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Ranjit Lall, Patrick Hamilton, Duncan Young, Claire Hulme, Peter Hall, Sanjoy Shah, Iain MacKenzie, William Tunnicliffe, Kathy Rowan, Brian Cuthbertson, Chris McCabe, Sallie Lamb & .

Ranjit Lall 1, Patrick Hamilton 2, Duncan Young 3,4,*, Claire Hulme 2, Peter Hall 2, Sanjoy Shah 5, Iain MacKenzie 6, William Tunnicliffe 6, Kathy Rowan 7, Brian Cuthbertson 8, Chris McCabe 2, Sallie Lamb 1,

1 Warwick Clinical Trials Unit, University of Warwick, Warwick, UK
2 University of Leeds, Leeds, UK
3 John Radcliffe Hospital, Oxford, UK
4 University of Oxford, Oxford, UK
5 Bristol Royal Infirmary, Bristol, UK
6 Queen Elizabeth Hospital, Birmingham, UK
7 Intensive Care National Audit & Research Centre, London, UK
8 Sunnybrook Health Sciences Centre, Toronto, ON, Canada
* Corresponding author Email: duncan.young@nda.ox.ac.uk

Funding: {{metadata.Funding}}

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Abstract

BACKGROUND

Patients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage.

OBJECTIVES

To determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation.

DESIGN

A parallel, randomised, unblinded clinical trial.

SETTING

UK intensive care units.

PARTICIPANTS

Mechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment.

INTERVENTIONS

Treatment armâ HFOV using a Novalung R100(®) ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning. Control armâ Conventional mechanical ventilation using the devices available in the participating centres.

MAIN OUTCOME MEASURES

The primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained.

RESULTS

One hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) -6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40; p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £ 78,260.

CONCLUSIONS

The use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN10416500.

Abstract

BACKGROUND

Patients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage.

OBJECTIVES

To determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation.

DESIGN

A parallel, randomised, unblinded clinical trial.

SETTING

UK intensive care units.

PARTICIPANTS

Mechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment.

INTERVENTIONS

Treatment armâ HFOV using a Novalung R100(®) ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning. Control armâ Conventional mechanical ventilation using the devices available in the participating centres.

MAIN OUTCOME MEASURES

The primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained.

RESULTS

One hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) -6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40; p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £ 78,260.

CONCLUSIONS

The use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN10416500.

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