Prospective randomized trial of heliox-driven continuous nebulizers in the treatment of asthma in the emergency department

doi:10.1016/S0736-4679(01)00454-1

The Journal of Emergency Medicine

Volume 22, Issue 2, February 2002, Pages 133-137

Presented in part at the Society for Academic Emergency Medicine Annual Meeting, May 1998, Chicago, Illinois.

https://doi.org/10.1016/S0736-4679(01)00454-1 Get rights and content

Abstract

The purpose of this study was to evaluate the efficacy of heliox-driven continuous nebulizers in the management of moderate to severe asthma exacerbations in the Emergency Department (ED). The trial was a prospective, randomized, double-blind, controlled trial in a university Emergency Department (volume 65,000 patients/year) of patients 18–55 years of age with acute asthma exacerbations. Patients were placed on continuous nebulizers driven by 70:30 heliox or air with 30% O₂. Respiratory rate, peak expiratory flow rate (PEFR), forced expiratory volume at 1 s (FEV1), and Borg dyspnea scale were measured at 0 and 2 h. Disposition and patient satisfaction were also assessed. A total of 36 patients completed the study (18 heliox, 18 air). There was no difference between groups in baseline variables. There was significant interval improvement within both groups at 2 h in PEFR, FEV1, Borg, and respiratory rate. There was no significant difference between heliox 70:30 and air/oxygen in PEFR [mean between-group improvement difference 17 liters/min, 95% confidence interval (CI) −20–51], FEV1 (0.03 liters/sec, 95% CI −0.22–0.30), or respiratory rate (mean between-group improvement difference 0.5, 95% CI −2.7–3.8). There was a significant improvement in the patients’ perceived dyspnea as measured by the Borg dyspnea scale at 2 h in the heliox group (1.6, 95% CI 0.3–3.0). In this trial of patients with moderate-severe asthma exacerbation, heliox-driven continuous nebulizers failed to demonstrate an improvement in respiratory rate, oxygen saturation, PEFR, or FEV1 at 2 h. However, there was a significant improvement in the patients’ perceived dyspnea on heliox over air/oxygen measured by the Borg dyspnea scale.

Introduction

Helium is an inert gas with no biologic effects that has been used in clinical medicine for over 60 years (1). Heliox is a mixture of helium and oxygen in varying proportions from 60:40 to 80:20 helium:oxygen. The primary advantage of heliox over air is due to the lower density of helium compared to nitrogen. A decrease in turbulent airflow in airways secondary to the lower density results in improved laminar air movement through most airways (2). These properties have led to the use of heliox in large airway disorders such as stridor post extubation, croup, and in chronic lung disease 3, 4. Heliox in asthma has received editorial support based on a growing research database; however, the evidence to date has been mixed as to the efficacy of heliox 5, 6. Some research has demonstrated improved pulsus paradoxicus, oxygenation, and initial spirometry with the use of heliox 7, 8, 9. Others have failed to demonstrate any benefit from heliox in acute asthma exacerbations 10, 11, 12. A majority of studies used intermittent hand-held nebulization to deliver the heliox, limiting the exposure to the mixture. Thus, we hypothesized that a more continuous exposure to heliox through heliox-driven continuous nebulization would improve particle deposition, resulting in a significant clinical response. We examined the efficacy of 70:30 heliox-driven continuous nebulization in asthmatics presenting to the Emergency Department (ED) with moderate to severe exacerbations not responding to initial therapy.

Section snippets

Methods

The study was a prospective, randomized, double blind, controlled trial. The setting was a university-based ED (volume 65,000 patients/year). The Human Subjects Committee of the study institution approved the protocol. A convenience sample of asthmatic patients who met inclusion criteria and consented to be entered were included. Asthma was diagnosed as defined by the American Thoracic Society’s Committee on Diagnostic Standards for Non-tuberculous Respiratory Disease (13). Inclusion criteria

Results

Patient enrollment, randomization, and withdrawals are summarized in the flowchart shown in Figure 1.

Table 1 summarizes the similar baseline characteristics of each group on entry into the ED. ED management prior to enrollment appears similar for each group. Of interest is that the mean duration of symptoms was greater than 24 h in both groups, suggesting these patients were well into the late-phase response at presentation. The baseline data in Table 1 was recorded on entry to the ED and

Discussion

Although heliox has been advocated for respiratory diseases since the 1930s, only recently has there been controlled research evaluating its effectiveness. Initial reports described impressive improvements with heliox. Gluck et al. reported a significant improvement in airway pressures and hypercarbia in intubated asthmatics by using a 60:40 mixture of heliox (15). Anderson found that a heliox mixture improved particle deposition in asthmatics (16). Recently, in a study of 27 severe asthmatics

Acknowledgements

Special thanks to Nate Kuppermann, M.D, MPH, for statistical support and to the respiratory therapists at UC Davis Medical Center.

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Heliox-driven β<inf>2</inf>-agonists nebulization for children and adults with acute asthma: A systematic review with meta-analysis
2014, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
Their pooled analysis showed that β2-agonist heliox-driven nebulization significantly decreased the severity of exacerbations in children (standard mean difference −0.74, 95% CI −1.45 to −0.03, I2 = 69%, P = .04). Seven trials with a total of 405 adults and 71 children with acute asthma reported hospital admissions.17–20,22–24 Beta-2–agonist heliox-driven nebulization significantly lowered the rate of hospital admissions.
The effect of heliox as a nebulizer β₂-agonist driving gas in acute asthma remains controversial.
To perform a systematic review with a meta-analysis of randomized trials designed to evaluate the efficacy of heliox versus oxygen in driving β₂-agonist nebulization in patients with acute asthma.
A search was conducted of all randomized controlled trials published before August 2013. Primary outcomes were change in spirometric measurements and severity composite score (pediatric studies); secondary outcomes were hospitalizations and serious adverse effects.
Eleven trials from 10 studies (697 participants) met the inclusion criteria (7 included adults and 3 included children). The mean duration of heliox therapy was 120 minutes and the most common helium–oxygen mixture used was 70:30. Patients receiving heliox presented a statistically significant difference for mean percentage of change in peak expiratory flow (17.2%; 95% confidence interval 5.2–29.2, P = .005). Post hoc subgroup analysis showed that patients with severe and very severe asthma showed a significant improvement in peak expiratory flow compared with those with mild to moderate acute asthma. Heliox-driven nebulization also produced significant decreases in the risk of hospitalizations (odds ratio 0.49, 95% confidence interval 0.31–0.79, P = .003) and severity of exacerbations (pediatric studies; standard mean difference −0.74, 95%% confidence interval −1.45 to −0.03, P = .04). There were no group differences for serious adverse effects.
This review suggests that heliox benefits in airflow limitation and hospital admissions could be considered clinically significant. Data support the use of heliox as a nebulizing β₂-agonist driving gas in the routine care of patients with acute asthma.
Recent Developments in Heliox Therapy for Asthma and Bronchiolitis
2009, Clinical Pediatric Emergency Medicine
Helium and oxygen gas mixtures (heliox) have become an area of renewed interest in pediatric emergency and critical care for the treatment of acute asthma exacerbations and bronchiolitis. After a review of recent literature on heliox, this article will provide an overview of delivery techniques. This article will primarily focus on heliox inhalation therapy and heliox-driven nebulizer therapy for acute asthma exacerbations. The emergence of heliox inhalation therapy for acute viral bronchiolitis will also be addressed.
Room air entrainment during β-agonist delivery with heliox
2006, Chest
Citation Excerpt :
β-agonists and corticosteroids form the mainstay of treatment for patients with acute asthma. The role of heliox as an adjunct to conventional medical treatment has been studied with mixed results.2,3,5,13,14,15,16,17,19,20 Most asthmatic patients get better after two to three sequential conventional treatments with β-agonists.42
Studies of the efficacy of heliox in patients with severe asthma have shown mixed results. Among the factors that are responsible for variable outcomes, the failure of heliox delivery systems to prevent room air entrainment (RAE) during β-agonist delivery is probably the most critical. While keeping the rotameter flow rate (FR) of heliox mixed 70:30 to a nebulizer at 10 L/min, the FR of heliox from a second gas source to a T-connector (TC) was increased during the delivery of the β-agonist with a conventional T-nebulizer delivery system (TNDS). A negative peak inspiratory flow (pneumotachometer reading) or a helium concentration of < 70% (quadralizer reading) were indicators of RAE. RAE was tested during spontaneous tidal breathing and acute asthma. A rotameter FR of 10 L/m to the nebulizer with no flow from a second gas source to a TC (conventional TNDS) resulted in a significant drop in helium concentration during tidal breathing (46.2%) and acute asthma (27.5%) due to RAE. This degree of helium dilution can negate the beneficial effects of heliox to lung mechanics almost completely. A rotameter FR of 10 L/m each to a nebulizer and a TC resulted in a helium concentration 69.8% during tidal breathing (no RAE), but 49% (significant RAE) during asthma events. A rotameter FR of 15 L/m (pressure regulator setting, 100 lbs per square inch) to a TC, while maintaining a rotameter FR of 10 L/m to a nebulizer prevented RAE during asthma (helium concentration, 69.9%). Conventional TNDS may be used to deliver the β-agonist with heliox during asthma without RAE.
Albuterol nebulized in heliox in the initial ED treatment of pediatric asthma: A blinded, randomized controlled trial
2006, American Journal of Emergency Medicine
A prospective blinded, randomized controlled trial was undertaken to compare the initial response of albuterol nebulized in heliox or control in the treatment of moderately severe asthma in children presenting to a pediatric ED.
Patients were randomized to receive heliox (n = 20) or control (n = 21). The primary outcome was to compare a modified dyspnea index score at 10 and 20 minutes after randomization. Secondary outcomes were to determine if heliox decreased admission rates or endotracheal intubation.
There was no statistically significant difference found at 10 or 20 minutes after randomization with heliox (P = .169 and P = .062, respectively). No statistical difference in admission rate was found, and no patients required endotracheal intubation in either group.
Our results demonstrate that albuterol nebulized with heliox offered no clinical benefit over standard therapy in the initial treatment of moderately severe asthma in the ED.
Beneficial effects of albuterol therapy driven by heliox versus by oxygen in severe asthma exacerbation
2005, Academic Emergency Medicine
Citation Excerpt :
That the pretreatment PEF, and thus the severity of airway obstruction, may determine the clinical response to heliox-driven albuterol therapy might explain in part the variable results in previous studies. The study by Rose et al. used a 70:30 mixture of heliox to nebulize albuterol in asthmatic patients with PEF <40% predicted, and they observed improvement in perceived dyspnea score but not respiratory rate, oxygen saturation, PEF, or FEV1 at two hours.16 The study by Kress et al. used an 80:20 mixture of heliox to drive the albuterol nebulization in patients with FEV1 about 32% of predicted, and they noted a significant improvement in FEV1 for the heliox group compared with the O2 group.15
To determine and define the beneficial effects of heliox-driven albuterol therapy on severe asthma exacerbation and clinical factors that affect greater response.
The authors conducted two randomized, double-blinded, controlled trials in patients with severe asthma exacerbation. The first trial recruited 80 patients in the emergency department (ED). They received three consecutive doses of albuterol delivered by a nebulizer powered by either O₂ (O₂ group) or heliox (He/O₂ = 80:20; heliox group). Changes in peak expiratory flow rate (PEF) were compared, and factors influencing the response to heliox-driven albuterol therapy were identified. The second trial of 80 patients was conducted in older patients, a subpopulation associated with greater response in the first trial.
In the first trial, the heliox group had more rapid and greater improvement in PEF compared with the O₂ group. There tended to be more patients in the heliox group reaching the predetermined dischargeable PEF (>60% predicted) after three albuterol treatments (odds ratio, 2.58; 95% confidence interval = 1.03 to 6.46; p = 0.069). For patients eventually discharged from the ED, the ED stay was shorter by 10 minutes per patient in the heliox group compared with the O₂ group (p = 0.007). Logistic regression showed older age and lower pretreatment PEF to be associated with favorable heliox responses. The second trial, which recruited older patients (older than 40 years), showed greater improvement in PEF and dyspnea score with heliox-driven albuterol therapy in patients with lower pretreatment PEF.
Heliox-driven albuterol may be a useful adjunct therapy for older asthmatic patients with severe asthma exacerbation.

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Original contributionProspective randomized trial of heliox-driven continuous nebulizers in the treatment of asthma in the emergency department

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgements

Heart Lung

J Pediatr

Chest

Ann Emerg Med

J Emerg Med

Chest

Therapeutic use of helium

JAMA

Effect of helium-oxygen on airflow in narrowed airways

Arch Surg

Original contribution
Prospective randomized trial of heliox-driven continuous nebulizers in the treatment of asthma in the emergency department