Progress in the clinical application of heliox
Year: 2025
Type: article
Abstract: Helium, the lightest noble gas, is characterized by its low molecular weight, rapid dispersion, and diffusion rate 2.5 times faster than that of nitrogen. It is chemically nonreactive with body tissues, has negligible solubility in blood, and lacks anesthetic effects. Helium-oxygen mixed gas (heliox), a mixture of helium and oxygen at specific ratios (typically 70:30 vs. 80:20), features low density and rapid diffusion. The use of heliox in the respiratory system has emerged as a significant therapeutic modality for managing chronic obstructive pulmonary disease (COPD), asthma, and pediatric pulmonary diseases. Its efficacy is primarily attributed to its physical properties, which improve laminar gas flow and diffusion, reduce airway pressure and resistance, and enhance respiratory function.1 Beyond its pulmonary applications, in other systems, its mechanism relies on the “nitrogen washout theory” proposed by VanDeripe.2 For example, Pagel et al.3 proposed that pretreatment with heliox (70% helium/30% oxygen) can exert a protective effect in a rabbit model of myocardial ischemia. During ischemia, adenosine triphosphate depletion and mitochondrial membrane integrity impairment lead to nitrogen influx into mitochondria and mitochondrial swelling. During reperfusion, nitrogen accumulation in mitochondria hinders oxygen entry, causing reperfusion injury. Inhalation of heliox accelerates nitrogen expulsion due to the low molecular weight of helium (4 g/mol vs. 28 g/mol), promotes oxygen utilization in mitochondria, and enhances mitochondrial function, providing protective effects (Figure 1). Based on these properties, heliox is hypothesized to mitigate damage caused by ischemia–reperfusion (I/R) injury.Figure 1: N2 washout theory.N2: Nitrogen.Currently, the clinical applications of heliox primarily focus on the treatment of respiratory diseases. In recent years, research on heliox has expanded to include the central nervous, circulatory, and immune systems, though predominantly confined to experimental studies. How to translate heliox from respiratory support into organ protection is a challenge that researchers currently face, and how to develop and recycle helium, which is a scarce resource, is another challenge. To optimize its clinical utility and maximize its potential, this perspective summarizes the progress in the clinical application of heliox. Heliox in the respiratory system: Heliox has been applied in the clinical treatment of respiratory diseases. It was initially used for obstructive pulmonary diseases and has recently been employed in the treatment of conditions such as asthma and acute exacerbations of COPD.4 Heliox reduces airway resistance in COPD patients, thereby decreasing the work of breathing and intrinsic positive end-expiratory pressure.5 In patients with acute exacerbations of COPD requiring mechanical ventilation, early use of heliox for ventilatory support has shown significant benefits. A prospective study demonstrated that in patients with mechanically ventilated COPD, the use of heliox (70% helium/30% oxygen) ventilation within 36 hours after intubation can reduce positive end-expiratory pressure, airway peak pressure and mean pressure.6 However, evidence for the application of heliox in pediatric patients remains limited. In studies comparing its effects with those of humidified oxygen, dexamethasone, and epinephrine in the treatment of pediatric laryngitis, heliox did not demonstrate significant advantages.7 However, some research suggests potential benefits for neonates, indicating that its use during mechanical ventilation may reduce the risk of lung injury.1 In a prospective crossover study, mechanical ventilation with heliox (60% helium/40% oxygen) significantly reduced respiratory resistance in children with respiratory syncytial virus infection.8 However, large-scale, multicenter studies are lacking. Heliox in the central nervous system: Currently, a single clinical trial on the effects of heliox in the central nervous system has been conducted. One study involved a healthy young woman inhaling ambient air or heliox (79% helium/21% oxygen), and the cerebral blood flow velocity was measured.9 Transcranial Doppler was used to assess the systolic peak velocity, mean flow velocity, pulsatility index in the right middle cerebral artery, pulse oxygen saturation, and heart rate. The results indicated that inhaling heliox did not affect cerebral blood flow in healthy young individuals. The author concluded that the beneficial effects of heliox on stroke patients are more likely attributed to neuroprotective mechanisms rather than hemodynamic changes. However, the study has significant limitations. First, the sample size was extremely small, involving only one healthy young female participant. Second, whether heliox exerts consistent effects on normal and pathological tissues requires further investigation. Third, this study investigated only the effects of heliox on cerebral blood flow, and it is unknown whether there are other neuroprotective effects. Heliox in the circulatory system: The application of heliox in the circulatory system has yielded inconsistent findings. In the study by Smit et al.,10 patients who underwent coronary artery bypass grafting received heliox (3 × 5 minutes of 70% helium/30% oxygen) pretreatment before aortic occlusion and heliox (15 minutes) posttreatment before aortic opening. Troponin-T was measured at 4, 12, 24, and 48 hours postoperatively, and the results were not statistically significant. In another study involving eight healthy male volunteers using a forearm I/R model, participants underwent 15 minutes of forearm ischemia.11 The experimental group inhaled 50% heliox for 15 minutes before ischemia until 5 minutes after reperfusion. Venous occlusion plethysmography was used to evaluate endothelial function and nitric oxide bioavailability at 15 and 30 minutes post-reperfusion. Although heliox had no apparent effect on post-ischemic endothelial dysfunction, it was associated with reduced expression of the proinflammatory markers recombinant integrin alpha-M (CD11b) and intercellular cell adhesion molecule-1 on leucocytes. Clinically, I/R injuries are common, and efforts to mitigate these injuries remain ongoing. The application of heliox provides a novel therapeutic approach. Existing evidence shows that it can have anti-inflammatory effects and reduce I/R. However, further extensive experimental studies are needed to confirm its efficacy and safety. Heliox in theimmune system: While studying the respiratory support and organ protection of heliox, it is also necessary to pay attention to whether it has an effect on the immune system. In a study on healthy male volunteers, the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, interferon-γ and interleukin-2 in the blood were measured by inhalation of heliox (79% helium/21% oxygen) for 30 and 60 minutes and air, respectively.12 Compared with air, inhaling heliox had no effect on cytokines in the immune system (P > 0.05). However, this study had certain limitations. It only studied healthy male volunteers and did not conduct experiments on diseased populations, which may affect human immune responses. Moreover, there is no research on gender differences. Additional Table 1https://links.lww.com/MGAR/A109 summarizes selected studies of the effects of heliox in various systems. Conclusion: This perspective has summarized the physical properties and progress in the clinical application of heliox. Its application in the respiratory system is well established, while studies in the nervous, circulatory, and immune systems remain largely confined to preclinical investigations. Considering its unique physical properties and the results of current studies, heliox shows great promise as an innovative therapeutic option for future applications. Further research is essential to define the most effective timing, concentration, and duration for its administration. The last critical consideration is that helium is a nonrenewable resource. The study of helium recycling technology and the optimization of gas delivery systems are urgently needed (Figure 2). With continued exploration and development, heliox is expected to offer significant therapeutic benefits to a broader range of patients in the near future.Figure 2: Progress in the clinical application of heliox.Its application in the respiratory system has achieved clinical validation, but in terms of organ protection, it is still mainly in the transition from basic to clinical. Owing to its unique biophysical properties, it holds transformative potential. Moreover, challenges such as recycling and delivery also exist. I/R: Ischemia‒reperfusion.Open access statement:This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Additional file Additional Table 1:https://links.lww.com/MGAR/A109Effects of heliox in various systems.
Source: Medical Gas Research
Author: Hao Ke
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4409910665