexâmico/uso terapêutico , Ferimentos e Lesões , Adulto , Antifibrinolíticos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Incidência , Escala de Gravidade do Ferimento , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
8.
J Trauma Acute Care Surg ; 88(5): 661-670, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068718

RESUMO

BACKGROUND: Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature. The aim of the study was to evaluate the effect of fibrinogen concentrate administration within the first 6 hours on 24-hour all-cause mortality in traumatic hemorrhagic shock using a causal inference approach. METHODS: Observational study from a French multicenter prospective trauma registry was performed. Hemorrhagic shock was defined as transfusion of four or more red blood cell units within the first 6 hours after admission. The confounding variables for the outcome (24-hour all-cause mortality) and treatment allocation (fibrinogen concentrate administration within the first 6 hours) were chosen by a Delphi method. The propensity score was specified with a data-adaptive algorithm and a doubly-robust approach with inverse proportionality of treatment weighting allowed to compute the average treatment effect. Sensitivity analyses were performed. RESULTS: Of 14,336 patients in the registry during the study period, 1,027 in hemorrhagic shock were analyzed (758 receiving fibrinogen concentrate within 6 hours and 269 not receiving fibrinogen concentrate). The average treatment effect, expressed as a risk difference, was -0.031 (95% confidence interval, -0.084 to 0.021). All sensitivity analysis confirmed the results. CONCLUSIONS: Fibrinogen concentrate administration within the first 6 hours of a traumatic hemorrhagic shock did not decrease 24-hour all-cause mortality. LEVEL OF EVIDENCE: Prognostic, level III.


Assuntos
Transfusão de Eritrócitos/estatística & dados numéricos , Fibrinogênio/administração & dosagem , Hemostáticos/administração & dosagem , Choque Hemorrágico/terapia , Choque Traumático/terapia , Adulto , Técnica Delfos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Traumático/etiologia , Choque Traumático/mortalidade , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
9.
J Trauma Acute Care Surg ; 88(2): 298-304, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31996655

RESUMO

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) and intermittent REBOA (iREBOA) are techniques to extend the therapeutic duration of REBOA by balloon titration for distal flow or cyclical balloon inflation/deflation to allow transient distal flow, respectively. We hypothesized that manually titrated pREBOA would reduce blood losses and ischemic burden when compared with iREBOA. METHODS: Following 20% blood volume controlled hemorrhage, 10 anesthetized pigs underwent uncontrolled hemorrhage from the right iliac artery and vein. Once in hemorrhagic shock, animals underwent 15 minutes of complete zone 1 REBOA followed by 75 minutes of either pREBOA or iREBOA (n = 5/group). After 90 minutes, definitive hemorrhage control was obtained, animals were resuscitated with the remaining collected blood, and then received 2 hours of critical care. RESULTS: There were no differences in mortality. Animals randomized to iREBOA spent a larger portion of the time at full occlusion when compared with pREBOA (median, 70 minutes; interquartile range [IQR], 70-80 vs. median, 20 minutes; IQR, 20-40, respectively; p = 0.008). While the average blood pressure during the intervention period was equivalent between groups, this was offset by large fluctuations in blood pressure and significantly more rescue occlusions for hypotension with iREBOA. Despite lower maximum aortic flow rates, the pREBOA group tolerated a greater total amount of distal aortic flow during the intervention period (median, 20.9 L; IQR, 20.1-23.0 vs. median, 9.8 L; IQR, 6.8-10.3; p = 0.03) with equivalent abdominal blood losses. Final plasma lactate and creatinine concentrations were equivalent, although iREBOA animals had increased duodenal edema on histology. CONCLUSION: Compared with iREBOA, pREBOA reduced the time spent at full occlusion and the number of precipitous drops in proximal mean arterial pressure while delivering more distal aortic flow but not increasing total blood loss in this highly lethal injury model. Neither technique demonstrated a survival benefit. Further refinement of these techniques is necessary before clinical guidelines are issued.


Assuntos
Oclusão com Balão/métodos , Procedimentos Endovasculares/métodos , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Animais , Aorta/cirurgia , Oclusão com Balão/efeitos adversos , Oclusão com Balão/instrumentação , Modelos Animais de Doenças , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Humanos , Masculino , Ressuscitação/efeitos adversos , Ressuscitação/instrumentação , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Análise de Sobrevida , Sus scrofa , Fatores de Tempo , Índices de Gravidade do Trauma , Resultado do Tratamento , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico
10.
J Surg Res ; 249: 104-113, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31926397

RESUMO

BACKGROUND: Hemorrhagic shock (HS) caused by rapid loss of a large amount of blood is the leading cause of early death after severe injury. When cells are damaged during HS, many intracellular components including DNA are released into the circulation and function as endogenous damage-associated molecular patterns (DAMPs) that can trigger excessive inflammatory response and subsequently multiple organ dysfunction. We hypothesized that the administration of deoxyribonuclease I (DNase I) could reduce cell-free DNA and attenuate tissue damage in HS. METHODS: Eight-week-old male C57BL/6 mice underwent HS by controlled bleeding from the femoral artery for 90 min, followed by resuscitation with Ringer's lactate solution (vehicle) or DNase I (10 mg/kg BW). RESULTS: At 20 h after HS, serum levels of cell-free DNA were increased by 7.6-fold in the vehicle-treated HS mice compared with sham, while DNase I reduced its levels by 47% compared with the vehicle group. Serum levels of tissue injury markers (lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) and proinflammatory cytokine interleukin 6 were significantly reduced in the DNase I-treated mice. In the lungs, messenger RNA levels of proinflammatory cytokines (interleukin 6 and interleukin 1 ß), chemoattractant macrophage inflammatory protein - 2, and myeloperoxidase activity were significantly decreased in HS mice after DNase I. Finally, DNase I significantly improved the 10-day survival rate in HS mice. CONCLUSIONS: Administration of DNase I attenuates tissue damage and systemic and lung inflammation, leading to improvement of survival in HS mice. Thus, DNase I may potentially serve as an adjunct therapy for managing patients with HS.


Assuntos
Ácidos Nucleicos Livres/sangue , Desoxirribonuclease I/administração & dosagem , Ressuscitação/métodos , Choque Hemorrágico/terapia , Síndrome de Resposta Inflamatória Sistêmica/terapia , Animais , Ácidos Nucleicos Livres/metabolismo , Ácidos Nucleicos Livres/toxicidade , Desoxirribonuclease I/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Choque Hemorrágico/sangue , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Taxa de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Ferimentos e Lesões/complicações
11.
J Cardiovasc Pharmacol Ther ; 25(2): 103-109, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31823646

RESUMO

Remote ischemic conditioning is the phenomenon whereby brief, nonlethal episodes of ischemia in one organ (such as a limb) protect a remote organ from ischemic necrosis induced by a longer duration of severe ischemia followed by reperfusion. This phenomenon has been reproduced by dozens of experimental laboratories and was shown to reduce the size of myocardial infarction in many but not all clinical studies. In one recent large clinical trial, remote ischemic conditioning induced by repetitive blood pressure cuff inflations on the arm did not reduce infarct size or improve clinical outcomes. This negative result may have been related in part to the overall success of early reperfusion and current adjunctive therapies, such as antiplatelet therapy, antiremodeling therapies, and low-risk patients, that may make it difficult to show any advantage of newer adjunctive therapies on top of existing therapies. One relevant area in which current outcomes are not as positive as in the treatment of heart attack is the treatment of shock, where mortality rates remain high. Recent experimental studies show that remote ischemic conditioning may improve survival and organ function in shock states, especially hemorrhagic shock and septic shock. In this study, we review the preclinical studies that have explored the potential benefit of this therapy for shock states and describe an ongoing clinical study.


Assuntos
Precondicionamento Isquêmico , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/terapia , Choque Cardiogênico/terapia , Choque Hemorrágico/terapia , Animais , Humanos , Precondicionamento Isquêmico/efeitos adversos , Precondicionamento Isquêmico/mortalidade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/mortalidade , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Recuperação de Função Fisiológica , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/mortalidade , Choque Hemorrágico/fisiopatologia , Resultado do Tratamento
12.
Ann Pharmacother ; 54(3): 213-218, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31625395

RESUMO

Background: Norepinephrine remains the first-line option to manage patients with circulatory shock. Limited evidence exists evaluating noncatecholamine compounds as first-line monotherapy for managing noncardiogenic shock. Objective: To compare vasopressin monotherapy with norepinephrine monotherapy for reversal of distributive and hemorrhagic shock. Methods: This was a retrospective cohort study including adult patients who were diagnosed with hypovolemic or septic shock, received fluids, and received norepinephrine or vasopressin monotherapy for at least 1 hour. Patients excluded lacked a clear diagnosis, were initiated on 2 or more vasopressors at once, or underwent cardiac surgery. The primary outcome was time to shock reversal. Secondary outcomes included mortality, lengths of stay, and safety end points. A multivariable Cox proportional hazards model was performed incorporating baseline and treatment variables. Results: A total of 85 and 160 patients were treated with vasopressin and norepinephrine, respectively. A decrease in time to shock reversal was observed in the vasopressin group (58.32 hours [95% CI, 50.88-66.00] vs 74.64 hours [95% CI, 60.96-88.32], P = 0.004). Mortality was lower in the vasopressin group (25% vs 41%, P = 0.01), and intensive care unit length of stay was longer (13 days [interquartile range, IQR = 7-19] vs 7 days [IQR = 5-9], P = 0.006). Remaining secondary outcomes were similar. The multivariable analysis revealed no difference in time to shock reversal. Conclusion and Relevance: First-line vasopressin exhibited faster time to distributive shock reversal in the unadjusted analysis but failed to maintain this difference in the multivariable analysis. These findings support safe use of vasopressin as first-line therapy or as an alternative to norepinephrine in distributive shock.


Assuntos
Norepinefrina/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico , Vasopressinas/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Estudos de Coortes , Creatinina/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Unidades de Terapia Intensiva , Ácido Láctico/sangue , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Norepinefrina/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Choque Hemorrágico/mortalidade , Choque Séptico/mortalidade , Resultado do Tratamento , Vasoconstritores/administração & dosagem , Vasoconstritores/efeitos adversos , Vasopressinas/administração & dosagem , Vasopressinas/efeitos adversos
13.
J Trauma Acute Care Surg ; 88(1): 33-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524836

RESUMO

INTRODUCTION: Recent evidence demonstrated that prehospital plasma in patients at risk of hemorrhagic shock was safe for ground transport and resulted in a 28-day survival benefit for air medical transport patients. Whether any beneficial effect of prehospital plasma varies across injury mechanism remains unknown. METHODS: We performed a secondary analysis using a harmonized data set derived from two recent prehospital plasma randomized trials. Identical inclusion/exclusion criteria and primary/secondary outcomes were used for the trials. Prehospital time, arrival shock parameters, and 24-hour transfusion requirements were compared across plasma and control groups stratified by mechanism of injury. Stratified survival analysis and Cox hazard regression were performed to determine the independent survival benefits of plasma across blunt and penetrating injury. RESULTS: Blunt patients had higher injury severity, were older, and had a lower Glasgow Coma Scale. Arrival indices of shock and coagulation parameters were similar across blunt and penetrating injury. The percentage of patients with a prehospital time less than 20 minutes was significantly higher for penetrating patients relative to blunt injured patients (28.0% vs. 11.6%, p < 0.01). Stratified Kaplan-Meier curves demonstrated a significant separation for blunt injured patients (n = 465, p = 0.01) with no separation demonstrated for penetrating injured patients (n = 161, p = 0.60) Stratified Cox hazard regression verified, after controlling for all important confounders, that prehospital plasma was associated with a 32% lower independent hazard for 28-day mortality in blunt injured patients (hazard ratio, 0.68; 95% confidence interval, 0.47-0.96; p = 0.03) with no independent survival benefit found in penetrating patients (hazard ratio, 1.16; 95% confidence interval, 0.4-3.1; p = 0.78). CONCLUSION: A survival benefit associated with prehospital plasma at 24 hours and 28 days exists primarily in blunt injured patients with no benefit shown in penetrating trauma patients. No detrimental effects attributable to plasma are demonstrated in penetrating injury. These results have important relevance to military and civilian trauma systems. LEVEL OF EVIDENCE: Therapeutic, I.


Assuntos
Transfusão de Componentes Sanguíneos/métodos , Primeiros Socorros/métodos , Plasma , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/terapia , Adulto , Fatores Etários , Estudos de Coortes , Soluções Cristaloides/administração & dosagem , Conjuntos de Dados como Assunto , Feminino , Escala de Coma de Glasgow , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/diagnóstico , Ferimentos Penetrantes/mortalidade
14.
Platelets ; 31(1): 94-102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30810451

RESUMO

The aim of this study was to investigate the association between nadir platelet count and acute kidney injury (AKI) or 28-day all-cause mortality induced by hemorrhagic shock (HS), and to determine the cutoff value of nadir platelet count in HS clinical practice. This retrospective study included hospitalized patients enrolled in a tertiary-care teaching hospital from January 1, 2010 to December 31, 2015. Clinical data from HS admitted to the intensive care unit (ICU) were evaluated. Nadir platelet count was defined as the lowest values in the first 48 h. Multivariate logistic regression and Cox proportional hazards regression were used to assess the correlation between nadir platelet count and AKI or 28-day all-cause mortality induced by HS, respectively; the area under receiver operating characteristic (AU-ROC) and Youde's index were used to determine the optimal cutoff value of nadir platelet count. Kaplan-Meier's method and log-rank test were assessed for the 28-day all-cause mortality in AKI and non-AKI groups. Of 1589 patients screened, 84 patients (mean age,37.1 years; 58 males) were included in the primary analysis in which 30 patients with AKI. Multiple logistic results indicated that nadir platelet count was a risk factor of AKI (OR = 0.71,95% confidence interval [CI] 0.54-0.93, P < 0.05). Cox regression analysis revealed that nadir platelet count was independent risk factors for 28-day all-cause mortality (Hazard ratios [HR]0.89,95%CI 0.76-0.99, P < 0.05). Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in patients with AKI than non-AKI (P < 0.001).These results suggest that nadir platelet count in the first 48 h is a new biomarker for AKI and 28-day all-cause mortality induced by HS. Moreover, the risk for AKI and 28-day all-cause mortality in HS patients decreased by 29% and 11%, respectively, for every 10 × 109/L increase in platelet count. Additional studies are needed to investigate whether elevation of nadir platelet count reduces the risk in different genders.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Biomarcadores , Contagem de Plaquetas , Choque Hemorrágico/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Causas de Morte , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Adulto Jovem
15.
Transfus Clin Biol ; 26(4): 198-201, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31645305

RESUMO

Massive hemorrhage remains the main cause of preventable death in combat settings and is also the main cause of year loss in developing countries. The management of these patients relies on blood transfusion and surgery. Time is a key factor, related to survival. Recent events highlight the need to be more efficient in the transfusion supply during terror attacks or mass casualties in civilian settings. Blood components therapy with a 1:1:1 ratio is associated with a decrease of mortality but encounters many logistic issues in those circumstances. Whole blood provides in one bag all the blood components in physiologic proportions with minimal amount of additive solution. Whole blood has been implemented in military as well as civilian settings worldwide. However, direct comparisons with component therapy in prospective clinical trials are scarce. Here we present the rational and the design of the T-STORHM (Trauma-Sang TOtal dans les Hémorragies Massives) trial. This prospective randomized multicentric clinical trial will test low titer group O whole blood to components therapy in the in-hospital management of trauma patients with massive hemorrhage. Sample size calculation, primary and secondary endpoints as trial blood products preparations are discussed. The trial is expected to start in 2019 in 6 civilians and military trauma centers. The French Military Health Service is promoting the study in collaboration with the French transfusion public service (Établissementfrançaisdusang).


Assuntos
Estudos de Equivalência como Asunto , Hemorragia/terapia , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Sistema ABO de Grupos Sanguíneos , Transfusão de Componentes Sanguíneos , Transfusão de Sangue , Determinação de Ponto Final , França , Hemorragia/etiologia , Hemorragia/mortalidade , Hospitais Militares , Humanos , Pacientes Internados , Procedimentos de Redução de Leucócitos , Seleção de Pacientes , Estudos Prospectivos , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Centros de Traumatologia , Ferimentos e Lesões/complicações
16.
Am J Surg ; 218(6): 1169-1174, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31540684

RESUMO

INTRODUCTION: The aim of our study was to evaluate if pre-hospital shock index (SI) can predict transfusion requirements, resource utilization and mortality in trauma patients. METHODS: We performed a 2-year analysis of all adult trauma patients in the TQIP database. Shock index was calculated by dividing heart-rate over systolic blood pressure. Patients were divided into two groups pre-hospital SI ≤ 1 and prehospital SI > 1. Regression and ROC curve analyses were performed. RESULTS: 144951 patients were included in the study. Mean age was 45 ±â€¯34 years, 61% were male, 84.7% had blunt injuries and median ISS was 13 [9-17]. Overall 9.1% of the patients had a pre-hospital SI > 1. Patients with pre-hospital SI > 1 had higher likelihood of requiring massive transfusion (25% vs. 0.012%, p < 0.02), interventional-radiology intervention (6.2% vs. 1%,p < 0.001) or operative intervention (14.7% vs. 2%,p < 0.001) compared to SI ≤ 1. Similarly, patients with SI > 1 had higher mortality (12.3% vs. 5.2%, p < 0.001) and were more likely to be discharged to Rehab/SNF (34.6% vs. 21.4%, p < 0.001). CONCLUSIONS: Pre-hospital SI predicts trauma-center resource utilization and can guide patient triage and trauma resource recruitment.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Ferimentos e Lesões/complicações , Adulto , Serviços Médicos de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Triagem , Sinais Vitais
17.
J Trauma Acute Care Surg ; 87(5): 1133-1139, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31389922

RESUMO

BACKGROUND: Trauma is a leading cause of death, and traumatic brain injury is one of the hallmark injuries of current military conflicts. Valproic acid (VPA) administration in high doses (300-400 mg/kg) improves survival in lethal trauma models, but effectiveness of lower doses on survival is unknown. This information is essential for properly designing the upcoming clinical trials. We, therefore, performed the current study to determine the lowest dose at which VPA administration improves survival in a model of lethal injuries. METHODS: Swine were subjected to traumatic brain injury (10-mm cortical impact), 40% blood volume hemorrhage, and multiple trauma (femur fracture, rectus crush, and Grade V liver laceration). After 1 hour of shock, animals were randomized (n = 6/group) to four groups: normal saline (NS) resuscitation; or NS with VPA doses of 150 mg/kg (VPA 150) or 100 mg/kg (VPA 100) administered over 3 hours or 100 mg/kg over 2 hours (VPA 100 over 2 hours). Three hours after shock, packed red blood cells were given, and animals were monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. RESULTS: Without resuscitation, all of the injured animals died within 5 hours. Similar survival rates were observed in the NS (17%) and VPA 100 (0%) resuscitation groups. Survival rates in the 100-mg/kg VPA groups were significantly (p < 0.05) better when it was given over 2 hours (67%) compared to 3 hours (0%). 83% of the animals in the VPA 150 group survived, which was significantly higher than the NS and VPA 100 over 3 hours groups (p < 0.05). CONCLUSION: A single dose of VPA (150 mg/kg) significantly improves survival in an otherwise lethal model of multiple injuries. This is a much lower dose than previously shown to have a survival benefit and matches the dose that is tolerated by healthy human subjects with minimal adverse effects. LEVEL OF EVIDENCE: Therapeutic, level V.


Assuntos
Lesões Encefálicas Traumáticas/terapia , Traumatismo Múltiplo/terapia , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ácido Valproico/administração & dosagem , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Transfusão de Eritrócitos , Feminino , Humanos , Traumatismo Múltiplo/complicações , Traumatismo Múltiplo/mortalidade , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Taxa de Sobrevida , Sus scrofa
18.
Transfus Clin Biol ; 26(3): 174-179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31262629

RESUMO

Whole blood, that is blood that is not manufactured into its component red blood cells (RBC) plasma, and platelets (PLT) units, was the mainstay of transfusion for many years until it was discovered that the component parts of a blood donation could be stored under different conditions thereby optimizing the storage length of each product. The use of low anti-A and -B titer group O whole blood (LTOWB) has recently been rediscovered for use in massively bleeding trauma patients. Whole blood has several advantages over conventional component therapy for these patients, including simplifying the logistics of the resuscitation, being more concentrated than whole blood that is reconstituted from conventional components, and providing cold-stored PLTs, amongst other benefits. While randomized controlled trials to determine the efficacy of using LTOWB in the resuscitation of massively bleeding trauma patients are currently underway, retrospective data has shown that massively bleeding recipients of LTOWB with traumatic injury do not have worse outcomes compared to patients who received conventional components and, in some cases, recipients of LTOWB have more favourable outcomes. This paper will describe some of the advantages of using LTOWB and will discuss the emerging evidence for its use in massively bleeding patients.


Assuntos
Transfusão de Sangue/métodos , Hemorragia/terapia , Doença Aguda , Anticoagulantes/efeitos adversos , Tipagem e Reações Cruzadas Sanguíneas/métodos , Preservação de Sangue/métodos , Substitutos Sanguíneos/efeitos adversos , Substitutos Sanguíneos/uso terapêutico , Citratos/efeitos adversos , Soluções Cristaloides/efeitos adversos , Soluções Cristaloides/uso terapêutico , Serviços Médicos de Emergência , Glucose/efeitos adversos , Hemorragia/etiologia , Humanos , Procedimentos de Redução de Leucócitos , Ressuscitação , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Reação Transfusional/prevenção & controle , Resultado do Tratamento , Ferimentos e Lesões/complicações
19.
J Surg Res ; 244: 69-76, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31279996

RESUMO

BACKGROUND: Acute hemorrhage-induced excessive excitation of sympathetic-adrenal-medullary system (SAS) leads to gut hypoperfusion and barrier dysfunction, which is a critical event during hemorrhagic shock-induced multiple organ injury. Stellate ganglion blockade (SGB) has been widely used for suppression of sympathetic-adrenal-medullary system in the clinical practice. However, whether SGB improves intestinal barrier function after hemorrhagic shock remains unclear. Here, we hypothesized that the implementation of SGB restores intestinal barrier function and reduces gut injury. MATERIALS AND METHODS: Male rats received the SGB pretreatment and underwent hemorrhagic shock followed by resuscitation. The 96-h survival rate, intestinal permeability and morphology, D-lactic acid concentration and diamine oxidase activity in plasma, and expressions of F-actin, Claudin-1, and E-cadherin in intestinal tissues were observed. RESULTS: Pretreatment with SGB significantly enhances the 96-h survival rate in rats subjected to hemorrhagic shock (from 8.3% to 66.7%). Hemorrhagic shock reduced the coverage scale of intestinal mucus and intestinal villus width and height, enhanced the intestinal permeability to fluorescein isothiocyanate-dextran 4 and D-lactic acid concentration in plasma, and decreased the expressions of F-actin, Claudin-1, and E-Cadherin in intestinal tissue. These hemorrhagic shock-induced adverse effects were abolished by SGB treatment. CONCLUSIONS: SGB treatment has a beneficial effect during hemorrhagic shock, which is associated with the improvement of intestine barrier function. SGB may be considered as a new therapeutic strategy for treatment of hemorrhagic shock.


Assuntos
Enteropatias/prevenção & controle , Mucosa Intestinal/patologia , Bloqueio Nervoso/métodos , Choque Hemorrágico/terapia , Gânglio Estrelado/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Animais , Modelos Animais de Doenças , Enteropatias/etiologia , Enteropatias/patologia , Mucosa Intestinal/inervação , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ressuscitação , Ropivacaina/administração & dosagem , Choque Hemorrágico/complicações , Choque Hemorrágico/mortalidade , Organismos Livres de Patógenos Específicos , Taxa de Sobrevida , Resultado do Tratamento
20.
J Trauma Acute Care Surg ; 87(3): 606-613, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31162330

RESUMO

BACKGROUND: Noncompressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 4 hours 0.9% NaCl/ALM "drip" in a rat model of uncontrolled hemorrhagic shock. METHODS: Male Sprague-Dawley rats (425 ± 8 g) were anesthetized and randomly assigned to saline controls (n = 10) or ALM therapy (n = 10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15 minutes, a single intravenous bolus of 3% NaCl ± ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl ± ALM stabilization "drip" (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-clamped and stored at -80°C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of amp-k, mtCO3, PGC-1α, and sirt-1 genes were determined. RESULTS: Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 ± 4.5 hours, and ALM animals, 72 ± 0 hours (p < 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of amp-k, PGC-1α, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls (p < 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1, and mtCO3 gene expression in liver was significantly 29-41% lower in the ALM group compared with controls, and PGC-1α was 75% lower. CONCLUSION: Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1α, sirt-1, and mtCO3 to presumably "boost" mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.


Assuntos
Adenosina/uso terapêutico , Hidratação/métodos , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Choque Hemorrágico/terapia , Adenosina/administração & dosagem , Animais , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Choque Hemorrágico/mortalidade , Fatores de Tempo
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