Search

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.

Among all organs, lungs are the last ones to grow and develop fully. As a result, extreme premature neonates may suffer from respiratory failure due to their immature lungs and will require respiratory support in the form of mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In addition, extreme prematurity is recognized as the primary cause of neonatal morbidity and mortality. The conventional standard of care for respiratory support of preterm neonates with respiratory failure are invasive and may lead to long-term morbidities and complications. Hence, a non-invasive respiratory support technique named “Artificial Placenta” has been developed to address the issues and challenges associated with the current technologies. An artificial placenta type device is one designed to provide required oxygenation in room air via non-invasive access to the umbilical vessels without the need of any external pump. In this thesis, microfluidic and microfabrication technologies have been employed in the development of a pumpless neonatal lung assist device (LAD) for preterm neonates in two approaches: 1) design and develop novel microfabrication techniques to fabricate advanced microfluidic blood oxygenators with high gas exchange capacity and reduced form factor and 2) design and construct several modular LADs based on the oxygenators that were developed to fulfill the required gas transfer needs for these babies. The new microfluidic blood oxygenators with double-sided gas transfer channels were found to enhance oxygenation up to 343 % in room air and be easily scaled-up to achieve higher gas exchange capacities without a noticeable increase in priming volume. Furthermore, this microfabrication method has been utilized to make the largest all PDMS ultra-thin double-sided blood oxygenator with higher gas exchange capabilities. Also, a novel composite material made of PDMS and PTFE was introduced that conferred high flexibility to the oxygenator to decrease the form factor of such devices. This device was one of the first microfluidic blood oxygenators with enough flexibility to be deformed, bent, or rolled without limitation and losing its functionality. In order to satisfy the gas transfer need of these preterm neonates, few microfluidic-based modular LADs were constructed to support different birth weights up to 2 kg. The main design criteria for such a LAD in this research was low pressure drops (capable of being operated by a baby’s heart), an oxygen transfer of 1.3 – 1.9 mL min-1 kg-1 of body weight (or an increase in oxygen saturation level from ~ 75 % to ~ 100 % and ideally in room air), and low priming volume (less than 10 % of the total blood volume of a baby). These LADs first were evaluated in vitro to measure their gas exchange capacities and those which could meet needed oxygenation would be tested in vivo. For the first time, it was shown that a pumpless microfluidic-based LAD could support a newborn piglet and provide adequate oxygenation in room air or the oxygen-rich environment. The application of these microfluidic blood oxygenators was not only limited to preterm neonates but also can be used to develop LADs for adult patients. Thesis Doctor of Philosophy (PhD)

Current artificial lungs fail in 1-4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N = 5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220-300 s (N ≥ 5). Here, DOPA-pCB reduced fibrin formation (p = 0.06) and gross thrombus formation by 59% (p 0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs. STATEMENT OF SIGNIFICANCE: Chronic lung diseases lead to 168,000 deaths each year in America, but only 2300 lung transplantations happen each year. Hollow fiber membrane oxygenators are clinically used as artificial lungs to provide respiratory support for patients, but their long-term viability is hindered by surface-induced clot formation that leads to premature device failure. Among different coatings investigated for blood-contacting applications, poly-carboxybetaine (pCB) coatings have shown remarkable reduction in protein adsorption in vitro. However, their efficacy in vivo remains unclear. This is the first work that investigates various pCB-coating methods on artificial lung surfaces and their biocompatibility in sheep and rabbit studies. This work highlights the promise of applying pCB coatings on artificial lungs to extend its durability and enable long-term respiratory support for lung disease patients.

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.

Background: Many oscillatory positive expiratory pressure (OPEP) devices exist and some of them use unique mechanism to produce air-flow oscillations. However their operational parameters and elicited therapeutic effects may vary. Objectives: To assess the mechanical performance of 6 OPEP devices at different resistance levels. Methods: Four gravity-dependent (Flutter, Gelomuc, Shaker, PARI-OPEP) and 2 gravity-independent OPEP devices (Acapella Choice and Aerobika) were tested at 3 resistance levels (low, medium, high). Each device was independently attached to an artificial lung driven by a ventilator in order to simulate an active exhalation. Ventilator settings were adjusted to produce peak expiratory flow rate between 40-45 L.min-1 at 10 breaths.min-1. The middle-third of the exhalation phase was used to compare positive expiratory pressure (PEP), oscillatory frequency (OF) and pressure amplitude (PA). Optimal operational parameters were defined as OFs of 12 Hz or above and PEP ranging between 10-20 cmH2O. Corresponding PAs at these settings were analysed. Results: Only gravity-dependent devices at medium and high resistance levels produced the desired OFs and PEP settings, ranging from 16 to 22 Hz and 12 to 18 cmH2O, respectively. Corresponding PAs ranged from 0.6 to 1.8 cmH2O. Compared to these devices, Acapella and Aerobika elicited higher PAs (from 1.7 to 4.2 cmH2O) although they did not achieve optimal PEP or OF parameters. Conclusions: The gravity-dependent devices displayed close mechanical performances and produced optimal operational parameters at the simulated exhalation settings. Acapella and Aerobika probably require higher expiratory pressure to reach theoretical therapeutic effectiveness.

Objective: Microfluidic artificial lungs (μALs) are being researched for future clinical use due to the potential for increased gas exchange efficiency, small blood contacting surface area, small priming volume, and biomimetic blood flow paths. However, a current roadblock to clinical use is the need to stack hundreds to thousands of these small-scale μALs in parallel to reach clinically relevant blood flows. The need for so many layers not only increases the complexity and projected cost to manufacture a μAL, but also could result in devices which are cumbersome, and, therefore, not suitable for portable artificial lung systems. Methods: Here, we describe the design analysis and optimization of a single-layer μAL that simultaneously calculates rated blood flow, blood contacting surface area, blood volume, pressure drop, and shear stress as a function of blood channel height using previously developed closed-form mathematical equations. A μAL designed using this procedure is then implemented and tested. Results: The resulting device exhibits a rated flow of 17 mL/min and reduces the number of layers required for clinically relevant μAL devices by a factor of up to 32X compared to previous work. Conclusion: This procedure could significantly reduce manufacturing complexity as well as eliminate a barrier to the clinical application of these promising devices. Significance: The described method results in the highest rated flow for any single-layer μAL to date.

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.

This response explores and discusses the critiques of Wagneret al.in their “Comment on ‘The promise of microfluidic artificial lungs’ by Joseph A. Potkay,Lab Chip, 2014,14, 4122–4138”.

Exposure reduction to exhaled air from a sick doctor wearing a personal exhaust unit incorporated in a headset-microphone was studied. Experiments were performed in a full-scale test room furnished as a double-bed hospital room with overhead ventilation at 3, 6, and 12 air changes per hour. Room air temperature was 22°C. A breathing thermal manikin with a body size and shape similar to the body of an average Scandinavian woman was used to mimic a “sick” doctor. The manikin was equipped with artificial lungs with a realistic breathing cycle (2.5-sec inhalation, 2.5-sec exhalation, and 1-sec pause) and a tidal flow rate of 6 L/min. A second thermal manikin and heated dummy were used to resemble lying patients. Exhaled air by the doctor was mixed with tracer gas to mimic pathogens. The wearable personal exhaust unit was positioned frontally by the mouth of the doctor at three distances: 0.02, 0.04, and 0.06 m. It was operated at 0.25 or 0.50 L/s under mixing background ventilation at three air changes per ho...

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.

Biomedical polymers have and still continue to play an important role in how we support and treat patients with various diseases through their use in tissue and blood interacting medical devices and drug delivery systems. Today, a wide variety of blood-contacting devices provide the means for the diagnosis, treatment, and support of life until organ transplantation. Their usage warrants their interaction with cells, bacteria, blood, tissue, and sometimes a combination of these complex living systems and the fates of such interactions are critical for applications including biomimetic surfaces, regenerative medicine, immunomodulation, smart biomaterials for drug delivery, and many more. For blood-contacting devices, their surface interactions with blood mostly lead to blood coagulation, inflammation, device failure, and patient complications. Their lifetimes are thus limited to hours and days due to clot formation. Use on the order of months is however needed for many of these devices including vascular grafts, catheters, artificial lungs, extracorporeal circulation circuits, and dialysis membranes, which rely on the free flow of blood over their surfaces. Clots, however halts this flow and causes the devices to fail. This chapter describes prominent challenges and new directions of hemocompatibility and specifically anticlotting biomaterials research.

Despite the promising potential of microfluidic artificial lungs, current designs suffer from short functional lifetimes due to surface chemistry and blood flow patterns that act to reduce hemocompatibility. Here, we present the first microfluidic artificial lung featuring a hemocompatible surface coating and a biomimetic blood path. The polyethylene-glycol (PEG) coated microfluidic lung exhibited a significantly improved in vitro lifetime compared to uncoated controls as well as consistent and significantly improved gas exchange over the entire testing period. Enabled by our hemocompatible PEG coating, we additionally describe the first extended (3 h) in vivo demonstration of a microfluidic artificial lung.

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

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

Extracorporeal membrane oxygenation (ECMO) 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.

Inhalation of indium-containing dusts is associated with the development of indium lung disease. Workers may be exposed to several different chemical forms of indium; however, their lung dosimetry is not fully understood. We characterized the physicochemical properties and measured the lung dissolution kinetics of eight indium-containing dusts. Indium dissolution rates in artificial lung fluids spanned two orders of magnitude. We used the International Commission on Radiological Protection (ICRP) human respiratory model (HRTM) to estimate pulmonary indium deposition, retention and biokinetic clearance to blood. For a two-year (median workforce tenure at facility) exposure to respirable-sized particles of the indium materials, modeled indium clearance (>99.99% removed) from the alveolar-interstitial compartment was slow for all dusts; salts would clear in 4 years, sintered indium–tin oxide (ITO) would clear in 9 years, and indium oxide would require 48 years. For this scenario, the ICRP HRTM predicted that indium translocated to blood would be present in that compartment for 3.5–18 years after cessation of exposure, depending on the chemical form. For a 40-year exposure (working lifetime), clearance from the alveolar–interstitial compartment would require 5, 10 and 60 years for indium salts, sintered ITO and indium oxide, respectively and indium would be present in blood for 5–53 years after exposure. Consideration of differences in chemical forms of indium, dissolution rates, alveolar clearance and residence time in blood should be included in exposure assessment and epidemiological studies that rely on measures of total indium in air or blood to derive risk estimates.

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.

BACKGROUND: Nasal noninvasive ventilation (NIV) is a common form of noninvasive respiratory mode used in newborn infants. A next-generation nasal cannula (Neotech RAM cannula) has recently been used to provide nasal NIV. The impact of the Neotech RAM cannula on the delivery of pressure needs to be studied. METHODS: In this ex vivo experimental design, a lung simulator (IngMar ASL 5000, version 3.4) was programmed to model a neonate (∼1–3 kg of body weight) with normal-to-moderately affected lungs. We used a Covidien PB840 ventilator with NIV software activated to compensate for leaks. Nasal NIV was set at peak airway pressures of 15, 20, and 25 cm H2O and PEEP of 5, 6, and 7 cm H2O. Three sizes of the Neotech RAM cannula were used (prong outer diameters of 3.0, 3.5, and 4.0 mm). The nose was designed to keep the leak of the nares by the prongs to 30%. We also created a worst case leak (58% leak) by using the largest simulated nostril diameter with the smallest diameter Neotech RAM cannula prong. The outcome measure was the difference in pressures, referred to as leak effect, measured by the lung simulator relative to the set peak airway pressure and PEEP on the ventilator. RESULTS: For the interface with 30% leak, leak effects of peak airway pressure during simulated nasal NIV were similar with all Neotech RAM cannula sizes, with 63–75% of peak airway pressure and 70–90% of PEEP being transmitted across the nasal interface. The worst case scenario produced a 92% leak effect in peak airway pressure and PEEP. CONCLUSIONS: When used with ≤ 30% leak, the Neotech RAM cannula interface results in clinically acceptable transmission of pressures. With > 50% leak, a clinically negligible amount of pressure is transmitted to the artificial lungs.

The influence of selenium-containing metal-complex substance πQ1983 on somatosensory cortex bioelectrical activity has been studied on cats (n = 22) during development of acute hypoxia. The condition of acute hypoxia was performed by making of loop including an animal, an apparatus for artificial lung ventilation, and a reservoir for respiration with 5 liter volume. Evoked activities of neurons were provided by direct electrical current irritations applied to the radial nerve of right superior extremity. Couple needle-shaped electrodes were used for mean evoked potentials registration. 100 mg/kg of the substance πQ1983 was introduced in the stomach 180 min before experiment. Also on any steps of the experiments ECG was registered. Containing of oxygen and carbon dioxide were determined by method of gas analysis in air enabled for respiration. It have been established that the substance πQ1983 taking internally increases cortex neurons functional activity period more than triple during acute hypoxia, stabilizes myocardial electrical activity, and helps animals to sustain the action of critical oxygen and carbon dioxide concentrations. Finally, the substance πQ1983 may be related to the high effectively antihypoxants because it significantly rises the resistance of animals with high CNS organization level (cats) to the acute hypoxia even after introduction per os.

Bronchopulmonary pathology is the most frequent cause of morbidity and mortality among newborn infants. Emergency aid and inten-sive care to newborn infants decrease death rate among children; at the same time, they cause an increase in pulmonary morbidity. The article deals with data concerning generation of bronchopulmonary diseases in children who underwent resuscitation in neonatal period, tracks pulmonary catamnesis, and analyzes hereditary load. The article confirms the adverse effect of artificial lung ventilation on lungs of both mature and premature babies. Neonatal pneumonia, together with iatrogenic factors of emergency care, is a dominating factor in formation of chronic non-specific pulmonary diseases in catamnesis.

In order to test the performance of the resulting membrane oxygenator, a model was constructed to simulate the inner and extracorporeal gas exchange of the human body. The oxygenation capacity of the membrane oxygenator was studied using fresh bovine blood with added anticoagulants as the test medium. The oxygenation performance of the prepared membrane was equal to that of the commercial membrane. After six hours of operation, the oxygen saturation (SaO2) was above 95%, and the partial pressure of oxygen (PaO2) was over 13.5 kPa (100 mmHg). This model was constructed in accordance with the basic principles of extracorporeal circulation, and could be used to investigate the oxygenation performance of a membrane oxygenator, as well as to study the basic principles of extracorporeal circulation.

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.

Providing partial respiratory assistance by removing carbon dioxide (CO2 ) can improve clinical outcomes in patients suffering from acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. An intravenous respiratory assist device with a small (25 Fr) insertion diameter eliminates the complexity and potential complications associated with external blood circuitry and can be inserted by nonspecialized surgeons. The impeller percutaneous respiratory assist catheter (IPRAC) is a highly efficient CO2 removal device for percutaneous insertion to the vena cava via the right jugular or right femoral vein that utilizes an array of impellers rotating within a hollow-fiber membrane bundle to enhance gas exchange. The objective of this study was to evaluate the effects of new impeller designs and impeller spacing on gas exchange in the IPRAC using computational fluid dynamics (CFD) and in vitro deionized water gas exchange testing. A CFD gas exchange and flow model was developed to guide a progressive impeller design process. Six impeller blade geometries were designed and tested in vitro in an IPRAC device with 2- or 10-mm axial spacing and varying numbers of blades (2-5). The maximum CO2 removal efficiency (exchange per unit surface area) achieved was 573 ± 8 mL/min/m(2) (40.1 mL/min absolute). The gas exchange rate was found to be largely independent of blade design and number of blades for the impellers tested but increased significantly (5-10%) with reduced axial spacing allowing for additional shaft impellers (23 vs. 14). CFD gas exchange predictions were within 2-13% of experimental values and accurately predicted the relative improvement with impellers at 2- versus 10-mm axial spacing. The ability of CFD simulation to accurately forecast the effects of influential design parameters suggests it can be used to identify impeller traits that profoundly affect facilitated gas exchange.

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.

Volatile organic compounds (VOCs) in breath may serve as biomarkers of pulmonary infection or inflammation. We developed and validated a new breath sampling method for VOC analysis in ventilated patients. Breath was collected from the ventilatory circuit using cheap disposables. VOCs were identified by gas-chromatography and mass-spectrometry (GC–MS) at various minute volumes during ventilation of an artificial lung (in vitro) and ventilated patients (in vivo). Sixty-four VOCs emendated from the ventilator and tubing. Their concentrations had an inverse correlation with minute volume in in vitro experiments (median correlation coefficient: −0.61 [25–75th percentile: −0.66 to −0.43]). Forty-four of these “ventilator-associated VOCs” were also observed in vivo, without correlations with minute volume. In vivo experiments showed that only positive end-expiratory pressure influenced the concentration of breath VOCs. The sampling method was highly reproducible (median intra-class correlation 0.95 [25–75th percentile: 0.87–0.97]). In conclusion, a novel, simple and repeatable sampling method was developed and validated for capturing exhaled VOCs in ventilated patients, which could allow for large-scale breath analysis in clinical studies.

The incidence of chronic lung disease is increasing worldwide due to the spread of risk factors and ageing population. An important advance in treatment would be the development of a bioartificial lung where the blood-gas exchange surface is manufactured from a synthetic or natural scaffold material that is seeded with the appropriate stem or progenitor cells to mimic the functional tissue of the natural lung.Articles relating to bioartificial lungs were sourced through PubMed and ISI Web of Knowledge.There is a consensus that advances in bioartificial lung engineering will be beneficial to patients with chronic lung failure. Ultimate success will require the concerted efforts of researchers drawn from a broad range of disciplines, including clinicians, cell biologists, materials scientists and engineers.As a source of cells for use in bioartificial lungs it is proposed to use human embryonic stem cells; however, there are ethical and safety concerns regarding the use of these cells.There is a need to identify the optimum strategies for differentiating progenitor cells into functional lung cells; a need to better understand cell-biomaterial/ECM interactions and a need to understand how to harness the body's natural capacity to regenerate the lung.Biomaterial technologies for recreating the natural lung ECM and architecture need further development. Mathematical modelling techniques should be developed for determining optimal scaffold seeding strategies and predicting gas exchange performance.

Summary Objective There is little available data on airway humidity during high-frequency ventilation (HFV). The purpose of this study is to evaluate the temperature drop in an endotracheal tube (ETT) during HFV. Methods We examined the airway temperature in a neonatal HFV system using Babylog® 8000 plus. We measured the temperature change of inspired gases in the ETT under various oscillatory frequencies and oscillatory volumes with a fixed base flow. The temperatures in the ETT during HFV were compared with the temperatures during conventional intermittent positive pressure ventilation (IPPV). Results As the oscillatory frequency was increased and the oscillatory volume (VThf) decreased, the difference in temperature between the Y piece and the inlet of an artificial lung in the ETT (ETT outside of body) increased. However, as the oscillatory frequency increased, there was no difference in the ETT temperature under constant oscillatory volume. In contrast, as the oscillatory volume was decreased, the difference in temperature in the ETT was greater under constant oscillatory frequency. Moreover, the temperature drop in the ETT with HFV was lower than that in the IPPV temperature with a similar respiratory volume. Conclusions The temperature change in the ETT was not dependent on the oscillatory frequency when the oscillatory volume was fixed; however, the temperature was dependent on the oscillatory volume when the oscillatory frequency was fixed. Pediatr Pulmonol. 2015; 50:173–178. © 2013 Wiley Periodicals, Inc.

Recent advances in technology have spurred the increasing use of extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure. However, this accounts for only a small percentage of patients with respiratory failure. We envision the application of ECMO in many other forms of respiratory failure in the coming years. Patients with less severe forms of acute respiratory distress syndrome, for instance, may benefit from enhanced lung-protective ventilation with the very low tidal volumes made possible by direct carbon dioxide removal from the blood. For those in whom hypercapnia predominates, extracorporeal support will allow for the elimination of invasive mechanical ventilation in some cases. The potential benefits of ECMO may be further enhanced by improved techniques, which facilitate active mobilization. Although ECMO for these and other expanded applications is under active investigation, it has yet to be proven beneficial in these settings in rigorous controlled trials. Ultimately, with upcoming and future technological advances, there is the promise of true destination therapy, which could lead to a major paradigm shift in the management of respiratory failure.