Liquid breathing 

is a postulated form of respiration in which a normally air-breathing organism breathes

an oxygen-rich liquid (such as aperfluorocarbon), rather than breathing air. In theory, liquid breathing
could assist in the treatment of patients with severe pulmonary or cardiactrauma, especially in pediatric
cases. Liquid breathing has also been proposed for use in deep diving[1][2] and space travel.[3] Despite
some recent advances in liquid ventilation, a standard mode of application has not been established yet.

Liquid breathing is sometimes called fluid breathing; however, this usage can be confusing as both
liquids and gases are fluid substances.

Contents
 [hide]

1 Approaches

o 1.1 Total liquid

ventilation

o 1.2 Partial liquid

ventilation

o 1.3 PFC vapor

o 1.4 Aerosol-PFC

2 Proposed uses

o 2.1 Diving

o 2.2 Medical

treatment

o 2.3 Space travel

3 Examples in fiction

4 See also

5 References

6 External links

[edit]Approaches

Because liquid breathing is still a highly experimental technique, there are several proposed approaches.

[edit]Total liquid ventilation

Although total liquid ventilation (TLV) with completely liquid-filled lungs is beneficial,[4] the necessity for the
liquid-filled tube system that contains pumps and heater and membrane oxygenator to deliver and
remove tidal volume aliquots of conditioned perfluorocarbon to the lungs is a disadvantage compared to
gas ventilation. One research group led by Thomas H. Shaffer has maintained that with the use
of microprocessorsand 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.[5][6][7][8].
Consequently, the total liquid ventilation necessitates a dedicated liquid ventilator similar to amedical
ventilator except that it uses a breatheable liquid. Many prototypes are used for animal experimentations,
but experts recommendcontinued development of a  liquid ventilator toward clinical applications[9].

[edit]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 (TLC)). Conventional mechanical ventilation delivers tidal volume breaths on top of this. This
mode of liquid ventilation is technically more viable than total liquid ventilation as it can utilise technology
currently in place in 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[10] 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

1. properly dose a patient to a specific lung volume (10-15 ml/kg) to recruit alveolar volume and
2. redose the lung with PFC liquid (1-2 ml/kg/hr) 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.[11]

[edit]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.[12]

Predominantly PFCs with high vapor pressure are suitable for vaporization

[edit]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.[13] 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.[14]

[edit]Proposed uses
[edit]Diving

In diving, the pressure inside the lungs must effectively equal the pressure outside the body, otherwise
the lungs collapse. Since external and internal pressures must be equal, the required gas pressure
increases with depth to match the increased external water pressure, rising to around 13 bar at 400 feet
(120 m), and around 500 bar on the oceans' abyssal plains. These high pressures may have adverse
effects on the body, especially when quickly released (as in a too-rapid return to the surface), including
air emboli and decompression sickness (colloquially known as "the bends"). (Diving mammals, as well
as free-diving humans who dive to great depths on a single breath, have little or no problem with
decompression sickness despite their rapid return to the surface; this is not because a single breath of
gas does not contain enough total nitrogen to cause tissue bubbles on decompression, but because of
the short bottom time. Humans who free-dive deep many times in succession (e.g. pearl fishers, well-
trained speargun fishers) may experience decompression sickness (see taravana). In very deep-diving
mammals and deep free-diving humans, the lungs almost completely collapse, see mammalian diving
reflex).

One solution is a rigid articulated diving suit, but these are bulky and clumsy. A more moderate option to
deal with narcosis is to breathe helioxor trimix, in which some or all of the nitrogen is replaced by helium.
However, this option does not deal with the problem of bubbles and decompression sickness, because
helium dissolves in tissues and causes bubbles when pressures are released, just as nitrogen does.

Liquid breathing provides a third option.[1][15] 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 gas partial
pressure 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. (This technology was dramatized
in James Cameron's 1989 film The Abyss.)

A significant problem, however, arises from the high viscosity of the liquid and the corresponding
reduction in its ability to remove CO2.[1][16] 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 CO2into the breathing liquid can never be much more than the pressure at which CO2 exists in
the blood (about 40 mm of mercury (Torr)).[16]
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.[17] This is a great
deal of fluid to move, particularly as liquids are generally more viscous than gases, (for example water is
about 850 times the viscosity of air[18]). Any increase in the diver's metabolic activity also increases
CO2production and the breathing rate, which is already at the limits of realistic flow rates in liquid
breathing.[1][19][20] 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.

[edit]Medical treatment
The most promising area for the use of liquid ventilation is in the field of pediatric medicine.[21][22][23] The
first medical use of liquid breathing was treatment of premature babies[24][25][26][27] 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,[28][29]
[30]
 improve ventilation-perfusion mismatch and to provide a novel route for the pulmonary administration
of drugs.[31][32][33] Clinical trials with premature infants, children and adults were 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 remains an open question.

In 1996 Mike Darwin and Dr. 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.[34] 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.[35] 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[36].
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. Preliminary phase I clinical trials are ongoing using this new therapeutic procedure.

[edit]Space travel
Liquid immersion provides a way to reduce the physical stress of G forces. Forces applied to fluids are
distributed as omnidirectional pressures. Because 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 10 G acceleration by surrounding them with water in a rigid suit.

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 15 to 20 G.[37] Extending acceleration protection
beyond 20 G 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. However effects will be felt
because of density differences between different body tissues, so an upper acceleration limit still exists.

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[38]. On the
other hand, although perfluorochemicals are denser than water, lung tissue floats within the PFC filled
lungs, and if the lungs are not over-filled, there is no compromise in pulmonary or systemic blood flow[39].
Therefore, if the astronaut is immersed in liquid and their lungs are filled with liquid PFC, they should not
experience adverse effects, in spite of the almost twofold density difference. Based on interviews with
adult patients that experienced partial liquid ventilation, when they became conscious they were unaware
that 20-30 ml/kg of PFC was in their lungs during recovery.

[edit]Examples in fiction

 In "The Lost Symbol" by Dan Brown, Robert Langdon (the protagonist) is completely submerged
in breathable liquid as a torture technique by Mal'akh (the antagonist). He goes through a near death
experience when he inhales the liquid and blacks out, losing control over his body, but is soon
revived.
 In the Paul W. S. Anderson film Event Horizon the crew of the rescue ship Lewis and
Clark submerge themselves in liquid tanks connected to a breathing apparatus during their high
 speed flight to Neptune. The ship's medic states that reason for this is "Without a tank, the force
would liquefy your skeleton." referring to the immense Gs the crew would experience.
 The James Cameron film The Abyss features a character using liquid breathing to dive thousands
of feet without compressing. The Abyssalso features a scene with a rat submerged in and breathing
fluorocarbon liquid, filmed in real life.[40]
 The aliens in the Gerry Anderson UFO series use liquid-breathing spacesuits.
 In the anime series Neon Genesis Evangelion (1995-96)- and continued on later in various
movies- the Evangelion pilots (who are all specifically fourteen-year old children) use liquid breathing
when they are inside their bio-mechanical mecha, whose cockpits are flooded with an oxygenated
liquid referred to as "LCL". Characters talk normally while submerged in LCL, although this is
impossible in real life.
 In the anime series Wolf's Rain, Cheza was kept in a liquid breathing dome.
 Hal Clement's 1973 novel Ocean on Top portrays a small underwater civilization living in a
'bubble' of oxygenated fluid denser than seawater.
 In an episode of the Adult Swim cartoon series Metalocalypse, the other members of the band
submerge guitarist Toki in a "liquid oxygen isolation chamber" while recording an album in
the Mariana Trench.
 In an episode of the SyFy Channel show Eureka, Sheriff Jack Carter is submerged in a tank of
"oxygen rich plasma" to be cured of the effects of a scientific accident.
 In the movie Mission to Mars, a character is depicted as being immersed in apparent breathable
fluid before a high-acceleration launch.
 In season 1, episode 13 of Seven Days chrononaut Frank Parker is seen breathing a hyper-
oxygenated perfluorocarbon liquid that is pumped through a sealed full body suit that he is wearing.
This suit and liquid combination allow him to board a Russian submarine through open ocean at a
depth of almost 1000 feet. Upon boarding the submarine he removes his helmet, expels the liquid
from his lungs and is able to breathe air again.
 In the 25th episode of the anime series Real Drive (RD 潜脳調査室 RD Sennō Chōsashitsu) the
protagonist, Masamichi Haru, used a special diving suit for deep diving (5000m+ below sea level),
which in theory is designed to allow movement for the diver even at 640 times normal atmospheric
pressure. To compensate for the high atmospheric compression, the diving suit is supplied with a
special breathable fluid.
 Ben Bova's novel Jupiter features a craft in which the crew are suspended in a breathable liquid
that allows them to survive in the high pressure environment of Jupiter's atmosphere.
 In the manga version of "Nausicaä of the Valley of the Wind", the main protagonist Nausicaä is
held in an Ohmu's stomach, where she is kept alive by being surrounded by "serum" which allows her
to breathe in her comatose state.
 In the book Mechanicum from the Horus Heresy series of novels, physically crippled Titan pilots
are encased in nutrient fluid tanks to allow them to continue operating beyond the limits normally
imposed by the body.
[edit]See also

 Mechanical ventilation
 Breathing gas
 Artificial gills (human)
 Liquid ventilator
[edit]References

1. ^ a b c d Kylstra JA (1977). The Feasibility of Liquid Breathing in Man.. Report to the US Office of Naval

Research. Durham, NC: Duke University. Retrieved 2008-05-05.

2. ^ "menfish". Retrieved 2008-05-17.

3. ^ "Liquid Breathing - Medical uses". Retrieved 2008-05-17.

4. ^ Wolfson et al. Multicenter comparative study of conventional mechanical gas ventilation to tidal liquid ventilation

in oleic acid injured sheep 54(3):236-269, 2008.

5. ^ Shaffer, T.H., M.R. Wolfson, and L.C. Clark: State of art review : Liquid ventilation. Pediatr. Pulmonol. 14:102

109, 1992

6. ^ Cox CA, Stavis RL. Wolfson MR, Shaffer TH: Long-term tida