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Dr. Manthous is Director of Internal Medicine and Medical Intensive Care, Bridgeport Hospital, and Assistant Clinical Professor of Medicine, Yale University School of Medicine.
Correspondence to: Constantine A. Manthous, MD, FCCP, Bridgeport Hospital, West Tower 6, 267 Grant St, Bridgeport, CT 06610-2870; e-mail: pcmant{at}bpthosp.org
In this issue of CHEST (see page 891), Carlos and Gustavo Rodrigo review studies that examine the clinical efficacy of heliox for the management of patients with asthma. To summarize, their meta-analysis concludes that the available data do not warrant the use of heliox for the treatment of most acute exacerbations of asthma. Heliox is a mixture of oxygen and helium that has a lower density and a higher viscosity than nitrogen-oxygen mixtures.1 These physical properties reduce the Reynolds number associated with its flow through hollow tubes (ie, the airways). Heliox should, therefore, promote the transformation of some areas of turbulent flow, as is thought to occur in the bronchioles of asthmatic patients, to laminar flow, thereby reducing the resistive-pressure work of breathing. Dynamic hyperinflation also contributes to increased elastic pressure work of breathing in patients with acute asthma. By promoting enhanced expiratory flow, heliox also should reduce the elastic-pressure work of breathing by allowing the passive exhalation to a lower end-expiratory volume. If this theory is applicable, heliox does not treat asthma. It merely reduces the inspiratory pressures that the patient (or a ventilator) is required to generate during tidal breathing at any given flow and tidal volume. So, heliox may temporize and give definitive treatments (bronchodilators and steroids) time to work. It also could improve the efficacy of definitive therapies if it better carried aerosolized medications to the target airways. So, heliox may impact outcomes in one of the following two ways: by reducing the work of breathing sufficiently to preclude the need for endotracheal intubation (and/or to reduce the sense of dyspnea in those with severe airflow obstruction); and as a carrier gas to improve the delivery of aerosols to the airways, thereby improving disposition outcomes.
To my knowledge, the successful clinical use of heliox was first published in anecdotal reports in the 1930s for the treatment of patients with severe asthma and upper airway obstruction.2 3 4 Between the 1930s and the 1990s, there are few published accounts of heliox use for status asthmaticus.1 Since 1990, numerous investigators have examined the utility of heliox for acute airflow obstruction, leading to the current meta-analysis showing no outcome benefits of this intervention. Nonetheless, the review points out that heliox can improve some physiologic variables (ie, peak flow and pulsus paradoxus) of patients with status asthmaticus.5 6 Thus, there are both theoretical and empiric data to suggest that heliox might be useful. In fact, in our study,5 heliox was associated with a 30% reduction in pulsus paradoxus, which is thought to reflect the work of breathing in patients with acute asthma. Why does that not translate to an observable difference in outcomes? The reason may be that most patients with acute asthma (ie, more than two thirds) get better without it.7 8 In my opinion, the correct experiment has not been performed yet. If we hypothesize that heliox reduces the rate of intubation of all patients with acute asthma from 1 to 0.2%, then one needs 654 patients (to demonstrate this fivefold reduction in intubation) at a power of 80%. Even if 5% of all patients are intubated (which is more than the number in most published series), 116 patients are required to demonstrate a fivefold difference at an 80% power. No study has been powered sufficiently to answer the question. It is not the right question anyway. Why use heliox on the two thirds of asthmatic patients who get better after three back-to-back aerosol treatments? What we really need to know is whether heliox can be used to reduce the need for intubation in those patients with the worst exacerbations. Thus, it is premature to conclude that heliox cannot be used to reduce the rate of intubation of patients with severe asthma.
Although Kress and colleagues9 showed that heliox, when used to carry aerosols to the lungs of patients with acute asthma, improves their expiratory flow rates, no study has demonstrated improved outcomes (eg, disposition, length of stay, and intubation) when heliox is used as the aerosol carrier gas. Finally, one may ask whether there is a role for heliox in mechanically ventilated patients. Studies by Menitove and Goldring10 and Darioli and Perret11 have demonstrated that mortality from mechanical ventilation for asthma can be eliminated using techniques to reduce dynamic hyperinflation. No similar data exist for heliox when it is used in such cases. Thus it should not be used in this situation unless permissive hypoventilation has failed to achieve safe airway pressures and/or the patient exhibits the cardiopulmonary effects of dynamic hyperinflation (ie, shock or barotrauma). Since I left my fellowship, where we used heliox in such patients occasionally, I have been successful in treating patients with the most severe cases of asthma using a plateau-pressure-targeted (ie, < 30 cm H2O) hypoventilation strategy. Heliox has never been required. Yet, it is nice to know that it can be "pulled out"1 as rescue therapy for "asthma from hell" when everything else is not working. Luckily, I have not encountered such a case in the past 10 years.
So to conclude, the review by Rodrigo and Rodrigo notwithstanding, no published study has examined the relevant question: does heliox, when inhaled to reduce the work of breathing or to propel therapeutic aerosols more efficiently, improve the outcomes of patients with refractory airflow obstruction, that is, those who do not get better after initial therapies in the emergency department? Until such studies are performed, the role of heliox to reduce the work of breathing for the purpose of forestalling intubation and to deliver aerosols is not certain. Heliox should not be used in all patients with acute asthma, but it may be effective (if used carefully1 ) in selected patients with the most severe, refractory status asthmaticus. Until such studies are published, heliox should be used cautiously by experienced personnel, preferably in study circumstances.
References
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