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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.

BACKGROUND: SARS-CoV-2 aerosolization during noninvasive positive-pressure ventilation may endanger health care professionals. Various circuit setups have been described to reduce virus aerosolization. However, these setups may alter ventilator performance. RESEARCH QUESTION: What are the consequences of the various suggested circuit setups on ventilator efficacy during CPAP and noninvasive ventilation (NIV)? STUDY DESIGN AND METHODS: Eight circuit setups were evaluated on a bench test model that consisted of a three-dimensional printed head and an artificial lung. Setups included a dual-limb circuit with an oronasal mask, a dual-limb circuit with a helmet interface, a single-limb circuit with a passive exhalation valve, three single-limb circuits with custom-made additional leaks, and two single-limb circuits with active exhalation valves. All setups were evaluated during NIV and CPAP. The following variables were recorded: the inspiratory flow preceding triggering of the ventilator, the inspiratory effort required to trigger the ventilator, the triggering delay, the maximal inspiratory pressure delivered by the ventilator, the tidal volume generated to the artificial lung, the total work of breathing, and the pressure-time product needed to trigger the ventilator. RESULTS: With NIV, the type of circuit setup had a significant impact on inspiratory flow preceding triggering of the ventilator (P < .0001), the inspiratory effort required to trigger the ventilator (P < .0001), the triggering delay (P < .0001), the maximal inspiratory pressure (P < .0001), the tidal volume (P = .0008), the work of breathing (P < .0001), and the pressure-time product needed to trigger the ventilator (P < .0001). Similar differences and consequences were seen with CPAP as well as with the addition of bacterial filters. Best performance was achieved with a dual-limb circuit with an oronasal mask. Worst performance was achieved with a dual-limb circuit with a helmet interface. INTERPRETATION: Ventilator performance is significantly impacted by the circuit setup. A dual-limb circuit with oronasal mask should be used preferentially.

The method of determining the accumulation of condensate by registering the noise level in the respiratory circuit of ventilators is substantiated. According to the proposed method, the condition and performance of the apparatus is monitored during artificial lung ventilation and oxygen therapy. With hardware ventilation, an increasing turbulent flow of a water or gas stream is formed in the respiratory circuit, accompanied by an increase in the noise effect and vibration. An increase in the level of acoustic noise from fluctuations in the accumulation of condensate in gaseous media was recorded by an instrument for objective measurement of sound level a sound level meter. Indicators of noise effects reached a higher level on the wet circuit (the presence of condensation droplets or accumulations of mucus) of the liquid compared with the indicators obtained on the dry breathing circuit. The difference in recorded noise levels reached 10 dB, and increased from 37,73 to 47,36 dB. Areas of the respiratory circuit with the greatest degree of narrowing of the lumen and critical accumulations of water condensate and mucus are a source of turbulence in the air flow and increased noise. In conditions of prolonged artificial ventilation of the lungs, the rate of humidified air-gas flow is constantly changing, especially with hardware modeling of the phases of inspiration and expiration, and an increase in temperature in the humidifier chamber. The proposed technique is designed to identify critical levels of water condensate in the apparatus breathing circuits by recording the intensity of the increase in noise level and choosing the rational mode of operation of medical equipment. Data on the emerging critical situation are displayed on the sound level meter screen and inform medical personnel about the need to rehabilitate the circuit of the artificial lung ventilation apparatus. The primary field of application is resuscitation and intensive care units, medical transport teams during in-hospital or inter-hospital transportation, and surgical operating rooms during inhalation anesthesia.

Background A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way. Methods The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2-2.5 L/min and 28-30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support. Results Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment. Conclusions These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.

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.

Annals of biomedical engineering 48(2), 747-756 (2020). doi:10.1007/s10439-019-02401-2, Published by Springer Science + Business Media B.V, Dordrecht [u.a.]

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.

Extracorporeal membrane oxygenation (ECMO) has become a mainstay of therapy for patients suffering from severe respiratory failure. Ambulatory ECMO systems aim to provide long-term out-of-hospital respiratory support. As a patient’s activity level changes, the required level of ECMO support varies with oxygen consumption and metabolic fluctuations. To compensate for such changes, an Auto-Regulatory ECMO system (AR-ECMO) has been developed and its performance was evaluated as a proof-of-concept in an acute ovine model. The AR-ECMO system consists of a regular ECMO circuit and an electromechanical control system. A custom fuzzy-logic control algorithm was implemented to adjust the blood flow and sweep gas flow of the ECMO circuit to meet the varying respiratory demand by utilizing two noninvasive sensors for venous oxyhemoglobin saturation and the oxygenator exhaust gas CO2 concentration. Disturbance responses of the AR-ECMO to induced acute respiratory distress were assessed for six hours in four juvenile sheep cannulated with a veno-pulmonary artery ECMO configuration, including acute ventilator shutoff, ventilator step-change (off-on-off), and forced desaturation. All sheep survived for the study duration. The AR-ECMO system was able to respond and maintain stable hemodynamics and physiological blood gas contents (SpO(2) = 96.3 % ± 4.29, pH = 7.44 ± 0.09, pCO(2) = 38.9 ± 9.9 mmHg, and pO(2) =237.9 ± 123.6 mmHg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO(2) and oxygenator outlet pCO(2) were observed (R(2)= 0.84). In summary, the AR-ECMO system successfully maintained physiologic control of peripheral oxygenation and carbon dioxide over the study period, utilizing only measurements taken directly from the ECMO circuit. The range of system response necessitates an adaptable system in the setting of variable metabolic demands. The ability of this system to respond to significant disturbances in ventilator support is encouraging. Future work to evaluate our AR-ECMO system in long-term, awake animal studies is necessary for further refinement.

Although lung transplantation can be used to treat lung failure, limited donor organ availability creates a pressing need for improved artificial lung technology. This review discusses recent developments and future research pathways for respiratory assist devices and regenerative therapies intended to treat advanced lung disease. Hollow fiber membrane gas exchangers can be used to bridge lung failure patients to transplantation. Engineering improvements to such devices are on the verge of enabling longer term wearable systems that simplify and improve support. Progress with microchannel-based devices provides hope of smaller, more biomimetic devices that may even enable implantation; however, further development and testing are needed. Advances in cell-based technologies and tissue engineering have enabled early proof of concept of bioartificial lungs with properties similar to the native organ. Recent progress with artificial lungs has enabled better treatment as a bridge therapy. Continued advances in both engineering and biology will be necessary to achieve a truly implantable artificial lung capable of destination therapy.

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.

Herein we describe the modular design and manufacturing of an emergency ventilator based on cyclical compression of a resuscitation bag to face the COVID-19 pandemic. This was done to mitigate the staggering conditions to supply these medical devices under challenging scenarios of need and logistics. The design is based on international standards and commissions for medical electrical equipment, particular requirements for basic safety, electromagnetic compatibility, and essential performance of critical care and emergency ventilators. The modular design is capable of providing four ventilation modes: volume/pressure mandatory ventilation and volume/pressure assisted ventilation. After testing with artificial lungs, calibration, and validation instruments it was found that the main ventilation parameters achieved are: maximum tidal volume of 700 mL, maximum pressure of 50 cmH2O, inspiration/expiration ratio up to 1:4 at 30 breaths per minute. The MEDIIK designation is derived from the mayan word ik’ which means wind.

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.

We consider the problem of controlling an invasive mechanical ventilator for pressure-controlled ventilation: a controller must let air in and out of a sedated patient’s lungs according to a trajectory of airway pressures specified by a clinician.Hand-tuned PID controllers and similar variants have comprised the industry standard for decades, yet can behave poorly by over- or under-shooting their target or oscillating rapidly.We consider a data-driven machine learning approach: First, we train a simulator based on data we collect from an artificial lung. Then, we train deep neural network controllers on these simulators. We show that our controllers are able to track target pressure waveforms significantly better than PID controllers.We further show that a learned controller generalizes across lungs with varying characteristics much more readily than PID controllers do.

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.

In this article, we introduce a portable and low-cost ventilator that could be rapidly manufactured, to meet the increasing demand of ventilators worldwide produced by COVID-19 pandemic. These ventilators should be rapidly deployable and with functional capabilities to manage COVID-19 patients with severe acute respiratory distress syndrome (ARDS). Our implementation offers robustness, safety and functionality absent in existing solutions to the ventilator shortage (i.e., telemonitoring, easy-to-disinfect, modularity) by maintaining simplicity. The design makes use of a manual resuscitator as the core respiration component activated by a compression mechanism which consist of two electronically controlled paddles. The quality measurements obtained after testing on a calibrated artificial lung demonstrate repeatability and accuracy exceeding human capabilities of manual ventilation. The complete design files are provided in the supplementary materials to facilitate ventilator production even in resource-limited settings. The implementation of this mechanical ventilator could eliminate device rationing or splitting to serve multiple patients on ICUs. (C) 2021 Pontificia Universidad Catolica del Peru. Published by Elsevier Ltd. This work has been funded by the 055-2020-FONDECYT GRANT from the Peruvian government and the donations of the enterprises mentioned in our webpage: https://www.proyectomasi.pe/.In addition,the authors would like to thank to all the members of the Masi team, especially to all of the collaborators working at the five institutions involved in this project (BREIN, DIACSA, EAT, PUCP and Zolid). Without all of their effort, professionalism and sacrifice while working steadily during the pandemic; this device would have not existed.

Cardiovascular engineering and technology : CVET 13(2), 318-330 (2022). doi:10.1007/s13239-021-00579-y, Published by Springer, New York, NY

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.

Mechanical ventilators are the instruments that assist breathing of the patients having respiratory diseases e.g., pneumonia and coronavirus disease 2019 (COVID-19). This paper presents a modified lung model under volume-controlled ventilation to describe the lung volume and air flow in terms of air pressure signal from the ventilator. A negative feedback is incorporated in the model to balance the lung volume that is influenced by a lung parameter called positive end expiration pressure. We partially solved the lung model equation which takes the form of a first-order differential equation and then unknown parameters associated with the model were computed using a nonlinear least-squares method. Experimental data required for parameter identification and validation of the lung model were obtained by running a volume-controlled ventilator connected to a reference device and an artificial lung. The proposed model considering negative feedback achieves a better accuracy than that without feedback as demonstrated by test results. The developed model can be used in intensive care units (ICU) to evaluate mechanical ventilation performance and lung functionality in real-time.

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.

Purpose Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration (“pulsed delivery”), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5–40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes.

Mechanical Ventilation is used to support the respiratory system malfunction by assisting recovery breathing process which could result from diseases and viruses such as pneumonia and COVID-19. Mathematical models are used to study and simulate the respiratory system supported by mechanical ventilation using different modes such as volume-controlled ventilation (VCV). In this research, a single compartment lung model ventilated by VCV is developed during real time mechanical ventilation using pressure signal. This mathematical model describes the lung volume and compliance correctly considering positive end expiration pressure (PEEP) value. The model is implemented using LabVIEW tools and can be used to monitor the volume, flow and compliance as outputs of the model. Two experiments are carried out on the proposed lung model at three input scenarios of volume (400, 500 and 600 ml) for each experiment considering a PEEP value. To validate the model, an artificial lung connected to a VCV with the same scenarios is used. Validation check is conducted by comparing the outputs of the lung model to that of the artificial lung. The experimental results showed that the measured lung model outputs with negative feedback are the same for pressure and flow as the outputs without negative feedback, whereas the measured volume is comparatively lower for negative feedback. Average percent error in the experiment with negative feedback (5.14%) is smaller compared to the experiment without negative feedback (9.28%). Furthermore, the average error of the calculated compliance decreases from 16% (without negative feedback) to 2% (with negative feedback). The obtained results of the proposed method showed good performance and acceptable accuracy. Thus, the model facilitates the clinicians and practitioners as a training tool to learn real-time mechanical ventilation functionalities.

Objectives Minimally invasive extracorporeal CO2 removal is an accepted supportive treatment in chronic obstructive pulmonary disease patients. Conversely, the potential of such technique in treating acute respiratory distress syndrome patients remains to be investigated. The aim of this study was: 1) to quantify membrane lung CO2 removal (VCO2ML) under different conditions and 2) to quantify the natural lung CO2 removal (VCO2NL) and to what extent mechanical ventilation can be reduced while maintaining total expired CO2 (VCO2tot = VCO2ML + VCO2NL) and arterial PCO2 constant. Design Experimental animal study. Setting Department of Experimental Animal Medicine, University of Gottingen, Germany. Subjects Eight healthy pigs (57.7 ± 5 kg). Interventions The animals were sedated, ventilated, and connected to the artificial lung system (surface 1.8 m, polymethylpentene membrane, filling volume 125 mL) through a 13F catheter. VCO2ML was measured under different combinations of inflow PCO2 (38.9 ± 3.3, 65 ± 5.7, and 89.9 ± 12.9 mm Hg), extracorporeal blood flow (100, 200, 300, and 400 mL/min), and gas flow (4, 6, and 12 L/min). At each setting, we measured VCO2ML, VCO2NL, lung mechanics, and blood gases. Measurements and main results VCO2ML increased linearly with extracorporeal blood flow and inflow PCO2 but was not affected by gas flow. The outflow PCO2 was similar regardless of inflow PCO2 and extracorporeal blood flow, suggesting that VCO2ML was maximally exploited in each experimental condition. Mechanical ventilation could be reduced by up to 80-90% while maintaining a constant PaCO2. Conclusions Minimally invasive extracorporeal CO2 removal removes a relevant amount of CO2 thus allowing mechanical ventilation to be significantly reduced depending on extracorporeal blood flow and inflow PCO2. Extracorporeal CO2 removal may provide the physiologic prerequisites for controlling ventilator-induced lung injury.

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.

Although the fundamentals of extracorporeal membrane oxygenation (ECMO) have not changed in 3 decades, the technical elements continue to improve and have evolved from an assemblage of individual components to more integrated systems with added features, enhanced safety, and improved maneuverability. The introduction of polymethylpentene (PMP) fiber technology has expanded the development of artificial membranes that have low resistance, are more biocompatible, and can be used for extended durations. Extracorporeal carbon dioxide removal techniques continue to be enhanced as stand alone technology and modified renal dialysis systems are introduced. Research continues in the development of compact and wearable artificial lungs that are intended to support patients for prolonged periods (eg, patients awaiting lung transplantation). The use of high-fidelity simulation training has become a standard and important method for reinforcing technical skills, refining troubleshooting sequences, and enhancing team interactions. Modifications to mannequins and ECMO systems coupled with clinical and physiologic scenarios will help achieve greater realism and enhance learning. ECMO technology continues to improve, with adaptability and versatility being essential attributes.

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.

Background Extracorporeal carbon dioxide removal (ECCO2R) systems have gained clinical appeal as supplemental therapy in the treatment of acute and chronic respiratory injuries with low tidal volume or non-invasive ventilation. We have developed an ultra-low-flow ECCO2R device (ULFED) capable of operating at blood flows comparable to renal hemodialysis (250 mL/min). Comparable operating conditions allow use of minimally invasive dialysis cannulation strategies with potential for direct integration to existing dialysis circuitry. Methods A carbon dioxide (CO2) removal device was fabricated with rotating impellers inside an annular hollow fiber membrane bundle to disrupt blood flow patterns and enhance gas exchange. In vitro gas exchange and hemolysis testing was conducted at hemodialysis blood flows (250 mL/min). Results In vitro carbon dioxide removal rates up to 75 mL/min were achieved in blood at normocapnia (pCO2 = 45 mmHg). In vitro hemolysis (including cannula and blood pump) was comparable to a Medtronic Minimax oxygenator control loop using a time-of-therapy normalized index of hemolysis (0.19 ± 0.04 g/100 min versus 0.12 ± 0.01 g/100 min, p = 0.169). Conclusions In vitro performance suggests a new ultra-low-flow extracorporeal CO2 removal device could be utilized for safe and effective CO2 removal at hemodialysis flow rates using simplified and minimally invasive connection strategies.

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.

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O2 min−1 m−2 cm Hg−1 with pure water and 1.71 ± 1.03 mL O2 min−1 m−2 cm Hg−1 with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.

Status asthmaticus is a life-threatening disorder that can manifest in dangerous levels of hypercapnia and acidosis. The use of extracorporeal carbon dioxide removal (ECCO2R) has been used successfully to control pH and PaCO2 in patients with acute severe asthma. The present report describes the use of this technology in near-fatal asthma with brain death, and awaiting organ harvest.The ProLUNG® system consists of a veno-venous hemoperfusion circuit with an artificial lung polymethylpentene membrane coated with phosphorylcholine with a surface of 1.81 m2. The system can reach a blood flow of 450 ml/min trough a double-lumen central venous catheter (13.0 Fr) placed in femoral, subclavian or jugular vein. The platform is provided with automated management of airflow and VCO2 monitoring during treatment.The patient was maintained on extracorporeal treatment ensuring stable arterial pH control and PaCO2 control.In acute status asthmaticus, complicated with cardiac arrest, mini-invasive ECCO2R was an effective method of controlling pH and PaCO2, for optimizing hemodynamic and aerobic metabolism and for performing protective ventilation for an optimal organ donor preservation until the organ harvest occurs. Keywords: Acute hypercapnic respiratory failure, Extracorporeal carbon dioxide removal, Hypercapnia, Near-fatal asthma, Respiratory dialysis, Status asthmaticus

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.

Ambulating patients on extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R) improves outcomes. These systems would further simplify ambulation if made more compact. This study investigates blood recirculation to decrease device size by increasing efficiency. The required hollow fiber membrane (HFM) area was determined by numerically modeling gas transfer. An oxygenation device with recirculating blood flow was designed using computational fluid dynamics (CFD). Hydrodynamic performance and shear stresses of the device were analyzed using CFD at 2,000, 2,250 and 2,500 RPM. A prototype (0.38 m) was manufactured for in-vitro oxygenation testing. Oxygenation was measured at a constant 3.5 L/min blood flow while recirculation flow rate varied up to 6.5 L/min. Hemolysis was measured at 3.5 L/min blood flow and 6.5 L/min recirculation flow. A 0.3 m prototype device was used to test in-vitro ECCO2R recirculation at a constant 500 ml/min blood flow rate and recirculation flow rates up to 5.5 L/min. Computational fluid dynamics analysis showed that the oxygenation device could produce over 250 mm Hg while maintaining 3.5 L/min blood flow and 6.5 L/min recirculation flow. The model predicted oxygenation within 8% and overestimated ECCO2R by up to 32%. Measured gas transfer was 180 ml O2/min and 62 ml CO2/min. Normalized index of hemolysis contribution of the HFM was 0.012 gm/100 L.

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

Chronic lung disease is the 4th leading cause of death in the United States. Due to a shortage of donor lungs, alternative approaches to support failing, native lungs have been attempted, including mechanical ventilation and various forms of artificial lungs. However, each of these support methods causes significant complications when used for longer than a few days and are thus not capable of long-term support. For artificial lungs, complications arise due to interactions between the artificial materials of the device and the blood of the recipient. A potential new approach is the fabrication of lungs from biological materials, such that the gas exchange membranes provide a more biomimetic blood-contacting interface. Recent advancements with three-dimensional, soft-tissue biofabrication methods and the engineering of thin, basement membranes demonstrate the potential of fabricating a lung scaffold from extracellular matrix materials. This scaffold could then be seeded with endothelial and epithelial cells, matured within a bioreactor, and transplanted. In theory, this fully biological lung could provide improved, long-term biocompatibility relative to artificial lungs, but significant work is needed to perfect the organ design and construction methods. Like artificial lungs, biofabricated lungs do not need to follow the shape and structure of a native lung, allowing for simpler manufacture. However, various functional requirements must still be met, including stable, efficient gas exchange for a period of years. Design decisions depend on the disease state, how the organ is implanted, and the latest biofabrication methods available in a rapidly evolving field.

Respiratory failure is one of the major causes of mortality and morbidity all over the world. Therapeutic options to treat respiratory failure remain limited. The objective of this study was to evaluate the gas transfer performance of a newly developed miniature portable integrated pediatric pump-lung device (PediPL) with small membrane surface for respiratory support in an acute ovine respiratory failure model. The respiratory failure was created in six adult sheep using intravenous anesthesia and reduced mechanical ventilation at 2 breaths/min. The PediPL device was surgically implanted and evaluated for respiratory support in a venovenous configuration between the right atrium and pulmonary artery. The hemodynamics and respiratory status of the animals during support with the device gas transfer performance of the PediPL were studied for 4 h. The animals exhibited respiratory failure 30 min after mechanical ventilation was reduced to 2 breaths/min, indicated by low oxygen partial pressure, low oxygen saturation, and elevated carbon dioxide in arterial blood. The failure was reversed by establishing respiratory support with the PediPL after 30 min. The rates of O2 transfer and CO2 removal of the PediPL were 86.8 and 139.1 mL/min, respectively. The results demonstrated that the PediPL (miniature integrated pump-oxygenator) has the potential to provide respiratory support as a novel treatment for both hypoxia and hypercarbia. The compact size of the PediPL could allow portability and potentially be used in many emergency settings to rescue patients suffering acute lung injury.

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.

Rationale. The nitrogen oxide molecule (NO) is a fundamental factor of the anti-infectious resistance of an organism. Research objective. To evaluate the effectiveness and safety of the prevention of sepsis by the inhalation of nitrogen oxide (iNO) in newborns with respiratory pathology on artificial pulmonary ventilation. Methods. Controlled, randomized, blind clinical trial included 97 newborns with respiratory pathology for artificial pulmonary ventilation. Patients received standard intensive therapy. The main group (n=44) received inhaled nitrogen oxide. The control group (n=53) did not receive inhaled nitrogen oxide. On Days 1, 3, and 20, the plasma concentrations of IL-1s, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, and nitrogen oxide were measured by capture ELISA. Results. Inhaled nitrogen oxide as a part of intensive care decreased the rate of sepsis development, the duration of mechanical ventilation, and the period of hospitalization. It provided a tendency towards a decrease in the rate of lethal outcomes and reduced cytokine aggression. Conclusions. Inhaled nitrogen oxide in standard intensive care effectively and safely prevented the development of sepsis in newborns with respiratory pathology on artificial lung ventilation. A decrease in the concentration of pro-inflammatory cytokines, including IL-6, against the background of nitrogen oxide inhalation, confirmed the possibility of using inhaled nitrogen oxide as a therapy for COVID-19.

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.

Background There is increasing evidence demonstrating the value of partial extracorporeal CO2 removal (ECCO2R) for the treatment of hypercapnia in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. Mechanical ventilation has traditionally been used to treat hypercapnia in these patients, however, it has been well-established that aggressive ventilator settings can lead to ventilator-induced lung injury. ECCO2R removes CO2 independently of the lungs and has been used to permit lung protective ventilation to prevent ventilator-induced lung injury, prevent intubation, and aid in ventilator weaning. The Low-Flow Pittsburgh Ambulatory Lung (LF-PAL) is a low-flow ECCO2R device that integrates the fiber bundle (0.65 m2) and centrifugal pump into a compact unit to permit patient ambulation. Methods A blood analog was used to evaluate the performance of the pump at various impeller rotation rates. In vitro CO2 removal tested under normocapnic conditions and 6-h hemolysis testing were completed using bovine blood. Computational fluid dynamics and a mass-transfer model were also used to evaluate the performance of the LF-PAL. Results The integrated pump was able to generate flows up to 700 mL/min against the Hemolung 15.5 Fr dual lumen catheter. The maximum vCO2 of 105 mL/min was achieved at a blood flow rate of 700 mL/min. The therapeutic index of hemolysis was 0.080 g/(100 min). The normalized index of hemolysis was 0.158 g/(100 L). Conclusions The LF-PAL met pumping, CO2 removal, and hemolysis design targets and has the potential to enable ambulation while on ECCO2R.

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.

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) is increasingly being used as a rescue therapy in patients with severe cardiac and/or respiratory failure. During ECMO, circulating blood from a patient is exteriorised onto the artificial surfaces of circuit tubing and an “artificial lung” (i.e. the oxygenator) membrane in order to provide circulatory and respiratory support. ECMO has been shown to exacerbate the pharmacokinetic (PK)/pharmacodynamic (PD) alterations observed during critical illness for some drugs leading to potential therapeutic failure or toxicity. An increase in volume of distribution and a decrease in drug clearance appear to be the predominant PK alterations induced by ECMO. Sequestration of drugs in the ECMO circuit and pathophysiologic changes induced by ECMO both appear to contribute to these ECMO-induced PK alterations. An advanced understanding of the PK/PD alterations in the setting of ECMO is critical to antibiotic drug dosing in these complex patients pending robust dosing guidelines.

AIM To determine the ability of intrapulmonary percussive ventilation (IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation. METHODS An artificial lung was used to simulate a spontaneously breathing patient (Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation (Group 2). An 8.5 mm endotracheal tube (ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally (mouth-piece filter) and distally (lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus. RESULTS In Group 1 (spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2 (the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung (P < 0.01). There was an overall statistically significant amount of mucus movement proximally towards the mouth-piece in the spontaneously breathing (SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated (MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.

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.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used to support adults with severe forms of respiratory failure. Fueling the explosive growth is a combination of technological improvements and accumulating, although controversial, evidence. Current use of ECMO extends beyond its most familiar role in the support of patients with severe acute respiratory distress syndrome (ARDS) to treat patients with various forms of severe hypoxemic or hypercapnic respiratory failure, ranging from bridging patients to lung transplantation to managing pulmonary hypertensive crises. The role of ECMO used primarily for extracorporeal carbon dioxide removal (ECCO2R) in the support of patients with hypercapnic respiratory failure and less severe forms of ARDS is also evolving. Select patients with respiratory failure may be liberated from invasive mechanical ventilation altogether and some may undergo extensive physical therapy while receiving extracorporeal support. Current research may yield a true artificial lung with the potential to change the paradigm of treatment for adults with chronic respiratory failure.

Patients assisted with left ventricular assist device (LVAD) may require prolonged mechanical ventilatory assistance secondary to postoperative respiratory failure. The goal of this work is the study of the interdependent effects LVAD like pulsatile catheter (PUCA) pump and mechanical ventilatory support or thoracic artificial lung (TAL), by the hemodynamic point of view, using a numerical simulator of the human cardiovascular system. In the simulator, different circulatory sections are described using lumped parameter models. Lumped parameter models have been designed to describe the hydrodynamic behavior of both PUCA pump and thoracic artificial lung. Ventricular behavior atrial and septum functions were reproduced using variable elastance model. Starting from simulated pathological conditions we studied the effects produced on some hemodynamic variables by simultaneous PUCA pump, thoracic artificial lung or mechanical ventilation assistance. Thoracic artificial lung was applied in parallel or in hybrid mode. The effects of mechanical ventilation have been simulated by changing mean intrathoracic pressure value from -4mmHg to +5mmHg. The hemodynamic variables observed during the simulations, in different assisted conditions, were: left and right ventricular end systolic (diastolic) volume, systolic/diastolic aortic pressure, mean pulmonary arterial pressure, left and right mean atrial pressure, mean systemic venous pressure and the total blood flow. Results show that the application of PUCA (without mechanical ventilatory assistance) increases the total blood flow, reduces the left ventricular end systolic volume and increases the diastolic aortic pressure. Parallel TAL assistance increases the right ventricular end diastolic (systolic) volume reduction both when PUCA is switched ''ON'' and both when PUCA is switched ''OFF''. By switching ''OFF'' the PUCA pump, it seems that parallel thoracic artificial lung assistance produces a greater cardiac output (respect to hybrid TAL assistance). Results concerning PUCA and TAL interaction produced by simulations cannot be compared with ''in vivo'' results since they are not presented in literature. But results concerning the effects produced by LVAD and mechanical ventilation have a trend consistent with those presented in literature.