Heliox

Heliox is a breathing gas mixture of helium (He) and oxygen (O₂). It is used medically to reduce airway resistance and improve ventilation in patients with obstructive respiratory conditions, and in deep diving to prevent nitrogen narcosis.^[1]^[2] Introduced clinically in the 1930s by Alvan Barach for the treatment of asthma and laryngeal obstructions, heliox leverages helium's low density—approximately one-seventh that of nitrogen—to convert turbulent airflow into more efficient laminar flow within narrowed airways, thereby decreasing the work of breathing and enhancing gas exchange.^[2]^[3]^[4] Common formulations include 70% helium and 30% oxygen (Heliox 70/30) or 80% helium and 20% oxygen (Heliox 80/20), with the oxygen proportion adjusted to meet the patient's needs while maintaining adequate oxygenation; higher oxygen blends, such as 50/50, may be used in cases of severe hypoxemia.^[4]^[2]^[3] In critical care settings, heliox is primarily indicated for acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD), where it reduces dynamic hyperinflation and respiratory effort; it is also effective for upper airway obstructions like croup, epiglottitis, and post-extubation stridor in children and adults, as well as bronchiolitis and vocal cord dysfunction.^[3]^[4]^[2] Administration requires specialized equipment, such as heated humidifiers and recalibrated ventilators, due to helium's high thermal conductivity and impact on gas density measurements, ensuring safe delivery via face mask, nasal cannula, or mechanical ventilation.^[3]

Composition and Properties

Definition and Common Mixtures

Heliox is a binary breathing gas mixture composed solely of helium (He) and oxygen (O₂), excluding nitrogen or any other gases. This composition leverages helium's inert and low-density properties to facilitate easier respiration in specific clinical and operational scenarios.^[5]^[6] In medical settings, the most common Heliox formulations are 70% helium and 30% oxygen (Heliox 70/30), utilized for general respiratory support in conditions involving airway obstruction, and 80% helium and 20% oxygen (Heliox 80/20), reserved for severe cases where supplemental oxygen demands remain low to avoid hypoxemia risks. These ratios balance helium's density-reducing effects with adequate oxygenation, and are commercially available as pre-mixed cylinders from suppliers adhering to pharmaceutical standards.^[3]^[7]^[8] For diving applications, Heliox mixtures are tailored to depth and partial pressure requirements to mitigate issues like nitrogen narcosis, with typical ratios such as 80% helium and 20% oxygen for deep commercial dives, or highly helium-dominant blends like 96% helium and 4% oxygen for extreme saturation dives below 100 meters to maintain safe oxygen partial pressures under high ambient pressures.^[9]^[10] Heliox is prepared by blending high-purity helium with oxygen in specialized cylinders or via inline blenders at the point of use, ensuring precise ratios through calibrated equipment. Medical-grade preparations comply with United States Pharmacopeia (USP) standards for purity and safety, typically using USP-grade gases to prevent contaminants that could impair respiratory function.^[7]^[11]^[12]

Physical and Chemical Properties

Heliox, a mixture primarily of helium and oxygen, is characterized by physical properties dominated by helium's low molecular weight of approximately 4 g/mol, in stark contrast to nitrogen's 28 g/mol. This results in a markedly reduced density for common Heliox mixtures compared to air; for instance, a 70/30 helium-oxygen blend has a density of about 0.55 g/L at standard temperature and pressure (STP), versus 1.29 g/L for air.^[13] Helium's contribution also imparts high thermal conductivity to Heliox, around 0.15 W/m·K for pure helium and approximately 0.13 W/m·K for an 80/20 mixture, far exceeding air's 0.026 W/m·K.^[14]^[13] Additionally, Heliox exhibits low viscosity, slightly higher than air at roughly 20 μPa·s compared to air's 18.5 μPa·s, though this difference is minor relative to the density reduction.^[13] The chemical properties of Heliox stem from helium's noble gas nature, rendering it chemically inert with no reactivity toward biological tissues or common substances under physiological conditions.^[15] The mixture is non-flammable as a whole, despite the oxidizing potential of its oxygen component. Helium's solubility in blood is notably low, with a Bunsen coefficient of about 0.0095 ml gas per ml blood per atm at 37°C, lower than nitrogen's 0.0115 under similar conditions, which minimizes inert gas accumulation in the body.^[16] Heliox's storage demands specialized cylinders due to helium's high diffusion rate through materials, necessitating enhanced seals and regular leak checks to contain the gas effectively, unlike storage for nitrogen-based mixtures.^[17] Key properties of Heliox compared to air and a typical nitrox mixture (32% oxygen, 68% nitrogen) are summarized below, highlighting differences in scale and impact:

Property	Air (79/21 N₂/O₂)	Heliox (80/20 He/O₂)	Nitrox (32/68 O₂/N₂)
Density (g/L at STP)	1.29	0.43	1.35
Viscosity (μPa·s at 20°C)	18.5	20.4	18.6
Specific heat capacity (J/kg·K at 25°C)	1005	2340	1010
Thermal conductivity (W/m·K at 25°C)	0.026	0.130	0.027

These values are approximate for illustrative purposes, based on weighted averages for ideal gas behavior; actual measurements may vary slightly with exact composition and conditions.^[13]^[14]^[13]

Mechanism of Action

Effects on Respiratory Flow

Heliox, a mixture of helium and oxygen, alters respiratory flow dynamics primarily through its lower gas density compared to air, which influences the nature of airflow in the airways. The Reynolds number (Re), defined as Re = \frac{\rho v d}{\mu} where \rho is gas density, v is flow velocity, d is airway diameter, and \mu is viscosity, determines whether flow is laminar (low Re) or turbulent (high Re). Due to helium's significantly lower density (approximately 0.14 times that of nitrogen in air), heliox reduces Re by about two-thirds at equivalent flow rates, shifting turbulent flow in narrowed airways toward laminar flow.^[18]^[19]^[20] This transition reduces airway resistance, as turbulent flow generates higher resistance than laminar flow in obstructed regions. According to Poiseuille's law for laminar flow, volumetric flow rate Q \propto \frac{1}{\eta} (where \eta is viscosity), but heliox's primary advantage stems from density reduction in turbulent segments, where resistance is density-dependent; although heliox has slightly higher viscosity, the net effect lowers overall resistance. In obstructive conditions, this can decrease the work of breathing, particularly where turbulence predominates.^[21]^[22]^[2] The benefits are especially pronounced in smaller airways like the bronchioles, where high-velocity flow with air often results in turbulence during obstruction, amplifying resistance. Heliox promotes smoother, more efficient gas movement in these distal segments by minimizing turbulence.^[6]^[23] In vitro studies using airway models with simulated stenosis confirm these effects, demonstrating that heliox maintains laminar flow through narrow passages where air induces turbulence, resulting in lower pressure drops and improved gas delivery efficiency. For instance, computational fluid dynamics simulations of laryngotracheal stenosis showed reduced airway resistance and pressure gradients with increasing helium concentrations in heliox mixtures.^[24]^[25]

Physiological Impacts

Heliox enhances oxygenation in the lungs primarily through its lower density compared to air, which facilitates faster diffusion of oxygen and better distribution to alveolar regions. This reduced density promotes more uniform gas mixing and penetration into peripheral lung areas, thereby improving ventilation-perfusion (V/Q) matching and reducing areas of mismatch that can impair gas exchange. In clinical settings, such as neonatal respiratory failure, heliox has been observed to alleviate V/Q mismatching, leading to improved oxygenation and decreased ventilatory requirements without significant alterations in overall respiratory mechanics.^[26]^[27] Despite these benefits, heliox introduces several potential side effects related to helium's physical properties. Its high thermal conductivity—approximately six times that of nitrogen—accelerates heat dissipation from the respiratory tract and body surfaces, increasing the risk of hypothermia, particularly during prolonged exposure or in cold environments. This heat loss can also manifest as a characteristic high-pitched voice change, resulting from the altered speed of sound propagation in the lower-density gas mixture, which raises vocal formants without affecting the fundamental frequency of phonation.^[28]^[29]^[30]^[31] Cardiovascular effects of heliox are generally minimal, with little influence on arterial blood gases or systemic hemodynamics in most applications. Breathing heliox typically does not alter pulmonary artery pressures, cardiac output, or ventricular filling pressures significantly, maintaining stable oxygenation and carbon dioxide levels during short-term use. Overall, heliox's inert nature ensures negligible disruption to blood gas homeostasis or cardiovascular function under normobaric conditions.^[32]^[33]

Medical Applications

Treatment of Obstructive Airway Diseases

Heliox serves as an adjunctive therapy in managing acute exacerbations of obstructive airway diseases, including asthma, chronic obstructive pulmonary disease (COPD) with hyperinflation, and pediatric croup, by reducing airway resistance and improving gas flow dynamics. In acute asthma exacerbations, it mitigates bronchospasm-related resistance, facilitating better bronchodilator delivery and symptom relief when used alongside standard treatments like beta-agonists. For COPD patients experiencing hyperinflation during exacerbations, Heliox decreases dynamic hyperinflation and enhances exercise tolerance by promoting laminar airflow in narrowed airways. In pediatric croup, it provides temporary relief from upper airway obstruction, particularly in moderate to severe cases, by lowering the work of breathing and hastening improvement in respiratory distress scores. Clinical evidence supports its efficacy in these settings, with a 2006 systematic review of 14 studies reporting an average 29.6% increase (95% CI 16.6–42.6%) in peak expiratory flow rate (PEFR) among asthma patients breathing Heliox compared to air-oxygen mixtures.^[34] Subgroup analyses in severe asthma have shown significant PEFR improvements of approximately 20 L/min with Heliox-driven nebulization.^[35] For croup, a 2021 Cochrane review of randomized trials indicated short-term benefits in moderate cases, with Heliox outperforming humidified oxygen in reducing croup severity scores, though evidence for mild cases remains inconclusive.^[36] The U.S. FDA has cleared Heliox delivery systems, such as the Precision Flow device, for emergency use in upper airway obstruction, including croup and asthma exacerbations.^[37] Administration typically involves short-term delivery of a 70:30 or 80:20 helium-oxygen mixture via non-rebreather mask at flow rates of 8–15 L/min to maintain FiO2 above 0.21, lasting from hours to a few days until clinical stabilization.^[38] Therapy is transitioned to standard air-oxygen mixtures as airway resistance decreases and oxygenation improves, avoiding prolonged use due to cost and logistical challenges. Recent developments include ongoing investigations into Heliox for chronic COPD maintenance. Earlier multicenter trials have confirmed reduced rates of mechanical ventilation and associated ICU admissions in severe exacerbations, supporting its role in averting intubation.^[39]

Other Clinical Uses

Heliox has been employed in the management of post-extubation stridor and laryngeal edema in intensive care unit (ICU) settings, where it provides effective respiratory support to alleviate upper airway obstruction and reduce the risk of reintubation.^[40] In a case involving a critically ill patient, heliox administration successfully mitigated severe stridor, avoiding immediate reintubation and associated complications such as prolonged mechanical ventilation.^[41] This benefit stems from heliox's lower density, which enhances laminar flow through narrowed airways.^[40] In pediatric care, heliox serves as an adjunct therapy for bronchiolitis caused by viral infections, such as respiratory syncytial virus (RSV), by improving gas exchange and reducing the work of breathing in affected infants.^[42] Delivered via high-flow nasal cannula, heliox may reduce clinical respiratory distress scores in the short term (e.g., within the first hour).^[43] Clinical trials indicate that this approach decreases respiratory system resistance, aiding in the stabilization of infants with moderate to severe symptoms.^[44] Emerging applications of heliox include its role as an adjunct in mechanical ventilation for acute respiratory distress syndrome (ARDS), where studies suggest potential reductions in ventilator days through decreased airway resistance and improved gas distribution.^[45] Experimental models have shown heliox to enhance ventilation efficiency in ARDS, though large-scale clinical validation remains ongoing.^[46] Additionally, heliox holds promise in hyperbaric therapy for decompression illness, where its use during recompression may accelerate bubble resolution compared to air-oxygen mixtures.^[47] Key contraindications for heliox include the risk of hypoxia in patients requiring high fractional inspired oxygen (FiO2) levels, as the helium component can dilute oxygen delivery if not properly balanced.^[2] It is not recommended for long-term use due to elevated costs and global helium scarcity, which limits widespread availability.^[48] Treatment sessions typically cost $30 to $100 as of the early 2020s, though helium prices have surged to record highs (up to $117,660 per metric ton in 2025), influenced by ongoing supply chain disruptions that have periodically restricted medical-grade helium access.^[49]

Diving Applications

Use in Deep-Water Diving

Heliox finds primary application in commercial saturation diving for underwater operations at depths exceeding 300 meters, such as maintenance on offshore oil rigs, where teams of divers reside in pressurized chambers for weeks to perform extended tasks without repeated decompression.^[9] In these scenarios, divers connect via umbilicals to surface-supplied gas systems, enabling prolonged exposure to high-pressure environments while mitigating issues like nitrogen narcosis.^[50] Similarly, in technical scuba diving beyond 50 meters, recreational and professional divers use heliox in rebreathers or open-circuit systems for exploratory or salvage work, allowing safer penetration into deeper wrecks or caves.^[51] Mixture selection in these contexts prioritizes maintaining a partial pressure of oxygen (PPO₂) equivalent to 0.21 atmospheres at the surface to ensure normoxia, with common ratios like 90% helium and 10% oxygen for bottom gases at extreme depths around 250 feet or more.^[9] For shallower segments above 100 meters, heliox is often blended with nitrogen to form trimix, reducing helium usage and costs while still preventing narcosis.^[50] These adjustments are calculated based on planned depth and duration, with PPO₂ limits typically capped at 1.3-1.5 atmospheres during active work.^[9] Operational procedures begin with pre-breathing heliox in the surface chamber to wash out residual nitrogen from prior air exposures, ensuring tissues saturate with helium during gradual compression to working depth.^[50] Once at depth, divers breathe the mixture at ambient pressure within saturation habitats or diving bells, transitioning seamlessly between chamber and underwater worksites via personnel transfer capsules.^[52] This setup supports multi-day excursions from the habitat, with gas supplied continuously to maintain physiological equilibrium. Specialized equipment, such as helium reclaim systems, captures and recycles over 90% of exhaled gas through scrubbing, compression, and purification processes, significantly lowering operational costs given helium's expense.^[53] These closed-loop systems, integrated into diving support vessels, filter out carbon dioxide and water vapor before reintroducing the mixture, enabling efficient use during long-duration saturation missions at depths up to 500 meters.^[53]

Advantages and Limitations

Heliox offers several key advantages in deep-water diving environments. By replacing nitrogen with helium, a non-narcotic inert gas, heliox eliminates the risk of nitrogen narcosis, which impairs cognitive function and coordination at depths beyond approximately 30 meters when breathing air.^[54] Additionally, helium's lower solubility in tissues compared to nitrogen facilitates faster off-gassing during decompression, thereby minimizing overall exposure to hyperbaric conditions.^[55] When oxygen partial pressure is carefully managed through appropriate mixture ratios, heliox also avoids central nervous system oxygen toxicity, a concern in high-pressure oxygen-enriched environments.^[56] Despite these benefits, heliox presents notable limitations that impact its practical use in diving. At depths exceeding 150 meters, rapid compression with helium-oxygen mixtures can induce high-pressure nervous syndrome (HPNS), characterized by tremors, myoclonic jerks, and reduced mental performance due to direct effects of inert gases under extreme pressure.^[29] Communication challenges arise from voice distortion, as the speed of sound in heliox—approximately 1,000 m/s compared to 343 m/s in air—alters vocal formants, resulting in high-pitched, unintelligible speech that requires specialized unscramblers for effective diver-surface interaction.^[57] Furthermore, the high cost of helium, often exceeding $1,000 per dive day in commercial operations due to its scarcity and consumption rates, significantly increases logistical expenses compared to air or nitrox diving.^[58] As of 2025, ongoing global helium shortages have exacerbated these cost issues, prompting increased exploration of alternatives like trimix or other gas blends in diving operations.^[59] To mitigate these risks, established safety protocols emphasize gradual depth increases during compression to minimize HPNS onset, alongside continuous monitoring for early signs of helium-induced tremors through physiological assessments.^[60] Recent studies from 2022 highlight temporary post-dive effects on lung function, such as a decline in forced expiratory volume in one second (FEV1) following deep heliox exposure, which typically resolves within 24 hours with proper recovery.^[61] As an alternative for dives in the 50-100 meter range where HPNS is less prevalent, trimix (a blend of helium, nitrogen, and oxygen) is often preferred, as the addition of nitrogen helps suppress HPNS symptoms while still reducing narcosis compared to air.^[62]

History

Early Development

The concept of using helium-oxygen mixtures, or heliox, for deep diving originated in the early 20th century amid efforts to address the limitations of air as a breathing gas. In 1919, researchers C.J. Cooke and Dr. Elihu Thompson proposed substituting helium for nitrogen to mitigate the intoxicating effects of nitrogen narcosis observed in deep dives, a problem increasingly evident during World War I-era salvage operations and submarine development where divers experienced impaired judgment and coordination at depths beyond 100 feet.^[63] This motivation stemmed from the U.S. Navy's need for safer gases following incidents of narcosis and decompression sickness in compressed-air diving, prompting initial animal experiments to validate helium's inertness and low narcotic potential.^[64] The first practical tests of heliox occurred in 1924 when the U.S. Navy conducted hyperbaric chamber dives, confirming that helium-oxygen blends avoided narcosis at pressures equivalent to 300 feet.^[63] Building on this, Lieutenant Commander Charles B. Momsen advanced heliox applications through the Navy's Experimental Diving Unit, established in the 1930s, where key chamber experiments in 1937 pushed divers to simulated depths of 500 feet using heliox mixtures, demonstrating clear mental function without narcotic impairment and shorter decompression times compared to air.^[64] These proofs-of-concept laid the groundwork for operational use, culminating in 1939 when Momsen led the heliox-assisted rescue of 33 crew members from the sunken USS Squalus at 243 feet, marking the first large-scale application.^[63] Parallel to diving advancements, heliox entered medical practice in 1934 through trials led by Dr. Alvan L. Barach at Columbia University, who tested helium-oxygen blends on patients with asthma and upper airway obstructions. Barach's experiments showed that heliox's lower density reduced turbulent airflow resistance, easing breathing in four adult asthma cases and two infant obstructions within minutes, with no adverse effects observed in supporting animal studies exposing mice to 79% helium-21% oxygen for extended periods.^[65] These findings, published in the Journal of the American Medical Association, highlighted heliox's therapeutic potential beyond diving. Commercial production of heliox mixtures emerged in the 1930s as helium extraction from natural gas fields scaled up, driven by post-WWI military demand; by 1937, costs had fallen to about $3 per cubic foot, enabling broader availability for both diving and medical uses.^[63] Early patents, such as Max Eugene Nohl's 1937 design for a helium-compatible diving helmet and rebreather, facilitated practical implementation.^[63] By the 1950s, the U.S. Navy formalized heliox protocols in its diving manuals, influencing international standards for mixed-gas breathing, including precursors to ISO guidelines on gas purity and mixture specifications for hyperbaric environments.^[64]

Evolution in Medicine and Diving

In the 1960s, the United States Navy's SEALAB projects marked significant milestones in saturation diving using heliox mixtures, enabling aquanauts to live and work at depths up to 610 feet for extended periods. SEALAB I, deployed in 1964 off Bermuda at 192 feet, and subsequent iterations like SEALAB II in 1965 near La Jolla, California, at 203 feet, utilized helium-oxygen breathing gases to mitigate nitrogen narcosis and facilitate prolonged underwater habitation.^[66] These experiments validated saturation techniques, paving the way for deeper operations. By the 1970s, heliox saturation diving boomed in commercial offshore applications, particularly during North Sea oil platform installations starting around 1970 at sites like Ekofisk, where divers routinely used heliox to reach depths exceeding 300 meters for construction tasks.^[67] This era saw widespread adoption amid the global oil crisis, with heliox enabling efficient, multi-day dives that supported the rapid expansion of underwater infrastructure.^[68] Key advancements in diving included contributions from figures like Allyn Vine, a Woods Hole Oceanographic Institution oceanographer whose advocacy for deep-sea exploration in the 1960s influenced the development of manned submersibles.^[69] More recent research from 2021 to 2024 has examined long-term physiological effects of single deep heliox dives, revealing temporary endothelial activation, oxidative stress, and skeletal muscle damage at depths around 80 meters sea water, with recovery typically within 24 hours but potential implications for repeated exposures.^[70] These studies, including breath marker analyses post-dive, highlight ongoing concerns about vascular and pulmonary responses even in controlled saturation scenarios.^[71] In medicine, heliox saw renewed interest in the 1980s for emergency management of acute airway obstructions, with clinical resurgence in treating severe asthma exacerbations to reduce work of breathing before intubation.^[72] The 2000s expanded its pediatric applications, particularly via nebulizers delivering bronchodilators like albuterol in heliox-driven aerosols, which improved clinical outcomes in acute asthma by enhancing drug delivery and airflow in children.^[73] By the 2020s, integration with mechanical ventilators became more routine amid global helium shortages exacerbated by supply chain disruptions since 2019, prompting innovations like heated heliox delivery systems for neonates and COVID-19 patients to optimize ventilation while conserving gas.^[74] Brief references to its efficacy in COPD align with these developments, though detailed protocols remain in specialized applications.^[75] Global adoption of heliox has been informed by publications from organizations like Divers Alert Network (DAN), which discusses heliox in mixed-gas protocols for commercial dives at depths beyond 150 feet to prevent narcosis.^[9] The European Respiratory Society (ERS) supports its use in respiratory guidelines for obstructive diseases, emphasizing reduced airway resistance in exercise and critical care settings.^[75] However, post-2010s helium supply volatility, including shortages from 2018-2020 and ongoing 2025 constraints, has challenged availability, raising costs for both diving operations and medical therapies while spurring research into gas conservation and alternatives.^[63]^[76]