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Dr. Kass is Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, The Cooper Health System, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson School of Medicine at Camden.
Correspondence to: Jonathan E. Kass, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Three Cooper Plaza, Suite 312, Camden, NJ 08103; e-mail: kass-jonathan{at}cooperhealth.edu
Helium is an inert, colorless gas. It was discovered by spectroscopic methods during an eclipse of the sun in India in 1868 and, thus, was named from the Greek word helios, which means sun. It was not isolated until 1895 by Sir William Ramsey, and by Nils Langlet and P.T. Cleve. Its first major uses in the first third of the 20th century were for filling airships and balloons during World War I and for divers in a mixture with oxygen. Alvan Barach1 first used it for medical purposes in 1934 and confirmed the biological inertness of helium by exposing mice to 79% helium and 21% oxygen for 2 months without deleterious effects.2 He reported the successful usage of helium-oxygen mixtures in four cases of asthma in adults and two cases of upper airway obstruction in infants.3 Of interest, the patients were relieved of their dyspnea in 6 to 10 breaths, and when the helium was removed the dyspnea came back in 3 or 4 breaths. After the explosion of the dirigible Hindenburg in 1937, Congress regulated the sale of helium, and its availability was further reduced during World War II. After the war, with the advent of pharmacologic bronchodilators with improving side-effect profiles, helium was cast aside as a treatment for asthma. It was relegated back to filling balloons at parties, where its effect on the voice, making one sound like "Donald Duck," was its main notoriety. There were a few reports of its respiratory usage showing the lack of significant improvement in asthmatic patients4 and in patients with emphysema.5 Helium-oxygen was shown to be an effective treatment of upper airway obstruction in 1976,6 and there were scattered reports for this usage until 1986.7 8 9
In 1987, the use of helium-oxygen in the treatment of patients with asthma resurfaced in Hartford, CT, and in France, and it became known as heliox. Within a few years, its use spread to Camden, NJ, Chicago, IL, Houston, TX and then to many other sites. Despite anecdotal reports of its efficacy,10 11 12 13 14 heliox therapy for asthma patients continued to be viewed as experimental because of the lack of randomized controlled trials.15 16
The theoretical basis behind the use of helium in asthma patients mainly relates to its low density. It has the lowest density of any gas except hydrogen. Asthma is a disorder of airways obstruction, and the pathophysiology includes an increased turbulent flow in the airways. Since airway resistance in turbulent flow is directly related to the density of a gas, helium with its lower density results in a lower airway resistance. It also reduces the Reynolds number, converting turbulent flow to laminar flow and further decreasing airway resistance. These effects result in a decreased work of breathing. Helium also increases the diffusion of carbon dioxide and may improve alveolar ventilation, resulting in improved gas exchange. Helium is an inert element and does not interact with any biochemical process. It is noncombustible, nonexplosive, and nondetectable by taste and smell. Its effect on the airways occurs and goes away within a few breaths. In summary, it is an extremely safe and rapid-acting therapeutic agent that reduces airway resistance, decreases the work of breathing, and may improve gas exchange.
So what is its downside? The cost for heliox is in the range of $30 to $70 for 8 h of usage, making it a rather low-cost medical modality.17 However, its usage takes a little knowledge and work. Heliox needs to be dispensed via a nonrebreathing mask, so it is not diluted with room air. The heliox tanks have to be obtained and, despite their large size, have to be easily accessible to the emergency department and/or ICU. Educational sessions have to be set up with respiratory therapists and with the staffs of the emergency department and ICU. There are few guidelines in the medical literature on optimal patient selection and usage.
In cases in which it has been beneficial, the rapidity and power of the therapeutic effect can be truly amazing. Two cases that I was involved with come to mind. In 1987, a young asthmatic patient went into respiratory failure and, despite all known treatments including halothane general anesthesia, was unable to be adequately ventilated. With heliox, the peak airway pressure and the PaCO2 markedly dropped in only a few minutes. Another young asthmatic patient, who had a pH of 6.95, refused endotracheal intubation. As with the prior patient, only a few minutes after initiating heliox, the patient had dramatic relief of dyspnea and the PaCO2 markedly diminished toward the normal range. However, not all asthmatic patients have such profound response to heliox. This anecdotal use of heliox in asthma patients led to three clinical studies11 12 13 at Hartford and Mount Sinai hospitals (Hartford, CT), which were published between 1989 and 1995. These studies, in patients with acute ventilatory failure who were and were not receiving mechanical ventilation, demonstrated a dramatic decrease in PaCO2 in a great majority of patients, but not all. Heliox was still not accepted as a therapeutic choice for the treatment of acute severe asthma and was relegated to a grab bag of unconventional treatments due to the lack of a randomized controlled study demonstrating its efficacy.15 16 However, this interest in heliox spawned other clinical trials across the country in patients with stridor,18 19 bronchiolitis,20 croup,21 and COPD,22 23 as well as investigations of its effect on nebulizer and ventilator function.24 25 26 27 28
In the article in this issue of CHEST (see page 882), Ho et al reviewed eight randomized controlled trials29 30 31 32 33 34 35 36 of heliox in acute severe asthma published between 1996 and 2002. Five of these studies used peak expiratory flow rate (PEFR) as the main variable.29 30 31 32 33 Two trials studied only children,29 30 two trials studied only adults,31 32 and one trial included both children and adults.33 One trial30 with children was excluded because it did not include percent predicted PEFR values. The data from the remaining four studies were pooled and evaluated with a meta-analysis. The authors found a small benefit in PEFR and dyspnea index with heliox and commented that the difference may have been even greater if the fifth study had been included. They also suggested that patients with more severe asthma might benefit more from heliox.
Markedly successful anecdotal reports of heliox treatment in asthma patients have been both a blessing and a curse for heliox. They have led to a wider but indiscriminate usage of heliox. In both of the hospitals where I have conducted clinical trials with heliox in asthma patients, its use in treating a small number of patients who had rapid and marked improvement with heliox has led to its regular use in patients with severe asthma. In reviewing the medical literature on heliox in asthma, Ho et al found that of the 13 randomized and nonrandomized clinical trials, 10 showed a benefit with heliox and 3 did not. However, even after the publication of randomized controlled trials of heliox in asthmatic patients, there was no widespread acceptance of heliox therapy. Despite the fact that heliox does not lead to improvement in every patient, it still has clinical value when used with the appropriate patients.
So who should receive heliox? Presently, it should be reserved for the "brittle" asthmatic patient who does not quickly respond to inhaled ß-agonist therapy and who has any of the following characteristics:
How should heliox be used?
As stated by Ho et al, further studies are needed, specifically to ascertain whether heliox reduces the incidence of endotracheal intubation. Since it is but a therapeutic bridge until the effect of corticosteroids occurs, it is unlikely that it will reduce hospital admissions, hospital or ICU length of stay, or hospital mortality. It will provide rapid and marked relief of dyspnea to many patients without any detrimental effects. Since its therapeutic index is so high and its onset and offset of action are so rapid, it may find a useful niche in the prehospital setting when used by emergency medical technicians and possibly by an occasional labile asthmatic patient at home.
References
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