Physiology and clinical use of heliox

INTRODUCTION — Helium is an inert, nontoxic gas that is lower in density than nitrogen and oxygen and second only to hydrogen in universal abundance. In 1934, Barach first described the airway physiology of breathing heliox and advocated for its use in a variety of diseases [1]. Heliox has been revisited over the years as a potential therapeutic option for a variety of upper and lower airway conditions.

The physiology and clinical applications of helium-oxygen mixtures in patients with pulmonary disease will be reviewed here. The general management of central airway obstruction is discussed separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

PHYSIOLOGY — Therapeutic interventions to improve ventilation often aim to increase static compliance (lung stiffness), decrease airway resistance, or both. To decrease resistance to airflow, bronchodilators and glucocorticoids are often used to increase airway caliber. Another potential method to improve airflow is to alter inhaled gas composition. While the density and viscosity of oxygen, nitrogen, and air are very similar (table 1), substituting helium, a low-density gas, for nitrogen changes the physical properties of the inhaled gas and underlies the theoretical rationale for the clinical application of heliox. Stated differently, by decreasing gas density, airflow resistance can be decreased in the absence of any anatomical change. The following discussion describes the physiology of the effect of gas density on airflow.

Airflow resistance — The mechanics of the respiratory system are determined by both static and dynamic properties. Static properties are measured in the absence of airflow and define the basic pressure-volume characteristics of the respiratory system. Respiratory system compliance (Crs) is a static property that is determined by the elastic recoil of the lung and chest wall.

Dynamic properties of the respiratory system are measured during inhalation or exhalation, when there is a gas flow. Airflow resistance is a dynamic property determined by multiple factors, including:

●Density and viscosity of the inspired gas

●Airway caliber

●Airway configuration (eg, branching)

●Flow rate

The relative importance of each of these factors is variable and complex. Principles of fluid dynamics can be applied to model their interrelationship and are discussed in the next section. The force (or work) required to generate and sustain air flow throughout the tracheobronchial tree is a function of both respiratory system compliance and airflow resistance.

Laminar versus turbulent flow — Movement of gas through a tube (eg, an airway) is modeled by laminar flow, turbulent flow, or a mixture of the two. In a tube, laminar flow occurs at lower flow rates and is characterized by the existence of streamlines parallel to the sides of the tube. Gas in the center of the tube moves more rapidly than gas at the edge of the tube and is more likely to be turbulent. In addition, turbulent flow typically occurs at branch points, sharp angles, and at changes in tube diameter (figure 1). Turbulent air requires a greater driving pressure to achieve a given gas flow.

In the airways, flow is influenced by these features, and also by two intrinsic physical characteristics of the inhaled gas, density and viscosity. The Reynolds number (Re), which is derived from fluid dynamics, describes the relationship between the density and viscosity of a gas in determining whether flow is turbulent or laminar. When Re is high, the force required to generate a given flow rate is determined to a greater degree by fluid density, and the flow is more turbulent. Conversely, at lower Re, the flow rate is determined to a greater degree by fluid viscosity, and flow is more laminar.

The formula for Re describes the relationship between tube diameter (d), gas velocity (V), gas density (p), and gas viscosity (u):

In a straight, smooth, unbranched tube, laminar flow predominates when Re is <2000, and turbulent flow predominates when Re is >4000. The lower density of heliox relative to nitrogen-oxygen mixtures (helium is one-tenth the density of air) decreases Re and increases the likelihood that the flow will be laminar (table 1). Of note, air and helium have a similar viscosity.

The Re also determines the entrance length (EL) of a tube, which is the distance from the beginning of a tube that is needed for laminar flow to become established (figure 2).

Thus, when Re is low, not only is there less of a tendency for turbulent flow, but laminar flow will become established more quickly after changes in airway caliber or configuration [2]. On the other hand, when there are frequent branch points (eg, in the airways), EL may be longer than the length of a particular airway. In combination, these factors inhibit laminar flow.

In the normal human lung, most resistance is due to the large airways; overall resistance is lower in the small airways due to the large total cross-sectional area (figure 3). Flow is primarily turbulent from the trachea to the start of the bronchioles, particularly when the flow rate is high. Even when heliox does not enable laminar airflow, it can reduce the airflow resistance of turbulent flow, as resistance is proportional to the density of the mixture [3,4]. This effect is explained by the following principle. Flow is created by a pressure gradient along the airway, and the determinants of the pressure gradient (∆P) can be expressed as:

In situations of persistently turbulent flow, the first factor is negligible. The second factor, k₂ is determined in part by density of the gas. Thus, the pressure gradient is reduced by lower gas density, as is the applied force (work of breathing) required to achieve a given flow rate.

CLINICAL APPLICATIONS — Potential use of helium has been explored in a variety of disease processes characterized by airflow limitation. The aim of therapeutic use of heliox is to capitalize on the physical properties of the gas to improve airflow as predicted by the fluid dynamic paradigm described above. However, there are no evidence-based guidelines regarding the use of heliox. Despite the absence of guidelines, a therapeutic trial of heliox may be reasonable in clinical situations associated with marked airway narrowing in which a temporizing therapy may provide a bridge to definitive treatment [5].

The energy expenditure required to overcome airflow resistance is negligible during resting ventilation in the normal lung. Thus, the physical properties of the inspired gas do not ordinarily play a significant role in determining the work of breathing or in limiting ventilation. However, with alterations in airway geometry, particularly during excessive ventilatory demand, the resistive work of breathing can become sufficiently elevated to limit ventilation and cause respiratory muscle fatigue [2]. Under these circumstances, decreasing the density of the inhaled gas with heliox should decrease the applied force required to achieve a given flow rate and, thereby, reduce the work of breathing.

Most clinical trials of heliox have enrolled fewer than thirty patients, as heliox is generally initiated in emergent situations that may preclude clinical trial enrollment. Inclusion criteria and clinical outcomes are not standardized across studies, making direct comparisons difficult. Furthermore, many patients (eg, asthma, bronchiolitis, COPD) are treated with multiple interventions simultaneously. With these limitations in mind, the following is a brief review of clinical trials of heliox therapy in both pediatric and adult patient populations.

Use in children — Children have smaller airways than adults and are more commonly affected by diseases that cause upper airway obstruction. There have been several reports describing the use of heliox in pediatric populations, although clear demonstration of clinically important benefits is lacking:

●Upper airway obstruction – Heliox is not a part of standard therapy for upper airway obstruction in children. However, a few cases have been described in which heliox was used as a temporizing measure while awaiting definitive management [6-11]. In the largest case series, 42 pediatric patients received a total of 44 heliox treatments with a positive response in 32 interventions [11]. The most common cause of upper airway obstruction was postextubation edema (29 patients); other causes included laryngomalacia, laryngotracheal stenosis, vocal cord paralysis, airway hemangioma, mucositis, and foreign body. The article did not specify whether responders had postextubation stridor or another diagnosis, nor was heliox compared against other therapies. The evaluation and management of upper airway obstruction in children is described separately. (See "Emergency evaluation of acute upper airway obstruction in children".)

●Postextubation stridor – Data are insufficient to support a role for heliox in the management of postextubation stridor in children. While a clinical trial found a reduction in respiratory distress with heliox and a case series suggested that heliox helped with avoidance of reintubation [12,13], no large clinical trials have been reported. In the case series of children with upper airway obstruction described above, heliox was thought to be beneficial in 20 of 29 children with postextubation airway edema, but it is unknown how much heliox added to traditional measures [11]. (See "Extubation management in the adult intensive care unit", section on 'Postextubation management'.)

●Croup – Some studies of heliox for moderate to severe croup have shown a modest short-term benefit, although data are mixed. A more detailed discussion of the use of heliox in croup can be found separately. (See "Management of croup", section on 'Respiratory care'.)

●Bronchiolitis – Heliox is not associated with clinically significant benefit in bronchiolitis in infants and children. The use of heliox in bronchiolitis is discussed separately. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)

●Asthma – Heliox has not shown a consistent benefit in children with acute asthma exacerbations. A systematic review pooled and analyzed results from ten trials enrolling over 500 patients with acute asthma [14]. Studies included both adult and pediatric populations. No significant improvement in recovery of pulmonary function was noted in children treated with heliox. Additionally, no significant differences in outcomes were noted when pediatric and adult populations were analyzed separately, or when high- versus low-helium ratio studies were compared. However, these studies focused on the use of heliox as a form of adjunct therapy. Three subsequent randomized trials evaluating the efficacy of heliox to deliver nebulized albuterol demonstrated mixed results [15-17]. These three studies were included in a meta-analysis of eleven randomized trials evaluating the efficacy of heliox-driven nebulizers. The pooled data included 113 children receiving continuous albuterol therapy for acute asthma exacerbations, and the use of heliox to deliver the nebulizers was associated with a significant improvement in peak expiratory flow [18]. A subsequent Cochrane review suggested a reduced risk of hospital admission among children with asthma exacerbations when heliox was added to standard care (low-certainty evidence) [19].

●Respiratory distress syndrome – Respiratory distress syndrome (RDS) is a major cause of respiratory distress in preterm infants. In RDS, insufficient surfactant leads to alveolar atelectasis and hypoxemia. One randomized trial assessed the effect of heliox versus air in infants requiring mechanical ventilation for RDS and did not find a significant clinical benefit [20]. In this trial, 30 infants with RDS were randomly assigned to treatment with either heliox (78:22) or "AirOx" (78 percent nitrogen:22 percent oxygen). After two days of mechanical ventilation, there was a significant increase in the transcutaneous ratio of arterial oxygen tension/fraction of inspired oxygen (PaO₂/FiO₂) in the group receiving heliox. In addition, mean airway pressure required for ventilation was significantly lower in the heliox group by day 4. However, only nonsignificant trends toward fewer days of mechanical ventilation, lower mortality, and decreased incidence of bronchopulmonary dysplasia were noted. (See "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis" and "Respiratory distress syndrome (RDS) in preterm infants: Management".)

●Bronchopulmonary dysplasia – Bronchopulmonary dysplasia (BPD) is a disease of premature infants that is sometimes associated with increased airway resistance. Heliox is not part of standard care for BPD. However, heliox has been assessed in two case series of premature infants with BPD who required mechanical ventilation. Heliox decreased airway resistance, improved oxygenation, and, in one series, increased tidal volume, although outcomes such as weaning from mechanical ventilation were not reported [21,22]. (See "Bronchopulmonary dysplasia (BPD): Management and outcome".)

●Meconium aspiration syndrome – Meconium aspiration syndrome (MAS) is a form of acute respiratory distress caused by fetal aspiration of amniotic fluid containing meconium. In a nonblinded trial, 71 neonates with MAS were randomly assigned to mechanical ventilation with heliox or oxygen-air for six hours; oxygen was titrated to a target pulse oxygen saturation of 90 to 95 percent. The PaO₂/FiO₂ (P/F) was significantly higher with heliox (301 ± 22 versus 260.64 ± 24.83), and time to extubation was shorter (78 ± 30 versus 114 ± 28.07 hours) [23]. Additional studies would be needed before implementing the use of heliox in such patients.

Use in adults — Numerous case reports describe clinical improvement following heliox in patients with upper airway obstruction due to thyroid masses, radiation injury, lymphoma, cancer, or angioedema [6,24-27]. As noted, the greatest theoretical benefit of heliox is achieved by decreasing turbulent flow in large airways and at branch points in the tracheobronchial tree. Thus, patients with upper airway obstruction would be expected to derive the greatest benefit from heliox therapy. However, because upper airway compromise is relatively rare and often a medical emergency, few controlled studies of heliox treatment in this setting have been published. For this reason, the use of heliox in adults has primarily focused on treating patients with severe asthma and chronic obstructive pulmonary disease (COPD), in which benefit of heliox remains unclear.

●Upper airway obstruction – Upper airway obstruction has been the most common indication for heliox. Case reports describe stabilization of the respiratory status with heliox as a bridge to definitive therapy (eg, rigid bronchoscopy, surgery, radiation therapy, chemotherapy) or reversal of the underlying process in patients with laryngeal cancer, laryngeal polyps, angioedema, lymphoma of the larynx and trachea, and vocal cord paralysis [3,6,24-27]. However, no controlled trials have been performed for this indication. In our practice, we often use heliox as a temporizing measure (usually while awaiting rigid bronchoscopy for tumor excision/dilation/stenting) in patients with severe upper airway obstruction with excellent clinical response.

●Asthma – While a few case series have suggested a beneficial effect of heliox in acute asthma, no studies in adults have demonstrated an advantage of heliox above and beyond standard oxygen therapy. Thus, the routine use of heliox has not been indicated in acute asthma.

•Asthma exacerbations without intubation – As noted above, a systematic analysis pooled and analyzed results from ten trials enrolling over 500 patients (both children and adults) and found no significant improvement in recovery of pulmonary function in patients who were treated with heliox [14]. Furthermore, no significant difference in outcome was noted when adults were analyzed separately, or when high versus low concentrations of helium were compared. Other systematic reviews have reached the same conclusions [28,29]. (See 'Use in children' above.)

•Asthma complicated by respiratory failure – Heliox has not demonstrated consistent benefit in patients with respiratory failure due to asthma [30-32]. Two small case series investigated the effects of heliox in intubated patients with status asthmaticus and found inconsistent improvements in respiratory acidosis [30,31]. Following ventilation with 60 to 80 percent helium, all patients in one series experienced significant improvement in respiratory acidosis (mean reduction in arterial carbon dioxide tension [PaCO₂] 35 mmHg [4.67 kPa]) [30]. In addition, six of seven patients had a dramatic reduction in peak airway pressures (mean fall 32 cm H₂O).

One series of twelve asthmatics presenting to an emergency department with hypercapnic respiratory failure analyzed both intubated and nonintubated patients treated with heliox (70:30 or 60:40) [31]. Treatment was associated with a mean rise in pH of 0.9 (from 7.23 to 7.32 mmHg) after one hour; however, results were not uniform, with eight patients demonstrating a positive response and four not improving.

•Heliox as the driving gas for nebulizer treatments – A meta-analysis of eleven randomized trials evaluated the efficacy of heliox as the driver for beta-agonist nebulizers in adults and children presenting with acute asthma exacerbations [18]. Seven studies included 584 adults, and helium-oxygen mixtures of 80:20, 79:21, and 70:30 were used. Heliox was associated with a significantly higher change in mean percentage peak expiratory flow, and post hoc subgroup analysis demonstrated that this improvement was greatest in patients with the most severe disease (PEF <50 percent predicted). Furthermore, the use of heliox to drive nebulizers was associated with a lower rate of hospital admission.

A study not included in the meta-analysis administered nebulized albuterol driven by heliox or air to 132 subjects with asthma of varying baseline severity [33]. The proportion of patient experiencing a greater than 12 percent or 200 mL increase in FEV₁ 30 minutes after treatment was significantly higher in the heliox group, though only in the subset of patients with a baseline FEV₁ less than 50 percent predicted.

●Stable COPD – In stable COPD, heliox is associated with slight improvements in some physiologic outcomes, but only modest improvement in clinically important outcomes, such as exercise tolerance [34-40]. In addition, it is substantially more expensive than supplemental oxygen alone (approximately 3.5 times more expensive than oxygen per tank and requires more tanks per day). Whether or not heliox is of benefit to patients with stable COPD remains unclear. Future studies are needed to determine if the use of heliox and the associated additional expense are justified. Examples of some of the larger trials are described below.

The effect of heliox on exercise performance in COPD was evaluated in a randomized, crossover trial in which 82 patients with moderate to severe COPD had their exercise performance and dyspnea evaluated while receiving one of four different gases: Heliox28 (72:28), Heliox21 (79:21), Oxygen28 (72 percent nitrogen:28 percent oxygen), or medical air (79 percent nitrogen:21 percent oxygen) [36]. Patients breathing Heliox28 had better exercise performance and less dyspnea than all other groups. Exercise performance and dyspnea were improved with all gases when compared with medical air. In a separate study of 12 patients with severe COPD (mean FEV₁ 45 percent predicted), the use of heliox (79 percent nitrogen:21 percent oxygen) during exercise decreased dynamic hyperinflation, improved exercise tolerance, and improved lower-extremity oxygen delivery and utilization [37].

The impact of heliox on pulmonary function during cardiopulmonary exercise testing was assessed in 10 patients with mild COPD. Heliox was associated with an increase in minute ventilation, in the absence of any change in the metabolic cost of breathing [38]. In a randomized trial of 30 patients with moderate-to-severe COPD, subjects underwent an exercise program for two months by conducting leg-cycle training three days a week while breathing either room air, 40 percent supplemental oxygen, or a 60:40 helium-oxygen mixture. There was no difference between groups with regards to the increase in power output achieved, peak workload, or total endurance time [39]. In a subsequent randomized, crossover study of 11 patients with GOLD stage II or III COPD, subjects exercised to achieve 80 percent of their predetermined maximal work rate while breathing either room air or a 79:21 heliox mixture [40]. The use of heliox was associated with a significant reduction in Borg ratings for both dyspnea and leg discomfort, in addition to a reduction in end-expiratory lung volume and hyperinflation. (See 'Cost and availability' below.)

●Acute exacerbation of COPD – Heliox has not demonstrated consistent benefit in patients with respiratory failure due to COPD, whether during mechanical ventilation [32] or noninvasive ventilation (NIV) [41-46]. Several studies have compared NIV with either air or heliox in patients with exacerbations of chronic obstructive pulmonary disease. Taken together, the data show that the addition of heliox to NIV decreases respiratory effort and intrinsic positive end expiratory pressure (PEEP), but does not improve outcomes such as requirement for intubation or mortality [41-46]. As an example, in a large, multicenter trial, 204 patients presenting with an acute exacerbation of COPD were randomly assigned to NIV with or without heliox [45]. Intubation rate, 28-day mortality, and dyspnea did not differ significantly between the groups, suggesting that the combination of NIV plus heliox was not superior to NIV alone. The use of NIV for acute exacerbations of COPD is discussed in detail elsewhere. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

Additionally, a randomized, open-label trial evaluated the utility of noninvasive ventilation using either heliox or oxygen in patients hospitalized with severe hypercapnic COPD exacerbations [46]. After 445 patients were randomized, the trial was stopped prematurely because of the low overall rate of NIV failure, which was the primary outcome. The heliox group demonstrated a faster improvement in the secondary outcomes of respiratory rate, pH, PaCO₂ and encephalopathy score. Additionally, in patients requiring intubation, those receiving heliox had significantly shorter duration of ventilation and length of ICU stay. However, there was no significant difference in the rate of NIV failure, time to non-invasive ventilation failure, ICU mortality, or six-month mortality.

●Postextubation dyspnea – In a study focusing on physiologic rather than clinical endpoints, researchers used an esophageal balloon in recently extubated patients without significant lung disease to quantify intrathoracic pressure swings and estimate the work of breathing [47]. Fifteen of 18 patients exhibited a decrease in their work of breathing with heliox, although gas exchange parameters were unchanged. Additionally, patients reported decreased dyspnea while breathing heliox.

●Lung-protective mechanical ventilation – The effect of heliox on carbon dioxide elimination during lung protective ventilation was evaluated in an observational study including 24 patients ventilated with a pressure control mode following a cardiac arrest. Both pressure and rate were targeted to maintain a tidal volume of 6 mL/kg and prespecified pH and PaCO₂ ranges. Following three hours of ventilation with a heliox (50:50) mixture, a decrease in both respiratory rate and PaCO₂ levels was noted [48]. However, there was no control group, and only one of the patients enrolled had an underlying pulmonary condition (COPD). As such, additional studies are needed to determine if heliox is useful in patients intubated for primary respiratory failure.  

Pulmonary function testing — Helium gas is used in pulmonary function testing to measure lung volumes by gas dilution. This application is not based on low density, but on the fact that helium is inert and has low solubility in blood. The measurement of lung volume by the inert gas dilution technique is performed routinely in pulmonary function laboratories around the world and accounts for the vast majority of helium used for medical purposes. (See "Overview of pulmonary function testing in adults", section on 'Lung volumes'.)

TECHNICAL ISSUES — There are two technical issues concerning both the clinical and research applications of heliox. First, significant changes in the delivery of nebulized medicine occur when heliox is employed as the driving gas. Second, because the difference in physical properties between air or oxygen and heliox, calibration and function of pneumotachometers and ventilator flow sensors can be significantly altered.

Optimizing helium-oxygen ratio — The optimal helium-oxygen ratio is not known, although most protocols employ a mixture that includes 70 to 80 percent helium and 30 to 20 percent oxygen. If 30 percent oxygen is insufficient to correct hypoxemia, a mixture of 40 percent oxygen with 60 percent helium may provide sufficient oxygen without sacrificing airflow [30]. However, increases in the oxygen fraction tend to diminish the beneficial effect of using a low-density gas. Lung parenchymal disease with high oxygen requirements is typically not amenable to heliox.

Aerosol delivery — Heliox affects the delivery of medications that are administered via nebulization and metered dose inhaler; nebulization time may be prolonged, particle size of nebulized medications decreased, and deposition of medications from metered dose inhalers increased. Some of these effects can be offset by increasing the flow rate of the heliox mixture. However, clinical trials designed to take advantage of improved medication delivery in asthma and COPD have yielded mixed results [49-51]. (See 'Clinical applications' above and "Delivery of inhaled medication in adults", section on 'Factors affecting drug delivery' and "Delivery of inhaled medication in adults", section on 'Metered dose inhaler'.)

For a given flow rate, the use of heliox as a driving gas (instead of compressed air) results in a lower pressure drop across the nebulizer orifice. This causes a lower inhaled mass of medication or longer nebulization time in order to deliver the same amount of drug [52]. One group concluded that when heliox is used as a driving gas for nebulization, the flow rate should be increased by approximately 50 percent [52,53]. To understand the effects of heliox on nebulizer function and aerosol delivery, it is important to consider that nebulizers use Bernoulli's principle to generate an aerosol. Mathematically, this can be described by the equation:

where P1-P2 is the pressure drop across the nebulizer orifice, m is the mass of the gas, and (V2)2 - (V1)2 is the change in velocity of the gas across the orifice [52]. On the other hand, heliox can decrease the particle size of the nebulized solution, which may enhance drug delivery to the lower airways. This hypothesis has been evaluated in several studies examining lung deposition of heliox-driven aerosols in humans. In one report, nine subjects with stable asthma inhaled radiolabeled Teflon particles suspended in either air or heliox [54]. Heliox inhalation resulted in significantly lower oral deposition as well as higher particle retention in the lungs at 24 hours. Another report found a similar increase in lung deposition in patients with induced bronchoconstriction who received heliox-driven nebulized therapy [55]. In contrast, a study involving 32 subjects with stable moderate-to-severe asthma found that deposition of radiolabeled bronchodilators to the middle and lower lung fields was enhanced with the addition of positive expiratory pressure; however, there was no significant difference in deposition between the oxygen and heliox groups [56].

Instrument recalibration — Graham's law states that the flow of gas through an orifice is inversely proportional to the square root of its density. Thus, the actual flow rate of heliox through an oxygen flow meter is 1.8 times greater than the indicated flow [53,55]. For this reason, mechanical ventilators and pneumotachometers need to be recalibrated when heliox is being used [57,58].

The changes in delivered FiO₂ and tidal volume induced by heliox vary among ventilators. Suggested correction factors are available for most ventilators in the United States and Europe (table 2A-B) [57,59,60]. In addition to errors of calibration, some of the most commonly used critical care ventilators, including the Puritan-Bennett 7200 and 980 series, are unable to function when heliox is used. Servo ventilators are able to deliver heliox and require relatively simple calibration.

The lack of a clearly defined calibration scheme for pneumotachometers has been raised as a possible confounder in many of the studies investigating the role of heliox in acute asthma [61]. It is possible, particularly in studies where peak expiratory flow (PEF) improved in the absence of a clear change in the forced expiratory volume in one second (FEV₁), that much of this effect might be due to inaccurate sensing of low-density gas flow rates [62].

Cost and availability — Helium-oxygen mixtures come in "H" cylinders (159 cubic feet) in ratios of 80:20, 70:30, or 60:40. Each cylinder is approximately 3.5 times the cost of a similar amount of oxygen. With flow rates of 12 to 15 L/min, three to six of these cylinders may be used each day in nonintubated patients [53], and approximately three tanks per day in patients receiving mechanical ventilation [42].

Medical staff should be familiar with the use of medical gas cylinders, as cylinders containing oxygen, heliox, or other medical gases may appear identical. The availability of heliox for clinical use is variable.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supplemental oxygen".)

SUMMARY AND RECOMMENDATIONS

●Helium is an inert, low-density gas; heliox is a mixture of helium (usually 70 to 80 percent) and oxygen (usually 20 to 30 percent). The potential therapeutic effects of heliox relate to its low density and its propensity towards laminar airflow. The reduction in turbulent flow acts to decrease airway resistance, pleural pressures swings, and dynamic hyperinflation. These factors in combination reduce the work of breathing. (See 'Physiology' above.)

●There are no evidence-based guidelines regarding the use of heliox. Rarely, a therapeutic trial may be reasonable in clinical situations associated with marked airway narrowing in which a temporizing therapy may provide a bridge to definitive treatment. (See 'Clinical applications' above.)

●Data are insufficient to recommend heliox for the routine management of postextubation stridor, croup, bronchiolitis in children, respiratory distress syndrome of the neonate, asthma, or chronic obstructive pulmonary disease (COPD). For children with severe respiratory symptoms due to croup who are at risk for respiratory failure, heliox may be used in an attempt to avoid the need for intubation. Similarly, in rare patients with a severe asthma exacerbation that is associated with difficulty ventilating despite maximal other therapy, heliox may enable oxygenation while waiting for asthma inflammation to respond to other therapies. (See 'Clinical applications' above.)

●The effects of heliox are typically seen within several minutes, so the patient and clinician can often assess its therapeutic efficacy quite quickly. We guide therapy based on serial clinical assessment, since the measurement of common indices of pulmonary status (eg, peak expiratory flow and forced expiratory volume in one second [FEV₁]) may be inaccurate unless instruments are calibrated for use with heliox. Careful attention must be given to respiratory rate, accessory muscle use, pulsus paradoxus, air entry, and the patient's subjective sense of dyspnea. (See 'Technical issues' above.)

●The optimal helium-oxygen ratio is not known, although most protocols employ helium-to-oxygen ratios of 80:20 or 70:30. Treatment with the highest helium ratio that will maintain the oxygen saturation above 90 percent is suggested, since the benefits of heliox are proportional to the percentage of helium in the inhaled gas. An important limitation of heliox is the low fractional concentration of inspired oxygen (FiO₂) in the gas mixture, which may not be adequate for patients with hypoxemia. (See 'Optimizing helium-oxygen ratio' above.)

●The use of heliox during mechanical ventilation requires appropriate calibration of the ventilator and meticulous respiratory monitoring due to the variable effect of heliox on ventilator performance. Calculation of delivered fraction of inspired oxygen (FiO₂) and tidal volume should be based on published algorithms (table 2A-B), and the use of heliox in this setting should probably be limited to centers with substantial experience. (See 'Instrument recalibration' above.)

●Heliox also affects the performance of diagnostic equipment and the delivery of aerosolized medication. When heliox is used as the driving gas to deliver nebulized medications, the flow rate of heliox should be increased to prevent prolongation of the delivery time. (See 'Technical issues' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David Feller-Kopman, MD and Carl O'Donnell, ScD, who contributed to an earlier version of this topic review.