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Chest Jan 2017Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple... (Review)
Review
Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS.
Topics: Humans; Prone Position; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory Mechanics; Treatment Outcome
PubMed: 27400909
DOI: 10.1016/j.chest.2016.06.032 -
The European Respiratory Journal Oct 2014This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in the lung, emphasising basic concepts and relating them to... (Review)
Review
This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in the lung, emphasising basic concepts and relating them to clinical scenarios. For each gas exchanging unit, the alveolar and effluent blood partial pressures of oxygen and carbon dioxide (PO2 and PCO2) are determined by the ratio of alveolar ventilation to blood flow (V'A/Q') for each unit. Shunt and low V'A/Q' regions are two examples of V'A/Q' mismatch and are the most frequent causes of hypoxaemia. Diffusion limitation, hypoventilation and low inspired PO2 cause hypoxaemia, even in the absence of V'A/Q' mismatch. In contrast to other causes, hypoxaemia due to shunt responds poorly to supplemental oxygen. Gas exchanging units with little or no blood flow (high V'A/Q' regions) result in alveolar dead space and increased wasted ventilation, i.e. less efficient carbon dioxide removal. Because of the respiratory drive to maintain a normal arterial PCO2, the most frequent result of wasted ventilation is increased minute ventilation and work of breathing, not hypercapnia. Calculations of alveolar-arterial oxygen tension difference, venous admixture and wasted ventilation provide quantitative estimates of the effect of V'A/Q' mismatch on gas exchange. The types of V'A/Q' mismatch causing impaired gas exchange vary characteristically with different lung diseases.
Topics: Humans; Hypoxia; Lung; Lung Diseases; Models, Biological; Pulmonary Gas Exchange; Ventilation-Perfusion Ratio
PubMed: 25063240
DOI: 10.1183/09031936.00037014 -
The Journal of Physiology Feb 2021The anaerobic threshold (AT) remains a widely recognized, and contentious, concept in exercise physiology and medicine. As conceived by Karlman Wasserman, the AT...
The anaerobic threshold (AT) remains a widely recognized, and contentious, concept in exercise physiology and medicine. As conceived by Karlman Wasserman, the AT coalesced the increase of blood lactate concentration ([La ]), during a progressive exercise test, with an excess pulmonary carbon dioxide output ( ). Its principal tenets were: limiting oxygen (O ) delivery to exercising muscle→increased glycolysis, La and H production→decreased muscle and blood pH→with increased H buffered by blood [HCO ]→increased CO release from blood→increased and pulmonary ventilation. This schema stimulated scientific scrutiny which challenged the fundamental premise that muscle anoxia was requisite for increased muscle and blood [La ]. It is now recognized that insufficient O is not the primary basis for lactataemia. Increased production and utilization of La represent the response to increased glycolytic flux elicited by increasing work rate, and determine the oxygen uptake ( ) at which La accumulates in the arterial blood (the lactate threshold; LT). However, the threshold for a sustained non-oxidative contribution to exercise energetics is the critical power, which occurs at a metabolic rate often far above the LT and separates heavy from very heavy/severe-intensity exercise. Lactate is now appreciated as a crucial energy source, major gluconeogenic precursor and signalling molecule but there is no ipso facto evidence for muscle dysoxia or anoxia. Non-invasive estimation of LT using the gas exchange threshold (non-linear increase of versus ) remains important in exercise training and in the clinic, but its conceptual basis should now be understood in light of lactate shuttle biology.
Topics: Anaerobic Threshold; Exercise; Exercise Test; Lactic Acid; Oxygen Consumption; Pulmonary Gas Exchange
PubMed: 33112439
DOI: 10.1113/JP279963 -
Comprehensive Physiology Mar 2016Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to... (Review)
Review
Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints.
Topics: Adaptation, Physiological; Animals; Humans; Lung; Pulmonary Gas Exchange
PubMed: 27065169
DOI: 10.1002/cphy.c150028 -
American Journal of Respiratory and... Mar 2020Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury... (Review)
Review
Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a analysis of that trial, a meta-analysis, and a large international multicenter observational study suggest that extracorporeal life support, when combined with lower Vt and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of ARDS. These findings raise important questions not only about the optimal ventilation strategies for patients receiving extracorporeal support but also regarding how various mechanisms of lung injury in ARDS may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.
Topics: Carbon Dioxide; Extracorporeal Circulation; Extracorporeal Membrane Oxygenation; Humans; Oxygen; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome; Ventilator-Induced Lung Injury
PubMed: 31726013
DOI: 10.1164/rccm.201907-1283CI -
Journal of Applied Physiology... Apr 2017The maximum rate of O uptake (i.e., V̇o), as measured during large muscle mass exercise such as cycling or running, is widely considered to be the gold standard... (Review)
Review
The maximum rate of O uptake (i.e., V̇o), as measured during large muscle mass exercise such as cycling or running, is widely considered to be the gold standard measurement of integrated cardiopulmonary-muscle oxidative function. The development of rapid-response gas analyzers, enabling measurement of breath-by-breath pulmonary gas exchange, has facilitated replacement of the discontinuous progressive maximal exercise test (that produced an unambiguous V̇o-work rate plateau definitive for V̇o) with the rapidly incremented or ramp testing protocol. Although this is more suitable for clinical and experimental investigations and enables measurement of the gas exchange threshold, exercise efficiency, and V̇o kinetics, a V̇o-work rate plateau is not an obligatory outcome. This shortcoming has led to investigators resorting to so-called secondary criteria such as respiratory exchange ratio, maximal heart rate, and/or maximal blood lactate concentration, the acceptable values of which may be selected arbitrarily and result in grossly inaccurate V̇o estimation. Whereas this may not be an overriding concern in young, healthy subjects with experience of performing exercise to volitional exhaustion, exercise test naïve subjects, patient populations, and less motivated subjects may stop exercising before their V̇o is reached. When V̇o is a or the criterion outcome of the investigation, this represents a major experimental design issue. This CORP presents the rationale for incorporation of a second, constant work rate test performed at ~110% of the work rate achieved on the initial ramp test to resolve the classic V̇o-work rate plateau that is the unambiguous validation of V̇o The broad utility of this procedure has been established for children, adults of varying fitness, obese individuals, and patient populations.
Topics: Exercise; Exercise Test; Heart Rate; Humans; Kinetics; Muscle, Skeletal; Oxygen; Oxygen Consumption; Pulmonary Gas Exchange
PubMed: 28153947
DOI: 10.1152/japplphysiol.01063.2016 -
Comprehensive Physiology Mar 2020The pulmonary blood-gas barrier represents a remarkable feat of engineering. It achieves the exquisite thinness needed for gas exchange by diffusion, the strength to... (Review)
Review
The pulmonary blood-gas barrier represents a remarkable feat of engineering. It achieves the exquisite thinness needed for gas exchange by diffusion, the strength to withstand the stresses and strains of repetitive and changing ventilation, and the ability to actively maintain itself under varied demands. Understanding the design principles of this barrier is essential to understanding a variety of lung diseases, and to successfully regenerating or artificially recapitulating the barrier ex vivo. Many classical studies helped to elucidate the unique structure and morphology of the mammalian blood-gas barrier, and ongoing investigations have helped to refine these descriptions and to understand the biological aspects of blood-gas barrier function and regulation. This article reviews the key features of the blood-gas barrier that enable achievement of the necessary design criteria and describes the mechanical environment to which the barrier is exposed. It then focuses on the biological and mechanical components of the barrier that preserve integrity during homeostasis, but which may be compromised in certain pathophysiological states, leading to disease. Finally, this article summarizes recent key advances in efforts to engineer the blood-gas barrier ex vivo, using the platforms of lung-on-a-chip and tissue-engineered whole lungs. © 2020 American Physiological Society. Compr Physiol 10:415-452, 2020.
Topics: Animals; Bioengineering; Blood-Air Barrier; Humans; Lung; Lung Diseases; Pulmonary Circulation; Pulmonary Gas Exchange
PubMed: 32163210
DOI: 10.1002/cphy.c190026 -
Respiratory Care Apr 2022Acute respiratory failure with inadequate oxygenation and/or ventilation is a common reason for ICU admission in children and adults. Despite the morbidity and mortality... (Review)
Review
Acute respiratory failure with inadequate oxygenation and/or ventilation is a common reason for ICU admission in children and adults. Despite the morbidity and mortality associated with acute respiratory failure, few proven treatment options exist beyond invasive ventilation. Attempts to develop intravascular respiratory assist catheters capable of providing clinically important gas exchange have had limited success. Only one device, the IVOX catheter, was tested in human clinical trials before development was halted without FDA approval. Overcoming the technical challenges associated with providing safe and effective gas exchange within the confines of the intravascular space remains a daunting task for physicians and engineers. It requires a detailed understanding of the fundamentals of gas transport and respiratory physiology to optimize the design for a successful device. This article reviews the potential benefits of such respiratory assist catheters, considerations for device design, previous attempts at intravascular gas exchange, and the motivation for continued development efforts.
Topics: Adult; Carbon Dioxide; Child; Humans; Pulmonary Gas Exchange; Respiration; Respiratory Distress Syndrome; Respiratory Insufficiency
PubMed: 35338096
DOI: 10.4187/respcare.09288 -
The European Respiratory Journal May 2014The structure of the lung, with its delicate network of airspaces and capillaries, means that gravity has a profound influence on its function. Studies of lung function... (Review)
Review
The structure of the lung, with its delicate network of airspaces and capillaries, means that gravity has a profound influence on its function. Studies of lung function in the absence of gravity provide valuable insight into how, for we Earth-bound individuals, its unavoidable effects shape our lung function. Gravity causes uneven ventilation in the lung through the deformation of lung tissue (the so-called Slinky effect), and uneven perfusion through a combination of the Slinky effect and the zone model of pulmonary perfusion. Both ventilation and perfusion exhibit persisting heterogeneity in microgravity, indicating important other mechanisms. However, gravity serves to maintain a degree of matching of these two processes, so that the ventilation/perfusion ratio, and thus gas exchange, remains efficient. Therefore, while both ventilation and perfusion are more uniform in spaceflight, gas exchange is seemingly no more efficient than on Earth. Despite the changes in lung function when gravity is removed, the lung continues to function well in weightlessness. Unlike many other organ systems, the lung does not appear to undergo structural adaptive changes when gravity is removed, and so there is no apparent degradation in lung function upon return to earth, even after 6 months in space.
Topics: Aerosols; Gravitation; Humans; Lung; Perfusion; Pulmonary Gas Exchange; Respiration; Respiratory Function Tests; Respiratory System; Space Flight; Weightlessness
PubMed: 24603820
DOI: 10.1183/09031936.00001414 -
Anesthesiology Mar 2014
Topics: Animals; Lung; Lung Volume Measurements; Pulmonary Gas Exchange; Pulmonary Surfactants
PubMed: 24534859
DOI: 10.1097/ALN.0000000000000105