A proof-of-concept trial of HELIOX with different fractions of helium in a human study modeling upper airway obstruction
Helium in oxygen (HELIOX) can relieve airway obstruction and lower the work of breathing because it increases the threshold at which turbulent gas flow is induced. Less turbulent and more laminar flow lowers the work of breathing. According to guidelines, the fraction of Helium in HELIOX should be maximized (e.g. to 79%). Here, we investigate whether HELIOX with less than 60% of Helium is able to relieve the sensation of dyspnea in healthy volunteers.
44 volunteers underwent resistive loading breathing different gases (medical air and HELIOX with a fraction of 25%, 50% or 75% helium in oxygen) in a double-blinded crossover design. Subjects rated their degree of dyspnea (primary outcome parameter) and the variability of noninvasively measured systolic blood pressure was assessed.
Dyspnea was significantly reduced by HELIOX-containing mixtures with a fraction of helium of 25% or more. Similarly, blood pressure variability was reduced significantly even with helium 25% during respiratory loading with the higher load, whereas with the smaller load an effect could only be obtained with the highest helium fraction of 75%.
In this clinical trial, HELIOX with less than 60% of helium in oxygen decreased the sensation of dyspnea and blood pressure variability, a surrogate parameter for airway obstruction. Therefore, higher oxygen fractions might be applied without losing the helium-related benefits for the treatment of upper airway obstruction.
Registration with clinical trials (NCT00788788) and EMA (EudraCT number: 2006-005289-37).
KeywordsUpper airway obstruction HELIOX Work of breathing Clinical proof-of-concept study
Bundesinstitut für Arzneimittel und Medizinprodukte
Fraction of inspired helium
Fraction of inspired oxygen
Institutional Review Board
Proof of concept
Systolic blood pressure
The conduct of this investigator-initiated study was supported by Linde Gas Therapeutics (Munich/Germany) by the provision of medical gases (Heliox, MA and Oxygen) and the Helontix-Vent™. The authors would also like to thank Dr. Ute Brauer and Dr. Rainer Köbrich for their advice and support with the study design; Dr. Rolf Lefering for his valuable scientific advice; and Dr. Scheffold for monitoring the study.
Conception and design: HT, SS, JS, TL, PT; acquisition of data: HT, ABR, HD, SS, JS; statistical planning: TO, DC; analysis and interpretation of data: HT, SW, TO; drafting of the manuscript HT, TO, DC, SS, JS, TL, PT; PB final approval: all authors.
Compliance with ethical standards
Conflict of interest
PD Dr. Hubert Truebel organized and conducted the trial as lead PI while working at HELIOS Klinikum Wuppertal/Germany until 2008. Since then he is a fulltime employee of Bayer Pharma AG. Support (including gas supply and access to a HELONTIX Vent) was received from Linde Gas Therapeutics/Germany as well as through an INSPIRA research grant by BOC/UK to cover insurance and travel costs of subjects. Philip Boehme received founding from Bayer Pharma Ag. No conflicts of interest were reported by all other authors.
- Allan PF, Thomas KV, Ward MR, Harris AD, Naworol GA, Ward JA (2009) Feasibility study of noninvasive ventilation with helium-oxygen gas flow for chronic obstructive pulmonary disease during exercise. Respira Care 54(9):1175–1182Google Scholar
- Chiappa GR, Queiroga F Jr, Meda E, Ferreira LF, Diefenthaeler F, Nunes M, Vaz MA, Machado MC, Nery LE, Neder JA (2009) Heliox improves oxygen delivery and utilization during dynamic exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 179(11):1004–1010. https://doi.org/10.1164/rccm.200811-1793OC CrossRefGoogle Scholar
- Colnaghi M, Pierro M, Migliori C, Ciralli F, Matassa PG, Vendettuoli V, Mercadante D, Consonni D, Mosca F (2012) Nasal continuous positive airway pressure with heliox in preterm infants with respiratory distress syndrome. Pediatrics 129(2):e333–e338. https://doi.org/10.1542/peds.2011-0532 CrossRefGoogle Scholar
- Diehl JL, Mercat A, Guerot E, Aissa F, Teboul JL, Richard C, Labrousse J (2003) Helium/oxygen mixture reduces the work of breathing at the end of the weaning process in patients with severe chronic obstructive pulmonary disease. Crit Care Med 31(5):1415–1420. https://doi.org/10.1097/01.CCM.0000059720.79876.B5 CrossRefGoogle Scholar
- Haussermann S, Schulze A, Katz IM, Martin AR, Herpich C, Hunger T, Texereau J (2015) Effects of a helium/oxygen mixture on individuals’ lung function and metabolic cost during submaximal exercise for participants with obstructive lung diseases. Int J Chron Obstr Pulm Dis 10:1987–1997. https://doi.org/10.2147/COPD.S88965 Google Scholar
- Haynes JM (2006) Heliox should be available in every community hospital. Respir care 51(11):1261Google Scholar
- Hess DR, Fink JB, Venkataraman ST, Kim IK, Myers TR, Tano BD (2006) The history and physics of heliox. Respir care 51(6):608–612Google Scholar
- Jolliet P, Tassaux D, Roeseler J, Burdet L, Broccard A, D’Hoore W, Borst F, Reynaert M, Schaller MD, Chevrolet JC (2003) Helium-oxygen versus air-oxygen noninvasive pressure support in decompensated chronic obstructive disease: a prospective, multicenter study. Crit Care Med 31(3):878–884. https://doi.org/10.1097/01.CCM.0000055369.37620.EE CrossRefGoogle Scholar
- Venkataraman ST (2006) Heliox during mechanical ventilation. Respir Care 51(6):632–639Google Scholar
- Vogiatzis I, Habazettl H, Aliverti A, Athanasopoulos D, Louvaris Z, LoMauro A, Wagner H, Roussos C, Wagner PD, Zakynthinos S (2011) Effect of helium breathing on intercostal and quadriceps muscle blood flow during exercise in COPD patients. Am J Physiol Regul Integr Comp Physiol 300(6):R1549–R1559. https://doi.org/10.1152/ajpregu.00671.2010 CrossRefGoogle Scholar