Carbon Dioxide Clearance Research Articles

Repeat-Swap Homology Modeling of the Anion Exchanger AE1 Reveals an Elevator-Like Antiport Mechanism

Anion Exchanger 1 (AE1), or band 3, is a membrane transporter found in erythrocytes and the kidney collecting duct. As part of the process of carbon dioxide clearance from these tissues, AE1 exchanges the accumulated bicarbonate for chloride in the blood plasma. After years of extensive biochemical and functional studies, the structure of the AE1 C-terminal domain (ACTD), which is the integral membrane domain catalyzing the anion exchange, has been finally solved at a resolution of 3.5 A. The structure comprises two structural repeats of inverted transmembrane topology, organized into what has been referred as ‘core’ and ‘gate’ domains. The two repeats are, however, structurally asymmetric and the protein adopts an outward-facing conformation. Here, we gain insights into the nature of the alternating-access mechanism of this transporter, by constructing a model of the inward-facing state using the so-called repeat-swap homology modeling method. Comparison of the resulting model of the inward-facing state with the outward-facing crystal structure reveals that anion translocation takes place by way of an elevator-type mechanism in which the core domain moves vertically relative to the gate domain, which forms the dimerization interface. Taken together, the structures can account qualitatively for a wide range of biochemical and functional data, and suggest new avenues of experimentation.

The use of Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) to facilitate Tracheostomy under sedation

SummaryTransnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) is an apnoeic oxygenation technique which has also been observed to allow a degree of carbon dioxide clearance [1]. We present the case of a 61‐year‐old patient with impending complete upper airway obstruction secondary to an advanced supraglottic neoplasm, precluding orotracheal intubation. The patient became agitated during tracheostomy under local anaesthesia and required sedation to the point of apnoea in order to complete the procedure safely. The use of THRIVE throughout this case was invaluable in bridging periods of ensuing hypoventilation and apnoea, preventing oxygen desaturation and hypercarbia.

Neonatal nasal intermittent positive pressure ventilation efficacy and lung pressure transmission

The objective of this study was to evaluate carbon dioxide (CO2) clearance, delivered pressures and tidal volume (VT) during neonatal nasal intermittent positive pressure ventilation (NIPPV) with two commonly used interfaces. A neonatal lung model, with either short binasal prongs (SBP) or a small caliber nasal cannula (RAM) interface, was tested over a range of clinically relevant settings. A fixed amount of CO2 was infused and the fraction remaining in the lung 100 s postinfusion was measured. Pressure transmission to the lung and VT was measured at the level of the trachea. CO2 elimination was directly proportional to the inspiratory pressure during NIPPV. At peak pressures of 22 to 34 cm H2O, CO2 clearance was greater (P<0.001) with SBP as compared with RAM. Relative to the set ventilator parameters, a substantial pressure dampening effect was documented at the lung level, which was significantly lower with RAM when compared with SBP (2.8% (0.2) versus 11.9% (1.5), P<0.0001). CO2 elimination was dependent on VT and effective despite only a small fraction of physiological VT (maximum delivered VT%: SBP 15.5 (0.7) versus RAM 6.1 (1.4), P<0.0001). NIPPV promotes CO2 elimination even at low transmitted airway pressures, but less effective with RAM as compared with SBP. CO2 elimination despite small VT suggests that NIPPV may depend on a non-conventional gas-exchange mechanism.

Ventilatory efficiency before and after lung volume reduction surgery.

Lung volume reduction surgery (LVRS) has been shown to improve the clearance of carbon dioxide and minute ventilation (V̇E) in select patients with COPD. One variable often assessed in COPD is ventilatory efficiency (V̇E/V̇CO2 ). We compared 55 LVRS subjects with 25 controls from the National Emphysema Treatment Trial. V̇E/V̇CO2 was calculated from cardiopulmonary exercise testing at baseline and 6-months. We sought to assess V̇E/V̇CO2 changes with LVRS compared with controls who only received standard medical care. At 6 months, the LVRS group significantly increased peak V̇O2 , work load, V̇E, V̇CO2 , and tidal volume while lowering peak and lowest V̇E/V̇CO2 (improved ventilatory efficiency) and end-tidal carbon dioxide pressure. The control group did not display these changes. The changes were greatest in the LVRS subjects who improved their exercise capacity after surgery (> 10 W). The changes were greatest in the LVRS subjects who showed the most functional improvement, indicating an association of improved ventilation with improved functional outcome.

Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep

IntroductionAcute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS.MethodsIn the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy.ResultsAfter administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema.ConclusionsWe concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.

Management of Severe Hypercapnia Post Cardiac Arrest with Extracorporeal Carbon Dioxide Removal

Normocapnia is recommended in intensive care management of patients after out-of-hospital cardiac arrest. While normocapnia is usually achievable, it may be therapeutically challenging, particularly in patients with airflow obstruction. Conventional mechanical ventilation may not be adequate to provide optimal ventilation in such patients. One of the recent advances in critical care management of hypercapnia is the advent of newer, low-flow extracorporeal carbon dioxide clearance devices. These are simpler and less invasive than conventional extracorporeal devices. We report the first case of using a novel, extracorporeal carbon dioxide removal device in Australia on a patient with out-of-hospital cardiac arrest where mechanical ventilation failed to achieve normocapnia.

Gas Dialysis

Gas Dialysis

Optimization of Mechanical Ventilator Settings for Pulmonary Disease States

The selection of mechanical ventilator settings that ensure adequate oxygenation and carbon dioxide clearance while minimizing the risk of ventilator-associated lung injury (VALI) is a significant challenge for intensive-care clinicians. Current guidelines are largely based on previous experience combined with recommendations from a limited number of in vivo studies whose data are typically more applicable to populations than to individuals suffering from particular diseases of the lung. By combining validated computational models of pulmonary pathophysiology with global optimization algorithms, we generate in silico experiments to examine current practice and uncover optimal combinations of ventilator settings for individual patient and disease states. Formulating the problem as a multiobjective, multivariable constrained optimization problem, we compute settings of tidal volume, ventilation rate, inspiratory/expiratory ratio, positive end-expiratory pressure and inspired fraction of oxygen that optimally manage the tradeoffs between ensuring adequate oxygenation and carbon dioxide clearance and minimizing the risk of VALI for different pulmonary disease scenarios.

Carbon Dioxide Clearance in Critical Care

Lung protective ventilation limiting tidal volumes and airway pressures were proven to reduce mortality in patients with acute severe respiratory failure. Hypercapnia and hypercapnic acidosis is often noted with lung protective ventilation. While the protective effects of lung protective ventilation are well recognised, the role of hypercapnia and hypercapnic acidosis remains debatable. Some clinicians argue that hypercapnia and hypercapnic acidosis protect the lungs and may be associated with improved outcomes. To the contrary, some clinicians do not tolerate hypercapnic acidosis and use various techniques including extracorporeal carbon dioxide elimination to treat hypercapnia and acidosis. This review aims at defining the effects of hypercapnia and hypercapnic acidosis with a focus on the pros and cons of clearing carbon dioxide and the modalities that may enhance carbon dioxide clearance.

Nasal High-Frequency Oscillation for Lung Carbon Dioxide Clearance in the Newborn

Background: Noninvasive ventilation has been used increasingly in recent years to minimize the duration of endotracheal mechanical ventilation in neonates due to its association with lung injury. Nasal high-frequency oscillation (nHFO) is a relatively new noninvasive modality but evidence for its use is limited. Objective: The goal of this study was to compare the CO₂ clearance efficacy of nHFO and noninvasive positive pressure ventilation (NIPPV) in a neonatal lung model. Design/Methods: A newborn mannequin with dimensions and anatomy similar to a term infant was utilized. It was connected to a commercially available neonatal mechanical ventilator using a manufacturer-provided nasal adaptor. Various modes of noninvasive ventilation were compared as CO₂ clearance was measured at the oropharynx by an end-tidal CO₂ analyzer following the addition of a known amount of CO₂ into the lung. Measurements were obtained at two different lung compliances using nHFO and compared with nCMV and nasal continuous positive airway pressure (nCPAP) as a control. Pressures near the nasal adaptor and the larynx were simultaneously measured with in-line pressure transducers. Results: Whereas no CO₂ elimination was observed under nCPAP, its clearance with nHFO was 3-fold greater as compared to NIPPV. On nHFO, CO₂ clearance was inversely proportional to frequency and maximal at 6 and 8 Hz. At a lower lung compliance, CO₂ clearance was significantly higher at 6 Hz as compared to 10 Hz. During nHFO set to deliver a MAP of 10.0, we documented pressures of 7.2 ± 0.3 at the nasal adaptor and only 2.3 ± 0.3 cm H₂O at the larynx. Conclusions: Nasal HFO is effective and superior to NIPPV at lung CO₂ elimination in a newborn mannequin model. The use of nHFO as the preferred mode of noninvasive ventilation warrants further clinical studies.

Bench to bedside review: Extracorporeal carbon dioxide removal, past present and future

Acute respiratory distress syndrome (ARDS) has a substantial mortality rate and annually affects more than 140,000 people in the USA alone. Standard management includes lung protective ventilation but this impairs carbon dioxide clearance and may lead to right heart dysfunction or increased intracranial pressure. Extracorporeal carbon dioxide removal has the potential to optimize lung protective ventilation by uncoupling oxygenation and carbon dioxide clearance. The aim of this article is to review the carbon dioxide removal strategies that are likely to be widely available in the near future. Relevant published literature was identified using PubMed and Medline searches. Queries were performed by using the search terms ECCOR, AVCO2R, VVCO2R, respiratory dialysis, and by combining carbon dioxide removal and ARDS. The only search limitation imposed was English language. Additional articles were identified from reference lists in the studies that were reviewed. Several novel strategies to achieve carbon dioxide removal were identified, some of which are already commercially available whereas others are in advanced stages of development.

The key to advanced airways during cardiac arrest: well trained and early

Airway management during cardiac arrests is a controversial area. There are advantages to the provision of a patent airway with an airway adjunct, especially as this can optimize oxygenation and carbon dioxide clearance as well as facilitate continuous compressions. These advantages come at a potential cost, in particular errors in placement of the devices and interruption to compressions necessitated for insertion. The widespread availability of supraglottic airways (SGAs), their ease of insertion, and their ability to be inserted without interruptions to compressions have meant that the role of the definitive airway device - the endotracheal tube - is being challenged. In the previous issue of Critical Care, a study from Japan reported the use of advanced airways in more than 5,000 victims of cardiac arrests. The authors were not able to demonstrate a survival advantage with either SGAs or endotracheal intubation (ETI). They did, however, demonstrate improved outcomes when the emergency life-saving technicians had been trained to perform ETI and when the advanced airway device was inserted earlier.

Knowledge of oxygen delivery among paediatric trainee doctors and experienced paediatric nurses

Aims Assess the knowledge of oxygen delivery among paediatric junior doctors and nurses. Methods A paper survey was developed, piloted, refined and completed by junior doctors at induction to a children9s hospital, and experienced paediatric nurses attending post registration courses. The purpose was to identify and direct address knowledge gaps. Respondents needed to identify various oxygen delivery devices (nasal cannulae, face mask, face mask and reservoir bag, head box, tracheostomy mask, bag-valve-mask (BVM) and Ayre9s T-piece), specify maximum percentage (%) of oxygen that can be delivered, flow rates required, use with spontaneously breathing patients and possibility of delivering continuous positive airway pressure. Results A total of 152 surveys were completed, 29 of these by nurses. Identification: Nasal cannulae, tracheostomy mask and BVM were correctly identified 98%, 89% and 94% of the time. There was confusion over headbox (63% correct), face mask and reservoir bag (22% correct) and Ayre9s t-piece (36% correct). Knowledge of maximum % oxygen delivered by each device was poor: nasal cannulae had 28% (32/114) correct answers; 42/114 responded that nasal cannulae delivered >40% oxygen. BVM and Ayre9s T-piece had the most correct answers (69% and 82%). Flow rate responses showed poor knowledge of carbon dioxide clearance with oxygen delivery: 30% (37/125) would give Conclusion There are significant knowledge gaps regarding oxygen therapy despite their frequent use. Maximum % oxygen delivery and flow rates were particularly poor, with potential negative impact on patient care including: delivering too little oxygen in emergencies with BVM and face masks and reservoir, or too low flow rates with face masks and head boxes leading to CO 2 retention. The correct use of BVM requires particular clarification. This survey informed interactive teaching focusing on this common, important and life-saving therapy.

Core Topics in Mechanical Ventilation

Contributors Foreword Timothy W. Evans Preface Introductory notes 1. Physiology of ventilation and gas exchange Hugh Montgomery 2. Assessing the need for ventilatory support Mick Nielsen and Iain Mackenzie 3. Oxygen therapy, continuous positive airway pressure and non-invasive ventilation Ian Clement, Leigh Mansfield and Simon Baudouin 4. Management of the artificial airway Peter Youn and Iain Mackenzie 5. Modes of mechanical ventilation Peter Macnaughton and Iain Mackenzie 6. Oxygenation Bill Tunnicliffe and Sanjoy Shah 7. Carbon dioxide clearance Brian Keogh and Simon Finney 8. Sedation, paralysis and analgesia Russell R. Miller III and E. Wesley Ely 9. Nutrition in the mechanically ventilated patient Clare Reid 10. Mechanical ventilation of the patient with asthma or chronic obstructive pulmonary disease David Tuxen and Matthew T. Naughton 11. Mechanical ventilation in patients with blast, burn and chest trauma injuries William T. McBrid and Barry McGrattan 12. Ventilatory support: extreme solutions Alain Vuylsteke 13. Heliox in airway obstruction and mechanical ventilation Hubert Trubel 14. Adverse effects and complications of mechanical ventilation Iain Mackenzie and Peter Young 15. Mechanical ventilation on the move Terry Martin 16. Special considerations in infants and children Rob Ross-Russell and Natalie Yeaney 17. Tracheostomy Abhiram Mallick, Andrew Bodenham and Iain Mackenzie 18. Weaning, extubation and de-cannulation Iain Mackenzie 19. Long-term mechanical ventilation Craig Davidson 20. The history of mechanical ventilation Iain Mackenzie Glossary Index.

Feasibility of very high-frequency ventilation in adults with acute respiratory distress syndrome*

To assess the feasibility of using respiratory frequencies up to 15 Hz during high-frequency oscillatory ventilation (HFO) of adults with acute respiratory distress syndrome (ARDS). Observational study. Medical intensive care unit at a tertiary care university hospital. Thirty adult patients receiving HFO at the discretion of their physicians for management of severe ARDS. Clinical management algorithm for HFO that minimized delivered tidal volumes by encouraging the use of the highest frequency that allowed acceptable clearance of carbon dioxide. This contrasts with the typical use of HFO in adults, in which frequencies generally do not exceed 6 Hz. Patients were 42 +/- 15 yrs old, weighed 83 +/- 25 kg, and had failed conventional lung-protective ventilation due to refractory hypoxia or respiratory acidosis and high plateau airway pressures. During HFO, 25 of 30 patients maintained acceptable gas exchange at frequencies > 6 Hz; 12 reached maximal frequencies of > or = 10 Hz. Among patients whose maximal frequencies exceeded 6 Hz, mean maximal frequency was 9.9 +/- 2.1 Hz, at a mean oscillation pressure amplitude of 81 +/- 11 cm H2O. At those settings, blood gases were pH 7.31 +/- 0.06, PaCO2 was 58 +/- 21 mm Hg, and PaO2 was 82 +/- 33 mm Hg. Survival to hospital discharge among this severely ill cohort was 37%. Most adults can maintain adequate gas exchange using HFO frequencies well above 5-6 Hz. Use of higher frequencies should minimize tidal volume and we speculate might thereby reduce ventilator-associated lung injury.

Carbon Dioxide Clearance in Rabbits During Expiratory Phase Intratracheal Pulmonary Ventilation

The purpose of this study was to compare the efficacy of CO2 removal during conventional mechanical ventilation (CMV) with and without expiratory phase intratracheal pulmonary ventilation (expiratory ITPV or Exp-ITPV); and to compare CO2 clearance during Exp-ITPV, in pressure-controlled ventilation (PCV) and in volume-controlled ventilation (VCV) modes. Seven anesthetized rabbits were tracheotomized and intubated using a 4 mm endotracheal tube. Venous and arterial lines were established. The rabbits were paralyzed, mechanically ventilated, and ventilation parameters were adjusted to achieve baseline arterial hypercapnia. Animals were then ventilated during 30-minute trials of CMV and Exp-ITPV, in both PCV and VCV modes. A custom-built, microprocessor-controlled solenoid valve was used to limit ITPV gas flow to the expiratory phase. Proximal and carinal airway pressures and hemodynamic variables were continuously recorded, and arterial blood gases were analyzed at the end of each trial. Exp-ITPV, as compared with CMV, reduced arterial PCO2 by 12% and 21% in PCV and VCV modes, respectively (p < 0.02 and p < 0.001; one-sided paired t test), without significant changes in other cardiorespiratory variables. In conclusion, Exp-ITPV is more effective than CMV in clearing CO2 through a small endotracheal tube. Exp-ITPV is also more effective in VCV mode than PCV mode.

The detrimental effects of ventilation during low-blood-flow states

In recent years, it has become increasingly apparent that resuscitative ventilatory procedures, classically thought to be life saving, may have profound detrimental effects. Most assisted breathing techniques during resuscitation involve the provision of intermittent positive pressure ventilation to inflate lung zones for erythrocyte oxygenation and clearance of carbon dioxide. A growing number of studies involving low-flow states, however, have demonstrated that provision of overzealous (or even 'normal') ventilatory rates with intermittent positive pressure ventilation can significantly diminish both systemic and coronary circulation, most likely through inhibition of venous return. Recent laboratory studies of hemorrhage have shown not only a direct detrimental impact of each positive pressure ventilation breath on coronary perfusion, but also how dramatic improvements in blood flow can be achieved, without loss of oxygenation, by delivering breaths infrequently during such low-flow states. Likewise, in cardiac arrest models, studies have shown that interrupting chest compressions, even to provide breaths, can be extremely deleterious by abruptly (and continually) lowering the aortic pressure head to the coronary arteries, thus impairing restoration of spontaneous circulation. Even with endotracheal intubation and uninterrupted chest compressions, frequent positive pressure ventilation still inhibits circulation during cardiopulmonary resuscitation. Despite directed training, paramedics (and other rescuers) have been shown to still excessively ventilate during cardiac arrest resuscitations. Ventilation can have profound detrimental hemodynamic effects in low-flow states, exacerbating the circulatory compromise. This underappreciated confounding variable may be one of the reasons many clinical trials of resuscitative interventions have failed despite dramatic successes in the laboratory.

Optimum cardiopulmonary resuscitation for basic and advanced life support: a simulation study.

Optimum cardiopulmonary resuscitation (CPR) for both basic and advanced cardiac life support depends on a compromise between the number of chest compressions delivered and the amount of ventilation provided. This study used theoretical models of blood flow and both arterial and venous blood gas values to investigate the influence of different compression to ventilation ratios on CPR efficiency, as well as the effects of different inspired oxygen concentrations. With mouth-to-mouth ventilation, greater numbers of compressions between each ventilation provided progressively greater blood flow. However, a greater the number of compressions, reduced the arterial oxygen levels and carbon dioxide clearance. There was an optimum ratio, in terms of both oxygen delivery and carbon dioxide clearance, of around 20:1 compressions to ventilation. Optimum oxygen delivery was 0.19 L/min at 20:1, which was better than the oxygen delivery for standard CPR based on a ratio of 15:2 (0.13 L/min). When patients were ventilated with supplemental oxygen (either 50 or 85%) the lungs rapidly became saturated with oxygen, and oxygen delivery depended more on blood flow. Higher numbers of compressions provided greater oxygen delivery, but at the cost of increasing hypercarbia, which is thought to affect resuscitation success rates adversely. The simulation results suggested ratios around 20:1 would be the best compromise between blood flow, oxygen delivery (0.25 L/min) and avoidance of hypercarbia. The best results were provided by continuous chest compressions and simultaneous, asynchronous ventilation in an intubated patient. Arterial and venous oxygen and carbon dioxide levels were well maintained, with very good oxygen delivery (0.32 L/min). Intubation with continuous chest compressions and asynchronous ventilation can therefore significantly improve the quality of CPR as a whole, and not just ventilation.

The issue of dynamic hyperinflation in acute respiratory distress syndrome patients.

Dynamic hyperinflation is produced by a diffuse expiratory flow limitation impairing exhalation under mechanical ventilation. It constitutes a serious clinical problem in patients exhibiting bronchial asthma or chronic obstructive pulmonary disease, when mechanical ventilation is required. But this phenomenon may also complicate respiratory support in acute respiratory distress syndrome (ARDS) patients. The presence of diffuse airflow limitation in ARDS patients has sometimes been noticed in the past, but its consequences have only recently been emphasised in a dynamic study, using bedside recording of flow/volume loops during respiratory support. More recently, by recording systematically a prolonged expiration, the current authors have observed a localised airflow limitation in a majority of ARDS patients, constituting another potential factor of dynamic hyperinflation under respiratory support. In the same report, the current authors' have emphasised the impact of this limitation on the shape of the pressure/volume loop. At a time when increasing respiratory support is proposed to improve carbon dioxide clearance in acute respiratory distress syndrome submitted to protective ventilation, dynamic hyperinflation may become a major clinical problem in this setting.

Heliox enhances carbon dioxide clearance from lungs of normal rabbits during low bias flow oscillation

To evaluate carbon dioxide clearance in normal rabbits during high-frequency oscillatory ventilation with helium-oxygen mixtures by using a low bias flow oscillation (LBFO) system designed to conserve expensive gas. A prospective, paired-controlled, interventional, in vivo animal laboratory study. Animal laboratory of a health science university. Twelve New Zealand White rabbits. Juvenile rabbits were anesthetized, paralyzed, and ventilated through a tracheostomy. LBFO was performed with a modified high-frequency oscillatory ventilation circuit that uses low bias flow (100 mL/kg) and a soda lime cartridge to clear carbon dioxide. LBFO-heliox trials were performed with 20%, 40%, 50%, 60%, and 70% helium (balanced with oxygen) for 30 mins. Each heliox trial was preceded by a paired control trial with 40% oxygen and 60% nitrogen for 30 mins. Ventilator settings in control and heliox trials were identical. During the second part of the study, four rabbits were made hypercapnic by decreasing the power (amplitude), and LBFO was performed with 70% helium against paired-control trials of 40% oxygen and 60% nitrogen. Arterial blood gases were measured at 15-min intervals and airway pressure amplitude was recorded. PaCO2 of control and heliox trials, alveolar PO2-PaO2 gradient of control, and 60% helium trials were compared by paired Student's t-test. At constant power, amplitude was unaffected by helium. Helium concentrations of 40%, 50%, 60%, and 70% decreased PaCO2 by 12%, 33%, 36%, and 46%, respectively. Alveolar PO2-PaO2 gradient was decreased by 40% during ventilation with 60% helium. Under hypercapnic conditions, 70% helium decreased PaCO2 by 20%. Helium concentrations > or = 40% facilitate carbon dioxide clearance from lungs of normal rabbits during LBFO. This could be accomplished inexpensively with LBFO due to preservation of heliox when using this device.