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Liquid breathing | |
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MeSH | D021061 |
Liquid breathing is a form of respiration in which a normally air-breathing organism breathes an oxygen-rich liquid which is capable of CO2 gas exchange (such as a perfluorocarbon). [1]
The liquid involved requires certain physical properties, such as respiratory gas solubility, density, viscosity, vapor pressure and lipid solubility, which some perfluorochemicals (PFCs) have. [2] Thus, it is critical to choose the appropriate PFC for a specific biomedical application, such as liquid ventilation, drug delivery or blood substitutes. The physical properties of PFC liquids vary substantially; however, the one common property is their high solubility for respiratory gases. In fact, these liquids carry more oxygen and carbon dioxide than blood. [3]
In theory, liquid breathing could assist in the treatment of patients with severe pulmonary or cardiac trauma, especially in pediatric cases.[ how? ] Liquid breathing has also been proposed for use in deep diving [4] [5] [6] and space travel. [7] [8] Despite some recent advances in liquid ventilation, a standard mode of application has not yet been established.
Gas solubility | |
Oxygen | 33–66 mL / 100 mL PFC |
Carbon dioxide | 140–166 mL / 100 mL PFC |
Vapor pressure | 0.2–400 torr |
Density | 1.58–2.0 g/mL |
Viscosity | 0.8–8.0 cSt |
As liquid breathing is still a highly experimental technique, there are several proposed approaches.
Although total liquid ventilation (TLV) with completely liquid-filled lungs can be beneficial, [9] the complex liquid-filled tube system required is a disadvantage compared to gas ventilation—the system must incorporate a membrane oxygenator, heater, and pumps to deliver to, and remove from the lungs tidal volume aliquots of conditioned perfluorocarbon (PFC). One research group led by Thomas H. Shaffer has maintained that with the use of microprocessors and new technology, it is possible to maintain better control of respiratory variables such as liquid functional residual capacity and tidal volume during TLV than with gas ventilation. [2] [10] [11] [12] Consequently, the total liquid ventilation necessitates a dedicated liquid ventilator similar to a medical ventilator except that it uses a breathable liquid. Many prototypes are used for animal experimentation, but experts recommend continued development of a liquid ventilator toward clinical applications. [13] Specific preclinical liquid ventilator (Inolivent) is currently under joint development in Canada and France. [14] The main application of this liquid ventilator is the ultra-fast induction of therapeutic hypothermia after cardiac arrest. This has been demonstrated to be more protective than slower cooling method after experimental cardiac arrest. [15]
In contrast, partial liquid ventilation (PLV) is a technique in which a PFC is instilled into the lung to a volume approximating functional residual capacity (approximately 40% of total lung capacity). Conventional mechanical ventilation delivers tidal volume breaths on top of it. This mode of liquid ventilation currently seems technologically more feasible than total liquid ventilation, because PLV could utilise technology currently in place in many neonatal intensive-care units (NICU) worldwide.
The influence of PLV on oxygenation, carbon dioxide removal and lung mechanics has been investigated in several animal studies using different models of lung injury. [16] Clinical applications of PLV have been reported in patients with acute respiratory distress syndrome (ARDS), meconium aspiration syndrome, congenital diaphragmatic hernia and respiratory distress syndrome (RDS) of neonates. In order to correctly and effectively conduct PLV, it is essential to
If PFC liquid is not maintained in the lung, PLV can not effectively protect the lung from biophysical forces associated with the gas ventilator.
New application modes for PFC have been developed. [17]
Partial liquid ventilation (PLV) involves filling the lungs with a liquid. This liquid is a perfluorocarbon such as perflubron (brand name Liquivent). The liquid has some unique properties. It has a very low surface tension, similar to the surfactant substances produced in the lungs to prevent the alveoli from collapsing and sticking together during exhalation. It also has a high density, oxygen readily diffuses through it, and it may have some anti-inflammatory properties. In PLV, the lungs are filled with the liquid, the patient is then ventilated with a conventional ventilator using a protective lung ventilation strategy. The hope is that the liquid will help the transport of oxygen to parts of the lung that are flooded and filled with debris, help remove this debris and open up more alveoli improving lung function. The study of PLV involves comparison to protocolized ventilator strategy designed to minimize lung damage. [18] [19]
Vaporization of perfluorohexane with two anesthetic vaporizers calibrated for perfluorohexane has been shown to improve gas exchange in oleic acid-induced lung injury in sheep. [20]
Predominantly PFCs with high vapor pressure are suitable for vaporization.
With aerosolized perfluorooctane, significant improvement of oxygenation and pulmonary mechanics was shown in adult sheep with oleic acid-induced lung injury.
In surfactant-depleted piglets, persistent improvement of gas exchange and lung mechanics was demonstrated with Aerosol-PFC. [21] The aerosol device is of decisive importance for the efficacy of PFC aerosolization, as aerosolization of PF5080 (a less purified FC77) has been shown to be ineffective using a different aerosol device in surfactant-depleted rabbits. Partial liquid ventilation and Aerosol-PFC reduced pulmonary inflammatory response. [22]
The most promising area for the use of liquid ventilation is in the field of pediatric medicine. [23] [24] [25] The first medical use of liquid breathing was treatment of premature babies [26] [27] [28] [29] and adults with acute respiratory distress syndrome (ARDS) in the 1990s. Liquid breathing was used in clinical trials after the development by Alliance Pharmaceuticals of the fluorochemical perfluorooctyl bromide, or perflubron for short. Current methods of positive-pressure ventilation can contribute to the development of lung disease in pre-term neonates, leading to diseases such as bronchopulmonary dysplasia. Liquid ventilation removes many of the high pressure gradients responsible for this damage. Furthermore, perfluorocarbons have been demonstrated to reduce lung inflammation, [30] [31] [32] improve ventilation-perfusion mismatch and to provide a novel route for the pulmonary administration of drugs. [30] [33] [34]
In order to explore drug delivery techniques that would be useful for both partial and total liquid ventilation, more recent studies have focused on PFC drug delivery using a nanocrystal suspension. The first image is a computer model of a PFC liquid (perflubron) combined with gentamicin molecules.
The second image shows experimental results comparing both plasma and tissue levels of gentamicin after an intratracheal (IT) and intravenous (IV) dose of 5 mg/kg in a newborn lamb during gas ventilation. Note that the plasma levels of the IV dose greatly exceed the levels of the IT dose over the 4 hour study period; whereas, the lung tissue levels of gentamicin when delivered by an intratracheal (IT) suspension, uniformly exceed the intravenous (IV) delivery approach after 4 hours. Thus, the IT approach allows more effective delivery of the drug to the target organ while maintaining a safer level systemically. Both images represent the in-vivo time course over 4 hours. Numerous studies have now demonstrated the effectiveness of PFC liquids as a delivery vehicle to the lungs. [35] [36] [37] [38] [34] [39] [33] [40] [30] [41]
Clinical trials with premature infants and adults have been conducted. [42] Since the safety of the procedure and the effectiveness were apparent from an early stage, the US Food and Drug Administration (FDA) gave the product "fast track" status (meaning an accelerated review of the product, designed to get it to the public as quickly as is safely possible) due to its life-saving potential. Clinical trials showed that using perflubron with ordinary ventilators improved outcomes as much as using high frequency oscillating ventilation (HFOV). But because perflubron was not better than HFOV, the FDA did not approve perflubron, and Alliance is no longer pursuing the partial liquid ventilation application. Whether perflubron would improve outcomes when used with HFOV or has fewer long-term consequences than HFOV remains an open question.
In 1996 Mike Darwin and Steven B. Harris proposed using cold liquid ventilation with perfluorocarbon to quickly lower the body temperature of victims of cardiac arrest and other brain trauma to allow the brain to better recover. [43] The technology came to be called gas/liquid ventilation (GLV), and was shown able to achieve a cooling rate of 0.5 °C per minute in large animals. [44] It has not yet been tried in humans.
Most recently, hypothermic brain protection has been associated with rapid brain cooling. In this regard, a new therapeutic approach is the use of intranasal perfluorochemical spray for preferential brain cooling. [45] The nasopharyngeal (NP) approach is unique for brain cooling due to anatomic proximity to the cerebral circulation and arteries. Based on preclinical studies in adult sheep, it was shown that independent of region, brain cooling was faster during NP-perfluorochemical versus conventional whole body cooling with cooling blankets. To date, there have been four human studies including a completed randomized intra-arrest study (200 patients). [46] [47] Results clearly demonstrated that prehospital intra-arrest transnasal cooling is safe, feasible and is associated with an improvement in cooling time.
Gas pressure increases with depth, rising 1 bar (14.5 psi (100 kPa)) every 10 meters to over 1,000 bar at the bottom of the Mariana Trench. Diving becomes more dangerous as depth increases, and deep diving presents many hazards. All surface-breathing animals are subject to decompression sickness, including aquatic mammals [48] and free-diving humans. Breathing at depth can cause nitrogen narcosis and oxygen toxicity. Holding the breath while ascending after breathing at depth can cause air embolisms, burst lung, and collapsed lung.
Special breathing gas mixes such as trimix or heliox reduce the risk of nitrogen narcosis but do not eliminate it. Heliox further eliminates the risk of nitrogen narcosis but introduces the risk of helium tremors below about 500 feet (150 m). Atmospheric diving suits maintain body and breathing pressure at 1 bar, eliminating most of the hazards of descending, ascending, and breathing at depth. However, the rigid suits are bulky, clumsy, and very expensive.
Liquid breathing offers a third option, [4] [49] promising the mobility available with flexible dive suits and the reduced risks of rigid suits. With liquid in the lungs, the pressure within the diver's lungs could accommodate changes in the pressure of the surrounding water without the huge partial pressure gas exposures required when the lungs are filled with gas. Liquid breathing would not result in the saturation of body tissues with high pressure nitrogen or helium that occurs with the use of non-liquids, thus would reduce or remove the need for slow decompression.
A significant problem, however, arises from the high viscosity of the liquid and the corresponding reduction in its ability to remove CO2. [4] [50] All uses of liquid breathing for diving must involve total liquid ventilation (see above). Total liquid ventilation, however, has difficulty moving enough liquid to carry away CO2, because no matter how great the total pressure is, the amount of partial CO2 gas pressure available to dissolve CO2 into the breathing liquid can never be much more than the pressure at which CO2 exists in the blood (about 40 mm of mercury (Torr)). [50]
At these pressures, most fluorocarbon liquids require about 70 mL/kg minute-ventilation volumes of liquid (about 5 L/min for a 70 kg adult) to remove enough CO2 for normal resting metabolism. [51] This is a great deal of fluid to move, particularly as liquids are more viscous and denser than gases, (for example water is about 850 times the density of air [52] ). Any increase in the diver's metabolic activity also increases CO2 production and the breathing rate, which is already at the limits of realistic flow rates in liquid breathing. [4] [53] [54] It seems unlikely that a person would move 10 liters/min of fluorocarbon liquid without assistance from a mechanical ventilator, so "free breathing" may be unlikely. However, it has been suggested that a liquid breathing system could be combined with a CO2 scrubber connected to the diver's blood supply; a US patent has been filed for such a method. [55] [56]
Liquid immersion provides a way to reduce the physical stress of G forces. Forces applied to fluids are distributed as omnidirectional pressures. As liquids cannot be practically compressed, they do not change density under high acceleration such as performed in aerial maneuvers or space travel. A person immersed in liquid of the same density as tissue has acceleration forces distributed around the body, rather than applied at a single point such as a seat or harness straps. This principle is used in a new type of G-suit called the Libelle G-suit, which allows aircraft pilots to remain conscious and functioning at more than 10g acceleration by surrounding them with water in a rigid suit. [57]
Acceleration protection by liquid immersion is limited by the differential density of body tissues and immersion fluid, limiting the utility of this method to about 15g to 20g. [58] Extending acceleration protection beyond 20g requires filling the lungs with fluid of density similar to water. An astronaut totally immersed in liquid, with liquid inside all body cavities, will feel little effect from extreme G forces because the forces on a liquid are distributed equally, and in all directions simultaneously. Effects will still be felt because of density differences between different body tissues, so an upper acceleration limit still exists. However, it can likely be higher than hundreds of G. [59]
Liquid breathing for acceleration protection may never be practical because of the difficulty of finding a suitable breathing medium of similar density to water that is compatible with lung tissue. Perfluorocarbon fluids are twice as dense as water, hence unsuitable for this application. [3]
This section needs additional citations for verification .(January 2013) |
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.
The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies greatly, depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals, the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs; in mammals and reptiles, these are called alveoli, and in birds, they are known as atria. These microscopic air sacs have a very rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi. These enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds, the bronchioles are termed parabronchi. It is the bronchioles, or parabronchi that generally open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration.
Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type 1 or Type 2, based on whether there is a high carbon dioxide level, and can be acute or chronic. In clinical trials, the definition of respiratory failure usually includes increased respiratory rate, abnormal blood gases, and evidence of increased work of breathing. Respiratory failure causes an altered state of consciousness due to ischemia in the brain.
Mechanical ventilation or assisted ventilation is the medical term for using a ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, with the main goal of helping the delivery of oxygen and removal of carbon dioxide. Mechanical ventilation is used for many reasons, including to protect the airway due to mechanical or neurologic cause, to ensure adequate oxygenation, or to remove excess carbon dioxide from the lungs. Various healthcare providers are involved with the use of mechanical ventilation and people who require ventilators are typically monitored in an intensive care unit.
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common.
In physiology, respiration is the movement of oxygen from the outside environment to the cells within tissues, and the removal of carbon dioxide in the opposite direction to the surrounding environment.
Salt water aspiration syndrome is a rare diving disorder suffered by scuba divers who inhale a mist of seawater, usually from a faulty demand valve, causing irritation of the lungs. It is not the same thing as aspiration of salt water as a bulk liquid, i.e. drowning. It can usually be treated by rest for several hours. If severe, medical assessment is required. First described by Carl Edmonds.
Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the body's metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation".
Infant respiratory distress syndrome (IRDS), also known as surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins.
Generalized hypoxia is a medical condition in which the tissues of the body are deprived of the necessary levels of oxygen due to an insufficient supply of oxygen, which may be due to the composition or pressure of the breathing gas, decreased lung ventilation, or respiratory disease, any of which may cause a lower than normal oxygen content in the arterial blood, and consequently a reduced supply of oxygen to all tissues perfused by the arterial blood. This usage is in contradistinction to localized hypoxia, in which only an associated group of tissues, usually with a common blood supply, are affected, usually due to an insufficient or reduced blood supply to those tissues. Generalized hypoxia is also used as a synonym for hypoxic hypoxia This is not to be confused with hypoxemia, which refers to low levels of oxygen in the blood, although the two conditions often occur simultaneously, since a decrease in blood oxygen typically corresponds to a decrease in oxygen in the surrounding tissue. However, hypoxia may be present without hypoxemia, and vice versa, as in the case of infarction. Several other classes of medical hypoxia exist.
Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia is usually caused by pulmonary disease. Sometimes the concentration of oxygen in the air is decreased leading to hypoxemia.
Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.
Perfluorohexane, or tetradecafluorohexane, is a fluorocarbon. It is a derivative of hexane in which all the hydrogen atoms are replaced by fluorine atoms. It is used in one formulation of the electronic cooling liquid/insulator Fluorinert for low-temperature applications due to its low boiling point of 56 °C and freezing point of −90 °C. It is odorless and colorless. Unlike typical hydrocarbons, the structure features a helical carbon backbone. In medical imaging it is used as a contrast agent.
A pulmonary shunt is the passage of deoxygenated blood from the right side of the heart to the left without participation in gas exchange in the pulmonary capillaries. It is a pathological condition that results when the alveoli of parts of the lungs are perfused with blood as normal, but ventilation fails to supply the perfused region. In other words, the ventilation/perfusion ratio of those areas is zero.
The Alveolar–arterial gradient, is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen. It is a useful parameter for narrowing the differential diagnosis of hypoxemia.
A pulmonary contusion, also known as lung contusion, is a bruise of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels (hypoxia). Unlike pulmonary laceration, another type of lung injury, pulmonary contusion does not involve a cut or tear of the lung tissue.
A liquid ventilator is similar to a medical ventilator except that it should be able to ensure reliable total liquid ventilation with a breatheable liquid. Liquid ventilators are prototypes that may have been used for animal experimentations but experts recommend continued development of a liquid ventilator toward clinical applications.
Heated humidified high-flow therapy, often simply called high flow therapy, is a type of respiratory support that delivers a flow of medical gas to a patient of up to 60 liters per minute and 100% oxygen through a large bore or high flow nasal cannula. Primarily studied in neonates, it has also been found effective in some adults to treat hypoxemia and work of breathing issues. The key components of it are a gas blender, heated humidifier, heated circuit, and cannula.
Modes of mechanical ventilation are one of the most important aspects of the usage of mechanical ventilation. The mode refers to the method of inspiratory support. In general, mode selection is based on clinician familiarity and institutional preferences, since there is a paucity of evidence indicating that the mode affects clinical outcome. The most frequently used forms of volume-limited mechanical ventilation are intermittent mandatory ventilation (IMV) and continuous mandatory ventilation (CMV). There have been substantial changes in the nomenclature of mechanical ventilation over the years, but more recently it has become standardized by many respirology and pulmonology groups. Writing a mode is most proper in all capital letters with a dash between the control variable and the strategy.
Medical gas therapy is a treatment involving the administration of various gases. It has been used in medicine since the use of oxygen therapy. Most of these gases are drugs, including oxygen. Many other gases, collectively known as factitious airs, were explored for medicinal value in the late eighteenth century. In addition to oxygen, medical gases include nitric oxide (NO), and helium-O2 mixtures (Heliox). Careful considerations and close monitoring needed when medical gases are in use. For the purpose of this article only gas mixtures are described.
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: CS1 maint: numeric names: authors list (link)A significant positive step was the use of PFC-associated gas exchange, now termed partial liquid ventilation (PLV).
Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury.
Aerosolized perfluorocarbon improved pulmonary gas exchange and lung mechanics as effectively as PLV did in surfactant-depleted piglets, and the improvement was sustained longer.
In a surfactant-depleted piglet model, aerosol therapy with perfluorocarbon but not LV-PLV reduces the initial pulmonary inflammatory reaction at least as potently as PLV at FRC volume.