Extracorporeal Lung Research Articles

Bivalirudin anticoagulation for an infant with heparin resistance on ECMO: A case report.

Extracorporeal membrane oxygenation (ECMO) technology in the field of intense care for children in China has developed rapidly, and it has become a key strategy for the rescue treatment of critically ill children and an advanced extracorporeal life support system. Compared with adults and children, neonatal respiratory disease with ECMO support has the best prognosis, with an average survival rate of 74%. Bleeding and thrombotic events during ECMO are common, morbid, and potentially lethal. Therefore, how to balance the coagulation state is the key to ECMO management. A full-term male infant (2h 5min) was hospitalized for respiratory distress and cyanosis. With a history of premature rupture of membranes (>7 hours) and a birth weight of 3000 g, the patient had Apgar scores of 7, 8, and 9 at 1, 5, and 10 minutes, respectively. This infant has the indication of extracorporeal membrane lung support. After full communication, venoarterial-ECMO was performed, and intravenous infusion of heparin was used for anticoagulation management. We encountered an unreliable heparin monitoring in an infant on ECMO, which considered as heparin resistance. Subsequently, we switched the anticoagulant from heparin to bivalirudin and managed by using multiple laboratory tests including activated clotting time (ACT) and activated partial thromboplastin time. The phenomenon of inconsistent monitoring results occurred later. To help the clinic to adjust the anticoagulation dose accurately, we adopted additional tests such as thrombin-antithrombin complex (TAT) and fibrin/fibrinogen degradation products and applied comparison of thrombela stogram (TEG)-ACT with anticoagulated specimens and bedside non-anticoagulated ACT, then recommended clinicians to use activated partial thromboplastin time combined with TAT. In collaboration with other symptomatic supportive treatments, the ECMO flow was gradually reduced, the respiratory and circulatory functions were stable after reducing the flow rate, there was no bleeding tendency, and the ECMO was finally evacuated. Due to the unique physiological characteristics of newborns, the hemostatic changes differ significantly from those in adults. Precise monitoring of anticoagulation becomes a critical and challenging task. Bivalirudin can be effectively used for anticoagulation management in neonatal ECMO; however, due to its unique characteristics, precise dose adjustment poses a challenge. Selecting the optimal laboratory monitoring indicators is crucial in this regard. In some cases, bedside ACT may not be the optimal anticoagulation monitoring parameter, and when necessary, comparative analysis can be conducted using anticoagulant-sample ACTs such as thrombela stogram-ACT. Traditional markers such as D-dimer/fibrinogen degradation products and newer indicators like TAT can reflect the activation of coagulation and assist in monitoring the anticoagulation effect, especially when there is conflicting information among the monitoring parameters.

Airway management for right thoracoscopic tracheal tumour resection after left pneumonectomy assisted by cardiopulmonary bypass: a case report

BackgroundThe incidence of secondary tracheal tumours following lung cancer surgery is notably low. Patients with tracheal tumours typically present with symptoms such as coughing, sputum production, haemoptysis, wheezing, stridor, and dyspnoea. In cases of peripheral structure invasion, symptoms may further extend to hoarseness and dysphagia. Initial symptoms may be notably non-distinct. However, the development of pronounced airway symptoms often signifies a critical condition.Case presentationA 70-year-old male with severe chest tightness and asthma was transferred to our hospital for emergency treatment. He had undergone left pneumonectomy for non-small cell carcinoma of the left upper lobe of the lung 3 years prior. The examination confirmed that a secondary tumour originated from the left main bronchus and extended to the carina, occupying 90% of the diameter of the tracheal lumen. To relieve the patient’s emergency airway, we chose right thoracoscopic resection of the tracheal tumour assisted by cardiopulmonary bypass (CPB), which provides extracorporeal lung support and a good surgical field.ConclusionIn patients with secondary tracheal tumours after left pneumonectomy for lung cancer, perioperative airway management is challenging for anaesthesiologists, and patients’ oxygenation should receive close attention. This article describes the airway management process of this patient for reference.

Donor Specific Antibodies in Extracorporeal Membrane Oxygenation-Bridged Lung Transplant Recipients

BackgroundExtracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. Although other mechanical circulatory support devices have been associated with anti-human leukocyte antigen antibody formation, including de novo donor-specific antibodies (dnDSA), it is unknown whether ECMO is a sensitizing exposure. MethodsThis was a single-center retrospective cohort study of lung transplant recipients. We compared dnDSA development in ECMO-bridged and non-ECMO exposed recipients. We also assessed differences in chronic lung allograft dysfunction-free survival between ECMO-bridged recipients with and without dnDSA, and between those who developed dnDSA with and without ECMO bridge. ResultsAmong 299 transplant recipients, 48 were ECMO-bridged and 251 were non-ECMO exposed. dnDSA developed in 33.3% of ECMO-bridged and 21.5% of non-ECMO exposed recipients. ECMO was associated with dnDSA development in bivariate (hazard ratio [HR], 2.08, 95% CI, 1.19-3.64, P = .01) but not multivariate analysis after adjusting for known confounders (HR, 1.10, 95% CI, 0.50-2.42, P = .82). Higher posttransplant transfusion volume was independently associated with dnDSA development (HR, 4.68, 95% CI, 2.25-9.72, P < .001). ECMO-bridged recipients with dnDSA did not have worse adjusted chronic lung allograft dysfunction-free survival than those without dnDSA (HR, 0.35, 95% CI, 0.07-1.87, P = .22) or compared to non-ECMO exposed recipients with dnDSA (HR, 0.40, 95% CI, 0.08-2.00, P = .27). ConclusionsA more restrictive posttransplant transfusion threshold among ECMO-bridged lung transplant recipients may reduce the risk of dnDSA. Surveillance for dnDSA, at least among ECMO-bridged recipients, may only be necessary in the presence of allograft dysfunction.

Dissolved Oxygen Relevantly Contributes to Systemic Oxygenation During Venovenous Extracorporeal Membrane Oxygenation Support.

When determining extracorporeal oxygen transfer (V ML O 2 ) during venovenous extracorporeal membrane oxygenation (VV ECMO) dissolved oxygen is often considered to play a subordinate role due to its poor solubility in blood plasma. This study was designed to assess the impact of dissolved oxygen on systemic oxygenation in patients with acute respiratory distress syndrome (ARDS) on VV ECMO support by differentiating between dissolved and hemoglobin-bound extracorporeal oxygen transfer. We calculated both extracorporeal oxygen transfer based on blood gas analysis using the measuring energy expenditure in extracorporeal lung support patients (MEEP) protocol and measured oxygen uptake by the native lung with indirect calorimetry. Over 20% of V ML O 2 and over 10% of overall oxygen uptake (VO 2 total ) were realized as dissolved oxygen. The transfer of dissolved oxygen mainly depended on ECMO blood flow (BF ML ). In patients with severely impaired lung function dissolved oxygen accounted for up to 28% of VO 2 total . A clinically relevant amount of oxygen is transferred as physically dissolved fraction, which therefore needs to be considered when determining membrane lung function, manage ECMO settings or guiding the weaning procedure.

Risk factors for long-term invasive mechanical ventilation: a longitudinal study using German health claims data

BackgroundLong-term invasive mechanical ventilation (IMV) is a major burden for those affected and causes high costs for the health care system. Early risk assessment is a prerequisite for the best possible support of high-risk patients during the weaning process. We aimed to identify risk factors for long-term IMV within 96 h (h) after the onset of IMV.MethodsThe analysis was based on data from one of Germany's largest statutory health insurance funds; patients who received IMV ≥ 96 h and were admitted in January 2015 at the earliest and discharged in December 2017 at the latest were analysed. OPS and ICD codes of IMV patients were considered, including the 365 days before intubation and 30 days after discharge. Long-term IMV was defined as evidence of invasive home mechanical ventilation (HMV), IMV ≥ 500 h, or readmission with (re)prolonged ventilation.ResultsIn the analysis of 7758 hospitalisations, criteria for long-term IMV were met in 38.3% of cases, of which 13.9% had evidence of HMV, 73.1% received IMV ≥ 500 h and/or 40.3% were re-hospitalised with IMV. Several independent risk factors were identified (p < 0.005 each), including pre-diagnoses such as pneumothorax (OR 2.10), acute pancreatitis (OR 2.64), eating disorders (OR 1.99) or rheumatic mitral valve disease (OR 1.89). Among ICU admissions, previous dependence on an aspirator or respirator (OR 5.13), and previous tracheostomy (OR 2.17) were particularly important, while neurosurgery (OR 2.61), early tracheostomy (OR 3.97) and treatment for severe respiratory failure such as positioning treatment (OR 2.31) and extracorporeal lung support (OR 1.80) were relevant procedures in the first 96 h after intubation.ConclusionThis comprehensive analysis of health claims has identified several risk factors for the risk of long-term ventilation. In addition to the known clinical risks, the information obtained may help to identify patients at risk at an early stage.Trial registration The PRiVENT study was retrospectively registered at ClinicalTrials.gov (NCT05260853). Registered at March 2, 2022.

First 24-Hour-Long Intensive Care Unit Testing of a Clinical-Scale Microfluidic Oxygenator in Swine: A Safety and Feasibility Study.

Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750-800 ml/min blood flow versus a standard hollow fiber membrane oxygenator (HFMO) in vivo during veno-venous extracorporeal life support for 24 hours in anesthetized, mechanically ventilated uninjured swine (n = 3/group). The objective was to assess feasibility, safety, and biocompatibility. Circuits remained patent and operated with stable pressures throughout 24 hours. No group differences in vital signs or evidence of end-organ damage occurred. No change in plasma free hemoglobin and von Willebrand factor multimer size distribution were observed. Platelet count decreased in BLOx at 6 hours (37% dec, P = 0.03), but not in HFMO; however, thrombin generation potential was elevated in HFMO (596 ± 81 nM·min) versus BLOx (323 ± 39 nM·min) at 24 hours ( P = 0.04). Other coagulation and inflammatory mediator results were unremarkable. BLOx required higher mechanical ventilator settings and showed lower gas transfer efficiency versus HFMO, but the stable device performance indicates that this technology is ready for further performance scaling and testing in lung injury models and during longer use conditions.

Differential early response of monocyte/macrophage subsets to intra-operative corticosteroid administration in lung transplantation

IntroductionLung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a major role. Corticosteroids are administered upon surgery as a standard-of-care but their action on the different myeloid cell subsets in that context is not known.MethodsTo address this issue, we used a cross-circulatory platform perfusing an extracorporeal lung coupled to cell mapping in the pig model, that enabled us to study the recruited cells in the allogeneic lung over 10 hours.ResultsMyeloid cells, i.e. granulocytes and monocytic cells including classical CD14pos and non-classical/intermediate CD16pos cells, were the dominantly recruited subsets, with the latter upregulating the membrane expression of MHC class II and CD80/86 molecules. Whereas corticosteroids did not reduce the different cell subset recruitment, they potently dampened the MHC class II and CD80/86 expression on monocytic cells and not on alveolar macrophages. Besides, corticosteroids induced a temporary and partial anti-inflammatory gene profile depending on cytokines and monocyte/macrophage subsets.DiscussionThis work documents the baseline effects of the standard-of-care corticosteroid treatment for early innate allo-responses. These insights will enable further optimization and improvement of lung transplantation outcomes.

Blood Gas Parameters and Acid–Base Balance during Extracorporeal Lung Support with Oxygenators: Semi-Empirical Evaluation

Membrane artificial lungs (oxygenators) are used in cardiopulmonary surgery as well as, in some cases, in severe lung disease to support the natural lung by means of ECMO (extracorporeal membrane oxygenation). The oxygen and carbon dioxide transfer rates of any oxygenator are usually assessed by considering several blood gas parameters, such as oxygen saturation, hemoglobin concentration, partial pressure of oxygen and carbon dioxide, bicarbonate concentration, and pH. Here, we report a set of semi-empirical equations that calculate such parameters directly from their partial pressures and assess the acid–base balance during ECMO. The implementation of this equation set permits the evaluation of any oxygenator, existing or prototypes in development, as well as the development of clinical decision-making tools for predicting the blood gas state and acid–base balance during surgical interventions and ECMO. The predicted results are then compared with experimental data obtained from in vitro gas exchange investigations with a commercial oxygenator using fresh porcine blood. The high correlation, R2&gt;0.95, between the predicted and the experimental data suggests a possibility of using such empirical equations in the simulation of gas transfer in a cardiopulmonary system with an oxygenator for any venous inlet blood gas data and also for estimating the acid–base balance during such therapy.

Recovery of extracorporeal lungs using cross-circulation with injured recipient swine

ObjectiveLung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia. MethodsSwine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation. ResultsRecipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours. ConclusionsWe demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application.

Curiosity, Opportunity, and Luck: Were the 1970s Different?

Control of Breathing Using an Extracorporeal Membrane Lung. By T Kolobow, L Gattinoni, TA Tomlinson, JE Pierce. Anesthesiology 1977; 46:138-41. Reprinted with permission. Body Position Changes Redistribute Lung Computed-Tomographic Density in Patients with Acute Respiratory Failure. By L Gattinoni, P Pelosi, G Vitale, A Pesenti, L D'Andrea, D Mascheroni. Anesthesiology 1991; 74:15-23. Reprinted with permission. Dr. Gattinoni's scientific career was primarily driven by curiosity. His generation was not formally trained, but he was part of a community of young and enthusiastic colleagues who were forging a new discipline: intensive care medicine. The most significant opportunity of Dr. Gattinoni's career was becoming the research fellow of a visionary genius, Dr. Theodor Kolobow, who focused on extracorporeal carbon dioxide removal after the failure of the first trial on extracorporeal membrane oxygenation. CO2 removal, by allowing control over the intensity of mechanical ventilation, opened the path to "lung rest" to prevent ventilator-induced lung injury. A unique opportunity for research was the spontaneous birth of a network of scientists who became friends in the European Group of Research in Intensive Care Medicine. In this environment, it was possible to develop core concepts such as the "baby lung" and to understand the mechanisms underlying computed tomography-density redistribution in the prone position. Physiology guided us in the 1970s, and understanding mechanisms remains of paramount importance today.

Extracorporeal Artificial Lungs: Co-Creating Future Technology - A Qualitative Analysis.

Terminal lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) in progression cause a large reduction in quality of life and may lead to bilateral lung transplantation (bLTx). An artificial portable lung could provide a bridge to lung transplantation, allowing patients to remain at home and mobile for longer. To advance the development of such an artificial lung, patient feedback is essential. The aim of this study is to analyze patient acceptance about an extracorporeal artificial lung and to implement these findings into the development. In collaboration with a medical device developer, we presented a portable dummy oxygenator to patients with advanced lung disease, as potential end users. Data collection in Germany and France was based on two different methods: an online questionnaire and face-to-face interviews (F2F). A total of 604 participants answered the online questionnaire and 17 participants were included in the F2F interviews. The majority of participants (COPD n=140, PH n=17) were able to walk more than 1 km with a mean suffering pressure of 2.87 and 3, respectively. Six of the 17 F2F participants who could walk <1 km were interested in an assistive device. The statistical value of Fisher's exact test for suffering pressure and desire for a portable oxygenator was 0.45. In patients with advanced lung disease, there is no statistically significant association between subjectively increased suffering pressure and desire for a portable oxygenator, so market introduction may be difficult. Potential end users should be implemented early in device development. Data collection via an online questionnaire combined with personal interviews has proven to be a successful approach here.

Acute exacerbation of interstitial lung disease in the intensive care unit: Principles of diagnostic evaluation and management.

Interstitial lung disease (ILD) is typically managed on an outpatient basis. Critical care physicians manage patients with ILD in the setting of an acute exacerbation (ILD flare) causing severe hypoxia. The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis, etc. Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation, while almost all patients will benefit from early palliative care. This review focused on the types of ILD, diagnosis, and management pathways for this challenging condition.

PULM2: Combining Extracorporeal Lung and Kidney Support: Evaluation of Fibre Configurations on Gas Exchange Preservation for the Development of a Novel Highly Integrated Device (RenOx)

Background: Combined lung and kidney dysfunction are frequent in extracorporeal membrane oxygenation (ECMO) patients affecting up to 70% of them. Current treatment relies on the use of two separate circuits combining ECMO and renal replacement therapy, increasing infection risks and the use of artificial surfaces. Therefore, we aim to develop a novel artificial lung that integrates lung and kidney support in a single device combining oxygenation and hemodialysis fibers. Thus, we analyzed how many oxygenation fibers could be substituted by hemodialysis fibers while still maintaining 90% of the oxygenator’s gas exchange capacity and the effect fiber configuration has on oxygen (O2) and carbon dioxide (CO2) transfer. Methods: Fiber bundles were composed of oxygenation fiber mats (Oxyplus™ 90/200, 3M) stacked perpendicularly at a 90° angle and/or crossed at a 24° angle on top of each other. We manufactured bundles with all oxygenation fibers open and bundles with oxygenation fibers closed in a way that they could not contribute to gas exchange, simulating hemodialysis fibers. Bundles in perpendicular configuration had 100% of fibers open (Oxy100P), 50% of fibers closed (Oxy50P), or 25% of fibers closed (Oxy75P), Figure 1. Bundles in crossed configuration had all fibers open (Oxy100C) or 33% of fibers closed (Oxy67C). Bundles were tested for gas exchange performance following in-vitro blood tests according to ISO 7199:2016. Results: Our results show that bundles with 25% of oxygenation fibers closed in perpendicular configuration were able to still maintain 90% of the O2 exchange and 80% of the CO2 exchange capacity of our oxygenator. Bundles with 25% oxygenation fibers closed had no statistically significant difference in O2 or CO2 transfer compared to a fully open oxygenator with the same fiber configuration, Figure 2. Additionally, Oxy75P bundles were able to keep O2 delivery above 55 mL/LBlood flow and CO2 removal above 52 mL/LBlood flow up to 140 mL/min. Fiber configuration did not affect gas exchange for fully open bundles, however, configuration significantly influenced O2 and CO2 exchange for bundles with closed fiber layers. Closing fibers in perpendicular configuration resulted in a lower decrease in gas transfer. Below 140 mL/min, this was demonstrated by a similar decrease in O2 transfer of 20% when 50% of perpendicular fibers or 33% of crossed fibers were closed Conclusions: We analyzed the effect of replacing oxygenation fibers with hemodialysis fibers on gas exchange efficiency. Our results demonstrate that 25% of oxygenation fibers in a perpendicular configuration could be replaced by hemodialysis fibers while still maintaining 90% of the O2 exchange of our oxygenator. Moreover, this type of bundle kept O2 delivery above 55 mL/LBlood flow up to 140 mL/min. This shows that gas exchange can be preserved to a desirable extent when oxygenation fiber layers are replaced. This is a step towards combining lung and kidney support in a single device.Figure 1. Illustration of a device combining extracorporeal lung and kidney support. Oxygen flows through the lumen of oxygenation fibers and dialysate flows inside hemodialysis fibers. In this work, fiber bundles were manufactured with a perpendicular and/or crossed configuration having a varying number of oxygenation fiber layers closed, simulating hemodialysis fibers (open fibers in white and closed fibers in blue). Perpendicular bundles had 50% of fibers closed (Oxy50P), 25% of fibers closed (Oxy75P), or 100% of fibers open (Oxy100P), while crossed bundles had 33% of fibers closed (Oxy67C), or all fibers open (Oxy100C).Figure 2. Oxygen exchange performance mL/LBlood flow ± standard deviation from the mean (n = 10) for bundles with different fiber configurations. We found no statistically significant difference in mean oxygen exchange between Oxy75P and the fully open oxygenator Oxy100P (ANOVA p > 0.38).

A cross-circulatory platform for monitoring innate allo-responses in lung grafts.

Lung transplantation is the only curative option for end-stage chronic respiratory diseases. However the survival rate is only about 50% at 5 years. Although experimental evidences have shown that innate allo-responses impact on the clinical outcome, the knowledge of the involved mechanisms involved is limited. We established a cross-circulatory platform to monitor the early recruitment and activation of immune cells in an extracorporeal donor lung by coupling blood perfusion to cell mapping with a fluorescent marker in the pig, a commonly-used species for lung transplantation. The perfusing pig cells were easily detectable in lung cell suspensions, in broncho-alveolar lavages and in different areas of lung sections, indicating infiltration of the organ. Myeloid cells (granulocytes and monocytic cells) were the dominant recruited subsets. Between 6 and 10 h of perfusion, recruited monocytic cells presented a strong upregulation of MHC class II and CD80/86 expression, whereas alveolar macrophages and donor monocytic cells showed no significant modulation of expression. This cross-circulation model allowed us to monitor the initial encounter between perfusing cells and the lung graft, in an easy, rapid, and controllable manner, to generate robust information on innate response and test targeted therapies for improvement of lung transplantation outcome.

Nonintubated versus Intubated Lung Volume Reduction Surgery in Patients with End-Stage Lung Emphysema and Hypercapnia.

Lung volume reduction surgery (LVRS) represents an important treatment option in carefully selected patients with end-stage lung emphysema. The aim of this study was to assess the efficacy and safety of nonintubated LVRS compared to intubated LVRS in patients with preoperative hypercapnia and lung emphysema. Between April 2019 and February 2021, n = 92 patients with end-stage lung emphysema and preoperative hypercapnia undergoing unilateral video-assisted thoracoscopic LVRS (VATS-LVRS) performed in epidural anesthesia and mild sedation (nonintubated, group 1) or conventional general anesthesia (intubated, control, group 2) were prospectively enrolled in this study. Data were retrospectively analyzed. In all patients, low-flow veno-venous extracorporeal lung support (low-flow VV ECLS) was applied as a bridge through LVRS. Ninety-day mortality was considered as the primary outcome. Secondary endpoints included: chest tube duration, hospital stay, intubation and conversion to general anesthesia. Intergroup analysis showed no significant difference between the baseline data and patients' demographics. N = 36 patients underwent nonintubated surgery. VATS-LVRS under general anesthesia was performed in n = 56 patients. The mean duration of postoperative VV ECLS support was 3 ± 1 day in group 1 compared to 4 ± 1 in group 2. The 90-day mortality rate was 3% in group 1 compared to 7% in group 2. In group 1, all chest tubes were removed 5 ± 1 day (range 4-32 days) and 8 ± 1 day (range 4-44 days) in the control group after the surgery (p < 0.02). Prolonged chest tube therapy (>8 days) was observed in n = 3 patients in group 1 and n = 11 patients in the control group. The mean ICU stay was 4 ± 1 days in group 1 compared to 8 ± 2 days in the control group (p = 0.04). The mean hospital stay was significantly shorter in the nonintubated group 1 (6 ± 2 days vs. 10 ± 4 days, p = 0.01). Conversion to general anesthesia was necessary in one patient due to severe pleural adhesions. Nonintubated VATS-LVRS in patients with end-stage lung emphysema and hypercapnia is effective and well tolerated. Compared to general anesthesia, a reduction in mortality, chest tube duration, ICU and hospital stay and lower rate of prolonged air leak was observed. VV ECLS increases intraoperative safety and mitigates postoperative complications in such "high-risk" patients.

Extracorporeal membrane oxygenation support in oncological thoracic surgery.

The use of extracorporeal lung support (ECLS) during thoracic surgery is a recent concept that has been gaining increasing approval. Firstly introduced for lung transplantation, this technique is now increasingly adopted also in oncological thoracic surgical procedures. In this review, we focus on the cutting-edge application of extracorporeal membrane oxygenation (ECMO) during oncological thoracic surgery. Therefore, we report the most common surgical procedures in oncological thoracic surgery that can benefit from the use of ECMO. They will be classified and discussed according to the aim of ECMO application. In particular, the use of ECMO is usually limited to certain lung surgery procedures that can be resumed such as in procedures in which an adequate ventilation is not possible such as in single lung patients, procedures where conventional ventilation can cause conflict with the surgical field such as tracheal or carinal surgery, and conventional procedures requiring both ventilators and hemodynamic support. So far, all available evidence comes from centers with large experience in ECMO and major thoracic surgery procedures.

A dual-action nitric oxide-releasing slippery surface for extracorporeal organ support: Dynamic in vitro hemocompatibility evaluation.

Numerous biomaterials have been developed for application in blood-contacting medical devices to prevent thrombosis; however, few materials have been applied to full-scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual-action slippery liquid-infused (LI) nitric oxide (NO)-releasing material modification (LINO) to full-scale blood circulation tubing for extracorporeal lung support and evaluated the tubing ex vivo using swine whole blood circulated for 6h at a clinically relevant flow. LINO tubing was compared to unmodified tubing (CTRL) and isolated LI and NO-releasing modifications (n=9/group). The primary objective was to evaluate safety and blood compatibility of this approach, prior to progression to in vivo testing of efficacy in animal models. The secondary objective was to evaluate coagulation outcomes relevant to hemocompatibility. No untoward effects of the coating, such as elevated methemoglobin fraction, were observed. Additionally, LINO delayed platelet loss until 6h versus the reduction in platelet count in CTRL at 3h. At 6h, LINO significantly reduced the concentration of platelets in an activated P-selectin expressing state versus CTRL (32 ± 1% decrease, p=.02). Blood clot deposition was significantly reduced on LINO blood pumps (p=.007) and numerically reduced on tubing versus CTRL. Following blood exposure, LINO tubing continued to produce a measurable NO-flux (0.20 ± 0.06 × 10-10 mol cm-2 min-1 ). LINO is a potential solution to reduce circuit-related bleeding and clotting during extracorporeal organ support, pending future extended testing in vivo using full-scale extracorporeal lung support devices.

Development and Blood Compatibility of a Stable and Bioactive Metal-Organic Framework Composite Coating for Blood-Circulation Tubing.

Medical devices that require substantial contact between blood and a foreign surface would be dramatically safer if constructed from materials that prevent clot formation and coagulation disturbance at the blood-biomaterial interface. Nitric oxide (NO), an endogenous inhibitor of platelet activation in the vascular endothelium, could provide anticoagulation at the blood-surface interface when applied to biomaterials. We investigated an application of a copper-based metal-organic framework, H3[(Cu4Cl)3(BTTri)8-(H2O)12]·72H2O where H3BTTri = 1,3,5-tris(1H-1,2,3-triazole-5-yl)benzene] (CuBTTri), which has been shown to be an effective catalyst to generate NO from S-nitrosothiols that are endogenously present in blood. A method was developed to apply a CuBTTri composite coating to Tygon medical tubing used for extracorporeal lung support devices. The stability and activity of the coating were evaluated during 72 h dynamic saline flow testing (1.5-2.5 L/min, n = 3) with scanning electron microscopy imaging and inductively coupled mass-spectroscopy analysis. Compatibility of the coating with whole blood was assessed with a panel of hemocompatibility tests during 6 h circulation of swine donor blood in an ex vivo circulation loop constructed with CuBTTri tubing or unmodified Tygon (1.5 L/min blood flow rate, n = 8/group). Thrombus deposition and catalytic activity of the CuBTTri tubing were assessed following blood exposure. The coating remained stable during 72 h saline flow experiments at clinically relevant flow rates. No adverse effects were observed relative to controls during blood compatibility testing, to include no significant changes in platelet count (p = 0.42), platelet activation indicated by P-selectin expression (p = 0.57), coagulation panel values, or methemoglobin fraction (p = 0.18) over the 6 h circulation period. CuBTTri within the coating generated NO following blood exposure in the presence of biologically relevant concentrations of an NO donor. CuBTTri composite coating was stable and blood compatible in this pilot study and requires further investigation of efficacy using in vivo models conducted with clinically relevant blood flow rates and study duration.

Trends, Advantages and Disadvantages in Combined Extracorporeal Lung and Kidney Support From a Technical Point of View.

Extracorporeal membrane oxygenation (ECMO) provides pulmonary and/or cardiac support for critically ill patients. Due to their diseases, they are at high risk of developing acute kidney injury. In that case, continuous renal replacement therapy (CRRT) is applied to provide renal support and fluid management. The ECMO and CRRT circuits can be combined by an integrated or parallel approach. So far, all methods used for combined extracorporeal lung and kidney support present serious drawbacks. This includes not only high risks of circuit related complications such as bleeding, thrombus formation, and hemolysis, but also increase in technical workload and health care costs. In this sense, the development of a novel optimized artificial lung device with integrated renal support could offer important treatment benefits. Therefore, we conducted a review to provide technical background on existing techniques for extracorporeal lung and kidney support and give insight on important aspects to be addressed in the development of this novel highly integrated artificial lung device.

Lung Volume Reduction Surgery Reduces Pulmonary Arterial Hypertension Associated With Severe Lung Emphysema and Hypercapnia.

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail.