PEDIATRICS Vol. 111 No. 2 February 2003, pp. 441-443
Heliox Questions
We read with great interest the article by Dr Weber and colleagues1 comparing heliox and racemic epinephrine in children with moderate to severe croup. Apart from the study limitations stated by the authors in the discussion, there are some points we would like to make about this article.
- Helium is an inert gas that is one-eighth the density of nitrogen; when blended with 21% oxygen, the resulting gas mixture (heliox, 79%He/21%O2) has a threefold reduction in density compared with air. This property reduces the pressure gradient associated with gas flow through airways with nonlaminar flow.2 The authors seem to have the misconception that because of its lower density, helium is less viscous than air. Actually, the absolute viscosity of helium is slightly higher than that of air, and its kinematic viscosity is about 7 times that of air: from the fluid-dynamical point of view, helium is much more viscous than air.2,3 These facts have been theoretically validated, and moreover, we now know that heliox does not need to be laminar to provide higher flow rates and that its benefits persist even under turbulent conditions.3
- We consider it important to highlight the fact that helium, a gas of inert nature, lacks biological properties. Consequently, the use of heliox in any clinical circumstance is not for treating the underlying disease or for influencing the anatomy of the airway. Rather, heliox is used to reduce resistance of the airways to gas flow and to decrease respiratory muscle work until definitive therapies act or the underlying condition spontaneously resolves.2 This means that heliox is a temporizing measure whose positive effects are maintained as long as it is held. In their article, Weber et al compared heliox with a biologically active therapy as epinephrine. Namely, epinephrine causes constriction of the precapillary arterioles via stimulation of the
-receptors, decreasing capillary hydrostatic pressure and then resulting in fluid resorption from the interstitial space and resolution of improvement of the laryngeal mucosal edema. Even accepting heliox and epinephrine as comparable therapies for croup and considering the lack of significant differences between both groups at the end of the observation period, one could wonder if the potential risks of administering epinephrine could have been avoided then in favor of the efficacy and safety of heliox.
- Regarding the logistics of heliox administration, it is essential to note that in spontaneously breathing patients, heliox should be delivered by a nonrebreather face mask with reservoir to reduce the amount of external air entrained on inspiration and subsequent dilution of helium concentration.2,4 Conventional oxygen masks produce dilution of supplied gas with air according to patient factors such as peak inspiratory flow rates, duration of expiratory pause, variation in tidal volume, and also according to "mask factors" such as fresh gas flow rate, tightness of fit, and deadspace of the device.2,4 All these factors clearly influence the concentration of helium reaching the upper airway and thus its effects. On the other hand, oxyhoods or tent houses, used with some of their patients, are ineffective and suboptimal for heliox delivery: helium concentrates at the top, and nitrogen increases progressively from top to bottom.2,4 It is possible that if the authors would have taken this into account, the differences between both arms of the study could have been more marked or even statistically significant.
- Regarding adverse effects, besides the isolated cases referred to by the authors of preterm infants who developed hypoxia secondary to heliox administration, probably related to the reduction of lung volume and the increase of intrapulmonary shunts, the risk of hypothermia should be further emphasized. Heliox must be used with caution because of its high thermal conductivity and subsequent risk of hypothermia when the temperature of the gas mixture is lower than 36°C, especially when heliox is administered for long periods.4
Finally, we would like to encourage the authors to keep on researching on the field of heliox, a therapeutic tool with multiple potential indications but lacking good, quality randomized, controlled trials assessing its real efficacy and impact in the pediatric setting. However, our concern is that when comparing oranges and apples, the chance of obtaining strong conclusions can be lessened.
Federico Martinón-Torres, MD, PhD
Antonio Rodriguez-Nuñez, MD, PhD
Jose Maria Martinón-Sánchez, MD, PhD
Department of Pediatrics
Hospital Clinico Universitario de Santiago
15706 Santiago de Compostela, Spain
REFERENCES
- Weber JE, Chudnofsky CR, Younger JG, et al. A randomized comparison of helium-oxygen mixture (heliox) and racemic epinephrine for the treatment of moderate to severe croup. Pediatrics.2001; 107(6) . Available at: http://www.pediatrics.org/cgi/content/full/107/6/e96
- Martinón-Torres F. Otros modos de terapia respiratoria: Heliox. In: Ruza T, ed. Manual de Cuidados Intensivos Pediátricos. Madrid, Spain: Norma-Capitel; 2001:456–462
- Papamoschou D. Theoretical validation of the respiratory benefits of helium-oxygen mixtures. Respir Physiol.1995; 99 :183 –190[CrossRef][Web of Science][Medline]
- Stillwell PC, Quick JD, Munro PR, Mallory GB. Effectiveness of open-circuit and oxyhood delivery of helium-oxygen.
Chest.1989; 95
:1222
–1224
[Abstract/Free Full Text]
To The Editor.—
In the introduction to the study by Weber et al,1 the authors state that helium has one-third the viscosity of air and reference this fact to a previous study. Unfortunately they are misinformed. The densities and viscosities of the relevant gases are detailed in Table 1 (see page 442) adapted from Ball et al2:
- As both the density and viscosity of gas mixtures can be accurately approximated to the concentration weighted sum of the constituents, the viscosity of air (at 298 K) can be considered to be 183.5µP whereas pure helium is 198.6µP3 and the mixture 70% helium: 30% oxygen 201µP. Hence, it is the reduction in density that reduces the proportion of turbulent flow in the upper airway and relieves the symptoms of obstruction, regardless of the underlying cause.4
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In addition to the evidence supporting the use of helium oxygen mixtures in the emergency treatment of upper airway obstruction, there is a growing body of evidence to support its use in other causes of respiratory failure.2 However, the use of such mixtures for updraft nebulization should be discouraged as these depend on the generation of turbulence, which is much reduced, resulting in a significant reduction in drug delivery.5 We would encourage the widespread availability of helium oxygen mixtures for use in patients with stridor.
Jonathan Ball, MRCP
St George’s Hospital Medical School
University of London
Cranmer Terrace
London SW17 ORE United Kingdom
Mike Grounds, MD, FRCA
St George’s Hospital
Blackshaw Road
London SW17 0QT United Kingdom
REFERENCES
- Weber JE, Chudnofsky CR, Younger JG, et al. A randomized comparison of helium-oxygen mixture (heliox) and racemic epinephrine for the treatment of moderate to severe croup. Pediatrics.2001; 107(6) . Available at: http://www.pediatrics.org/cgi/content/full/107/6/e96
- Ball J, Rhodes A, Grounds RM. The role of helium in the treatment of acute respiratory failure. In: Vincent J-L, ed. Yearbook of Intensive Care and Emergency Medicine. Berlin, Germany: Springer-Verlag; 2001:446–463
- Turner MJ, MacLeod IM, Rothberg AD. Effects of temperature and composition on the viscosity of respiratory gases.
J Appl Physiol.1989; 67
:472
–477
[Abstract/Free Full Text] - Smith SW, Biros M. Relief of imminent respiratory failure from upper airway obstruction by use of helium-oxygen: a case series and brief review. Acad Emerg Med.1999; 6 :953 –956[Web of Science][Medline]
- Goode ML, Fink JB, Dhand R, Tobin MJ. Improvement in aerosol delivery with helium-oxygen mixtures during mechanical ventilation.
Am J Respir Crit Care Med.2001; 163
:109
–114
[Abstract/Free Full Text]
To the Editor.—
We read with some concern the randomized comparison of heliox and epinephrine for the treatment of croup.1 Unlike racemic epinephrine, heliox causes no airway dilatation but provides symptomatic relief of stridor by altering gas flow dynamics and, as such, does not treat the underlying problem of mucosal edema; it simply masks it.
The diagnosis of croup is made with a degree of uncertainty. As the authors correctly observe, the differential diagnosis of stridor in this age group includes epiglottitis, bacterial tracheitis, and neck abscesses. Treating such life-threatening airway pathologies, which may progress rapidly, with heliox can hide an impending obstruction with catastrophic results. By the time a child becomes hypoxic on heliox the window for endotracheal intubation may have been missed as the decompensation may be rapid.
In our practice, the use of heliox is reserved for airway obstruction in palliative care only.
Angus Waddell, MD
Kate Evans, MD
Department of Otolaryngology
Gloucester Royal Hospital
Gloucester, United Kingdom
REFERENCE
- Weber JE, Chudnofsky CR, Younger JG, et al. A Randomised comparison of helium-oxygen mixture (heliox) and racemic epinephrine for the treatment of moderate to severe croup. Pediatrics.2001; 107(6) . Available at: http://www.pediatrics.org/cgi/content/full/107/6/e96
In Reply.—
We thank the authors for their constructive comments.
In our article, we noted that helium is a biologically inert gas that possesses a very low specific gravity (density) and is one-third the viscosity of air. This is incorrect. Correctly stated, heliox has one-third the density of air. Although this point is noteworthy, rigid definitions and endpoints were used in this study, and this error in no way poisons the methodology or conclusions.
Assessment of the gas transfer characteristics based on viscosity, kinematic viscosity, and the Reynold’s number for heliox versus oxygen or air at STP is essentially insignificant. The variation in viscosity between heliox and oxygen is only 3%.1 Although higher viscosity gases will have a thicker boundary layer that will help reduce turbulence, this difference in not likely clinically significant. A clearer picture of how the viscosity and kinematic viscosity affects gas transfer is the calculated Reynold’s number for the gases in a similar situation.2 The Reynold’s number is used to determine whether turbulence will occur during gas transport, and is calculated as follows: Nr = 
D/
, where Nr is the Reynold’s number, is the gas density, is the kinematic viscosity, D is the diameter of the pipe, and is the viscosity of the gas.
A Reynold’s number below 2000 indicates laminar flow; 2000 to 3000 is inconsistent, and over 3000 indicates turbulent flow2 (Table 1). If one assumes the diameter of the pediatric trachea ranges from 3 mm to 10 mm and further assumes that the flow velocity is 100 cm/s, then all gases mentioned will have laminar flow in the trachea. It should be noted that experimentally the measured Reynold’s numbers could be quite different when taking into account the characteristics of a biological system. However, given the same pressure head or pressure differential, heliox, based on density, will allow a higher flow rate. This is irrespective of laminar or turbulent flow. Clinically, the work of breathing would decrease with a corresponding increase in the amount of ventilation.
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Dr Martinón-Torres and colleagues further point out that heliox does not need to be laminar to provide higher flow rates and that its benefits persist even under turbulent conditions.3 Given our experience with heliox in the clinical setting, this statement is likely true. However, the authors also note that work by Papamoschou provides the theoretical validation for this argument.4 It is important to point out that facts are never theoretically validated. Only experimental data can validate theory. The authors further note that the use of oxyhoods or tent houses is ineffective and suboptimal for heliox delivery. We allowed for the use of tent houses in small children who were resistant to the use of a facemask. We agree that the efficacy of heliox may be reduced in such cases. Interestingly, an incremental benefit (ie, reduction in croup scores) was noted in patients who were subjected to tent houses as well as those receiving facemasks.
Drs Waddell and Evans noted that heliox does not treat the underlying problem of mucosal edema, but rather masks it, and suggest that heliox should be reserved for airway obstruction in palliative care only. The authors’ suggestions may be reflective of differences in practice environments. We agree that the beneficial effects of heliox are temporizing and dependent on application of the gas. This point is further supported by Dr Martinón-Torres’ argument that heliox is used to reduce resistance of the airways to gas flow and to decrease respiratory muscle work until definitive therapies act or the underlying condition spontaneously resolves.3 In the emergency department or pediatric intensive care unit setting, the most important and challenging enigma we confront on a daily basis is airway control for patients with impending respiratory failure. That said, any adjunct that could potentially extend the clinician time with regard to definitive airway control should be considered useful. The authors additionally note that heliox may mask hypoxia, thus creating a potentially missed opportunity for prompt definitive airway placement. Hypoxia in and of itself is a late finding, regardless of whether or not heliox is used, and is, therefore, a dangerous endpoint to utilize when determining the need to provide a definitive airway. Additional objective findings, including vital signs upon presentation, degree of stridor, retractions, and dyspnea, also require prompt recognition. We now possess data for over 200 children who presented with moderate to severe croup and subsequently received heliox; only 1% ultimately required intubation. Although we are underpowered to conclude that heliox obviates the need for intubation, we report no subsequent complications attributable to airway control in children receiving heliox either. Therefore, although the argument constructed by Drs Waddell and Evans is noteworthy, we have not found this to be of clinical relevance in our emergency department or pediatric intensive care unit settings.
Dr Martinón-Torres and colleagues indicated that comparing heliox and racemic epinephrine was analogous to comparing "apples to oranges." We in no way inferred that we were comparing apples to oranges. Suggesting such a design implies that racemic epinephrine, in contrast to heliox, is a definitive treatment modality. We disagree with this assumption and feel that both are "temporizing" agents, because in our experience, many children with moderate to severe croup require a second treatment of racemic epinephrine, indicating either progression of disease or a time-dependent, transient effect of racemic epinephrine (rebound). In fact, we feel that the true definitive treatment to reduce airway edema in patients with croup is the use of steroids, which each study subject received. In addition, we are in no way suggesting that heliox replace racemic epinephrine. We specifically stated this was a small pilot study that requires validation. Our outcome measure was clearly defined as the comparative change in croup scores over time between heliox and racemic epinephrine. We, therefore, feel that our conclusions are conservative and based on the data provided. We invite and encourage investigators to conduct future, large-scale trials to either validate or refute our findings.
James E. Weber, DO
Department of Emergency Medicine
University of Michigan Medical School
Ann Arbor, MI
Hurley Medical Center
Flint, MI, USA
Marc Rosenthal, PhD, DO
Saginaw Cooperative Hospitals, Inc
Michigan State University College of Human Medicine
Ann Arbor, MI, USA
REFERENCES
- Physics Vad Mecum. Anderson HL, ed. AIP, 1981:183
- Reynold’s numbers. In: Sears F, Zemansky M, eds. 2nd ed. Boston, MA: Addison-Wesley; 1957
- Marintón-Torres F. Otros modos de terapia respiratoria: Heliox. In: Ruza T, ed. Manual de Cuidados Intensivos Pediatricos. Madrid, Spain: Norma-Capitel; 2001:456–482
- Papamoschou D. Theoretical validation of the respiratory benefits of helium-oxygen mixtures. Respir Physiol.1995; 99 :183 –190
PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics
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  C Vorwerk and T J Coats Use of helium-oxygen mixtures in the treatment of croup: a systematic review Emerg. Med. J., September 1, 2008; 25(9): 547 - 550. [Abstract] [Full Text] [PDF]
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