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Introduction: Complete tracheal rings are a rare pathology occurring in 1 out of 100,000 live births. It is rare isolated tracheal or tracheobronchial anomaly resulting from abnormal cartilage growth, forming a complete ring, and leading to airway stenosis. A sliding tracheoplasty, primarily described by Tsang et al. and later widely presented by Grillo et al., overlaps the tracheal stenosing segments and shortens the trachea itself, and thus increases the diameter and circumference of the stenosing area double up. Materials and Methods: We have performed four slide tracheoplasties in the period between February 2019 and December 2020 in children who underwent medical treatment in the department of thoracic surgery in our center. Median age was 10 ± 5.5 months (2 months-1 year 6 months). Median weight was 6.9 ± 1.9 kg (4.5-9 kg). Slide tracheoplasty was performed using central venoarterial extracorporeal membrane oxygenation in 3 cases and using cardiopulmonary bypass in 1 case. Results: Patients were on artificial lung ventilation for 2-6 days in the postoperative period. Patients were discharged 14-18 days after the surgery. There were no lethal outcomes in our study. Discussion: Long segment congenital tracheal stenosis is an often and serious life-threatening anatomical malformation that bounded the length of trachea >50%. There is no unique treatment strategy for patients with such pathology. Sliding tracheoplasty can be recommended for all, but not for the shortest segments of stenosis, as it creates permissible voltage fluctuations during tracheal anastomosis. Excellent results in management of such severe patients can be achieved only through the collaboration of multidisciplinary team of specialists sharing organized and consistent patient-oriented approach.

Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s42242-021-00164-1.

There are many studies of single lung ventilation (SLV), which are mostly limited to reducing lung damage by changing ventilation strategies or comparing differences in lung damage caused by different lung isolation devices. There is no study comparing the morphological changes of ventilated lungs using different strategies of artificial lung ventilation. The aim of the study was to examine pathomorphological changes in the ventilated lung during thoracic surgery using SLV. A randomized study was performed on 40 patients who underwent thoracic surgery using SLV. After signing the informed consent, the patients were divided into two groups. In the control group (40 patients) with ventilation “by volume” (VCV), in the study group – ventilation “by pressure” (PCV) with the addition of PEEP 5 mm. During surgery in the thoracic cavity with the help of SLV performed transbronchial biopsy of the parenchyma of the ventilated lung to study the pathomorphological changes after ventilation with different modes. The biopsy was performed using a bronchoscope, which was inserted through the endotracheal tube into the lung, opposite the side of the operation (after the end of SLV and “inclusion” of the collapsed lung). The morphological changes caused by the ventilator were investigated. Pathomorphological examination of the non-collapsed lung (which participated in gas exchange during SLV) was as follows: the control group found significant changes in the alveolar wall with its edema, thickening of the interstitial lung, vascular occlusion, severe inflammatory cell infiltration and damage to alveolar structures. The alveoli collapsed and disappeared. The alveolar structures of the study group were better than the control group: pulmonary interstitial and alveolar exudates, as well as inflammatory cell infiltration were significantly reduced compared to those in the control group. The results of the study suggest that the use of PCV with “moderate” PEEP can significantly improve oxygenation and reduce acute ventilatory injury of the lungs compared to VCV during SLV.

Poor adherence to inhaled drug therapy is considered to be a major factor in asthma related morbidity and it has been shown, in a significant number of patients, that estimates of adherence by patients or parents of children is not accurate. Inaccurate reporting may lead to higher dose of drug or more potent drugs being prescribed. A number of adherence sensors are available for some commercial inhaler devices. However, existing adherence monitoring mainly focuses on how the hardware of an inhaler has been actuated and does not provide evidence of drug aerosol inhalation. Valved holding chambers are now first choice for aerosol drug delivery for young children, who inhale drug by breathing in and out of the device several times and are increasingly used by older children and adults who inhale drug aerosol by taking a single deep breath. To the best knowledge of the authors, there is no adherence sensor in the market that provides evidence of actuation of the drug into a valved holding chamber and evidence that it is inhaled by different age groups. We therefore developed a novel adherence sensor system embedded into a valved holding chambers to achieve this. Our customised algorithm ensures that correct use is recorded, and incorrect use flagged. It also distinguishes a deep breath from tidal breaths and in combination measurement of actuation into the device triggers different classifiers for registering usage as good technique or not. A good technique or poor technique is immediately fed back to users using a visual light signal, while the data recorded is Bluetoothed to a paired mobile device for historical recording and statistical analysis. The entire system, including battery, micro-controller, sensors and Bluetooth, is integrated on a $66 \times 22$ mm2 printed circuit board and weighs only 8 grams. The system has been evaluated on a custom-made artificial lung which mimics the breathing patterns confirming recognition of tidal and deep breaths. The low-power device operates from a 3.3 V, 560 mAh battery and lasts 14 months if used daily.

Introdução: A pandemia pelo novo coronavírus provocou rotura em hospitais de vários países por falta de recursos para ventilaçãoinvasiva. Assim, a Ordem dos Médicos convidou intensivistas que, em colaboração com a SYSADVANCE S.A., desenvolveram o SYSVENT OM1, um ventilador capaz de operar em modos controlados e assistidos (volume e pressão) e apto para tratar doentes em cuidados intensivos. Neste estudo fazemos a prova de conceito, comparando volume-corrente, pressão inspiratória e pressão positiva tele-expiratória programados, com os valores medidos pelo ventilador e por um equipamento de medição externo.Material e Métodos: Montámos o ventilador em série com um pulmão artificial e um analisador de fluxos. Medimos o volume-corrente expiratório e a pressão inspiratória, em três níveis de compliance e seis patamares de volume-corrente. A pressão positiva tele-expiratória foi medida com incrementos de 2 cmH2O ao longo de oito patamares. Para cada medição realizámos três leituras.Resultados: Considerando cada uma das três variáveis isoladamente, a média da diferença máxima entre os valores programados e os valores medidos situa-se, para todas elas, dentro do que considerámos ser aceitável para um modelo protótipo (volume-corrente = -28,1 mL, pressão inspiratória = 0,8 cmH2O e pressão positiva tele-expiratória = -1,1 cmH2O). Essa diferença é maior quando avaliada com o equipamento de medição externa comparativamente com o ventilador.Discussão: Os resultados mostraram uma boa capacidade de monitorização e de precisão. Documentaram-se limitações técnicas relacionadas com o pulmão artificial e com o analisador de fluxos que não desvirtuam os resultados, mas limitam a sua amplitude.Conclusão: Para os parâmetros testados, o ventilador apresenta boa performance de funcionamento, está de acordo com as premissasiniciais e tem potencial para uso clínico.

Objectives: To assess the in vivo hemodynamic effects on the pressure overloaded right ventricle of RAS-Q® technology, the world’s first gas exchanger with a fully integrated compliance. Methods: In six acute in vivo trials RAS-Q was implanted in sheep between the pulmonary artery and left atrium. Right ventricular pressure overload was induced by pulmonary artery banding. Pressures and flows were recorded in baseline, moderate and severe pulmonary hypertension conditions. In one trial, RAS-Q was benchmarked against the pediatric Quadrox-i®. Results: With 1.00 and 1.17 L/min, RAS-Q delivered 31% and 39% of the total cardiac output in moderate and severe pulmonary hypertension, respectively. Pulmonary artery pressures and mean pulmonary artery pressure/mean arterial blood pressure ratio successfully decreased, implying a successful right ventricular unloading. Cardiac output was restored to normal levels in both pulmonary hypertension conditions. With both devices in parallel, RAS-Q provided three times higher flow rates and a 10 times higher pressure relief, compared to the pediatric Quadrox-i. Conclusion: A gas exchanger with a fully integrated compliance better unloads the right ventricle compared to a non-compliant gas exchanger and it can restore cardiac output to normal levels in cases of severe pulmonary hypertension.

The idea of proportional assist ventilation, in which the patient himself sets the respiratory pattern — the frequency and depth of breathing — was suggested in 1992, but has not yet found widespread practical application. One of the possible reasons for this is the complex algorithm of regime adjustment on first-generation respiratory devices. Over time, the accumulated body of information on the early damage of the diaphragm because of its atrophy in patients on respiratory support formed the basis of the awareness of the importance of maintaining the physiological state of the diaphragm during artificial lung ventilation and led to the emergence of the term “myotrauma”.At the turn the 21st century, the idea of the maximum possible preservation of spontaneous breathing of the patient during mechanical lung ventilation realized in the formation of the concept of “diaphragm-protective ventilation”. The need for further development of assisted lung ventilation technologies designed to reduce the risk of diaphragm damage, the frequency of asynchrony in the pair “respirator-patient”, and to facilitate the process of weaning of the patient from the artificial lung ventilation became apparent. This article, based on scientific literature and own clinical experience of using proportional ventilation, describes the peculiarities of regime adjustment on different respirators, places the accents necessary for successful practical use of proportional lung ventilation. Describes key conditions for its use, advantages and limitations.

Extracorporeal CO(2) removal (ECCO(2)R) can permit lung protective or noninvasive ventilation strategies in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). With evidence supporting ECCO(2)R growing, investigating factors which affect CO(2) removal is necessary. Multiple factors are known to affect the CO(2) removal rate (vCO(2)) which can complicate the interpretation of changes in vCO(2); however, the effect of hematocrit on the vCO(2) of artificial lungs has not been investigated. This in vitro study evaluates the relationship between hematocrit level and vCO(2) within an ECCO(2)R device. In vitro gas transfer was measured in bovine blood in accordance with the ISO 7199 standard. Plasma and saline were used to hemodilute the blood to hematocrits between 33% and 8%. The vCO(2) significantly decreased as the blood was hemodiluted with saline and plasma by 42% and 32%, respectively, between a hematocrit of 33% and 8%. The hemodilution method did not significantly affect the vCO(2). In conclusion, the hematocrit level significantly affects vCO(2) and should be taken into account when interpreting changes in the vCO(2) of an ECCO(2)R device.

EDAC is defined by an abnormal expiratory reduction of the tracheal lumen leading to an elevation of airflow resistance. No data supports the clinical threshold of 50% closure. The aim of our study was to develop an experimental model of EDAC in order to assess the consequences of airway collapse on the work of breathing (WOB) and evaluate the impact of CPAP. We have modelled and manufactured a realistic 3D silicon trachea and a static compression system to simulate tracheal collapse. The trachea was linked to a dummy head with realistic upper airways and to an artificial lung (ASL 5000, IngMar Medical) which simulated tidal breathing (TB) from three lung models (normal, COPD and restrictive). We simulated tracheal compressions (length 4 or 8 centimeters, closure of 0,31,49,63 and 87%) at rest and on exercise, without and with CPAP (PEP 5, 10, 15 and 20cmH2O). We measured pressure on both sides of collapse and computed expiratory resistance Rexp, flow Qexp and pressure time product (PTPexp which reflects WOB). There was a significant impact of the degree of collapse on Rexp, Qexp and PTPexp for a closure ≥49%. During TB, median Rexp was 8,05 [6,60;9,90]cmH2O.s/L at 87% collapse versus 0,12 [0,11;0,14]cmH2O.s/L without collapse (p Our experimental model supports the 49% closure threshold associated with significant consequences on WOB.

Background Artificial lungs have the potential to serve as a bridge to transplantation or recovery for children with end-stage lung disease dependent on extracorporeal life support, but such devices currently require systemic anticoagulation. We describe our experience using the novel Nitric Oxide (NO) Surface Anticoagulation (NOSA) system—an NO-releasing circuit with NO in the sweep gas—with the Pediatric MLung—a low-resistance, pumpless artificial lung. Methods NO flux testing: MLungs (n = 4) were tested using veno-venous extracorporeal life support in a sheep under anesthesia with blood flow set to 0.5 and 1 L/min and sweep gas blended with 100 ppm NO at 1, 2, and 4 L/min. NO and NO2 were measured in the sweep and exhaust gas to calculate NO flux across the MLung membrane. Pumpless implants: Sheep (20–100 kg, n = 3) underwent thoracotomy and cannulation via the pulmonary artery (device inflow) and left atrium (device outflow) using cannulae and circuit components coated with an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N2O2) and argatroban. Animals were connected to the MLung with 100 ppm NO in the sweep gas under anesthesia for 24 h with no systemic anticoagulation after cannulation. Results NO flux testing: NO flux averaged 3.4 ± 1.0 flux units (x10−10 mol/cm2/min) (human vascular endothelium: 0.5–4 flux units). Pumpless implants: 3 sheep survived 24 h with patent circuits. MLung blood flow was 716 ± 227 mL/min. Outlet oxygen saturation was 98.3 ± 2.6%. Activated clotting time was 151±24 s. Platelet count declined from 334,333 ± 112,225 to 123,667 ± 7,637 over 24 h. Plasma free hemoglobin and leukocyte and platelet activation did not significantly change. Conclusions The NOSA system provides NO flux across a gas-exchange membrane of a pumpless artificial lung at a similar rate as native vascular endothelium and achieves effective local anticoagulation of an artificial lung circuit for 24 h.

Objective. To identify risk factors for acute cardiac surgery-associated kidney damage in 214 newborns and infants with congenital heart defects. Results. 54.7% of 95 newborns and 46.2% of 119 infants have acute cardiac surgery-associated kidney injury. There have been determined statistically significant risk factors of acute cardiac surgery-associated kidney injury: in newborns – the level of lactate in blood plasma more than 2.5 mmol/l and artificial lung ventilation (87.1% as compared to 39.1% without these factors; 93.8 and 46.8% accordingly; р<0.001), in infants – level of lactate in blood plasma more than 2.5 mmol/l before surgery as compared to those without these factors (96.4% as compared to 30.8% without this factor; р<0.001).

The article describes the successful experience of treating a female patient with severe poisoning by a mixture of drugs with a predominant cardiotoxic effect. The number of drugs taken was many times higher than the potentially lethal dose. Hemodynamics has been supported by vasopressors and inotropic drugs for a long time, antidotes, sorbents, detoxification agents were used. Due to inadequate spontaneous ventilation, the patient was on artificial lung ventilation for 24 days. After 26 days in the intensive care unit, she was transferred to the therapeutic department in a stable state and without neurological deficit. We believe that this material will be useful for intensive care physicians when providing emergency care to patients in such situations., Стаття присвячена успішному досвіду лікування пацієнтки з тяжким отруєнням сумішшю медикаментів з переважною кардіотоксичною дією. Кількість вжитих препаратів багатократно перевищувала потенційно смертельну дозу. Гемодинаміка тривалий час підтримувалася вазопресорами та препаратами інотропної дії, застосовувалися антидоти, сорбенти, дезінтоксикаційні середники. У зв’язку з неадекватною спонтанною вентиляцією 24 дні пацієнтка перебувала на штучній вентиляції легень. Через 26 діб перебування у відділенні інтенсивної терапії переведена до терапевтичного відділення у стабільному стані та без неврологічного дефіциту. Вважаємо, що цей матеріал буде корисним для лікарів відділень інтенсивної терапії при наданні невідкладної допомоги хворим у подібних ситуаціях.

Artificial lung technology is advancing at a startling rate raising hopes that it would better serve the needs of those requiring respiratory support. Whether to assist the healing of an injured lung, support patients to lung transplantation, or to entirely replace native lung function, safe and effective artificial lungs are sought. After 200 years of bioengineering progress, artificial lungs are closer than ever before to meet this demand which has risen exponentially due to the COVID-19 crisis. In this review, the critical advances in the historical development of artificial lungs are detailed. The current state of affairs regarding extracorporeal membrane oxygenation, intravascular lung assists, pump-less extracorporeal lung assists, total artificial lungs, and microfluidic oxygenators are outlined.

Optimizing patient care based on precision oncology will inevitably become the standard of care. If we accept the principle that every persons’ cancer is different then the most effective therapies will have to be designed for the individual patient and for their tumors genetic profile. Access to tumor mutational profiling is now widely available but continues to be limited by cost and actionable information. For example, novel combinations of approved drugs are rarely considered. These considerations lead us to hypothesize that artificially induced Lung Adenocarcinoma (LUAD) derived lung organoids could provide a novel, alternate approach for LUAD disease modeling and large-scale targeted drug screening.In this project, we used data from a commercially available tumor mutation profile to generate and then validate the artificially induced LUAD-derived lung organoid simulations (aiLUNG-LUAD) to model LUAD and identify several drug combinations that effectively reverse the tumors’ genotypic and phenotypic features when compared with placebo. These results complement previous LUAD-derived lung organoids research and provide a novel and widely applicable cancer drug-screening approach for precision/individualized oncology.

Introduction: An important phase in surgical training is gaining experience in real human anatomical situations. When a cadaver is available it may complement the various artificial practice models. However, it is often necessary to supplement the characteristics of the cadavers with a simulation of a tumor. Our objective was to develop an easy-to-create, realistic artificial tumor-mimic model for peripheral lung tumor resection practice.Methods: In our work we injected barium sulphate enriched silicone suspension into 10 isolated, non-fixed lungs of human cadavers, through the puncture of the visceral pleura. Four lesions–apical, hilar and two peripheral–were created in each of ten specimens. After fixation CT scans were obtained and analyzed. The implanted tumor-mimics were examined after anatomical preparation and slicing. Also performed CT-guided percutaneous puncture was also performed to create the lesions in situ in two lungs of human cadavers.Results: Analyzing the CT data of 10 isolated lungs, out of 40 lesions, 34 were nodular (85.0%) and in the nodular group five were spiculated (12.5%). Satellite lesions were formed in two cases (5.0%). Relevant outflow into vessels or airway occurred in five lesions (12.5%). Reaching the surface of the lung occured in 11 lesions (27.5%). The tumor-mimics were elastic and adhered well to the surrounding tissue. The two lesions, implanted via percutaneous puncture, both were nodular and one also showed lobulated features.Conclusion: Our artificial tumor-mimics were easy to create, varied in shape and size, and with percutaneous implantation the lesions provide a model for teaching every step of a surgical procedure.

In COVID-19 therapy with artificial lungs such as extracorporeal membrane oxygenation (ECMO) machines, platelets in the extracorporeal circulation are often activated by their contact with the artificial materials, leading to the formation of blood clots followed by serious complications such as stroke and heart attack. However, anticoagulation and antithrombotic management is challenging due to the lack of testing tools to evaluate the circulation. Here we demonstrate real-time monitoring of thrombogenesis in the circulation of an ECMO-equipped goat with an intelligent platelet aggregate characterizer (iPAC), which is based on imaging flow cytometry and deep-learning-based analysis of numerous platelet aggregates in blood.

Whole-body plethysmography (WBP) is an established method to determine physiological parameters and pathophysiological alteration of breathing in animals and animal models of a variety of diseases, reaching from pulmonary diseases to complex neurological syndromes. Although frequently used, there is ongoing debate about what exactly is measured by whole-body-plethysmography and how reliable the data derived from this method are? Here, we designed a simple device that can serve as an artificial lung model that enables a thorough evaluation of different predictions about and around whole-body plethysmography. Using our lung model, we confirmed that during WBP two components contribute to the pressure changes detected in the chamber: 1) the increase of the pressure due to heating and moistening of the air, termed as conditioning, during inspiration; 2) changes of chamber pressure that depend on airway resistance. Both components overlap and contribute to the temporal pressure-profile measured in the chamber or across the wall of the chamber. Our data showed that a precise measurement of the breathing volume appears to be hindered by at least two factors: 1) the unknown relative contribution of each of these components; 2) not only the air in the inspired volume is conditioned during inspiration, but also air within the residual volume and death space that is recruited during inspiration. Moreover, our data suggest that the expiratory negative pressure peak that is used to determine the so called “enhanced pause” (Penh) parameter is not a measure for airway resistance as such but rather a consequence of the animal’s response to the airway resistance, using active expiration to overcome the resistance by a higher thoracic pressure.

Background: For children with severe lung disease that cannot wean from ECMO, an implantable artificial lung would permit extubation and support gradual lung recovery from acute disease or provide a bridge to transplantation. We evaluate the function of the novel Pediatric MLung—an efficient, implantable, pumpless artificial lung developed specifically for children—in healthy animal subjects. Methods: Adolescent “mini sheep” weighing 12-20 …

Left ventricular assist devices (LVADs) are increasingly used as destination therapy or as a bridge to future cardiac transplant in patients with end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) can be used to bridge patients in cardiogenic shock or with decompensated heart failure to durable mechanical circulatory support. We assessed outcomes in patients in critical cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1) who underwent implantation of a continuous-flow (CF)-LVAD, with or without preoperative ECMO bridging. For this retrospective study, we selected INTERMACS profile 1 patients who underwent CF-LVAD implantation at our institution between Sep 1, 2004 and Nov 30, 2018. Of 768 patients identified, 133 (17.3%) were INTERMACS profile 1; 26 (19.5%) received preoperative ECMO support, and 107 (80.5%) did not. Postimplantation outcomes were compared between the ECMO and no-ECMO groups. No significant differences were found in 30-day mortality (15.4 vs. 15.9%, P = 0.95) or survival at 1 year (53.8 vs. 60.9%, P = 0.51). Three patients who received ECMO before CF-LVAD implantation subsequently underwent cardiac transplant. In the ECMO group, the lactate level 1 day after ECMO initiation was lower in survivors than nonsurvivors (2.7 ± 2.2 vs. 7.4 ± 4.2 mmol/L, P = 0.02; area under the curve = 0.85, P = 0.01) after CF-LVAD implantation. Bridging with ECMO to CF-LVAD implantation in carefully selected INTERMACS profile 1 patients (those who are at the highest risk for critical cardiogenic shock and for whom palliation may be the only other option) produced acceptable postoperative outcomes. Field of research: Artificial lung/ECMO.

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy.

Once pulmonary disease progresses to end-stage pulmonary disease, treatment options are very limited. An important advance in the field is the development of a bioartificial lung derived from a generic matrix scaffold populated with patients' own cells. Significant progress has already been made in the engineering of bioartificial lungs.This review explains how previous and current research contributes to the goal of creating a successful bioartificial lung, and the barriers faced in doing so. We will also highlight some of the design considerations being explored to optimize bioartificial lungs and considerations for clinical translation.While current bioartificial lungs are able to provide short-term gas exchange in large-animal studies, much work is still required to combine the disciplines of cell biology, materials science, and tissue engineering to create such clinically useful and functioning artificial lungs.

Mechanical ventilators are essential to patients who become critically ill from acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We utilized cost-effective, on-demand 3D printing (3DP) technology to produce critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swines. As one of the first studies to demonstrate splitting one anesthesia gas machine between two swines, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for individualized patient therapy. Our studies underscore that while possible, ventilator multiplexing is a complicated synergy between machine settings, circuit modification, and patient monitoring. Consequently, ventilator multiplexing is reserved only as a last emergency resource, by trained clinicians and respiratory therapists with ventilator operative experience.

Circulating venous blood outside the body, through an artificial lung (membrane oxygenator), and returning oxygenated blood to the patient is extracorporeal gas exchange. Oxygen and carbon dioxide exchange in a membrane lung is controlled by regulating blood flow, blood composition, and device design. With this control, lung function can be replaced for weeks by artificial organs. © 2020 American Physiological Society. Compr Physiol 10:879-891, 2020.

Blood contact with high surface area medical devices, such as dialysis and extracorporeal life support (ECLS), induces rapid surface coagulation. Systemic anticoagulation, such as heparin, is thus necessary to slow clot formation, but some patients suffer from bleeding complications. Both problems might be reduced by 1) replacing heparin anticoagulation with artificial surface inhibition of the protein adsorption that initiates coagulation and 2) selective inhibition of the intrinsic branch of the coagulation cascade. This approach was evaluated by comparing clot formation and bleeding times during short-term ECLS using zwitterionic polycarboxybetaine (PCB) surface coatings combined with either a potent, selective, bicyclic peptide inhibitor of activated Factor XII (FXII900) or standard heparin anticoagulation. Rabbits underwent venovenous ECLS with small sham oxygenators for 60 min using three means of anticoagulation (n = 4 ea): (1) PCB coating + FXII900 infusion, (2) PCB coating + heparin infusion with an activated clotting time of 220-300s, and (3) heparin infusion alone. Sham oxygenator blood clot weights in the PCB + FXII900 and PCB + heparin groups were 4% and 25% of that in the heparin group (p < 10-6 and p < 10-5), respectively. At the same time, the bleeding time remained normal in the PCB + FXII900 group (2.4 ± 0.2 min) but increased to 4.8 ± 0.5 and 5.1 ± 0.7 min in the PCB + heparin and heparin alone groups (p < 10-4 and 0.01). Sham oxygenator blood flow resistance was significantly lower in the PCB + FXII900 and PCB + heparin groups than in the heparin only group (p < 10-6 and 10-5). These results were confirmed by gross and scanning electron microscopy (SEM) images and fibrinopeptide A (FPA) concentrations. Thus, the combined use of PCB coating and FXII900 markedly reduced sham oxygenator coagulation and tissue bleeding times versus the clinical standard of heparin anticoagulation and is a promising anticoagulation method for clinical ECLS.

A pediatric artificial lung (PAL) is under development as a bridge to transplantation or lung remodeling for children with end-stage lung failure (ESLF). In order to evaluate the efficiency of a PAL, a disease model mimicking the physiologic derangements of pediatric ESLF is needed. Our previous right pulmonary artery ligation (rPA-LM) ovine model achieved that goal, but caused immediate mortality in nearly half of the animals. In this study, we evaluated a new technique of gradual postoperative right pulmonary artery (rPA) occlusion using a Rummel tourniquet (rPA-RT) in seven (25–40 Kg) sheep. This technique created a stable model of ESLF pathophysiology, characterized by high alveolar dead space (58.0±3.8 %), pulmonary hypertension (38.4±2.2 mmHg), tachypnea (79±20 breaths per minute), and intermittent supplemental oxygen requirement. This improvement to our technique provides the necessary physiologic derangements for testing a PAL, while avoiding the problem of high immediate perioperative mortality.

Children with end-stage lung failure awaiting lung transplant would benefit from improvements in artificial lung technology allowing for wearable pulmonary support as a bridge-to-transplant therapy. In this work, we designed, fabricated, and tested the Pediatric MLung-a dual-inlet hollow fiber artificial lung based on concentric gating, which has a rated flow of 1 L/min, and a pressure drop of 25 mm Hg at rated flow. This device and future iterations of the current design are designed to relieve pulmonary arterial hypertension, provide pulmonary support, reduce ventilator-associated injury, and allow for more effective therapy of patients with end-stage lung disease, including bridge-to-transplant treatment.

Although lung transplantation is an effective treatment for end-stage lung failure, its limitations have led to renewed interest in artificial lung support for patients with lung failure. The use of ventricular assist devices has significantly improved the quality of life and survival of patients with end-stage heart failure. In contrast, there are no devices that can be used long term as destination therapy for end-stage lung failure, and there is a strong need for them. Extracorporeal membrane oxygenation is widely used as a temporary treatment for acute lung failure and as a bridge to lung transplant. Many patients with advanced lung failure cannot return home with good quality of life once they are hospitalized. In this review, the authors discuss the history, status, and future of artificial lungs, focusing on long-term artificial respiratory support as a destination therapy. Respiratory assist devices, such as artificial lungs, could eventually become analogous to ventricular assist devices.

The use of extracorporeal membrane oxygenation to support patients with cardiac and respiratory failure has increased substantially in the last decade. Although the evidence base for its use in adults with respiratory failure is growing, many questions remain to be answered. Ongoing research is aimed at clarifying the role of extracorporeal membrane oxygenation, as well as extracorporeal carbon dioxide removal, in various forms of hypoxemic and hypercapnic respiratory failure, and at defining the optimal techniques for its use. This, of course, is a moving target, as advances in the technology of extracorporeal membrane oxygenation, and the potential development of a true artificial lung, continue at a brisk pace.

Myocarditis is an inflammatory condition of the myocardium and is usually categorised as acute nonfulminant and acute fulminant myocarditis. Myocardial injury can result via viral infections, direct injury or immune responses. Fulminant myocarditis can be characterised by severe and sudden cardiac inflammation that may result from cardiogenic shock, ventricular arrhythmias or multi-organ system failure. Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support, is an effective technique for patients with fulminant myocarditis, providing heart and lung support and adequate gas exchange or perfusion to sustain life. Essentially, ECMO pumps blood out of the body to an oxygenator that acts as an artificial lung, which adds oxygen to the blood and removes carbon dioxide. This report aims to review recent advances in ECMO and relate case studies of fulminant myocarditis patients. The types of ECMO, predictive factors for success, clinical studies and recent technological advances in the field will be discussed.

The compliant thoracic artificial lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL's long-term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic artificial lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL's resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.

Current hollow fiber membrane lungs feature a predominantly straight blood path length across the fiber bundle, resulting in limited oxygen transfer efficiency due to the diffusion boundary layer effect. Using computational fluid dynamics and optical flow visualization methods, a hollow fiber membrane lung was designed comprising unique concentric circular blood flow paths connected by gates. The prototype lung, comprising a fiber surface area of 0.28 m2, has a rated flow of 2 L/min and the oxygenation efficiency is 357 mL/min/m2. The CO2 clearance of the lung is 200 mL/min at the rated blood flow. Given its high gas transfer efficiency, as well as its compact size, low priming volume, and propensity for minimal thrombogenicity, this lung design has the potential to be used in a range of acute and chronic respiratory support applications, including providing total respiratory support for infants and small children and CO2 clearance in adults.

Elective or emergence surgery often is closely connected with development of hypercatabolism-hypermetabolism syndrome. Non-effective and late nutritional support in surgical critically ill patients lead to several consequences and complications such as: wound and nosocomial infectons, gastric stress ulcers, pressure ulcers, prolonged artificial lung ventilation, increased length of stay in ICU and hospital. Energy deficit is one of the important components of critical illness and it corresponds with multiple organ dysfunction progression. Prospective study was provided in 18 beds surgical intensive care unit (SICU). 106 patient medical cards were divided into 4 groupstwo control and two basic with espiratory support (subgroup with artificial lung ventilation and subgroup without artificial lung ventilation). We compared the effectiviness of two methods for the estimation of patients energy needsspecial equations and indirect calorimetry. As a result we found out that main markers of energy and protein metabolism and nutritive status were significantly higher in indirect calorimetry groupswith and without artificial lung ventilation. Conclusion: Indirect calorimetry method usage for the estimation of energy needs in surgical ICU patients is more effective than special equations method during first 7 days of critical illness and may be recommended for clinical practice implication.

Identifying patients who are ready for weaning and liberation from veno-venous extracorporeal membrane oxygenation (ECMO) is challenging in clinical practice. Compared to the several trials addressing the safety and efficacy of ECMO in severe ARDS [1–4], the body of literature regarding ECMO weaning is remarkably scarce. Therefore, this essential component of the management of patients on ECMO is highly variable and often lacks of a systematic approach [5], analogously to the weaning protocols and spontaneous breathing trials used for liberation from mechanical ventilation [6]. The trajectory from ECMO cannulation to lung recovery and ECMO decannulation consists in the transition from a phase in which ECMO is essential to meet the patient’s metabolic needs (i.e. metabolic oxygen consumption and CO2 production) to a phase in which the native lung function has recovered to satisfy completely the metabolic demands, even if with a degree of ventilatory support considered “safe”. In between these two phases is a continuum of lung healing, during which lung function becomes sufficient to maintain a gas exchange compatible with life, but at the expenses of a high respiratory drive and large swings in transpulmonary pressures. In these conditions, ECMO has the role of maintaining lung protection partially contributing to the patient’s gas exchange [5]. In the effort to track the progress of an individual patient along this imaginary line, it is necessary to measure the relative contribution of the membrane and native lungs in terms of gas exchange, as well as the response of the patient’s respiratory drive and mechanics to the variation in ECMO settings. We propose a physiology-based assessment protocol, which combines an objective assessment of the native and artificial lung function and quantifies the patient’s response to a standardised weaning trial.

One in five children with end-stage lung failure (ESLF) die while awaiting lung transplant. No suitable animal model of ESLF exists for the development of artificial lung devices for bridging to transplant. Small lambs weighing 15.7 ± 3.1 kg (n = 5) underwent ligation of the left anterior pulmonary artery (PA) branch, and gradual occlusion of the right main PA over 48 hours. All animals remained hemodynamically stable. Over seven days of disease model conditions, they developed pulmonary hypertension (mean PA pressure 20 ± 5 vs. 33 ± 4 mm Hg), decreased perfusion (SvO2 66 ± 3 vs. 55 ± 8%) with supplemental oxygen requirement, and severe tachypneic response (45 ± 9 vs. 82 ± 23 breaths/min) (all p < 0.05). Severe right heart dysfunction developed (tricuspid annular plane systolic excursion 13 ± 3 vs. 7 ± 2 mm, fractional area change 36 ± 6 vs. 22 ± 10 mm, ejection fraction 51 ± 9 vs. 27 ± 17%, all p < 0.05) with severe tricuspid regurgitation and balloon-shaped dilation of the right ventricle. This model of pediatric ESLF reliably produces pulmonary hypertension, right heart strain, and impaired gas exchange, and will be used to develop a pediatric artificial lung.

In the last decade, primarily following the H1N1 pandemics [1], the extracorporeal respiratory assist is increasingly used [2, 3]. The acronym “ECMO”, i.e., ExtraCorporeal Membrane Oxygenation, is, however, somehow misleading as the artificial extracorporeal assist may affect both oxygenation and CO2 removal, as well as the hemodynamics, depending on how it is applied. In this commentary, we will limit our discussion to the respiratory extracorporeal support in veno-venous mode, primarily discussing the aspects, which are usually under-evaluated. Various options for extracorporeal support Table 1 was first published more than 40 years ago [4] and summarizes the main characteristics and options through which the extracorporeal support may be applied. As shown, all the possible application were foreseen and most of them actually tested in the following years. As shown, two main features characterize the extracorporeal support: cannulation (veno-venous vs veno-arterial) and extracorporeal blood flow. In the veno-venous configuration, the artificial and the natural lung are connected in series, as the blood flow entering the membrane lung is re-directed into the natural lung, after the artificial gas exchange. The hemodynamics are not affected by this configuration, which works solely as a respiratory support. In contrast, in the veno-arterial configuration, the artificial and the natural lung are arranged in parallel: the flow leaving the artificial lung is diverted in the arterial section and the natural lung is proportionally under-perfused. The greatest difference between veno-venous and veno-arterial approach is not related to the gas exchange, as the amount of oxygen transferred and CO2 removed are exactly the same (if the operating conditions of the membrane lung are the same), but to the hemodynamic impact, as the veno-arterial configuration provides both respiratory and cardiac support. The second feature is the amount of blood flow and gas flow used to ventilate the artificial lung: to oxygenate venous blood entering the membrane lung, the gas flow required equals the oxygen sufficient to fully saturate the hemoglobin passing through the artificial lung. As an example, if 1 l of venous blood with10 g/dL of hemoglobin and saturation 70% enters the membrane lung every minute, a transfer of 42 ml of 100% oxygen per minute from the gas compartment of the membrane lung would be sufficient to fully saturate the blood leaving the membrane lung. Therefore, being the possibility to “charge” oxygen limited by the hemoglobin concentration and its saturation in the venous blood, the oxygen transfer to the membrane lung is primarily function of the extracorporeal blood flow. In the previous example, 4 l of extracorporeal blood flow, in the absence of re-circulation, would provide fully saturated blood with a gas flow into the membrane lung of only 168 ml/min. All the gas is absorbed, and no gas leaves the membrane lung Table 1 Comparative technical difficulty of hemodialysis, extracorporeal removal of carbon dioxide, and extracorporeal oxygenation

Background Despite significant progress in nursing premature babies, neonatal pneumonia, along with artificial lung ventilation (ALV), is a significant factor in formation of chronic non-specific lung diseases later in life. The study aims to compare long-term effects of artificial lung ventilation sustained in the neonatal period in dependence on newborn babies` gestational age and the mechanical parameters of ventilation. Materials 127 patients aged 8–11 (84 full-term babies, 43 premature babies) who were treated in the intensive care unit of St. Petersburg Children`s Hospital No. 1 in the neonatal period, underwent follow-up examination of respiratory system. Of them, 27 children were born with the gestational age of 30–34 weeks, 16 of 35–36 weeks, and 84 at the gestational age of 37–42 weeks. The control group consisted of 43 children with uncomplicated neonatal period. Results In the neonatal period, pathology of the respiratory system was detected much more often in the premature infants (56% and 88%; p Conclusions Neonatal pneumonia, along with iatrogenic effects of resuscitation, is the dominant factor in formation of chronic nonspecific pulmonary diseases in catamnesis. Children treated in ICU in the early neonatal period should be considered a high-risk group for development of bronchopulmonary system pathology later in life, and they must be carefully supervised by pediatrician and pulmonologist.

Extracorporeal support (ECMO) is indicated in severe heart or lung failure with 80% risk of mortality. In experienced centers, overall survival to discharge ranges from 40% in cardiac arrest (ECPR) to 70% for respiratory failure in adults, 80% in children and newborns with prolonged ECMO support, severe lung injury can recover to normal function, re-defining irreversible lung injury. In the future ECMO will be automatically controlled with care out of ICU or at home.

The purpose is to review the development and current application of extracorporeal life support [ECLS, extracorporeal membrane oxygenation (ECMO)] in acute severe respiratory failure.Extracorporeal support (ECMO) is used for acute severe respiratory failure in advanced ICUs. The current survival rate is 60-70%. Three controlled trials all demonstrated 20-30% improvement in survival compared to conventional care. Patients may now be maintained awake and ambulatory with spontaneous breathing.ECMO is the next step in the algorithm for management of severe respiratory failure unresponsive to conventional care.

Acute respiratory failure, either hypoxemic or hypercapnic, arises as the consequence of an inadequate response to the respiratory workload demanded by the organism. Several, often interlaced, factors contribute to the pathophysiology of this acute syndrome, whose treatment is essentially based on the resolution of the underlying critical illness. However, the use of ventilatory support might sustain or completely replace lung function and allow the patient more time to be treated. The pursuit of a noninvasive ventilatory strategy can be considered as a first-line option. Nevertheless, endotracheal intubation and invasive mechanical ventilation should be initiated in case of a persisting or progressive condition. The aim of mechanical ventilation is to maintain an adequate alveolar ventilation and oxygen delivery, thus restoring acid-base balance and reducing the patient’s work of breathing. Among others, the well-known risk of ventilator-induced lung injury must be taken into account. Accordingly, a protective ventilatory approach must be adopted. In case of a severe refractory disease, extracorporeal membrane oxygenation (ECMO) might be the only possibility to rescue patients with an otherwise fatal respiratory failure. Again, bypassing lung function through the use of an artificial lung must be weighed against the challenges and hazards of such an advanced life support treatment.

Extracorporeal life support (ECLS) (commonly named venoarterial extracorporeal membrane oxygenation, VA-ECMO) allows cardiocirculatory assistance and blood decarboxylation and oxygenation in patients with cardiac or cardiorespiratory failure. Blood is drained from the venous system, pushed through an artificial lung for CO2 removal and oxygenation, and then backs into the systemic circulation via an artery (VA configuration). Common indications for VA-ECMO are reversible causes of cardiac failure (myocardial infarction, cardiomyopathy, myocarditis, postcardiotomy cardiac failure, or cardiac arrest) or bridge to long-term therapy (ventricular assist devices or cardiac transplantation). Over the last 10 years, VA-ECMO application has been progressively increasing with significant improvement in the outcome of patients with acute cardiocirculatory failure.

Introduction: Clinical situations and anatomic variants in tracheal stenosis (TS) are quite various so different approaches for artificial lung ventilation (ALV) during tracheal resection are required. The choice of the method of ALV depends on the extent of the lesion, the width of the lumen of the stenotic area, the presence of tracheostomy, and the stage of the operation. Aims: The aim of the study is to elaborate tactics of ALV which should provide good conditions for the surgeon as well as proper gas exchange at every stage of the operation. Methods: The tactics of ALV was developed during circular resection of the trachea in 52 patients with TS located in cervical part of the trachea. Orotracheal tube was inserted in any case. At the stage of trachea dissection and preparation for resection convective mandatory ventilation (CMV) was conducted when the orotracheal tube could be passed distal to the lesion. If the diameter of the stenotic area was too small the catheter was passed from the tube via the stenosis, and high frequency jet ventilation (HFJV) was conducted. The regimen of HFJV was selected to prevent barotrauma and hypoxemia. In the presence of tracheostoma CMV was conducted via the stoma. At the stage of anastomosis suturing the HFJV regimen was continued via the cateter. After the anastomosis completion the tube was passed to the distal trachea, and CMV was continued. Results: No complications occurred during the operation. A proper gas exchange was provided. Conclusions: The combination of CMV and HFJV provided proper conditions for surgical manipulation and adequate gas exchange at any stage of tracheal resection irrespectively of the duration of open airways period.

The treatment with a mechanical ventilator is required whenever a patient’s respiratory system becomes unable to keep the concentrations of O2 and CO2 in blood at tolerable levels. However, in particular cases, the thoracic artificial lung (TAL) can be regarded as a viable alternative to mechanical ventilation (MV). We aim at studying the effects of mechanical ventilators and thoracic artificial lungs devices will have on the cardiovascular system. We will give careful consideration to cardiovascular energetic parameters, such as left and right ventricular external work, pressure-volume area, and cardiac mechanical efficiency. We simulated both, mechanically ventilated patients who are not subject to the application of an artificial lung and patients who are provided with a thoracic artificial lung (TAL). In the case of a thoracic artificial lung, we involved in our simulation studies all the usual operating modes of a TAL, viz. series mode, parallel mode, and hybrid mode of the TAL with regard to the native lung. In particular, the presented simulation results will contribute to elucidate the specific characteristics of each of the aforementioned operating modes. Generally, the energetic variables are influenced by different values of input TAL resistance in both modes: parallel and in series. In this paper, we concentrated on simulation studies of the effects evoked by TAL assistance on cardiac energetic and some other important circulatory parameters. The simulation results presented show that at all modes of TAL assistance exists a strong dependency on the TAL input variables and on the value of the mean intrathoracic pressure which has been assumed for a given situation.

Purpose: Partial pressure of carbon dioxide (Pco2), strong ion difference (SID), and total amount of weak acids independently regulate pH. When blood passes through an extracorporeal membrane lung, Pco2 decreases. Furthermore, changes in electrolytes, potentially affecting SID, were reported. We analyzed these phenomena according to Stewart's approach. Methods: Couples of measurements of blood entering (venous) and leaving (arterial) the extracorporeal membrane lung were analyzed in 20 patients. Changes in SID, Pco2, and pH were computed and pH variations in the absence of measured SID variations calculated. Results: Passing from venous to arterial blood, Pco2 was reduced (46.5 ± 7.7 vs 34.8 ± 7.4 mm Hg, P < .001), and hemoglobin saturation increased (78 ± 8 vs 100% ± 2%, P < .001). Chloride increased, and sodium decreased causing a reduction in SID (38.7 ± 5.0 vs 36.4 ± 5.1 mEq/L, P < .001). Analysis of quartiles of {increment}Pco2 revealed progressive increases in chloride (P < .001), reductions in sodium (P < .001), and decreases in SID (P < .001), at constant hemoglobin saturation variation (P = .12). Actual pH variation was lower than pH variations in the absence of measured SID variations (0.09 ± 0.03 vs 0.12 ± 0.04, P < .001). Conclusions: When Pco2 is reduced and oxygen added, several changes in electrolytes occur. These changes cause a Pco2-dependent SID reduction that, by acidifying plasma, limits pH correction caused by carbon dioxide removal. In this particular setting, Pco2 and SID are interdependent.

New oxygenator technologies widened the application of extracorporeal life support significantly in the last decade. Currently the use is still limited within intensive care units. Compared to ventricular assist devices for heart failure, lung replacement technology is lagging behind, not allowing discharge on device. Challenges to achieve a true artificial lung for long term use are discussed in this article.

Recent studies show improved outcomes in ambulated lung failure patients. Ambulation still remains a challenge in these patients. This necessitates development of more compact and less cumbersome respiratory support specifically designed to be wearable. The Paracorporeal Ambulatory Assist Lung (PAAL) is being designed for providing ambulatory support in lung failure patients during bridge to transplant or recovery. We previously published in vitro and acute in vivo results of the PAAL. This study further evaluates the PAAL for 5 days. Five-day in vivo studies with the PAAL were conducted in 50-60 kg sheep after heparinization (activated clotting time range: 190-250 s) and cannulation with a 27 Fr. Avalon Elite dual-lumen cannula. The animals were able to move freely in a stanchion while device flow, resistance, and hemodynamics were recorded hourly. Oxygenation and hemolysis were measured daily. Platelet activation, blood chemistry, and comprehensive blood counts are reported for preoperatively, on POD 0, and POD 5. Three animals survived for 5 days. No study termination resulted from device failure. One animal was terminated on POD 0 and one animal was terminated at POD 3. The device was operated between 1.93 and 2.15 L/min. Blood left the device 100% oxygenated. Plasma-free hemoglobin ranged 10.8-14.5 mg/dl. CD62-P expression was under 10%. Minimal thrombus was seen in devices at explant. Chronic use of the PAAL in awake sheep is promising based on our study. There were no device-related complications over the study course. This study represents the next step in our pathway to eventual clinical translation.

For the patients with progressively decompensating acute or acute-on-chronic respiratory failure, the first-choice treatment remains as mechanical ventilation. Despite the consistent value of mechanical ventilation, the majority of lung specialists are aware of its limitations, in particular for the patients with advanced lung failure, and inherent drawbacks that augment disease progression. More recently, the concept of allowing the lungs to 'rest and recover' has been supported by quite a few clinical studies. The pressure and volume of gas delivered to the lungs are reduced compared with mechanical ventilation. Based on recent remarkable evidence and experiences using extracorporeal lung support (ECLS) before, during and after lung transplant, there is growing interest in and expectations for the use of ECLS beyond lung transplant to encompass the entire field of pulmonary medicine. The purpose of this review article is to provide an update on evolving ECLS technologies and their effectiveness and discuss the future of ECLS for advanced lung failure as a new subspecialty in cardiothoracic surgery.

Extracorporeal Membrane Oxygenation (ECMO) has become well established technique of the treatment of severe acute respiratory failure (Veno-Venous ECMO) or circulatory failure (Veno-Arterial ECMO) which enables effective blood oxygenation and carbon dioxide removal for several weeks. Veno-Venous ECMO (V-V ECMO ) is a lifesaving treatment of patients in whom severe ARDS makes artificial lung ventilation unlikely to provide satisfactory blood oxygenation for preventing further vital organs damage and progression to death. The protocol below regards exclusively veno-venous ECMO treatment as a support for blood gas conditioning by means of extracorporeal circuit in adult patients with severe ARDS. V-V ECMO does not provide treatment for acutely and severely diseased lungs, but it enables patient to survive the critical phase of severe ARDS until recovery of lung function. Besides avoiding patients death from hypoxemia, this technique can also prevent further progression of the lung damage due to artificial ventilation. Recent experience of ECMO treatment since the outbreak of AH1N1 influenza pandemic in 2009, along with technical progress and advancement in understanding pathophysiology of ventilator-induced lung injury, have contributed to significant improvement of the results of ECMO treatment. Putative factors related to increased survival include patients retrieval after connecting them to ECMO, and less intensive anticoagulation protocols. The aim of presenting this revised protocol was to improve the effects of ECMO treatment in patients with severe ARDS, to enhance ECMO accessibility for patients who might possibly benefit from this treatment, to reduce time until patient's connection to ECMO, and to avoid ECMO treatment in futile cases. The authors believe that this protocol, based on recent papers and their own experience, can provide help and advice both for the centers which develop V-V ECMO program, and for doctors who will refer their patients for the treatment in an ECMO center.