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).GAEDEKE NORMS, M., RN, MSN, CCRN, CS, et al. Liquid Ventilation: It's Not Science Fiction Anymore. AACN Clin Issues Crit Care Nurs. 1994;5(3):246-254. Cited in: Your Journals@Ovid.
The liquid involved requires certain physical properties, such as respiratory gas solubility, density, viscosity, vapor pressure and lipid solubility, which some perfluorochemicals (PFCs) have. 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 does.
In theory, liquid breathing could assist in the treatment of patients with severe pulmonary or cardiac trauma, especially in pediatric and neonatal cases. Liquid breathing has also been proposed for use in deep divingFeatured on the ABC television program That's Incredible, including a demonstration of a mouse surviving a prolonged dunking in perfluorocarbon. and space travel.Featured on the ABC television program That's Incredible. Cathy Lee Crosby describing diving and spaceflight applications. Voiceover with stock video. Despite some recent advances in liquid ventilation, a standard mode of application has not yet been established.
Approaches + Physicochemical properties (37 °C at 1 atm) of 18 perfluorochemical liquids used for biomedical applications. This table characterizes the most significant physical properties related to systemic physiology and their range of properties. Gas solubility 33–66 mL / 100 mL PFC 140–166 mL / 100 mL PFC Vapor pressure 0.2–400 torr Density 1.58–2.1 g/mL Viscosity 1–8.0 cSt
As liquid breathing is still a highly experimental technique, there are several proposed approaches.
Total liquid ventilation
Although total liquid ventilation (TLV) with completely liquid-filled lungs can be beneficial, 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. 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. Specific preclinical liquid ventilator (Inolivent) is currently under joint development in Canada and France. 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.
Partial liquid ventilation
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. 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 properly dose a patient to a specific lung volume (10–15 ml/kg) to recruit alveolar volume redose the lung with PFC liquid (1–2 ml/kg/h) to oppose PFC evaporation from the lung. 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.
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. (editorial)
PFC vapor
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.
Predominantly PFCs with high vapor pressure are suitable for vaporization.
Aerosol-PFC
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. 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.
Human usage
Medical treatment The most promising area for the use of liquid ventilation is in the field of pediatric medicine. The first medical use of liquid breathing was treatment of premature babies 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, improve ventilation-perfusion mismatch and to provide a novel route for the pulmonary administration of drugs.
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.
Clinical trials with premature infants and adults have been conducted. 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). However, 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. 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. 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. 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). Results clearly demonstrated that prehospital intra-arrest transnasal cooling is safe, feasible and is associated with an improvement in cooling time.
Proposed uses
Diving
Gas pressure increases with depth, rising 1 bar () every 10 meters to over 1,100 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 and humans scuba-diving. 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, in the case of trimix, do not eliminate it. Heliox eliminates the risk of nitrogen narcosis but introduces the risk of helium tremors below about . 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.