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1.
Nat Commun ; 14(1): 2560, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37137915

RESUMO

Pulmonary fibrosis results from dysregulated lung repair and involves multiple cell types. The role of endothelial cells (EC) in lung fibrosis is poorly understood. Using single cell RNA-sequencing we identified endothelial transcription factors involved in lung fibrogenesis, including FOXF1, SMAD6, ETV6 and LEF1. Focusing on FOXF1, we found that FOXF1 is decreased in EC within human idiopathic pulmonary fibrosis (IPF) and mouse bleomycin-injured lungs. Endothelial-specific Foxf1 inhibition in mice increased collagen depositions, promoted lung inflammation, and impaired R-Ras signaling. In vitro, FOXF1-deficient EC increased proliferation, invasion and activation of human lung fibroblasts, and stimulated macrophage migration by secreting IL-6, TNFα, CCL2 and CXCL1. FOXF1 inhibited TNFα and CCL2 through direct transcriptional activation of Rras gene promoter. Transgenic overexpression or endothelial-specific nanoparticle delivery of Foxf1 cDNA decreased pulmonary fibrosis in bleomycin-injured mice. Nanoparticle delivery of FOXF1 cDNA can be considered for future therapies in IPF.


Assuntos
Células Endoteliais , Fibrose Pulmonar Idiopática , Camundongos , Animais , Humanos , Células Endoteliais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , DNA Complementar/metabolismo , Pulmão/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Bleomicina/toxicidade , Fatores de Transcrição Forkhead/metabolismo , Fibroblastos/metabolismo
2.
Curr Opin Organ Transplant ; 28(2): 71-75, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409266

RESUMO

PURPOSE OF REVIEW: This review is intended to provide an update on the logistics, technique, and outcomes associated with normothermic regional perfusion (NRP), as well as provide a discussion of the associated ethical issues. RECENT FINDINGS: There has been renewed interest in utilizing NRP to increase quality and availability of organs from donation after circulatory death (DCD) donors. Our institution has increasing experience with thoraco-abdominal NRP (TA-NRP) in controlled DCD donors (cDCD), whereas abdominal NRP (A-NRP) has been used with success in both cDCD and uncontrolled DCD (uDCD). There is increasing evidence that NRP can be conducted in a practical and cost-efficient manner, and that the organ yield may be of better quality than standard direct procurement and perfusion (DPP). SUMMARY: NRP is increasingly successful and will likely prove to be a superior method for cDCD recovery. However, before TA-NRP can be widely accepted the ethical debate surrounding this technique must be settled. VIDEO ABSTRACT: http://links.lww.com/COOT/A11.


Assuntos
Preservação de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Preservação de Órgãos/métodos , Doadores de Tecidos , Perfusão/métodos , Morte , Sobrevivência de Enxerto
3.
J Heart Lung Transplant ; 42(7): 859-867, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36435685

RESUMO

INTRODUCTION: Right ventricular failure (RVF) is a major cause of mortality in pulmonary hypertension (PH). Mechanical circulatory support holds promise for patients with medically refractory PH, but there are no clinical devices for long-term right ventricular (RV) support. Investigations into optimal device parameters and circuit configurations for PH-induced RVF (PH-RVF) are needed. METHODS: Eleven sheep underwent previously published chronic PH model. We then evaluated a low-profile, ventricular assist device (VAD)-quality pump combined with a novel low-resistance membrane oxygenator (Pulmonary Assist Device, PAD) under one of four central cannulation strategies: right atrium-to-left atrium (RA-LA, N = 3), RA-to-pulmonary artery (RA-PA, N=3), pumpless pulmonary artery-to-left atrium (PA-LA, N = 2), and RA-to-ascending aorta (RA-Ao, N = 3). Acute-on-chronic RVF (AoC RVF) was induced, and mechanical support was provided for up to 6 hours at blood flow rates of 1 to 3 liter/min. Circuit parameters, physiologic, hemodynamic, and echocardiography data were collected. RESULTS: The RA-LA configuration achieved blood flow of 3 liter/min. Meanwhile, RA-PA and RA-Ao faced challenges maintaining 3 liter/min of flow due to higher circuit afterload. Pumpless PA-LA was flow-limited due to anatomical limitations inherent to this animal model. RA-LA and RA-Ao demonstrated serial RV unloading with increasing circuit flow, while RA-PA did not. RA-LA also improved left ventricular (LV) and septal geometry by echocardiographic assessment and had the lowest inotropic dependence. CONCLUSION: RA-LA and RA-Ao configurations unload the RV, while RA-LA also lowers pump speed and inotropic requirements, and improves LV mechanics. RA-PA provide inferior support for PH-RVF, while an alternate animal model is needed to evaluate PA-LA.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca , Hipertensão Pulmonar , Animais , Ovinos , Hipertensão Pulmonar/terapia , Ventrículos do Coração , Átrios do Coração , Hemodinâmica
4.
J Heart Lung Transplant ; 42(3): 335-344, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36456408

RESUMO

BACKGROUND: Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support and recovery that could expand the pool of donor lungs suitable for transplantation. The objective of this study was to establish and validate a standardized, reproducible, and broadly applicable technique for performing xenogeneic XC to support and recover injured human donor lungs ex vivo. METHODS: Human donor lungs (n = 9) declined for transplantation were procured, cannulated, and subjected to 24 hours of xenogeneic XC with anesthetized xeno-support swine (Yorkshire/Landrace) treated with standard immunosuppression (methylprednisolone, mycophenolate mofetil, tacrolimus) and complement-depleting cobra venom factor. Standard lung-protective perfusion and ventilation strategies, including periodic lung recruitment maneuvers, were used throughout xenogeneic XC. Every 6 hours, ex vivo donor lung function (gas exchange, compliance, airway pressures, pulmonary vascular dynamics, lung weight) was evaluated. At the experimental endpoint, comprehensive assessments of the lungs were performed by bronchoscopy, histology, and electron microscopy. Student's t-test and 1-way analysis of variance with Dunnett's post-hoc test was performed, and p < 0.05 was considered significant. RESULTS: After 24 hours of xenogeneic XC, gas exchange (PaO2/FiO2) increased by 158% (endpoint: 364 ± 142 mm Hg; p = 0.06), and dynamic compliance increased by 127% (endpoint: 46 ± 20 ml/cmH2O; p = 0.04). Airway pressures, pulmonary vascular pressures, and lung weight remained stable (p > 0.05) and within normal ranges. Over 24 hours of xenogeneic XC, gross and microscopic lung architecture were preserved: airway bronchoscopy and parenchymal histomorphology appeared normal, with intact blood-gas barrier. CONCLUSIONS: Xenogeneic cross-circulation is a robust method for ex vivo support, evaluation, and improvement of injured human donor lungs declined for transplantation.


Assuntos
Transplante de Pulmão , Humanos , Suínos , Animais , Transplante de Pulmão/métodos , Pulmão , Perfusão/métodos , Doadores de Tecidos , Preservação de Órgãos/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-36270862

RESUMO

OBJECTIVES: Refractory hypoxemia can occur in patients with acute respiratory distress syndrome from COVID-19 despite support with venovenous (VV) extracorporeal membrane oxygenation (ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit. METHODS: We performed a retrospective cohort study of all patients with COVID-19-related acute respiratory distress syndrome who received VV-ECMO with an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020, and March 1, 2022. We report demographic characteristics and clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and before removal of the circuit in parallel, and outcomes. RESULTS: Of 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median duration of ECMO was 40.0 days (interquartile range, 31.6-53.1 days), of which 19.0 days (interquartile range, 13.0-33.0 days) were spent with a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge. CONCLUSIONS: In select patients, the additional use of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes.

7.
J Cyst Fibros ; 21(6): 1027-1035, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35525782

RESUMO

BACKGROUND: Manifestations of cystic fibrosis, although well-characterized in the proximal airways, are understudied in the distal lung. Characterization of the cystic fibrosis lung 'matrisome' (matrix proteome) has not been previously described, and could help identify biomarkers and inform therapeutic strategies. METHODS: We performed liquid chromatography-mass spectrometry, gene ontology analysis, and multi-modal imaging, including histology, immunofluorescence, and electron microscopy for a comprehensive evaluation of distal human lung extracellular matrix (matrix) structure and composition in end-stage cystic fibrosis. RESULTS: Quantitative proteomic profiling identified sixty-eight (68) matrix constituents with significantly altered expression in end-stage cystic fibrosis. Over 90% of significantly different matrix peptides detected, including structural and basement membrane proteins, were expressed at lower levels in cystic fibrosis. However, the total abundance of matrix in cystic fibrosis lungs was not significantly different from control lungs, suggesting that cystic fibrosis leads to loss of diversity among lung matrix proteins rather than an absolute loss of matrix. Visualization of distal lung matrix via immunofluorescence and electron microscopy revealed pathological remodeling of distal lung tissue architecture and loss of alveolar basement membrane, consistent with significantly altered pathways identified by gene ontology analysis. CONCLUSIONS: Dysregulation of matrix organization and aberrant wound healing pathways are associated with loss of matrix protein diversity and obliteration of distal lung tissue structure in end-stage cystic fibrosis. While many therapeutics aim to functionally restore defective cystic fibrosis transmembrane conductance regulator (CFTR), drugs that target dysregulated matrix pathways may serve as adjunct interventions to support lung recovery.


Assuntos
Fibrose Cística , Humanos , Fibrose Cística/terapia , Proteômica , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Pulmão/metabolismo
8.
ASAIO J ; 67(1): e44-e48, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346995

RESUMO

Pulmonary hypertension (PH) is a progressive disease that leads to cardiopulmonary dysfunction and right heart failure from pressure and volume overloading of the right ventricle (RV). Mechanical cardiopulmonary support has theoretical promise as a bridge to organ transplant or destination therapy for these patients. Solving the challenges of mechanical cardiopulmonary support for PH and RV failure requires its testing in a physiologically relevant animal model. Previous PH models in large animals have used pulmonary bead embolization, which elicits unpredictable inflammatory responses and has a high mortality rate. We describe a step-by-step guide for inducing pulmonary hypertension and right ventricular hypertrophy (PH-RVH) in sheep by left pulmonary artery (LPA) ligation combined with progressive main pulmonary artery (MPA) banding. This approach provides a controlled method to regulate RV afterload as tolerated by the animal to achieve PH-RVH, while reducing acute mortality. This animal model can facilitate evaluation of mechanical support devices for PH and RV failure.


Assuntos
Modelos Animais de Doenças , Hipertensão Pulmonar , Hipertrofia Ventricular Direita , Disfunção Ventricular Direita , Animais , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/fisiopatologia , Ligadura , Masculino , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Ovinos , Disfunção Ventricular Direita/fisiopatologia
9.
ASAIO J ; 67(9): 995-999, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315654

RESUMO

Extracorporeal life support (ECLS) is a resource-intensive technology. Disposable components are modifiable through device selection. Cost analysis tools are needed to inform cost-conscious device selection. We generated a disposable cost analysis to forecast estimated costs of device disposables that included an assumption table, net present value (NPV) analysis, and sensitivity analysis to examine device disposable costs over 5 years with different case volumes and device mixes. To demonstrate the function of the analysis, we included four device options using the following assumptions: 100 cases in year 1, 2.5% case growth rate, 10% discount rate, and $5,000 incremental cost (Device 4 only). Using estimated device costs of $3,000, $12,000, $13,000, and $20,000 and device mix percentages of 65%, 8%, 25%, and 2% for Device 1, 2, 3, and 4, respectively, the 5 year unadjusted and NPV of disposable device costs were $3,691,000 and $2,765,000, respectively. The sensitivity analysis incorporated six separate models with different device mix percentages. The highest and lowest estimated costs were found in Model F (75% Device 3 and 25% Device 4; NPV = $6,64,400) and Model B (100% Device 1; NPV = 1,246,000) respectively. Extracorporeal life support programs may apply this disposable cost analysis tool to reduce programmatic costs.


Assuntos
Oxigenação por Membrana Extracorpórea , Análise Custo-Benefício
10.
Crit Care Med ; 48(12): e1226-e1231, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33031151

RESUMO

OBJECTIVES: Venovenous extracorporeal carbon dioxide removal may be lifesaving in the setting of status asthmaticus. DESIGN: Retrospective review. SETTING: Medical ICU. PATIENTS: Twenty-six adult patients with status asthmaticus treated with venovenous extracorporeal carbon dioxide removal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data and characteristics of current and prior asthma treatments were obtained from the electronic medical record. Mechanical ventilator settings, arterial blood gases, vital signs, and use of vasopressors were collected from the closest time prior to cannulation and 24 hours after initiation of extracorporeal carbon dioxide removal. Extracorporeal carbon dioxide removal settings, including blood flow and sweep gas flow, were collected at 24 hours after initiation of extracorporeal carbon dioxide removal. Outcome measures included rates of survival to hospital discharge, ICU and hospital lengths of stay, duration of invasive mechanical ventilation and extracorporeal carbon dioxide removal support, and complications during extracorporeal carbon dioxide removal. Following the initiation of extracorporeal carbon dioxide removal, blood gas values were significantly improved at 24 hours, as were peak airway pressures, intrinsic positive end-expiratory pressure, and use of vasopressors. Survival to hospital discharge was 100%. Twenty patients (76.9%) were successfully extubated while receiving extracorporeal carbon dioxide removal support; none required reintubation. The most common complication was cannula-associated deep venous thrombosis (six patients, 23.1%). Four patients (15.4%) experienced bleeding that required a transfusion of packed RBCs. CONCLUSIONS: In the largest series to date, use of venovenous extracorporeal carbon dioxide removal in patients with status asthmaticus can provide a lifesaving means of support until the resolution of the exacerbation, with an acceptably low rate of complications. Early extubation in select patients receiving extracorporeal carbon dioxide removal is safe and feasible and avoids the deleterious effects of positive-pressure mechanical ventilation in this patient population.


Assuntos
Dióxido de Carbono/sangue , Oxigenação por Membrana Extracorpórea/métodos , Estado Asmático/terapia , Adulto , Feminino , Humanos , Masculino , Respiração Artificial , Estudos Retrospectivos , Estado Asmático/complicações , Estado Asmático/patologia , Estado Asmático/fisiopatologia , Resultado do Tratamento
11.
Am J Crit Care ; 29(4): 262-269, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32607573

RESUMO

BACKGROUND: Despite the growing use of extracorporeal membrane oxygenation (ECMO) in intensive care units (ICUs), no standardized ECMO training pathways are available for ECMO-naive critical care nurses. OBJECTIVES: To evaluate a critical care nurse ECMO curriculum that may be reproducible across institutions. METHODS: An ECMO curriculum consisting of a basic safety course and an advanced user course was designed for critical care nurses. Courses incorporated didactic and simulation components, written knowledge examinations, and electronic modules. Differences in examination scores before and after each course for the overall cohort and for participants from each ICU type were analyzed with t tests or nonparametric equality-of-medians tests. Differences in postcourse scores across ICU types were examined with multiple linear regression. RESULTS: Critical care nurses new to ECMO (n = 301) from various ICU types participated in the basic safety course; 107 nurses also participated in the advanced user course. Examination scores improved after completion of both courses for overall cohorts (P < .001 in all analyses). Median (interquartile range) individual score improvements were 23.1% (15.4%-38.5%) for the basic safety course and 8.4% (0%-16.7%) for the advanced user course. Postcourse written examination scores stratified by ICU type, compared with the medical ICU/cardiovascular ICU group (reference group), differed only in the neurovascular ICU group for the basic safety course (percent score difference, -3.0; 95% CI, -5.3 to -0.8; P = .01). CONCLUSIONS: Implementation of an ECMO curriculum for a high volume of critical care nurses is feasible and effective.


Assuntos
Enfermagem de Cuidados Críticos/educação , Oxigenação por Membrana Extracorpórea/métodos , Unidades de Terapia Intensiva/organização & administração , Currículo , Avaliação Educacional , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/normas , Humanos , Unidades de Terapia Intensiva/normas
12.
Nat Med ; 26(7): 1102-1113, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32661401

RESUMO

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.


Assuntos
Lesão Pulmonar Aguda/terapia , Transplante de Pulmão/métodos , Pulmão/irrigação sanguínea , Preservação de Órgãos/métodos , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/fisiopatologia , Animais , Circulação Extracorpórea/métodos , Humanos , Pulmão/fisiopatologia , Perfusão/métodos , Suínos , Doadores de Tecidos
13.
ATS Sch ; 1(4): 406-415, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-33870310

RESUMO

Background: Despite the rapid integration of extracorporeal membrane oxygenation (ECMO) into intensive care units over the past decade, established programs for training critical care clinicians to provide ECMO are lacking.Objective: To evaluate the development and implementation of a multidisciplinary ECMO training program for the rapid deployment of ECMO training for a high volume of critical care clinicians.Methods: We performed a prospective cohort study examining a program for rapid training of multiple disciplines of critical care clinicians to deliver ECMO during the implementation of ECMO services across the intensive care units of an academic tertiary care center between October 2018 and January 2019. The multidisciplinary ECMO training program included didactic and simulation-based teaching and emphasized new, universal clinical protocols to improve consistency of care across the institution. Pre- and post-program written examinations evaluated knowledge acquisition, and an electronically distributed program evaluation assessed perceptions of content and delivery.Results: Among the 97 clinicians who completed the program, 49 (51%) were physicians and 48 (49%) were advanced practice providers from the departments of surgery (n = 42), medicine (n = 29), and anesthesia (n = 26). There was a significant difference in knowledge about ECMO between the pre- and post-program examination score (median [interquartile range] 70% [60-80%] vs. 90% [80-90%], respectively, P < 0.001). The median (interquartile range) individual gain from pre- to post-program score was 20% (10-30%). The program was perceived as useful and applicable to safe care.Conclusion: Rapid deployment of a multidisciplinary ECMO training program across a large academic center was feasible, achieved knowledge acquisition, and was positively perceived.

14.
ASAIO J ; 66(6): 652-656, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31425269

RESUMO

Patients receiving extracorporeal membrane oxygenation (ECMO) often require prolonged mechanical ventilation. Providers may be reluctant to perform tracheostomies on patients during ECMO due to their tenuous clinical status and systemic anticoagulation. We report our experience with performing open and percutaneous tracheostomies on patients supported on ECMO from August 2009 to December 2017. Of the 127 patients who underwent tracheostomy during ECMO support, the median age was 42 years (interquartile range [IQR], 29-54), 99 (78%) patients had venovenous (VV) cannulation, 22 (17%) patients had venoarterial (VA) cannulation, and six (5%) patients had hybrid configurations. Percutaneous tracheostomy was performed in 110 (87%) patients. Median-activated partial thromboplastin time (aPTT) at the time of tracheostomy was 47.5 seconds (IQR, 41-57.6 seconds). The median time from ECMO initiation to tracheostomy was 7 days (IQR, 4-11 days). A total of 55 patients (43%) received packed red blood cell (pRBC) transfusions within 48 hours after tracheostomy with a median transfusion of 2 units (IQR, 1-3). There was no procedural mortality. Overall, 88 (69%) patients survived to decannulation and 74 (58%) survived to hospital discharge. Our experience with the largest published series of tracheostomies during ECMO demonstrates that excellent outcomes can be achieved without significant morbidity.


Assuntos
Oxigenação por Membrana Extracorpórea , Respiração Artificial/métodos , Traqueostomia , Adulto , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/mortalidade , Estudos Retrospectivos , Traqueostomia/efeitos adversos , Traqueostomia/mortalidade
15.
Ann Thorac Surg ; 109(4): 1047-1053, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31863760

RESUMO

BACKGROUND: Single-site, dual-lumen venovenous extracorporeal membrane oxygenation ECMO) facilitates mobilization, reduces recirculation, and mitigates insertion and infectious risks of an additional access site. This study reports the experience with a bicaval dual-lumen cannula that comprises a robust physical design allowing for easy and safe cannulation, precise positioning and monitoring, and appropriate physiologic support for patients with acute respiratory failure. METHODS: Statistical analysis was performed from data gathered retrospectively from the electronic medical records of 20 adult patients who were cannulated for ECMO with this bicaval dual-lumen cannula from August 2018 through May 2019. RESULTS: Gas exchange and blood flow were optimized in all patients after cannulation (median pH, 7.42 [interquartile range {IQR}, 7.39, 7.44], ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, 186.5 [Pao2:Fio2, 116.5, 247.0]; pump flow, 3.9 L/min [IQR, 3.1, 4.3]). Eleven patients (55%) were able to be freed from mechanical ventilation after cannulation, 9 (45%) patients underwent a tracheostomy procedure while undergoing ECMO, and no patients required reintubation. No morbidity or mortality was related to the cannulation strategy or the catheter. Two patients required cannula repositioning. Survival to decannulation was 90%, and survival to hospital discharge was 80%. CONCLUSIONS: The bicaval dual-lumen cannula maintains the advantages of upper body single-site configuration to provide the adjunctive respiratory support necessary to facilitate awakening and rehabilitation while minimizing the use of invasive mechanical ventilation. This cannula introduces design qualities that may offer advantages for acute respiratory failure requiring venovenous ECMO.


Assuntos
Cânula , Oxigenação por Membrana Extracorpórea/instrumentação , Insuficiência Respiratória/terapia , Doença Aguda , Adulto , Cateterismo , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos
16.
J Thorac Cardiovasc Surg ; 159(4): 1640-1653.e18, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31761338

RESUMO

OBJECTIVES: Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine. METHODS: A swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorporeal lungs and recipient swine. Lungs were ventilated and perfused in a normothermic chamber for 4 days. Longitudinal analyses of extracorporeal lungs (ie, functional assessments, multiscale imaging, cytokine quantification, and cellular assays) and recipient swine (eg, vital signs and blood and tissue analyses) were performed. RESULTS: Throughout 4 days of normothermic support, extracorporeal lung function was maintained (arterial oxygen tension/inspired oxygen fraction >400 mm Hg; compliance >20 mL/cm H2O), and recipient swine were hemodynamically stable (lactate <3 mmol/L; pH, 7.42 ± 0.05). Radiography revealed well-aerated lower lobes and consolidation in upper lobes of extracorporeal lungs, and bronchoscopy showed healthy airways without edema or secretions. In bronchoalveolar lavage fluid, granulocyte-macrophage colony-stimulating factor, interleukin (IL) 4, IL-6, and IL-10 levels increased less than 6-fold, whereas interferon gamma, IL-1α, IL-1ß, IL-1ra, IL-2, IL-8, IL-12, IL-18, and tumor necrosis factor alpha levels decreased from baseline to day 4. Histologic evaluations confirmed an intact blood-gas barrier and outstanding preservation of airway and alveolar architecture. Cellular viability and metabolism in extracorporeal lungs were confirmed after 4 days. CONCLUSIONS: We demonstrate feasibility of normothermic maintenance of extracorporeal lungs for 4 days by cross-circulation with conscious swine. Cross-circulation approaches could support the recovery of damaged lungs and enable organ bioengineering to improve transplant outcomes.


Assuntos
Circulação Extracorpórea/métodos , Transplante de Pulmão/métodos , Preservação de Órgãos/métodos , Animais , Modelos Animais , Suínos , Fatores de Tempo
17.
Ann Thorac Surg ; 107(5): 1456-1463, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30790550

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has become a critical component of caring for patients with end-stage lung disease. This study examined outcomes of patients who received ECMO as a BTT. METHODS: Statistical analysis was performed on data gathered retrospectively from the electronic medical records of adult patients who received ECMO as BTT at Columbia University Medical Center from April 2009 through July 2018. RESULTS: A total of 121 adult patients were placed on ECMO as BTT, and 70 patients (59%) were successfully bridged to lung transplantation. Simplified Acute Physiology Score II, unplanned endotracheal intubation, renal replacement therapy, and cerebrovascular accident were identified as independent predictors of unsuccessful BTT. Ambulation was the only independent predictor of successful BTT (odds ratio, 7.579; 95% confidence interval, 2.158 to 26.615; p = 0.002). Among the 64 patients (91%) who survived to hospital discharge, survival was 88% at 1 year and 83% at 3 years. Propensity matching between BTT and non-BTT lung transplant recipients did not show a significant difference in survival (log-rank = 0.53) despite significant differences in the lung allocation score (median, 92.2 [interquartile range, 89.0 to 94.2] vs 49.6 [interquartile range, 40.6 to 72.3], p < 0.01). CONCLUSIONS: ECMO can be used successfully to bridge patients with end-stage lung disease to lung transplantation. When implemented by an experienced team with adherence to stringent protocols and patient selection, outcomes in BTT patients were comparable to patients who did not receive pretransplant support.


Assuntos
Oxigenação por Membrana Extracorpórea , Pneumopatias/terapia , Transplante de Pulmão , Adulto , Idoso , Feminino , Humanos , Pneumopatias/etiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
J Thorac Cardiovasc Surg ; 157(4): 1696-1706, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30655061

RESUMO

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is used to provide support for patients with cardiopulmonary failure. Best available medical management often fails in these patients and referring hospitals have no further recourse for escalating care apart from transfer to a tertiary facility. In severely unstable patients, the only option might be to use ECMO to facilitate safe transport. This study aimed to examine the characteristics and outcomes of patients transported while receiving ECMO. METHODS: Statistical analysis was performed on data gathered retrospectively from the electronic medical records of adult patients transported while receiving ECMO to Columbia University Medical Center between January 1, 2008, and December 31, 2017. RESULTS: Two hundred sixty five adult patients were safely transported while receiving ECMO with no transport-related complications that adversely affected outcomes. Transport distance ranged from 0.2 to 7084 miles with a median distance of 16.9 miles. One hundred eighty-three (69%) received on veno-venous, 72 (27%) veno-arterial, and 10 (3.8%) veno-venous arterial or veno-arterial venous configurations. Two hundred ten (79%) cannulations were performed at our institution at the referring hospital. Sixty-four percent of patients transported while receiving ECMO survived to hospital discharge. CONCLUSIONS: Interfacility transport during ECMO was shown to be safe and effective with minimal complications and favorable outcomes when performed at an experienced referral center using stringently applied protocols.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Transferência de Pacientes , Insuficiência Respiratória/terapia , Adulto , Registros Eletrônicos de Saúde , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Alta do Paciente , Segurança do Paciente , Encaminhamento e Consulta , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Transporte de Pacientes , Resultado do Tratamento
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