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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.

Microfluidic artificial lungs (µALs) have the potential to improve the treatment and quality of life for patients with acute or chronic lung injury. In order to realize the full potential of this technology (including as a destination therapy), the biocompatibility of these devices needs to be improved to produce long-lasting devices that are safe for patient use with minimal or no systemic anticoagulation. Many studies exist which probe coagulation and thrombosis on polydimethyl siloxane (PDMS) surfaces, and many strategies have been explored to improve surface biocompatibility. As the field of µALs is young, there are few studies which investigate biocompatibility of functioning µALs; and even fewer which were performed in vivo. Here, we use both in vitro and in vivo models to investigate two strategies to improve µAL biocompatibility: 1) a hydrophilic surface coating (polyethylene glycol, PEG) to prevent surface fouling, and 2) the addition of nitric oxide (NO) to the sweep gas to inhibit platelet activation locally within the µAL. In this study, we challenge µALs with clottable blood or platelet-rich plasma (PRP) and monitor the resistance to blood flow over time. Device lifetime (the amount of time the µAL remains patent and unobstructed by clot) is used as the primary indicator of biocompatibility. This study is the first study to: 1) investigate the effect of NO release on biocompatibility in a microfluidic network; 2) combine a hydrophilic PEG coating with NO release to improve blood compatibility; and 3) perform extended in vivo biocompatibility testing of a µAL. We found that µALs challenged in vitro with PRP remained patent significantly longer when the sweep gas contained NO than without NO. In the in vivo rabbit model, neither approach alone (PEG coating nor NO sweep gas) significantly improved biocompatibility compared to controls (though with larger sample size significance may become apparent); while the combination of a PEG coating with NO sweep gas resulted in significant improvement of device lifetime. STATEMENT OF SIGNIFICANCE: The development of microfluidic artificial lungs (µALs) can potentially have a massive impact on the treatment of patients with acute and chronic lung impairments. Before these devices can be deployed clinically, the biocompatibility of µALs must be improved and more comprehensively understood. This work explores two strategies for improving biocompatibility, a hydrophilic surface coating (polyethylene glycol) for general surface passivation and the addition of nitric oxide (NO) to the sweep gas to quell platelet and leukocyte activation. These two strategies are investigated separately and as a combined device treatment. Devices are challenged with clottable blood using in vitro testing and in vivo testing in rabbits. This is the first study to our knowledge that allows statistical comparisons of biocompatible µALs in animals, a key step towards eventual clinical use.

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.

Electrical impedance tomography (EIT) is an intensively researched noninvasive diagnostic method for medical use, that can help to improve the lung diagnostics, artificial lung ventilation and prevent lung injuries. Further improvements of reconstruction algorithms and measurement devices are essential to widen the use of EIT as a lung diagnostic method. To test potential of Radial Basis Neural Networks (RBNN) and Hopfield Neural Networks (HNN) for image reconstruction experiment is carried. Said neural networks are compared with Gauss – Newton (GN) algorithm. Results of the experiment show higher reconstruction accuracy with RBNN and HNN over GN algorithm.

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.

State of the art artificial membrane lungs incorporate hollow fiber membranes. The creeping blood flow in hollow fiber bundles forms a boundary layer that represents a diffusive resistance to gas transfer. Advances in additive manufacturing allow for the fabrication of novel membrane designs that overcome this limitation. The goal of this study is fabrication and subsequent experimental evaluation of blood gas transfer of novel membrane designs based on triply periodic minimal surface (TPMS) geometries in comparison to the predominantly present hollow fiber geometry. A fabrication process was established based on a casting process with a dissolvable 3D-printed mold. Modules were manufactured containing different membrane designs: three TPMS designs, namely Schwarz-P (SWP), Schwarz-D (SWD), Schoen-G (SGY), and a hollow fiber shaped design (HFM) as reference. Each membrane consists of silicone and has a wall thickness of 800 μm. To assure comparable results, the design of the module considers matching inlet conditions, smallest membrane distance and the same gas exchange area. Gas transfer was tested in vitro under standardized conditions in accordance with ISO 7199 for blood gas exchangers. The oxygen transfer rate for TPMS geometries is at least by 26% and up to 69.8% higher than the state of the art hollow fiber design within a flow range of 20–100 mL/min.

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.

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.

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.

Recently, physical modelling of human and animal organs has become very popular. The objective of this invention was to construct a physical lung model – an apparatus comprising an artificial lung and an automatic self-controlled system working on a principle of a negative feedback loop. This contribution is focused mainly on the function of the control system with a special attention paid to the sensor network. The control system is equipped with sensors measuring various physical variables (e.g. air flow, pressure difference) necessary for a proper system operation. Sampling frequency, sensorstype and their accuracy play an important part in the quality of measurement and directly affect the accuracy of the control response. The physical lung model and the sensor system have been successfully built and fully completed from the hardware and software's point of view. In the future, this lung model is expected to be used in different testing applications, e.g. in studies comparing physiological and pathological breathing patterns or observing effects of different aerosols on the lung tissue.

Background Conventional extracorporeal membrane oxygenation is bulky and non-ambulatory and requires multiple blood transfusions. We hypothesized that a percutaneous, paracorporeal artificial lung (PAL) could be established through a single venous cannulation to provide long-term ambulatory respiratory support. Methods Our PAL system was tested in 11 healthy sheep. An Avalon Elite dual-lumen cannula (DLC), inserted through the right jugular vein into the superior vena cava, right atrium, and inferior vena cava, was connected to a CentriMag pump and compact hollow-fiber gas exchanger, forming a short-circuit PAL system. All sheep were moved to intensive care unit and were ambulatory after anesthesia recovery. Hemodynamics and device performance were measured daily. Results The ambulatory PALs were successfully established in all sheep. The sheep were awake, ate, and moved freely in the metabolic cage, with no need of artificial nutrition or blood transfusion. All sheep had stable hemodynamics, with 2 liters/min of average circuit flow and hemoglobin levels exceeding 9.2 g/dl throughout the experiment. A progressive decrease of oxygen transfer and carbon dioxide removal capacity was observed. Sheep were euthanized between 10 and 24 days for bleeding ( n = 2), gas exchanger failure ( n = 6), and DLC issues ( n = 3). Conclusions We successfully established long-term ambulatory PAL for up to 24 days in 11 animals using our patented DLC through a single-site percutaneous venous cannulation. Critical bleeding/thrombosis formation and gas exchanger durability remain two major challenges for long-term-ambulatory PAL.

To compare a novel, pressure-limited, flow adaptive ventilator that enables manual triggering of ventilations (MEDUMAT Easy CPR, Weinmann, Germany) with a bag-valve-mask (BVM) device during simulated cardiac arrest.Overall 74 third-year medical students received brief video instructions (BVM: 57s, ventilator: 126s), standardised theoretical instructions and practical training for both devices. Four days later, the students were randomised into 37 two-rescuer teams and were asked to perform 8min of cardiopulmonary resuscitation (CPR) on a manikin using either the ventilator or the BVM (randomisation list). Applied tidal volumes (V(T)), inspiratory times and hands-off times were recorded. Maximum airway pressures (P(max)) were measured with a sensor connected to the artificial lung. Questionnaires concerning levels of fatigue, stress and handling were evaluated. V(T), pressures and hands-off times were compared using t-tests, questionnaire data were analysed using the Wilcoxon test.BVM vs. ventilator (mean±SD): the mean V(T) (408±164ml vs. 315±165ml, p=0.10) and the maximum V(T) did not differ, but the number of recorded V(T)200ml differed (8.1±11.3 vs. 17.0±14.4 ventilations, p=0.04). P(max) did not differ, but inspiratory times (0.80±0.23s vs. 1.39±0.31s, p0.001) and total hands-off times (133.5±17.8s vs. 162.0±11.1s, p0.001) did. The estimated levels of fatigue and stress were comparable; however, the BVM was rated to be easier to use (p=0.03).For the user group investigated here, this ventilator exhibits no advantages in the setting of simulated CPR and carries a risk of prolonged no-flow time.

Patients who are excellent candidates for lung transplantation often die on the waiting list because they are too sick to survive until an organ becomes available. Improvements in lung transplant outcomes, patient selection, and artificial lung device technologies have made it possible to bridge these patients to successful life-saving transplantation. Extracorporeal life support (ECLS) should be tailored to minimize morbidity and provide the appropriate mode and level of cardiopulmonary support for each patient's physiologic requirements. Novel device refinements and further development of ECLS in an ambulatory and simplified manner will help maintain these patients in better condition until transplantation.

Cardiopulmonary bypass (CPB) allows cardiac surgery to be performed in a motionless, bloodless surgical field. It incorporates an extracorporeal circuit to provide physiological support. Typically, blood is gravity drained from the heart and lungs to a reservoir via venous cannulation and tubing, and returned oxygenated to the arterial system by utilizing a pump and artificial lung (oxygenator or gas exchanger). In the last 20 yr, improvements in CPB have occurred rapidly due to advances in biomaterials, manufacturing, computer microsystem technology, and electronics.

This study examined the effects of multiple mechanical forces on gas exchange and hemolysis in intravascular lung assist devices (IVLAD). Specific attention was paid to on the effect of membrane vibration. This study adhered to the recommended practice for the assessment of hemolysis described by the American Society of Testing and Materials (ASTM). The results showed a higher oxygen (O 2 ) transfer rate and carbon dioxide (CO 2 ) removal rate in each excited frequency bandwidth than those without vibration. The maximum oxygen transfer and carbon dioxide removal rate occurred at frequency band of 7 Hz. The gas exchange improved maximum 52%. The plasma-free hemoglobin was 11.2 ± 0.57 and 14.4 ± 0.74 mg/100 ml by exciting a piezo-vibrator with a sinusoidal wave magnitude of DC10 V and DC50 V, respectively. The NIHO value was determined to be 59 ± 2.76 and 95 ± 4.32 mg/100 ml by exciting a piezo-vibrator with a sinusoidal wave magnitude of DC10 V and DC50 V, respectively. In conclusion, piezoelectric lead zirconate titanate (PZT) materials are exciting systems for improving the oxygen transfer efficiency and blood suitability of hollow fiber membrane in the development of new IVLAD.

Background There is no mechanical device available to support patients with end-stage lung failure for weeks and months until appropriate donor organs for lung transplantation are available. Methods In a 38-year-old female patient with primary pulmonary hypertension a paracorporeal artificial lung (PAL) system was placed parallel to the pulmonary circulation with connections to the pulmonary artery and to the left atrium. The key component of the PAL was a low-resistance membrane oxygenator. Results After institution, the PAL had a blood flow of 3.5 L/min and created a PaO 2 /fraction of inspired oxygen ratio of 270, while the oxygenator was provided with oxygen 3L/min. The pulmonary artery pressure declined by almost 50%. The PAL worked well over 62 days until appropriate donor lungs were available. With resuming more physical activity, an increased flow through the native lung augmented the fraction of unsaturated blood arriving at the left atrium, which mandated increasing oxygen flow to the PAL. Conclusions The data obtained with this case encourage further research into PAL systems, which may hopefully serve as a bridge to lung transplant device in appropriate patients in the future.

Background A thoracic artificial lung, the MC3 Biolung, is being developed as a bridge to lung transplantation or as a treatment for acute respiratory insufficiency. Methods The thoracic artificial lung was tested in 10 sheep with the goal of 7 days of respiratory support. The sheep were recovered from surgery and monitored awake for 7 days. Hemodynamics, blood gases, blood cell counts, and organ function were recorded, and after 7 days, all sheep were euthanized and necropsied. Results Seven sheep survived the full duration. Cardiac output and mean arterial blood pressure were unchanged, averaging 4.7 ± 0.8 L/min and 98 ± 10 mm Hg, respectively. Arterial oxygen tension and device oxygen transfer rate were also unchanged, averaging 110 ± 26 mm Hg and 97.7 ± 35 mL/min, respectively. Arterial carbon dioxide tension was within normal ranges during the entire experiment, averaging 37.4 ± 3.8 mm Hg. Artificial lung blood flow decreased from 51% ± 14% of cardiac output on day 1 to 30% ± 16% by day 7 because of changes in natural and artificial lung resistance. White blood cell counts were significantly elevated on days 5 and 7, and lastly, kidney and liver function remained normal, although signs of kidney infarction or hemorrhage were noted. Conclusions The thoracic artificial lung is suitable for 7-day attachment, but improvements in blood biocompatibility are warranted.

While most chronic diseases are on the decline, medical pulmonary disease is on the increase. The unrelenting nature of chronic lung disease has long energized the pulmonary community to seek technologies to replicate the capacity of the lungs to exchange oxygen for carbon dioxide. While most such artificial lung technologies work by delivering oxygen to the blood through a system of hollow fibers or tubes, our approach employs photolytic energy to generate oxygen from the water already present in blood, thus eliminating the need for gas delivery. To this end, progress in the development of a photolytic artificial lung (PAL) is reported. The device provides photolytically driven electrochemistry for blood oxygenation or for maintenance of breathing air in confined spaces. The device is based on the catalyzed photoactivity of a transition metal oxide such as titanium dioxide (TiO2). Photoactive anatase TiO2 films have been developed for use in a photolytic artificial lung. The PAL is capable of facilitating gas exchange in the blood, thereby bypassing alveolar–capillary interfaces. The device will eventually be used in ex-vitro and in-vitro devices. The direct photolytic process, using UV laser radiation, converts water to liquid phase oxygen (dissolved oxygen), with commensurate reduction of carbon dioxide. The test cell consisted of an indium tin oxide coating, an anatase TiO2 coating (∼2 μm thick), and a MnO2 overcoat deposited on fused silica by reactive magnetron sputtering. Blood flowed over the coated side and oxygen exchange occurred at the MnO2 interface. Three hundred and fifty-four nanometers UV radiation was incident on the silica/indium tin oxide (ITO) side. Electron–hole pairs were generated in the TiO2 layer by the laser radiation, which catalyzed a redox reaction with water in the blood. The MnO2 was also used as a catalyst to dissolve oxygen in the blood. Oxyhemoglobin increased as much as 90% with this process. The maximum rate of oxygen generation was 1.08 ml O2/(m2 min), thus projecting an alveolar surface area of 75 m2. We conclude that it is feasible to photolytically oxygenate the hemoglobin contained in whole blood with oxygen derived from the blood's own water content.

In the basic research on cerebral perfusion disorders, a new method for measurement of oxygen extraction fraction (OEF) and cerebral metabolic rate for oxygen (CMRO2) has been desired. Although the O-15-labeled gas inhalation method is performed in clinical studies, application of the inhalation method to small animals requires too many intensive procedures. Therefore, this study investigated a new method of assessing OEF in small animals using intravenously injectable oxygen (injectable 15O-O2). Additionally, it was compared with the inhalation method, using a monkey for further validation. Using injectable 15O-O2, 72 MBq/ml of radioactivity was obtained after 15O-O2 gas circulation into an artificial lung. OEF with injectable 15O-O2 was calculated using the same equation as that applied to the bolus inhalation method. The OEF value obtained by injectable 15O-O2 was well in accordance with that evaluated by the arterial-venous difference of oxygen concentration. Furthermore, the OEF and CMRO2 images obtained with two methods using a monkey brain showed a similar distribution. These results indicate that this method is useful for the estimation of OEF and CMRO2 in small animals using an animal positron emission tomography system and may accelerate the basic research of cerebral perfusion diseases.

In the basic research about cerebral perfusion disorders, a new method for measurement of oxygen extraction fraction (OEF) and cerebral metabolic rate for oxygen (CMRO 2 ) has been desired. Although O-15-labeled gas inhalation method is performed in clinical studies, application of the inhalation method to small animals requires too many intensive procedures. Therefore, this study investigated a new method of assessing OEF in small animals using intravenously injectable oxygen (injectable 15 O-O 2 ). Moreover, OEF after transient ischemia–reperfusion was estimated to validate the usefulness of the method. Injectable 15 O-O 2 , 72 MBq/ml of radioactivity, was obtained after 15 O-O 2 gas circulation into the artificial lung. OEF after injection of injectable 15 O-O 2 was calculated using the same equation as that applied to the bolus inhalation method. OEF value obtained by injectable 15 O-O 2 was well in accordance with that evaluated by arterial-venous difference of oxygen concentration. Furthermore, misery perfusion was depicted in the lesioned hemisphere after transient ischemia–reperfusion. These results indicated that this method is useful for the estimation of OEF and CMRO 2 in small animals using an animal positron emission tomography (PET) system and may accelerate the basic research of cerebral perfusion diseases.

During cardiac surgery a cardiopulmonary bypass (CPB) is necessary to temporarily replace the functions of the heart and the lung. This paper describes a process model for the gas transfer in an oxygenator (artificial lung) based on first principles. It is intended to use the model both as design tool and as process model for the automation of the blood gas management during CPB. Based on the model it is shown that the process gains vary markedly with the blood flow. Furthermore it became obvious that the time constant of most of the available blood gas analyzers will prevail over those of the process.

Background: Lung transplantation is the only treatment for patients with end-stage lung disease. However, the scarcity of donor organs illustrates the need for alternatives. Recent success in the use of ventricular assistance has stimulated research in technology designed as a bridge to lung transplantation. Some laboratories have demonstrated significant advances in the development of artificial lungs, and clinical applications are on the horizon. In preparation, we sought to gather information from the lung transplant community regarding issues related to testing and potential trials of artificial lungs. Methods: We constructed a survey and distributed it to lung transplant program directors recognized by the United Network for Organ Sharing. Topics included required animal studies, preferred designs, logistics of clinical trials, and patient diagnoses most appropriate for such a trial. Results: The 31 programs responding to the survey performed 72% of all lung transplants in the United States in 1999. Ninety-seven percent supported a Phase I trial using an artificial lung as a bridge to lung transplantation. Additionally, 58% specifically supported a trial in which organ allocation would be prioritized to enrolled patients. Idiopathic pulmonary fibrosis was the diagnosis thought most appropriate for inclusion in initial clinical trials. Conclusions: Widespread support exists for the development and use of an artificial lung as a bridge to lung transplantation. Information from transplant centers regarding device design and application can influence laboratories developing artificial lungs, and such communication will be essential as this technology progresses from the bench-top to the bedside.

An artificial lung small enough to be carried in a backpack has been shown to work in sheep. It's one of several devices that could transform the lives of people whose lungs are failing, and who are completely dependent on large machines. William Federspiel of the University of Pittsburgh and his team has developed a device that combines both pump and gas exchanger. It can be carried in a backpack and would connect to the patient's neck via a short tube. Experiments in four sheep show that the device could fully oxygenate the animals' blood for 6 hours. Federspiel says that they have since demonstrated that it works for five days.

Objective: Artificial lungs may have a role in supporting patients with end-stage lung disease as a bridge or alternative to lung transplantation. This investigation was performed to determine the effect of an artificial lung, perfused by the right ventricle in parallel with the pulmonary circulation, on indices of right ventricular load in a model of pulmonary hypertension. Methods: Seven adult male sheep were connected to a low-resistance membrane oxygenator through conduits anastomosed end to side to the pulmonary artery and left atrium. Banding of the distal pulmonary artery generated acute pulmonary hypertension. Data were obtained with and without flow through the device conduits. Outcome measures of right ventricular load included hemodynamic parameters, as well as analysis of impedance, power consumption, wave reflections, cardiac efficiency, and the tension-time index. Results: The model of pulmonary hypertension increased all indices of right ventricular load and decreased ventricular efficiency. Allowing flow through the artificial lung significantly reduced mean pulmonary artery pressure, zero harmonic impedance, right ventricular power consumption, amplitude of reflected waves, and the tension-time index. Cardiac efficiency was significantly increased. Conclusions: An artificial lung perfused by the right ventricle and applied in parallel with the pulmonary circulation reduces ventricular load and improves cardiac efficiency in the setting of pulmonary hypertension. These data suggest that an artificial lung in this configuration may benefit patients with end-stage lung disease and pulmonary hypertension with right ventricular strain.

Background . We previously reported a 50% incidence of immediate right heart failure using a rigidly housed, noncompliant inflow artificial lung in series with the pulmonary circulation in a healthy ovine survival model. Three device modifications resulted: (1) an inflow cannula compliance chamber, (2) an inlet blood flow separator, and (3) modification of the artificial lung outlet geometry, all to reduce resistance and mimic the compliance of the pulmonary vascular bed. Methods . In 7 sheep, arterial grafts were anastomosed end-to-side to the proximal and distal main pulmonary artery, with the paracorporeal artificial lung interposed. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the artificial lung for up to 72 hours. Results . Six of 7 sheep exhibited good cardiac function throughout the test period: mean central venous pressure was 6.8 mm Hg (range, 4 to 11 mm Hg), mean cardiac output, 4.17 ± 0.12 L/min (range, 2.4 to 6.3 L/min); before and after device mean pulmonary arterial pressure, 21.8 and 18.5 mm Hg, and left atrial pressure, 10.8 mm Hg. Conclusions . This modified artificial lung prototype with an inflow compliance chamber, blood flow separator, and modified outlet geometry has greatly improved cardiac function and initial survival in our healthy ovine model.

Effects of hollow fiber packing fraction on gas transfer rate, blood pressure drop and blood flow characteristics of an intravascular oxygenator (IVOX) were evaluated by in vitro experiments. An IVOX module was prepared by packing hollow fiber membranes, of which packing fraction ranged from 0.056 to 0.338, in a pipe corresponding to vena cava. Overall mass transfer coefficients for oxygen and carbon dioxide were evaluated using water, and gas transfer rates through blood were estimated. Blood flow in the IVOX was evaluated by both pulse response method and electrode method. Blood flow was not uniform and depended on the hollow fiber packing fraction. Easy-flow channels between vascular wall and bundle of the hollow fibers were produced and stagnation of blood flow occurred in the bundle of the hollow fibers at the blood inlet. More uniform blood flow was obtained by optimizing the hollow fiber packing fraction. With respect to gas transfer rate, blood pressure drop and uniformity of the blood flow, the optimum hollow fiber packing fraction was approximately 0.28 when the outside diameter of the hollow fiber was 300 μm. Effect of inner diameter of the hollow fibers was also evaluated, demonstrating that reduction in the inner diameter was an effective way to increase oxygen transfer rate.

We evaluated effects of the number of tied hollow fibers of an outside blood flow membrane oxygenator with cross-wound hollow fibers on the blood flow pattern and oxygen transfer rate. The number of tied hollow fibers in a bundle was varied from one to six, and the blood flow pattern was observed by X-ray computed tomography. The oxygen transfer rate and blood pressure drop were measured by in vitro experiments using bovine blood. Uniform blood flow patterns were obtained for each number of tied hollow fibers. A decrease in the number of tied hollow fibers caused more effective contact of blood with the tied hollow fibers and oxygen transfer rate was enhanced, demonstrating that single hollow fiber was the most effective. Empirical equations were obtained based on these results and optimum structure parameters of the membrane oxygenator were determined by simulation analysis. Optimum membrane surface area and axial jacket length of the oxygenator were 3.0 m 2 and 320 mm, respectively, at a hollow fiber outside diameter of 250 μm.

Sergei S. Brukhonenko designed and constructed one of the earliest heart-lung machines. He was the first to experimentally perform a total body perfusion with the heart of the animal isolated from the circulation. His work paved the way to the first experimental operations on heart valves. Although Brukhoneko's pioneering contributions have not received the recognition they deserve, his work represents an important landmark in cardiac surgery.

Background . An artificial lung with 1 to 6 month work life could act as a bridge to transplantation. A pumpless artificial lung has been developed. Methods . The artificial lung was placed in series with the native lungs of adult sheep. Hemodynamics were observed, as the right ventricle generated flow through the device. Through a left thoracotomy, two 20-mm grafts were anastomosed in an end-to-side fashion to the pulmonary artery. The grafts were externalized, and directed flow through the chest wall, to the extracorporeal lung. The animals were recovered, weaned from the ventilator, and when standing, flow was diverted through the device. Results . Five of 7 animals survived 24 hours with 75% to 100% of the cardiac output diverted through the device. All animals were active, with interest in food and water, and able to stand. Conclusions . The right ventricle perfused the artificial lung with 75% to 100% of the cardiac output for 24 hours. This device demonstrates the feasibility of a pumpless pulmonary assist device relying on the right ventricle for perfusion.

Background Our study evaluated the efficacy and feasibility of a pumpless respiratory assist device and determined its capacity for carbon dioxide removal. Methods In five adult pigs the left femoral vein and artery were cannulated with a 20F cannula and connected to a low-pressure hollow-fiber artificial lung. After we had obtained baseline values of mean arterial pressure, cardiac output, and blood flow across the artificial lung, the mean arterial pressure was reduced 20% and 40% relative to baseline; in a second phase, it was raised 20% and 40. Cardiac output and artificial lung flow were simultaneously recorded. We determined the carbon dioxide removal capacity of the artificial lung by gradually increasing the arterial partial carbon dioxide tension of the animal. Results An increase of 10 mm Hg in mean arterial pressure resulted in an increase of flow of 0.14 L/min. The mean pressure drop across the artificial lung was measured at 17 ± 9 mm Hg. The shunt flow over the artificial lung varied between 14 and 25% of the cardiac output of the animal. Depending on inlet conditions, carbon dioxide removal by the artificial lung was between 62 ± 22 mL/L/min and 104 ± 25 mL/L/min. Conclusions A pumpless respiratory assist device can remove a significant proportion of the metabolic carbon dioxide production. However, adequate mean arterial pressure is mandatory to maintain sufficient flow across the device. The technique seems attractive because of its simplicity and can be used in acute lung injury in conjunction of apneic oxygenation for prolonged respiratory support.

The potential use of the enzyme catalase to oxygenate blood was investigated. A microcalorimetric technique was used to study the kinetics of oxygen generation in human blood serum at 25 and 37°C. Experiments carried out in serum and in phosphate buffer provided the apparent rate constants for the enzymatic and non-enzymatic oxygen-generation reactions. A simplified mathematical model was then developed to analyse the behavior of a hollow-fiber membrane oxygenator with catalase covalently bound to the membrane surface. The model was used to simulate an extracorporeal oxygenation treatment and outline differences with current devices.

This study reports on a ventilator system that consists of several intelligent modules for controlling ventilator operation. These modules are software programs in two controllers. One controller is a personal computer used for diagnoses, determining settings and checking the effects of settings. The other controller is a single-chip microprocessor in a ventilator that controls the ventilator's settings in accordance with the computer settings. After setting up the system, an artificial lung model simulating a patient's lung is used to test the system. The result of test run indicated that it always responds to a patient's lung condition in a stable manner. Thus, the proposed system with its intelligent modules may assist clinicians in caring for patients and managing ventilator operation.

Designing an effective intravenous membrane oxygenator requires selecting hollow fiber membranes (HFMs) which present minimal resistance to gas exchange over extended periods of time. To evaluate HFMs, we developed a simple apparatus and methodology for measuring HFM permeability in a gas-liquid environment which has the capability of studying a variety of fiber types in any liquid of interest, such as blood. Using this system, we measured the O2 and CO2 exchange permeabilities of Mitsubishi MHF 200L composite HFMs and KPF 280E microporous HFMs in water at 37°C. The membrane permeability measured for the MHF 200L composite fiber was 7.9 × 10−6 ml/s/cm2/cmHg for O2 and 8.4 × 10−5 ml/s/cm2/cmHg for CO2, and for the KPF 280E microporous fiber, 1.4 × 10−5 ml/s/cm2/cmHg for O2 and 3.2 × 10−4 ml/s/cm2/cmHg for CO2. The permeabilities of the microporous HFMs were over two orders of magnitude less than what would be measured in a gas-gas system due to liquid infiltration of the pores, emphasizing the importance of measuring permeability in a gas-liquid system for relevant applications such as intravenous oxygenation. Furthermore, both O2 and CO2 permeabilities of the microporous fiber were consistent with a liquid infiltration depth of only 1%. The O2 permeability of the MHF fiber was found to be less than the overall exchange permeability ultimately required of our intravenous oxygenation device (K ≈ 1 × 10−5 ml(STP)/s/cm2/cmHg). Consequently, the MHF 200L composite fiber appears unsuitable for intravenous oxygenation devices such as ours.

Regulation of gas exchange in artificial lungs (oxygenators) during cardiopulmonary bypass is normally achieved by manual control of the gas composition and flow in response to intermittent sampling of the arterial partial pressures of oxygen ( P a O 2 ) and carbon dioxide ( P a CO 2 ). Manual control often results in abnormal blood gases which have been implicated in patient morbidity as well as influencing perfusion safety. Fine control of P a O 2 and P a CO 2 may be achieved by a combination of an in-line blood gas monitoring system and a membrane type oxygenator which is automatically regulated. The overall dynamics of the oxygenation process and control system components are complex and have nonlinear, multivariable and time-varying characteristics. Consequently, an adaptive control system approach is necessary. The implementation of a digital self-tuning control regime for P a O 2 is described here. The controller is based on an explicit Linear Quadratic Gaussian (LQG) self-tuning control design which is presented using a polynomial equation approach. The controller performance was investigated in in vitro experiments. The self-tuner performed satisfactority with various sensor/oxygenator combinations for blood flow and temperature load disturbances. In contrast, a nonadaptive (proportional-integral, PI) type of control system was found to be unsuitable.

A novel sampler has been designed to collect biological aerosols in a manner which mimics the mammalian lung. Breathing patters are adjustable within the human range. The sampler is divided into parts resembling the upper respiratory tract and pulmonary area. In tests with bacterial aerosols, capture was 100% and deposition showed separation related to particle size and airflow velocity. Recovery of viable bacteria appeared superior to that obtained with an impinger.

The non-conventional techniques for ventilatory support represent a new approach to the management of patients with respiratory failure. A large number of studies indicate that these techniques can maintain adequate gas exchange under conditions in which the traditional concepts of gas transport no longer hold. We have reviewed the group of techniques, collectively called high frequency ventilation (HFV), in which the tidal volumes are much less (1 to 5 ml per kg) than those observed during conventional mechanical ventilation. Although HFV has theoretical advantages in some clinical settings, it has been shown to be superior to conventional mechanical ventilation in but a few. HFV appears to provide adequate ventilation while still allowing access to tracheal and laryngeal surgical fields. It has been successful during pneumonectomy, and in the treatment of bronchopleural fistulae. The relevance of tracheal insufflation (TRIO) of oxygen and constant flow ventilation (CFV) to the human clinical setting is uncertain. TRIO may be useful to oxygenate patients who are difficult to intubate, or TRIO could be applied for ventilation of patients involved in mass casualties. Although CFV does not maintain normal levels of PaCO2 in humans, it can provide adequate oxygenation. It might be clinically applicable during thoracic surgery, in which movement of the abdominal and thoracic contents associated with conventional mechanical ventilation is undesirable. During CFV, the lung is kept motionless with sufficient airway pressures to maintain patency of airways and alveoli. CFV is useful as a tool for studying phenomena affected by breathing. The rationale for the use of an artificial lung during extracorporeal membrane oxygenation (ECMO) or extracorporeal carbon dioxide removal with low positive pressure ventilation (ECCO2R-LFPPV) in the treatment of acute respiratory failure is to provide temporary respiratory function while the pulmonary lesion is being treated or is resolving. The factors that most limit the usefulness of ECMO are not technical but relate to the ability of the lung to recover structurally and functionally after a severe insult. Poor survival figures in the published series of ECMO in adults reflect the gravity of illness prior to treatment. However, results in neonates have been quite encouraging. ECCO2R allows less exposure of blood to the extracorporeal circuit and avoids the reduction in pulmonary blood flow associated with ECMO. Although the reported survival of adults with severe acute respiratory failure treated with ECCO2R is extremely promising, it is important to point out that none of the published reports are controlled, randomized studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical use of a single cannula would make extracorporeal membrane oxygenation simpler and less aggressive. It would probably limit the occurrence of the complications of currently used techniques (double-cannula, venoarterial, or venovenous bypass). In this experimental study an original system is described that is composed of a single cannula, an alternating clamp, and a nonocclusive roller pump, the characteristics of which permit its use as a venous reservoir. To overcome the limitations of the oxygenation in any venovenous bypass, we used the method of “apneic oxygenation” through the natural lungs, which we previously proved efficient in infants and children. The optimal setting of the alternative clamp was first tested in vitro to obtain the maximal flow in the circuit and the minimal amount of recirculation. The single-cannula bypass then was compared with a two-cannula circuit regarding the efficiency of carbon dioxide removal and the hemodynamic consequences. At less than 50% of the maximal speed of the pump, flows were equivalent in both types of circuits. The efficiency of carbon dioxide removal was only slightly decreased by the use of a single cannula (30 ± 2 ml/min versus 36 ± 2 ml/min with two cannulas). This could easily be offset by increasing the gas flow/blood flow ratio in the oxygenator. Arterial carbon dioxide tension was maintained at normal levels in both types of circuits. Hemodynamic condition was only slightly affected by the alternative flow of the bypass. This system of single-cannula membrane lung support thus seems to be adequate for clinical use.

Introduction: The disposable laryngeal tube suction (LTS-D, VBMMedizintechnikGmbH, Germany) is a single-use supra-glottic device included in the international resuscitation guidelines. The aim of the study was to evaluate how well emergency nurses can insert it in a manikin after a quick education program. Materials and methods: No details of the protocol were revealed before the study. Our nurses followed a one-hour theoretical teaching about the LTS-D by a manufacturer delegate without any practice. They had tomanage airway of a manikin head in neutral position using a LTS-D size 4. At the beginning of the test, the LTS-D, the empty syringe for cuff inflation and a bag-valve ventilator were ready on the table. Data collected were: time needed for insertion (started when the nurse took the device, stopped at the first complete and symmetrical inflation of the artificial lungs), numbers of attempts and if additional instructions were needed. Theywere also asked to complete a sheet about demographics data and previous acquaintance with the LT. Results: 159 fire and rescue nurses were included in the study. 77Menand82Women, agewas34±7. Thirty-ninepercent of them knew the device theoretically before the study and 12.6% practically. Mean insertion time was 17.5±6 s (min: 9, max: 40, Q1: 13, Q3: 20). In 97.5% the device was correctly inserted on first attempt. No failed attempt and no significant mistake were collected. Additional oral instructions were needed in 22 cases (most frequent in 7 cases: improper insertion depth). All of them found the insertion easy and comfortable. Conclusion: Implementation of the LTS-D in our nurses’ resuscitation algorithms seems feasible and safe. Its use is instinctive and it offers, in less than 20 s, a reliable airwaymanagement. A skill retention assessment is intended.

ObjectiveWe sought to investigate the safety and feasibility of implanting the pumpless interventional lung assist device (Novalung; Novalung GmbH, Hechingen, Germany) to the axillary vessels either by means of direct cannulation or end-to-side graft interposition and the capability of either type of vascular access to provide respiratory support during apneic ventilation in adult pigs.MethodsTen pigs were ventilated for 4 hours (respiratory rate, 20-25 breaths/min; tidal volume, 10-12 mL/kg; fraction of inspired oxygen, 1.0; positive end-expiratory pressure, 5 cm H2O). Thereafter, the interventional lung assist device was surgically connected to the right axillary artery and vein by using direct cannulation (n = 5) or end-to-side ringed polytetrafluoroethylene graft interposition (n = 5), and ventilatory settings were reduced to achieve near apneic ventilation (respiratory rate, 4 breaths/min; tidal volume, 1-2 mL/kg; fraction of inspired oxygen, 1.0; positive end-expiratory pressure, 20 cm H2O). Hemodynamic and intrathoracic volumes and lung cytokine levels were measured.ResultsBlood flow through the interventional lung assist device was 1.7 ± 0.4 L/min or 30% ± 14% of the cardiac output, and the mean pressure gradient across the interventional lung assist device was 10 ± 2 mm Hg. The interventional lung assist device allowed an O2 transfer of 225.7 ± 70 mL/min and a CO2 removal of 261.7 ± 28.5 mL/min. Although the amount of blood flow perfusing the interventional lung assist device was significantly higher (P < .01) with direct cannulation (2.1 ± 0.3 L/min) compared with that seen in graft interposition (1.3 ± 0.3 L/min), the latter allowed similar respiratory support with reduced hemodynamic instability.ConclusionsThe axillary vessels are a safe and attractive cannulation site for pumpless partial respiratory support. Compared with direct cannulation, graft interposition was equally able to support the interventional lung assist device–driven gas exchange requirements during apneic ventilation with better hemodynamic stability.

The ultimate treatment of chronic respiratory insufficiency is pulmonary replacement by an artificial organ, homologous lung transplantation, or chronic paracorporeal respiratory supplementation. The woven capillary membrane oxygenator appears to be a major development toward implantable artificial organs. The four units tested are made up of screens 3.5 by 4.0 cm. of capillary tubing 0.3 mm. I.D. by 0.64 mm. O.D. assembled into rectangular blocks. Units made up of five, ten, twenty, and forty screens have been assembled and tested according to the protocol suggested by Galletti. The maximum oxygen transfer rate with blood was 48 ml. per minute per square meter. Water carbon dioxide transfer rate was 23.1 ml. per minute per square meter. The pressure drops in the liquid phase were 8.5, 15.3, 13.8, 17.6 mm. Hg at 1 L. per minute flow. These results indicate that the woven capillary membrane lung is an acceptably efficient oxygenator. The characteristics of design and performance suggest that this oxygenator can be made to be implanted into the chest or used as a paracorporeal respiratory assistance device.

Closed-circuit spirometry techniques were used to study gas exchange (oxygen and carbon dioxide transport) across the native lung and membrane lung in ten neonates treated with extracorporeal membrane oxygenation (ECMO). Initially there was negligible oxygen transport across the native lung (0.4 +/- 0.4 mL/kg/min). An increase in native lung oxygen transport (2.0 +/- 1.5 mL/kg/min) at low ventilator settings and high levels of extracorporeal support heralded recovery of the native lung and predicted weaning from ECMO. Measurement of oxygen consumption and carbon dioxide production permitted the energy expenditure to be calculated in these critically ill neonates. The metabolic rates varied widely in each neonate over time and among neonates. (mean 57 +/- 11 kcal/kg/d, range 38 to 80 kcal/kg/d). This emphasizes the need to determine energy expenditure in order to guide nutritional support.