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Liquid breathing
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Liquid breathing
Computer-generated model of perflubron and gentamicin molecules in liquid suspension for pulmonary administration
MeSHD021061

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.

Approaches

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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
Oxygen 33–66 mL / 100 mL PFC
Carbon dioxide 140–166 mL / 100 mL PFC
Vapor pressure 0.2–400 torr
Density 1.58–2.1 g/mL
Viscosity 1–8.0 cSt
Computer models of three perfluorochemical molecules used for biomedical applications and for liquid ventilation studies: a) FC-75, b) perflubron, and c) perfluorodecalin.

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

Total liquid ventilation

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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]

Partial liquid ventilation

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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

  1. properly dose a patient to a specific lung volume (10–15 ml/kg) to recruit alveolar volume
  2. 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.[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]

PFC vapor

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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.

Aerosol-PFC

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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]

Human usage

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Medical treatment

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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]

Comparison of IT and IV administration of gentamicin.

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.

Proposed uses

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Diving

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Gas pressure increases with depth, rising 1 bar (14.5 psi (100 kPa)) 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[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, 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 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 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.[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]

Space travel

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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 a 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]

Examples in fiction

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Literary works

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  • Alexander Beliaev's 1928 science fiction novel Amphibian Man is based on a scientist and a maverick surgeon, who makes his son, Ichthyander (etymology: "fish" + "man") a life-saving transplant – a set of shark gills. There is a film by the same name based on the novel.
  • L. Sprague de Camp's 1938 short story "The Merman" hinges on an experimental process to make lungs function as gills, thus allowing a human being to "breathe" under water.
  • Hal Clement's 1973 novel Ocean on Top portrays a small underwater civilization living in a 'bubble' of oxygenated fluid denser than seawater.
  • Joe Haldeman's 1975 novel The Forever War describes liquid immersion and breathing in great detail as a key technology to allow space travel and combat with acceleration up to 50 G.
  • In the Star Trek: The Next Generation novel The Children of Hamlin (1988) the crew of the Enterprise-D encounter an alien race whose ships contain a breathable liquid environment.
  • Peter Benchley's 1994 novel White Shark centers around a Nazi scientist's experimental attempts to create an amphibious human, whose lungs are surgically modified to breathe underwater, and trained to reflexively do so after being flooded with a fluorocarbon solution.
  • Judith and Garfield Reeves-Stevens' 1994 Star Trek novel Federation explains that before the invention of the inertial dampener, the stresses of high-G acceleration required starship pilots to be immersed in liquid-filled capsules, breathing an oxygen-rich saline solution to prevent their lungs from being crushed.
  • Nicola Griffith's novel Slow River (1995) features a sex scene occurring within a twenty cubic foot silvery pink perflurocarbon pool, with the sensation described as "like breathing a fist".
  • Ben Bova's novel Jupiter (2000) 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 Scott Westerfeld's sci-fi novel The Risen Empire (2003), the lungs of soldiers performing insertion from orbit are filled with an oxygen-rich polymer gel with embedded pseudo-alveoli and a rudimentary artificial intelligence.[60]
  • The novel Mechanicum (2008) by Graham McNeill, Book 9 in the Horus Heresy book series, describes physically crippled Titan (gigantic war machine) pilots encased in nutrient fluid tanks. This allows them to continue operating beyond the limits normally imposed by the body.[61]
  • In Liu Cixin's novel The Dark Forest (2008), the warships of humanity in the 23rd century flood their compartments with an oxygen-rich liquid called 'deep-sea acceleration fluid' to protect the crew against the forces of extreme acceleration that the ships undergo. Ships enter a 'deep-sea state' where the crew are immersed in the fluid and sedated before acceleration can commence.[62]
  • In the 2009 novel The Lost Symbol by Dan Brown, Robert Langdon (the protagonist) is completely submerged in breathable liquid mixed with hallucinogenic chemicals and sedatives as a torture and interrogation 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 Greg van Eekhout's 2014 novel California Bones, two characters are put into tanks filled with liquid: "They were given no breathing apparatus, but the water in the tank was rich with perfluorocarbon, which carried more oxygen than blood."[63]
  • In author A.L. Mengel's science fiction novel The Wandering Star (2016), several characters breathe oxygenated fluid during a dive to explore an underwater city. They submerge in high pressure "bubbles" filled with the perfluorocarbon fluid.
  • In Tiamat's Wrath, a 2019 novel in The Expanse series by James S. A. Corey, The Laconian empire utilizes a ship with full-immersion liquid-breathing pods that allow the crew to undergo significantly increased g-forces. As powerful and fuel-efficient fusion engines in the series have made the only practical limitations of a ships' acceleration the survivability of the crew, this makes the ship the fastest in all of human-colonized space.

Films and television

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  • The aliens in the Gerry Anderson UFO series (1970-1971) use liquid-breathing spacesuits.
  • The 1989 film The Abyss by James Cameron features a character using liquid breathing to dive thousands of feet without compressing. The Abyss also features a scene with a rat submerged in and breathing fluorocarbon liquid, filmed in real life.[64]
  • In the 1995 anime Neon Genesis Evangelion, the cockpits of the titular mecha are filled with a fictional oxygenated liquid called LCL which is required for the pilot to mentally sync with an Evangelion, as well as providing direct oxygenation of their blood, and dampening the impacts from battle. Once the cockpit is flooded the LCL is ionized, bringing its density, opacity, and viscosity close to that of air. Protagonist Shinji Ikari notes that LCL smells like blood.
  • In the movie Mission to Mars (2000), a character is depicted as being immersed in apparent breathable fluid before a high-acceleration launch.
  • In season 1, episode 13 of Seven Days (1998-2001) 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 an episode of the Adult Swim cartoon series Metalocalypse (2006-2013), the other members of the band submerge guitarist Toki in a "liquid oxygen isolation chamber" while recording an album in the Mariana Trench.
  • In a Series 11 episode of Dalziel and Pascoe (1996-2007) entitled Demons on Our Shoulders, magician Lee Knight, played by Richard E Grant, performs an underwater trick using breathable fluid.
  • In an episode of the Syfy Channel show Eureka (2006-2012), Sheriff Jack Carter is submerged in a tank of "oxygen rich plasma" to be cured of the effects of a scientific accident.
  • In the anime series Aldnoah.Zero (2014-2015), episode 5 shows that Slaine Troyard was in a liquid-filled capsule when he crashed. Princess Asseylum witnessed the crash, helped him to get out of the capsule, then used CPR on him to draw out the liquid from his lungs.
  • In the 2024 anime Bang Brave Bang Bravern, the titular mecha Bravern fills its cockpit with liquid during underwater combat, telling pilot Ao Isami that it will supply oxygen directly to him while also counteracting the pressure. Bravern directly compares this to the scene from The Abyss, prompting Ao to ask how Bravern knows about the film.

Video games

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See also

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References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Liquid breathing

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Liquid breathing, also known as liquid ventilation, is a specialized respiratory technique in which the lungs are filled with an oxygenated perfluorocarbon (PFC) liquid rather than air, enabling gas exchange through the dissolution of oxygen and carbon dioxide in the inert, biocompatible fluid. This method leverages the high solubility of respiratory gases in PFCs, such as perflubron, to support ventilation in scenarios where traditional gas-based breathing fails, including acute lung injury and severe respiratory distress. There are two primary forms: total liquid ventilation (TLV), which completely replaces air with liquid tidal volumes, and partial liquid ventilation (PLV), which involves instilling PFC into the lungs while maintaining conventional gas ventilation. The concept of liquid breathing emerged from early 20th-century experiments but gained scientific traction in 1966 when researchers Leland Clark and Frank Gollan demonstrated that mice could survive immersion in oxygenated PFC liquids, highlighting the potential for mammals to respire via fluid media. Over subsequent decades, studies explored PFCs—fluorinated hydrocarbons with low , high , and no —for applications beyond initial animal models, including human trials in the 1990s for neonatal and adult respiratory conditions. Key mechanisms include the liquid's ability to recruit collapsed alveoli, reduce inflammation, and improve oxygenation by evenly distributing throughout the lungs, outperforming gas ventilation in models of (ARDS). Clinically, liquid breathing has been investigated primarily for premature infants with severe respiratory distress syndrome and adults with ARDS, where PLV with perflubron improved and in phase II trials, though larger phase III studies showed mixed results on mortality reduction. Advantages include enhanced oxygen delivery due to the PFC's high gas-carrying capacity, with oxygen solubility of 40–50 vol% compared to about 20 vol% , and protective effects against ventilator-induced through reduced shear forces. However, challenges such as the need for specialized , potential perfluorocarbon retention in the lungs, and losses have limited widespread adoption, with ongoing research focusing on refined delivery systems and hybrid approaches. Despite these hurdles, liquid breathing remains a promising adjunctive in critical care, particularly for protecting vulnerable tissue during mechanical support.

Overview and History

Definition and Basic Concept

Liquid breathing is a form of respiration in which a normally air-breathing inhales and exhales an oxygen-rich capable of carbon dioxide exchange, rather than gaseous air. This technique typically employs perfluorocarbons (PFCs), inert fluorinated hydrocarbons that dissolve high volumes of respiratory gases due to their . In practice, the lungs are filled with the oxygenated PFC , which facilitates gas transport across the alveolar-capillary membrane while minimizing in the airways. Unlike conventional gas breathing, where oxygen is delivered via low-density air (with an effective dissolved oxygen content in plasma of approximately 0.3 mL per 100 mL), liquid breathing uses PFCs with a of about 1.9 g/cm³ and far superior gas —up to 50-60 mL of O₂ per 100 mL of liquid at standard conditions. This higher requires the lungs to be completely filled with the liquid, necessitating to actively cycle the fluid in and out, as spontaneous breathing is not feasible without significant physiological adaptations or assistive devices due to the resistance imposed by the liquid's and weight. Key advantages of liquid breathing include enhanced oxygen delivery, particularly under elevated pressures where PFCs maintain high gas , and reduced risk of injury such as , as the liquid distributes more evenly and provides a protective hydrostatic effect against overdistension. These properties make it a promising alternative for scenarios involving compromised , though it remains experimental and limited to controlled settings.

Historical Development

The concept of liquid breathing emerged in the mid-20th century through pioneering animal experiments aimed at supporting respiration with oxygen-rich fluids. In the 1960s, physiologist Johannes A. Kylstra at Duke University conducted early studies showing that mice and dogs could maintain gas exchange by breathing hyperoxygenated saline solutions under pressures of up to 6 atmospheres, though survival times were limited to minutes due to inadequate carbon dioxide removal. A major breakthrough occurred in 1966 when Leland C. Clark Jr. and Frank Gollan at Cincinnati Children's Hospital demonstrated that small mammals, including spontaneously breathing rats, mice, and cats, could survive for extended periods—up to several hours—fully immersed in perfluorocarbon (PFC) liquids equilibrated with oxygen at . This work highlighted the superior gas-carrying capacity of PFCs compared to saline, enabling normobaric liquid ventilation without hyperbaric chambers. During the and , research shifted toward clinical applications, with the first human application of partial liquid ventilation using PFCs conducted in 1989 on a near-terminally ill premature with severe respiratory distress (RDS) at St. Christopher's Hospital for Children in . This case demonstrated feasibility and short-term improvements in oxygenation, though the ultimately died. Alliance Pharmaceutical subsequently developed perflubron (branded as LiquiVent), a PFC formulation, which underwent multicenter phase II/III trials in the mid-1990s, including a 1996 study in 13 premature infants with RDS that reported improved and oxygenation in severe cases compared to conventional . The early 2000s brought significant setbacks, as Alliance Pharmaceutical halted LiquiVent development in 2001 following disappointing results from a phase II/III trial in adults with acute respiratory distress syndrome (ARDS), where partial liquid ventilation did not demonstrate clear superiority in survival or efficacy over standard gas ventilation, leading to regulatory and commercial challenges. In 2013, the clinical trial data was acquired by OriGen Biomedical for potential further development. In October 2025, a Japanese team published the first human trial of rectal liquid ventilation using in the journal Med, involving 27 healthy volunteers who safely retained the PFC liquid for up to one hour, suggesting viability as an adjunct therapy for lung failure by providing supplemental enteral .

Physiological and Scientific Basis

Respiratory in Liquid Breathing

In liquid breathing, the lungs are filled with an oxygenated perfluorocarbon (PFC) liquid, which displaces air from the alveoli and enables through dissolution and processes. The alveoli adapt by accommodating the liquid, allowing dissolved oxygen in the PFC to diffuse across the thin alveolar-capillary membrane into the deoxygenated blood in the pulmonary capillaries, much like in conventional air . However, this diffusion occurs at a slower rate compared to gaseous ventilation due to the higher of the PFC liquid, which impedes fluid movement and requires adjusted ventilatory mechanics to maintain adequate flow. Carbon dioxide elimination in liquid breathing relies on the high of in PFCs, which exceeds that of oxygen by approximately 4-fold, facilitating efficient uptake from the blood into the liquid. During , the CO2-enriched PFC is removed from the lungs via , preventing accumulation and . This process necessitates continuous cycling of the liquid to refresh its gas content, as passive diffusion alone is insufficient for sustained CO2 clearance. The presence of dense PFC liquid in the lungs increases pulmonary (PVR) primarily through mechanical compression of extra-alveolar vessels and heightened hydrostatic pressure in the . This elevation in PVR can strain the right ventricle, potentially reducing if not managed. Conversely, in diseased s, the liquid's ability to distribute evenly and recruit collapsed alveoli improves ventilation-perfusion matching, enhancing overall oxygenation and reducing shunt fractions in models of acute . Key limitations of liquid breathing include the elevated imposed by the liquid's , which demands greater energy for generation and can lead to respiratory without mechanical assistance. Additionally, the use of room-temperature PFCs risks inducing , as the liquid's high thermal conductivity rapidly cools pulmonary flow, though this effect can be leveraged therapeutically. Long-term in humans remains unfeasible without ongoing mechanical support, as spontaneous liquid breathing exceeds physiological tolerances for sustained and circulation. Animal studies have demonstrated feasibility across , with mice and rats surviving several hours to days under total or partial liquid ventilation, highlighting effective short-term despite viscosity challenges. Larger models like pigs, whose size approximates human proportions, have been used to scale up experiments, showing prolonged survival (up to 24 hours or more) and improved pulmonary compliance in simulations, validating physiological mechanisms before clinical translation.

Role of Perfluorocarbons and Oxygen Carriers

Perfluorocarbons (PFCs) are fully fluorinated in which all atoms in the parent hydrocarbon structure are replaced by atoms, resulting in strong carbon-fluorine (C-F) bonds that confer chemical inertness and biological non-toxicity. Common examples include (PFD, C₁₀F₁₈) and perflubron (PFOB, C₈F₁₇Br), which exhibit high densities ranging from 1.8 to 2.0 g/cm³ and low (typically 10–20 dynes/cm), properties that facilitate their distribution within the lungs during liquid ventilation. These characteristics make PFCs denser than and more fluid than biological fluids, enabling efficient filling of alveolar spaces without excessive resistance. The capacity of PFCs to serve as oxygen carriers stems from their high solubility for respiratory gases, governed by , which describes the linear relationship between the concentration of a dissolved gas (C) and its (P) in the liquid phase: C=α⋅PC = \alpha \cdot P, where α is the specific to the gas and PFC. For oxygen, PFCs dissolve approximately 50 vol% (50 mL O₂ per 100 mL PFC) at 1 atm , while solubility is even higher at around 200 vol%, allowing effective far exceeding that of aqueous media. This solubility enables PFCs to transport and release gases directly to tissues, with oxygen delivery enhanced by the steep diffusion gradients in fluorinated liquids compared to air or saline. In applications involving partial liquid ventilation, PFCs are frequently emulsified with biocompatible to create stable water-in-PFC formulations that improve homogeneity and prevent , while their low volatility ensures slow post-administration, allowing gradual clearance over hours to days. These emulsions maintain the inert nature of PFCs, minimizing inflammatory responses and supporting prolonged exposure in the . Alternatives to PFCs for oxygen carriage in liquid media include saline solutions and hemoglobin-based carriers, though both are less effective due to saline's minimal oxygen (about 0.3 vol% at 1 atm) and the higher and potential of hemoglobin solutions, which limit their suitability for direct pulmonary delivery. Recent advancements as of 2025 have explored non-oxygenated PFC variants, such as administered rectally, to assess feasibility for enteral oxygen delivery without initial gas loading, demonstrating tolerability in early human trials. PFCs exhibit a favorable profile, being biologically inert and non-metabolized, with clearance primarily through pulmonary and exhalation or, in alternative routes, via the . Their radiolucency (except for brominated variants like perflubron) aids in radiographic imaging during treatment, and their ability to dissolve lipophilic compounds positions them as carriers for , such as antibiotics, enhancing in the lungs.

Techniques and Methods

Total Liquid Ventilation

Total liquid ventilation (TLV) involves the complete replacement of gas in the lungs with oxygenated perfluorocarbon (PFC) liquid, utilizing a closed-circuit mechanical system to facilitate respiratory . The process begins by filling the lungs to their , typically around 30 mL/kg of body weight, with oxygenated PFC. A of 10-15 mL/kg is then cyclically instilled and withdrawn using a or , mimicking inspiratory and expiratory phases to ensure continuous ventilation. The system maintains normothermia by incorporating a to keep the PFC at 37°C, preventing during prolonged support. Specialized equipment is essential for TLV, including a dedicated liquid ventilator that drives the tidal liquid flow, a membrane oxygenator to saturate the PFC with oxygen prior to inspiration, and mechanisms for such as a bubbler or chemical absorber integrated into the expiratory circuit. Examples of such systems include prototypes like the Inolivent ventilator designed for precise control of liquid volumes and pressures in preclinical settings. Ventilation rates are generally set at 5-10 breaths per minute, fine-tuned based on end-tidal CO2 monitoring to optimize clearance and maintain arterial levels within normal ranges. TLV offers advantages such as uniform recruitment of lung units, which enhances gas distribution and oxygenation compared to conventional gas ventilation, particularly in models of acute respiratory distress. It also provides protection against barotrauma by eliminating high-pressure gas interfaces, reducing ventilator-induced lung injury in experimental settings. In animal models, including lambs and pigs, TLV has sustained viable gas exchange for up to 48 hours with improved survival rates, demonstrating its potential for severe respiratory failure support. Despite these benefits, TLV faces significant challenges, including the high complexity of the required equipment, which demands precise calibration and monitoring to avoid complications. A key risk is PFC retention in the lungs or airways, potentially leading to impaired clearance upon transition back to gas ventilation. TLV remains experimental, with no approval for routine or prolonged human use, though pilot human trials for specific applications like ultra-rapid therapeutic hypothermia post-cardiac arrest are underway as of 2025 (e.g., the OverCool study), while applications remain primarily limited to short-term use in animal studies due to these technical and safety hurdles.

Partial Liquid Ventilation

Partial liquid ventilation (PLV) involves the intratracheal instillation of perfluorocarbons (PFCs), such as perflubron, into the lungs of intubated patients while maintaining conventional gas ventilation, typically at doses of 10-30 mL/kg body weight. The PFC is administered through the side port of the endotracheal tube, initially at a rate of about 1 mL/kg per minute until the tube is filled, followed by slower infusion to achieve , with sequential dosing every 30 minutes to sustain lung filling. Due to its higher density than air, the PFC distributes gravity-dependently, preferentially pooling in the dependent (posterior or dorsal) lung regions, and is combined with (CPAP) or mechanical breaths to facilitate . This approach serves as a less invasive alternative to total liquid ventilation, which requires complete replacement of lung gas with . The primary benefits of PLV include enhanced oxygenation in conditions like acute respiratory distress syndrome (ARDS) and respiratory distress syndrome (RDS) by dissolving and delivering high amounts of oxygen and carbon dioxide to the alveoli. It promotes recruitment of atelectatic (collapsed) lung areas through surface tension reduction and hydrostatic pressure from the liquid, thereby improving lung compliance and ventilation-perfusion matching. Additionally, PLV can mitigate ventilator-induced lung injury by allowing lower tidal volumes and pressures during mechanical ventilation, as the inert PFC stabilizes alveolar structures. Clinical development of PLV began in the with initial trials focused on neonates suffering from severe RDS, where perflubron instillation demonstrated short-term improvements in arterial oxygen tension (PaO2) and overall . Pilot studies in premature infants reported clinical stabilization and survival in select cases unresponsive to standard therapies, with eight of 13 treated neonates reaching 36 weeks' corrected . However, subsequent larger randomized trials, including a phase III study in adults with ARDS, found no significant long-term survival benefits or reductions in ventilator dependence despite initial oxygenation gains. Monitoring during PLV relies on serial chest X-rays to visualize PFC distribution, appearing as a radiodense layer in dependent zones, which helps assess volume adequacy and detect complications like . Reinstillation of PFC every 30-60 minutes is necessary to counteract evaporative losses from the warmed, humidified circuit, maintaining therapeutic lung volumes. Key limitations of PLV include substantial evaporation of the volatile PFC, necessitating frequent dosing and increasing procedural demands, as well as potential for uneven distribution limited by gravitational effects, which may underfill non-dependent regions and exacerbate ventilation heterogeneity.

Alternative Methods

Alternative methods of liquid breathing explore delivery routes beyond direct lung instillation, aiming to enhance oxygenation through inhalation of perfluorocarbon (PFC) vapors, aerosolized droplets, or non-pulmonary administration. These approaches seek to address limitations in traditional techniques by targeting partial support or systemic effects, often tested in preclinical models. Inhalation of PFC vapors, such as , involves delivering low-boiling-point gases to provide partial oxygenation without full liquid filling of the s. This method has been investigated in animal models of acute lung injury, where vaporization at concentrations around 18% of inspired gas significantly improved oxygenation and while reducing inflammatory responses. In healthy and oleic acid-injured animals, short-term exposure to 18% vapor enhanced pulmonary function without notable adverse effects, supporting its potential for or transient respiratory aid. These vapors modulate blood flow distribution in surfactant-depleted s, partially reversing hypoxic shifts toward better-ventilated areas. Aerosolized PFC delivery uses nebulizers to generate fine droplets of perfluorocarbons, such as perfluorodecalin, for inhalation targeting the upper airways and alveoli. In neonatal swine models of respiratory distress, aerosolized perflubron improved gas exchange and pulmonary mechanics, though efficacy remains limited by uneven deposition in the upper conducting airways. Nebulizer type and PFC properties influence droplet size and distribution, with phospholipid-stabilized aerosols showing promise for minimal airway resistance in physical models of infant lungs. However, challenges in achieving deep lung penetration often result in reduced therapeutic impact compared to liquid instillation. Rectal liquid ventilation, sometimes referred to as "butt breathing," represents an experimental enteral approach using oxygenated enemas to support patients with severe lung failure. In a first-in-human dose-escalation trial conducted in in October 2025, intrarectal administration of was safe and well-tolerated, with participants retaining the fluid for up to 60 minutes and reporting only mild gastrointestinal symptoms, no serious adverse effects. This method leverages the large surface area of the intestinal mucosa for , potentially benefiting cases of blocked airways where conventional ventilation fails. Other innovative routes include intraperitoneal and intravascular PFC emulsions for systemic oxygenation. Peritoneal perfusion with oxygenated perfluorocarbons augments overall oxygen delivery in hypoxic large-animal models, increasing arterial saturation without direct lung involvement. Intravascular PFC nano-emulsions, administered intravenously, enhance tissue perfusion by loading oxygen in the lungs and releasing it in hypoxic areas, demonstrating efficacy in reducing ischemic damage in preclinical studies. These emulsions avoid rapid clearance issues of earlier formulations, supporting their exploration as adjuncts to respiratory support.

Medical Applications

Current Clinical Uses

Liquid breathing, particularly through partial liquid ventilation (PLV) using perfluorocarbons (PFCs) like perflubron, has been investigated in neonatal intensive care units (ICUs) for managing respiratory distress syndrome (RDS) in preterm infants. In this context, PLV has been studied as an adjunct therapy to conventional , where the lungs are partially filled with oxygenated PFC liquid to improve alveolar recruitment and . Clinical trials from the 1990s demonstrated that PLV enhances , reduces the requirements, and stabilizes oxygenation in severe cases unresponsive to standard treatments. For instance, a multicenter study involving premature infants with severe RDS showed significant improvements in pulmonary function, though it remains experimental and not routinely adopted. In adult patients with (ARDS), short-term PLV with perflubron has been employed investigatively to stabilize oxygenation during critical phases of lung injury. Phase III trials in the early 2000s evaluated perflubron at varying doses alongside conventional , reporting temporary reductions in ventilator days and improved short-term in some cohorts, though overall mortality benefits were not consistently observed. Despite these findings, PLV remains non-standard for ARDS due to mixed trial outcomes and is typically reserved for compassionate or rescue use in refractory cases, as evidenced by recent case reports of its application in severe ARDS patients under investigational protocols. PFCs have also been utilized as carriers for pulmonary in the treatment of immature lungs affected by RDS, facilitating better distribution and efficacy of . This approach leverages the liquid properties of PFCs to enhance delivery to distal alveoli, potentially lowering the incidence of chronic in preterm neonates by improving ventilation-perfusion matching and reducing . Animal-derived combined with PFCs have shown promise in preclinical models, with limited clinical translation indicating reduced need for prolonged mechanical support, though routine integration remains adjunctive rather than primary. In veterinary medicine, total liquid ventilation (TLV) has been applied experimentally in large animal models, such as pigs and piglets, to translate research findings toward human applications in respiratory failure. Studies in porcine models of ARDS and post-cardiopulmonary bypass injury have demonstrated that TLV reduces biochemical markers of lung damage, improves oxygenation, and minimizes histological injury compared to gas ventilation, informing device development and safety profiles for potential clinical crossover. While not yet routine in equine practice like foals, these veterinary uses highlight TLV's role in bridging preclinical testing for severe respiratory conditions. Regulatory oversight limits widespread clinical adoption of liquid breathing techniques; perflubron for PLV is not approved by the U.S. (FDA) for standard use, following the discontinuation of its development by Pharmaceutical in 2001 after phase III trials for ARDS showed insufficient . In , approvals are similarly restricted, with no broad authorization for routine neonatal or adult applications, confining use to investigational or compassionate settings under ethical review. This status underscores the need for further trials to establish and benchmarks.

Ongoing Research and Trials

In 2025, researchers in conducted a first-in-human Phase I trial evaluating the safety and tolerability of intrarectal administration for enteral ventilation, a novel approach to oxygen delivery in cases of . The study involved 27 healthy male volunteers who received escalating doses of non-oxygenated via , with no serious adverse events reported and the procedure deemed feasible and well-tolerated. This trial builds on preclinical animal models demonstrating the potential of rectal oxygen-rich liquid delivery to support in lung-compromised states, with future phases planned to test oxygenated formulations for applications in conditions like (COPD) and (ARDS). Ongoing multicenter trials are exploring perfluorocarbon (PFC)-surfactant combinations for preterm infant lung support to mitigate . Preclinical studies have shown that partial liquid ventilation with PFC mixed with exogenous enhances lung recruitment and reduces inflammation in immature lungs, prompting human investigations into prophylactic administration during . These efforts aim to improve outcomes in neonatal respiratory distress syndrome by leveraging PFCs' ability to distribute evenly and facilitate oxygen diffusion. PFC emulsions are under investigation as vectors for of agents in post-COVID-19 sequelae and injuries. In vitro and animal models indicate that PFCs can carry therapeutics like corticosteroids directly to hypoxic alveolar regions, reducing storms and while enhancing oxygenation. A 2025 preclinical study demonstrated improved pulmonary function and when PFC liquid ventilation was combined with payloads during extracorporeal support in porcine models of injury. Translational research from animal to human models is addressing long-term safety concerns in total liquid ventilation, particularly PFC retention in tissues and potential immune responses. Large-animal studies in 2024-2025 confirmed that total liquid ventilation supports superior without significant histological damage after prolonged use, though monitoring for perfluorocarbon accumulation remains critical. The OverCool pilot trial, initiated in 2025, evaluates total liquid ventilation for ultra-rapid therapeutic hypothermia in resuscitated out-of-hospital patients, assessing safety endpoints like immune activation and PFC clearance over 24 hours. Current challenges in liquid breathing research include optimizing liquid warming to prevent during ventilation and reducing PFC for improved flow dynamics in clinical devices. Innovations in bioengineered oxygen carriers, such as hemoglobin-based alternatives to PFCs, are being tested to enhance and while minimizing -related resistance in tidal liquid flow. These advancements aim to bridge gaps in scalability for human trials, focusing on real-time and lower-density formulations.

Proposed and Experimental Uses

Deep-Sea Diving

Liquid breathing offers a promising approach for deep-sea diving by addressing key limitations of traditional gas-based systems, particularly the risks of and (DCS). , caused by high partial pressures of inert gases like , impairs cognitive function at depths beyond approximately 30 meters, while DCS arises from inert gas bubbles forming in tissues during ascent. Perfluorocarbons (PFCs), the liquid medium used in liquid breathing, enable the delivery of pure oxygen without inert gases, thereby eliminating narcosis since no or is inhaled. Additionally, PFCs' high oxygen —up to 25 times greater than in —counters the reduced oxygen availability under , ensuring adequate even at extreme depths. The proposed system for deep-sea application involves total liquid ventilation, where the diver's is filled with oxygenated PFC circulated via a specialized or rebreather apparatus connected to a supply tank. This setup would replace conventional scuba or mixed-gas systems, potentially enabling dives exceeding 100 meters without helium-oxygen () mixtures, which are cumbersome and limited by narcosis and toxicity issues. The liquid would be pumped in and out of the lungs to facilitate oxygen uptake and carbon dioxide removal, with the PFC's providing adjustments and reducing the compared to dense compressed gases at depth. Preclinical studies have established proof-of-concept through animal models subjected to hyperbaric conditions simulating deep dives. In landmark experiments from the and 1970s, rats were successfully immersed and ventilated with oxygenated PFCs in hyperbaric chambers equivalent to depths of up to 100 meters (about 11 atmospheres), surviving for extended periods, though with challenges such as CO2 retention, pulmonary strain, and fatigue, without gas . These precedents demonstrated that liquid ventilation maintains lung function and prevents inert gas accumulation under pressure, paving the way for potential human adaptation. Despite these advances, significant challenges remain in translating liquid breathing to practical deep-sea use. Equipment must be engineered to resist extreme beyond 100 meters, where structural integrity is critical to prevent leaks or failures in the ventilation circuit. Maintaining consistent liquid flow is complicated by the high of PFCs, which increases resistance in narrow airways and tubing under pressure, potentially requiring advanced pumps. Thermal regulation poses another hurdle, as deep water temperatures near can rapidly cool the , risking unless integrated heating systems are incorporated without compromising portability. Liquid breathing for deep-sea diving remains in the experimental phase, with conceptual explorations by the US Navy in the focusing on integration with diving suits for extended operations. No human trials involving actual deep dives have been reported, though ongoing research into PFC emulsions and ventilation devices continues to address physiological and engineering barriers, indicating growing feasibility for future applications.

Space Exploration

Liquid breathing has been proposed as a technology to address key respiratory challenges in space exploration, including microgravity-induced pulmonary issues and high-acceleration stresses during launch and re-entry. In microgravity, astronauts experience cephalad fluid shifts that reduce and promote , the partial collapse of lung tissue due to uneven ventilation and surfactant redistribution. Total liquid ventilation with perfluorocarbons (PFCs) could counteract this by completely filling the s with a dense, inert fluid that ensures uniform expansion and prevents gas-liquid interfaces susceptible to gravitational effects, thereby maintaining and efficiency. Studies in animal models of acute lung injury have shown that PFC-based liquid ventilation reexpands atelectatic regions and increases end-expiratory lung volume elevenfold compared to gas ventilation, while also improving compliance, providing a conceptual basis for its application in zero-gravity environments. The superior oxygen solubility of PFCs—up to 50 volumes percent at —enables higher oxygen delivery than gaseous , which could support extended extravehicular activities (EVAs) by integrating liquid-perfused systems into suits, reducing reliance on bulky oxygen tanks and minimizing bubble formation risks in low-pressure conditions. In the early 2000s, NASA funded research to develop an Earth-based simulation of microgravity pulmonary using total liquid ventilation in animal models, where PFC filling eliminated air-mediated gravitational artifacts, allowing prolonged study of function alterations relevant to long-duration missions such as those to Mars. This work highlighted liquid 's potential to stabilize ventilation during extended exposure to zero-G, where traditional air exacerbates atelectasis risks. The (ESA) has evaluated liquid ventilation combined with whole-body water immersion as an advanced countermeasure for high-G acceleration, filling the lungs with oxygenated PFC to eliminate compressible air spaces that cause , effectively creating a "perfect " capable of sustaining loads beyond current limits without adverse effects. Experiments confirmed PFC's for short- and long-term use, with no observed in immersed subjects. Despite these benefits, implementation faces significant hurdles, including PFC fluid redistribution in microgravity, which may require active pumping to avoid pooling and ensure even alveolar ; seamless integration with spacecraft environmental control and systems (ECLSS) for continuous PFC oxygenation, CO2 scrubbing, and ; and astronaut psychological adaptation to submersion and liquid respiration, potentially necessitating pre-mission conditioning protocols.

Other Potential Applications

Liquid breathing has been explored as a potential intervention in emergency rescue scenarios, particularly for victims of or chemical exposure where conventional ventilation is compromised. Partial liquid ventilation using perfluorocarbons (PFCs) has shown promise in animal models of injury by improving and reducing in the lungs, though delayed administration may limit efficacy. For instance, studies in models demonstrated that early partial liquid ventilation could mitigate acute lung injury from wood smoke, suggesting viability for rapid deployment kits in fire or hazardous material incidents. However, human applications remain experimental, with portable total liquid ventilation systems proposed to deliver oxygenated PFCs directly to affected individuals in field conditions. In military contexts, liquid breathing could enhance soldier endurance in toxic environments by protecting against airborne contaminants and enabling operations in scenarios. Historical experiments by the U.S. Navy SEALs investigated liquid ventilation to allow prolonged submersion or exposure without gas masks, integrating it with protective suits for underwater or contaminated atmospheres. Early military research from the highlighted its potential for submarine escape at greater depths, avoiding gas toxicity and decompression issues through fluid-based respiration. Integration with powered exosuits has been conceptualized to support extended missions in hazardous zones, where PFCs provide a barrier against inhaled toxins while maintaining oxygenation. For high-altitude applications, liquid breathing offers a means to combat hypoxia during or as an alternative to hyperbaric . PFCs' high oxygen-carrying capacity could supplement respiration in low-oxygen environments, potentially aiding high-altitude accidents or expeditions above 8,000 meters. Patents describe hybrid systems where liquid breathing pairs with oxygen-scavenging mechanisms to sustain climbers without bulky air tanks, reducing the risk of acute mountain sickness. This approach might serve as a portable hyperoxic , delivering dissolved oxygen directly to the alveoli in scenarios where supplemental oxygen fails. Bioengineering efforts have proposed hybrid systems combining liquid breathing with artificial gills to enable extended submersion without surface breaks. These designs use perfluorocarbon liquids alongside semi-permeable modules to extract oxygen from and expel , mimicking respiration while filling lungs with oxygenated fluid. Such systems, featuring concatenated gill units with blood-flow diversion, could support deep operations or rescue in aquatic environments, with surface areas up to 40 m² for efficient at depths exceeding 100 meters. Initial concepts from the envisioned bulky artificial gills integrated with liquid ventilation for undersea habitats, though remains a challenge. Ethical considerations surrounding liquid breathing include accessibility barriers due to high costs, with medical-grade PFCs like perfluorooctyl bromide priced at approximately $2,000 per kg for high-purity grades as of 2025, equivalent to about $3,800 per liter given their . Specialized training is required for deployment, raising concerns over equitable distribution in or settings, where only well-resourced entities might afford implementation. Additionally, the invasive nature of total liquid ventilation necessitates rigorous protocols, particularly in speculative uses, to balance potential benefits against risks like fluid imbalances or procedural complications.

Cultural Depictions

In Literature

Liquid breathing has appeared in science fiction literature as early as the , often as a speculative solution to extreme environmental challenges. In E. E. "Doc" Smith's Triplanetary (1948), characters are immersed in a heavy liquid medium during high-acceleration maneuvers, allowing them to withstand intense G-forces while maintaining and respiration, though the liquid is not explicitly described as oxygen-saturated for breathing. This early depiction framed liquid immersion primarily as a protective for and aerial travel rather than direct pulmonary respiration. By the mid-20th century, the concept evolved to emphasize . Arthur C. Clarke's The Deep Range (1957) portrays advanced diving technology for deep-sea operations, where the protagonist engages in sustained dives to depths of 1,100 feet, enabling human presence in oceanic environments akin to cattle herding on the seafloor. Later works built on this for broader speculative applications. Hal Clement's Ocean on Top (1973) depicts an underwater civilization inhabiting a "bubble" of denser-than-seawater oxygenated , where inhabitants breathe the directly, highlighting societal adaptations to submerged living. Similarly, Joe Haldeman's The Forever War (1974) details immersion in perfluorocarbon emulsions pumped through bodily orifices, allowing soldiers to endure up to 50 G-forces during interstellar and travel, with vivid descriptions of the disorienting physiological process. Thematically, liquid breathing serves as an enabler for human expansion into hostile realms, symbolizing technological transcendence over biological limits. In Clarke's narrative, it facilitates harmonious interaction with ecosystems, portraying the as a for sustainable resource management. In contrast, Haldeman and Clement use it to explore isolation and , where the intimacy of liquid-filled lungs underscores vulnerability in alien or abyssal settings. While not always horrific, the invasive nature of immersion—such as surgical implants for fluid drainage in The Forever War—evokes elements, evoking discomfort with altered physiology. Post-1966 experiments by Leland C. Clark, who demonstrated liquid breathing in mice using perfluorocarbons, influenced more accurate depictions, grounding speculative elements in emerging biomedical realities. Works like Ocean on Top and The Forever War, published shortly after, reflect this shift toward plausible respiratory mechanics, prioritizing scientific fidelity over fantastical invention.

In Film and Television

Liquid breathing has been vividly portrayed in film and television as a groundbreaking technology enabling humans to explore extreme environments, often emphasizing the visceral challenge of adapting to breathe a fluid medium. The most iconic depiction occurs in the 1989 The Abyss, directed by , where the technology is central to a high-stakes deep-sea mission. In an early scene, Navy SEALs demonstrate the concept by submerging a live rat in a clear, oxygenated perfluorocarbon liquid called , which allows the animal to breathe underwater without harm; this was achieved using real perfluorocarbon fluid, with six rats filmed in the sequence, all of which survived the process. The production team consulted respiratory physiologists from to ensure scientific plausibility, marking one of the earliest mainstream cinematic uses of authentic liquid ventilation research. Later, protagonist Bud Brigman (played by ) fills his diving suit with the liquid to withstand crushing pressures at over 2,000 feet, visually capturing the disorienting transition from air to fluid respiration and underscoring themes of human endurance against oceanic depths. The concept appeared in other films exploring isolation and extraterrestrial frontiers, though often as a variant integrated into broader speculative tech. In Sphere (1998), directed by Barry Levinson and based on Michael Crichton's novel, a team of scientists investigates a submerged alien spacecraft at extreme ocean depths, where the narrative evokes the psychological and physiological strains of deep-sea immersion akin to liquid breathing scenarios, though the film focuses more on helium-oxygen mixtures for decompression. On television, liquid breathing featured in the 1990s series , which chronicled underwater adventures aboard a advanced submarine. In the episode "The Regulator" (Season 1, Episode 9, aired November 22, 1993), the technology is referenced during a tense rescue operation, with dialogue noting that "one man has used liquid breathing for 45 minutes" to extend dive times in a contaminated zone, highlighting its potential for prolonged submersible missions. The series portrayed it as a practical enhancement for , aligning with the show's optimistic vision of future marine technology. These depictions have profoundly influenced public perception of liquid breathing, popularizing it as a symbol of transcending biological limits in underwater and extraterrestrial settings. scene, in particular, has endured as a cultural touchstone, inspiring renewed interest in real-world applications; as of 2025, discussions of emerging respiratory innovations, such as experimental ventilation techniques, frequently reference the film's realistic portrayal to bridge fiction and advancing .

In Video Games

Liquid breathing appears in video games primarily as a science fiction mechanic to enable extended exploration in underwater or high-pressure environments, often integrating with survival, combat, or platforming gameplay while drawing on real-world concepts like perfluorocarbon fluids for oxygen delivery. One early example is Banjo-Tooie (2000), where the witch doctor Mumbo Jumbo casts a spell in Jolly Roger's Lagoon to oxygenate the surrounding seawater, allowing protagonists Banjo and Kazooie to breathe indefinitely underwater without traditional air supplies or time limits, facilitating puzzle-solving and collection in the submerged level. This mechanic eliminates drowning risks, emphasizing fluid navigation over oxygen management. In more recent titles, (2024) incorporates liquid breathing through the "Liquid-Ventilated Cockpit" stratagem , which floods fighter jet cockpits with breathable perfluorocarbon liquid to distribute G-forces evenly across the pilot's body, enabling sharper maneuvers and higher speeds during aerial combat without blacking out. This adds tactical depth to multiplayer missions, where players must balance upgrade slots against other enhancements. Common gameplay integration includes power-ups or abilities that grant temporary or permanent liquid immersion effects, such as extended dive times in survival games like (2018) via community mods introducing liquid oxygen systems with refill stations for . HUD elements often display saturation levels or fluid oxygen reserves, mimicking physiological limits and heightening immersion in sci-fi tropes of human augmentation for extreme conditions. These depictions frequently reference (1989) for visual and conceptual inspiration, portraying liquid breathing as a transformative technology for deep dives or zero-gravity scenarios.

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