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Three Part Question

In [patients with acute COPD] does [the administration of heliox] improve [survival, Peak flow, reduce time in hospital or reduce the need for mechanical ventilation]?

Clinical Scenario

A 45 year old male smoker attends the Emergency department with exacerbation of COPD. Repeated doses of nebulised Salbutamol and Ipratropium Bromide has been administered and Aminophyllin infusion has been commenced. You feel that the patient will require intubation and ventilation. You have got access to Heliox and you feel that it might improve the condition of the patient and might avoid intubation. Is there any evidence to support use of Heliox in such situation?

Search Strategy

Medline (1951 to date) Embase (1974 to date)
Using the Dialog Datastar web (Athens) search terms heliox, oxygen and chronic obstructive pulmonary disease – HELIUM#.W..DE., OXYGEN#.W..DE. and PULMONARY-DISEASE-CHRONIC-OBSTRUCTIVE#.DE.
Dialog Datastar web (Athens) search terms [HELIUM#.W..DE., OXYGEN#.W..DE. and PULMONARY-DISEASE-CHRONIC-OBSTRUCTIVE#.DE.]-
Cochrane Library: Heliox
Reference review: A search of references from articles found by electronic searching was done.
BOC Medical Group: (manufacturer firm for Heliox) was contacted. No new articles found.

Search Outcome

Altogether 35 articles were found, of which 9 were relevant to the clinical question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Andrews R et al, 2004 UK	185 patients in Medical ICU, ED, ward and Respiratory outpatient	Meta-analysis: Diverse settings- Search strategy: Embase and Medline database from 1966 to 2002 using Ovid and Athens interphase. Citation taken from publications. BOC medical 8 studies were included Quality assessment- by Method of Jadad and Chalmers scale	Outcome measures-Decrease in partial pressure of arterial PCO2 and intubation rates.Analysis excluding all papers with low methodological quality (Jadad <2) Etimated reduction in PaCO2 in heliox group was 0.22 kPa (+0.57 to -0.14, p=0.2)Odd ratio of intubation was 0.096 (0.03 to 0.27)- 82% reduction in risk.	Definitive beneficial evidence of heliox is lacking	8 studies were included in this meta-analysis. Quality assessments were done by method of the Jadad and Chalmers scales. Using quantitative and qualitative measures of validity author found that most trials were unsatisfactory; chief concerns being poor concealment of allocation and lack of blinding. Analysis after excluding all papers with low methodological quality (Jadad <2) revealed that definitive evidence of a beneficial role of heliox in treatment of severe COPD is lacking and therefore its wide scale use can not be recommended based on this analysis.
G Rodrigo et al, 2001	Adults >18 years of age with clinical diagnosis of COPD experiencing an exacerbation of their COPD, presenting to emergency rooms or other acute care settings. All patients were treated with either helium:oxygen or air:oxygen administered in random order.	Systematic review	primary outcome- changes in peak expiratory flow and FEV1,	No significant differences in the change of FEV1, PEF & FVC	Conclusion in this systematic review is based on review of only two papers
			Physiological measures	PaO2 increased with both gases, but PaCO2 decreased more with heliox
			symptoms & signs/symptom score (Dyspnoea score)	dyspnoea score decreased more with heliox, no clinical outcome data available
Jolliet P et al, 2003 Switzerland	123 consecutively admitted patients with dcompensated COPD over 24 months period patients for NIV in ICU of 3 University Hospitals. Intervention- NIV with either He/oxygen or air/oxygen for 30 minutes Additional trail if any of the following: RR >30/min PaO2 <8kPa PaCO2>8kPa Intubated if resp arrest, severe resp distress, impaired consciousness, agitation or CVS collapse Mean duration of trial102± 228 minutes	Prospective randomised multicentre study (Patients partially blinded) Jadad score 2.	Intubation rate	air/O2 20% vs. He/O2 13%	The patients were blinded but investigators were not: due to considerable technical difficulties. Even though ITU discharge followed the practice guidelines, no such guidelines were present for discharge of patients from the hospital. NIPSV was not strictly protocol led, nor were mechanical ventilation and weaning in intubated patients. The study does not mention how randomisation was carried out.
			Length of stay in ITU post-ITU hospital stay	ITU stayair/O2 6.25± 5.5 vs. He/O2 5.1± 4 days
			post-ITU hospital stay	air/O2 19± 12 vs. He/O2 13± 6days
			Total hospitalization cost	lower by $3,348 per patient with He/O2
Diedl JL et al, 2003	13 patients over 1 year in two medical ICU were evaluated just before and after extubation. Heiox and air/O2 were administered sequentially in randomised order, for 20 minutes each, just before extubation. The study was repeated after extubation in 5 patients.	Prospective randomised cross-over study Jadad score 1	Work of breathing	Heliox reduced work of breathing from 1.442±0.718 joules/L to 1.133±0.5 joules/L (p <0.05)	The methodological quality is low (Jadad = 1). The size of sample is not sufficient (13 patients over one year). comparison after extubation was possible only in 5 patients (out of 13)
			PEEPi (intrinsic positive end expiratory pressure)	Slight reduction in PEEPi from 2.9±2.1 cm water to 2.1±1.8 cm water(p<0.05)
Gerbeaux P et al, 2001	81 patients with exacerbation of COPD over 18 months in Emergency department. intervention- Heliox was administered by using tight fitting mask at 10 l/min with supplemental oxygen. In the standard group only oxygen was administered.	Retrospectivecase note review with historical control group	Intubation rate	Significant decrease in intubation rate (50 vs 8%)	Conclusions made from retrospective studies. Lack of blinding. Lack of data on concerning patients receiving heliox therapy. The type of intervention the patient received was decided by the treating emergency physician with varying skills, without any standardized protocol. There were only 3 out of 7 clinicians in the department who favoured the use of heliox.
			Mortality	Significant decrease in mortality rate (24 vs 3%).
			ICU stay & In-hospital stay.	Significant decrease in ICU stay(8+/- 4 vs 18+/- 12 days) and In-hospital stay(11+/-7 vs 17+/-13 days) for survivors in the heliox group.
Jaber S et al, 2000 France	10 patients in Medical ICU having recent exacerbation of COPD with either tachypnoea acidosis or hypoxia- NIV. Intervention- NIV with 15-25 cm H2O PS, breathing air:oxygen then 78:22 heliox for 20 min, measurements were made in final final 5 min of treatment.	Prospective randomised cross-over study Single blind (patient) No details of allocation sequence generation or concealment. Jadad score 2	Gas exchange	PaCO2 fell by 2 mm Hg without oxygenation being affected	No details of allocation sequence generation or concealment has been described. There was no blinding of the clinicians or statisticians. Size of study is small (10 patients, out of which one withdrew his consent).
			Work of breathing and Effort of breathing (respiratory muscle pressure-time index)	Significant reduction
deBoisblanc BP et al, 2000 USA	Convenience sample of 47 normoxic patients with acute exacerbation of COPD in ED- randomised for treatment. Intervention: Nebuliser treatments using heliox or compressed air were administered at 0, 20, 40 and 120 minutes after randomisation. Spirometry was performed immediately before the first nebulizer and 1 & 2 hours later	Prospective randomised case control study Jadad score 2	Early changes in spirometry	No significant differences in the change of FEV1 and FVC between the two groups by either 1 or 2 hours point.	Randomised allocation of treatment on a convenience sample of 50 normoxic patients presenting to ED, from a pool of approximately 250 patients. Its methodological quality was low (Jadad score = 2) and it did not report concealment allocation. The most common cause for exclusion from the study was the non-availability of one of the investigators (approx. 120 patients).
Tassaux D et al, 2000 Switzerland	23 sedated, paralysed and mechanically ventilated patients in medical ICU. Out of 25 eligible patients 2 were excluded because they could not be consented Intervention- Intubated and ventilated patients were administered He-O2 for 45 minutes Obs were recorded at baseline, after 45 min with He-O2 and then 45 min after return to air-O2. the results were compared to those obtained in a test lung model using the same ventilator settings.	Prospective interventional study Non-randomised. No blinding Jadad score 1	Trapped ling vol.	Decrease- 215 ±125 ml vs. 99 ±15 ml (p<0.05)	The strength of evidence is poor. Attempts for blinding and randomisation are not mentioned, The method of treatment has not been properly described. Some patients were receiving excessive tidal volumes and respiratory rates. These patients had been intubated for surgery rather than for acute respiratory failure. Hence the severity of obstruction might have been less.
			Intrinsic PEEP	decrease- 9 ±2.5 cm vs. 5 ±2.7 cm of H2O (p<0.05)
			Peak airway pressure	decline 30 ±5 cm vs. 25 ±6 cm of H2O (p<0.05)
			Mean airway pressure	decline 8±2 cm vs. 7±2 cm of H2O (p<0.05)
			ABG, heart rate or mean systemic arterial BP	No change
Jolliet P et al, 1999 Switzerland	19 patients with severe COPD (FIV1 of 0.83± 0.3 l) in intensive care unit for NIV after initial stabilization with NIV for no more than 24 hrs after ICU admission. Out of 25 eligible paients 5 were excluded (3 required an FiO2 >0.3 and 2 were intubated), Technical problem with data of one patient.	Prospective randomised cross-over study Single blinded Jadad score 3	Dyspnoea and PaCO2	NIV with heliox reduced dyspnoea and PaCO2 more than air:oxygen-	No concealment allocation. Study was performed in the absence of acute respiratory failure. All invasive techniques were prohibited by the ethical committee so work of breathing could not be determined .
Harrison P et al, 1995	10 patients with acute exacerbation of COPD in ICU. Intervention: 70:30 heliox breathing compared with air:oxygen in addition to conventional treatment.	Non-randomised & non-blinded crossover study Jadad score 1	PaCO2 (ABG)	52 v 44 mm Hg decrease in PaCO2 in heliox group but also fall in PaO2 129 to 73 mm Hg	No indication of duration of treatment No details on statistical analysis
Swidwa D et al, 1985	15 male volunteer patients in Respiratory outpatient with stable but severe COPD. Intervention: 80:20 heliox breathing for 15 minutes compared with baseline air-oxygen breathing	Non-randomised & non-blinded crossover study Jadad score 1	PaCO2 (ABG)	Reduction of PaCO2 of 2 mm Hg	Low quality study Non-randomised & non-blinded Effect of heliox breathing in stable severe COPD

Comment(s)

The physical properties of heliox become increasingly similar to those of air-oxygen mixture when the concentration of oxygen exceeds 40%. The cost of heliox is significant. Most trials are unsatisfactory; chief concerns being poor concealment of allocation and lack of blinding.

Clinical Bottom Line

There is not enough evidence available from high quality studies dealing with NIV-Heliox in acute exacerbation of COPD patients to support the use of heliox to treat acute exacerbation of COPD in either ventilated or non-ventilated patients. Indeed, the clinical studies have actually shown that heliox does not really benefit more than air: oxygen mixture in decompensated COPD patients. Use of heliox increases the cost of treatment as well. Therefore, Heliox should not be used routinely in the management of acute COPD unless further strong evidence suggests its clinical benefit in acute COPD.

References

1. Andrews R, Lynch M. Heliox in the treatment of chronic obstructive pulmonary disease. Emergency Medical Journal, Nov 2004, vol. 21, no. 6, p. 670-5, ISSN: 1472-0213.
2. G Rodrigo, C Pollack, C Rodrigo, B Rowe, EH Walters Heliox for treatment of exacerbations of chronic obstructive pulmonary disease Cochrane Database of Systematic Reviews 2001, 2001, Issue 1. Art. No.: CD003571. DOI: 10.1002/14651858.CD003571.
3. Jolliet P, Tassaux D, Roeseler J, Burdet L, et al. Helium-oxygen versus air-oxygen noninvasive pressure support in decompensated chronic obstructive disease: A prospective multi-center study. Critical Care Medicine Mach 2003, Vol. 31, no. 3, page 878-84, ISSN: 0090-3493.
4. Diedl JL, Mercat A, et al. Helium/oxygen mixture reduces the work of breathing at the end of the weaning process in patients with severe chronic obstructive pulmonary disease. Critical Care Medicine May 2003, vol. 31, no. 5, p. 1415-20, ISSN: 0090-3493.
5. Gerbeaux P, Gainnier M, et al. Use of heliox in patients with severe exacerbation of chronic obstructive pulmonary disease. Critical Care Medicine Dec 2001, vol. 29, no. 12, p. 2322-4, ISSN: 0090-3493.
6. Jaber S, Fodil R, Carlucci A, Boussarsar M, et al. Noninvasive ventilation with Helium-oxygen in acute exacerbation of chronic obstructive pulmonary disease. Am J Resp Crit Care Med 2000, vol. 161, p 1191-1200.
7. deBoisblanc BP, DeBleiux P, et al. Randomized trial of the use of heliox as a driving gas for updraft nebulization of bronchodilators in the emergent treatment of acute exacerbation of chronic obstructive pulmonary disease. Critical Care Medicine May 2003, vol. 31, no. 5, p. 1415-20, ISSN: 0090-3493.
8. Tassaux D, Jolliet P, Roeseler J, Chevrolet JC. Effects of Helium-oxygen on intrinsic positive end-expiratory pressure in intubated and mechanically ventilated patients with severe chronic obstructive pulmonary disease. Critical Care Medicine August 2000, vol. 28, no. 8, p. 2721-8, ISSN: 0090-3493.
9. Jolliet P, Tassaux D, Thouret JM, Chevrolet JC Beneficial effects of Helium :oxygen versus air :oxygen noninvasive pressure support in patients with decompensated chronic obstructive pulmonary disease. Critical Care Medicine Nov 1999, vol. 27, no.11, p 2422-9, ISSN: 0090-3493.
10. Harrison P, Onorato D. The clinical effects of Helium-oxygen mixtures on gas exchange in exacerbation of COPD. Chest 1995;108:156s.
11. Swidwa D, Montenegro H, Goldman M, et al Helium-oxygen breathing in severe COPD Chest 1985;87:790-6.