Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care: the Breathe RCT

Gavin D. Perkins, Dipesh Mistry, Ranjit Lall, Fang Gao-Smith, Catherine Snelson, Nicholas Hart, Luigi Camporota, James Varley, Coralie Carle, Elankumaran Paramasivam, Beverly Hoddell, Adam de Paeztron, Sukhdeep Dosanjh, Julia Sampson, Laura Blair, Keith Couper, Daniel McAuley, J. Duncan Young, Tim Walsh, Bronagh BlackwoodLouise Rose, Sarah E. Lamb, Melina Dritsaki, Mandy Maredza, Iftekhar Khan, Stavros Petrou, Simon Gates

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Background: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. Objective: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. Design: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis.Setting: A total of 51 critical care units across the UK. Participants: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. Interventions: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient’s condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient’s condition. Main outcome measures: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. Results: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57-351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5-297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2-11 days) vs. non-invasive weaning 1 day (IQR 0-7 days); adjusted mean difference -3.1 days, 95% CI -5.75 to -0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Conclusions: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections.

Original languageEnglish
Pages (from-to)vii-114
Number of pages114
JournalHealth technology assessment (Winchester, England)
Issue number48
Publication statusPublished - 1 Sept 2019




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