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, 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.
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.
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.
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). 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.
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.
Liquid breathing offers a third option, 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 firstly from its high density which is that perfluorocarbons are twice as dense as water which makes a significant effort to move the liquid in and out of the lungs, and secondly is its high viscosity of the liquid and the corresponding reduction in its ability to remove CO2. 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)).
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. 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). 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. 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.
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.
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.
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.
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"About Capsuleers - EVE Fiction - EVE Online Forums". https://forums.eveonline.com/default.aspx?g=posts&m=3479925#post3479925