Use of Helium-Oxygen Mixtures in the Treatment of Acute Asthma: A Systematic Review

doi:10.1378/chest.123.3.891

Chest

Volume 123, Issue 3, March 2003, Pages 891-896

https://doi.org/10.1378/chest.123.3.891 Get rights and content

Study objective

To determine the effect of the addition of heliox to standard medical care on the course of acute asthma.

Design

Systematic review of randomized and nonrandomized prospective, controlled trials of children and adults that compared heliox to placebo when used in conjunction with other standard acute treatments.

Main outcome measures

Pulmonary function tests, hospital admissions, physiologic measures, side effects, and clinical outcomes.

Results

Seven trials were selected for inclusion, with a total of 392 patients with acute asthma. Six studies involved adults, and one study dealt solely with children. The main outcome variable was spirometric measurements (peak expiratory flow or FEV₁) in six trials. Two studies evaluated the effect of heliox on airways resistance. No significant differences were demonstrated between heliox or oxygen/air groups (standardized mean difference [SMD], − 0.20; 95% confidence interval [CI], − 0.91 to 0.51; p = 0.6). However, the four studies that used heliox to deliver nebulized therapy showed a nonsignificant increase in pulmonary function (SMD, − 0.21; 95% CI, − 0.43 to 0.01; p = 0.06). In two studies of the same subgroup, heliox mixtures produced a significantly greater increase of heart rate than oxygen/air (weighted mean difference, 9.0; 95% CI, 1.27 to 16.8; p = 0.02). However, the four studies that used heliox to deliver nebulized therapy reported a nonsignificant difference in hospital admissions (odds ratio, 1.07; 95% CI, 0.46 to 2.48; p = 0.9). Overall, heliox appears to be safe and well tolerated.

Conclusions

The existing evidence does not provide support for the administration of helium-oxygen mixtures to emergency department patients with moderate-to-severe acute asthma. However, these conclusions are based on between-group comparisons and small studies, and these results should be interpreted with caution.

Section snippets

Search Strategy for Identification of Studies

A search was carried out using five search strategies to identify potentially relevant trials. Firstly, we searched MEDLINE (1966 through 2002), EMBASE (1980 through 2002), and CINAHL (1982 through 2002) databases using the following medical subject headings, full text, and keyword terms: Emerg* OR acute asthma OR status asthmaticus OR severe asthma AND heliox OR helium AND oxygen. Secondly, an advanced search of the Cochrane Controlled Trials Register was completed using the above-mentioned

Results

The initial search produced 89 potentially relevant citations. Of these, 21 studies were reviewed in full text for possible inclusion. Fourteen studies were excluded for the following reasons: noncontrolled trials,⁷⁸²¹²² hospitalized patients,¹⁰ patients receiving mechanical ventilation,²³ anecdotal evidence,²⁴²⁵ patients with COPD,²⁶²⁷²⁸²⁹ patients with bronchiolitis,³⁰ and out-of-hospital setting.³¹ A total of seven controlled, prospective trials conducted in North America were selected for

Discussion

This systematic review has attempted to incorporate the best available evidence on heliox use in patients with acute asthma. We found five randomized trials and one prospective, nonrandomized, placebo-controlled clinical trial that compared heliox to other forms of standard care. There was only one study in children. Several important conclusions arise from the analysis. Overall, the addition of heliox to standard medical care during the course of acute asthma is not more effective, in terms of

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La maladie asthmatique reste un vrai problème de santé publique avec jusqu’à 100 000 hospitalisations en France par an. Le diagnostic de gravité d’une crise d’asthme nécessite la mesure du débit expiratoire de pointe. L’asthme aigu grave se définit par un débit expiratoire de pointe inférieur à 30 % de la théorique. Les β2-agonistes inhalés associés au bromure d’ipratropium constituent le traitement de première intention de l’asthme aigu grave. Les corticoïdes sont à administrer le plus précocement possible et systématiquement. Les indications d’intubation se raréfient. L’éducation du patient est un élément fort de limitation des fréquences des crises.
In hospital, admission related to acute asthma represents 100,000 cases a year in France. The peak flow measurement is the cornerstone of the evaluation of the severity of asthma crisis. Severe acute asthma is defined by a peak flow less than 30% of theoretical value. The first line treatment is based on inhalation of β2-agonists and ipratropium bromure. Corticosteroids need to be administered as soon as possible. Orotracheal intubation is less and less frequently required. Patient’ education has an important preventive role on the occurrence of crisis.
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La maladie asthmatique reste un vrai problème de santé publique avec jusqu’à 100 000 hospitalisations en France par an. Le diagnostic de gravité d’une crise d’asthme nécessite la mesure du débit expiratoire de pointe. L’asthme aigu grave se définit par un débit expiratoire de pointe inférieur à 30 % de la théorique. Les β2-agonistes inhalés associés au bromure d’ipratropium constituent le traitement de première intention de l’asthme aigu grave. Les corticoïdes sont à administrer le plus précocement possible et systématiquement. Les indications d’intubation se raréfient. L’éducation du patient est un élément fort de limitation des fréquences des crises.
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Citation Excerpt :
Anaesthetists and intensivists are well versed in delivery of i.v. drugs, their immediate effects, and are able to deal with the results; those who have used the i.v. route for asthma drugs (and the patients who have received them) can attest to the safety, efficacy, and immediate reversal of bronchoconstriction. Research proving an advantage of the i.v. route for asthma drugs (or heliox68 to deliver anaesthetic vapour) using blinded controlled studies may be impossible in life-threatening asthma; anecdotal case reports, especially about managing severe asthma, should be recognized as opinions and experience and may be defined as category IV evidence, the strongest evidence available to help manage infrequent emergency situations.69 Future research to determine the dose of i.v. magnesium and the timing before i.v. salbutamol to protect the atria from β1-induced tachycardia can be studied in volunteers; the possible bronchodilating effect of norflurane needs investigating, and the use of heliox to drive nebulizers70 or to deliver anaesthetic vapours.
Management of life-threatening acute severe asthma in children and adults may require anaesthetic and intensive care. The inhaled route for drug delivery is not appropriate when only small respiratory gas volumes are shifted; the i.v. route may be associated with greater side-effects. Magnesium sulphate i.v. has a place in acute asthma management because it is a mild bronchodilator, and has a stabilizing effect on the atria which may attenuate tachycardia occurring after inhaled and i.v. salbutamol. If intubation and ventilation are required, a reduction in bronchoconstriction by any means before and during these procedures should reduce morbidity. This narrative review aims to show strengths and weakness of the evidence, present controversies, and forward opinions of the author. The review contains a practical guide to the setting up, use and efficiency of nebulizers, metered dose inhalers, and spacers (chambers). It also presents a commonsense approach to the management of severe asthmatics in whom delay in bronchodilatation would cause clinical deterioration. When self-inhaled agents have had no effect, i.v. drugs may help avoid intubation and ventilation. The review includes suggestions for the use of inhaled anaesthetics, anaesthetic induction, and brief notes on subsequent ventilation of the lungs.

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Chest

ReviewsUse of Helium-Oxygen Mixtures in the Treatment of Acute Asthmaa: A Systematic Review

Study objective

Design

Main outcome measures

Results

Conclusions

Section snippets

Search Strategy for Identification of Studies

Results

Discussion

Chest

Chest

Chest

J Pediatr

Ann Emerg Med

Clin Epidemiol

Control Clin Trials

J Emerg Med

Chest

Am J Emerg Med

J Emerg Med

The use of helium in the treatment of asthma and obstructive lesions in the larynx and trachea

Ann Intern Med

Deposition in asthmatics of particles inhaled in air or in helium-oxygen

Am Rev Respir Dis

Improvement in aerosol delivery with helium-oxygen mixtures during mechanical ventilation

Am J Respir Crit Care Med

Effect of helium-oxygen on delivery of albuterol in pediatric volume cycled lung model

Pharmacotherapy

The use of helium-oxygen mixtures in the support of patients with status asthmaticus and respiratory acidosis

J Asthma

Heliox improves pulsus paradoxus and peak expiratory flow in nonintubated patients with severe asthma

Am J Respir Crit Care Med

Reviews
Use of Helium-Oxygen Mixtures in the Treatment of Acute Asthma^a: A Systematic Review