Abstract
BACKGROUND: Daily assessment of patient readiness for liberation from invasive mechanical ventilation can reduce the duration of ventilation. However, there is uncertainty about the effectiveness of this in a paediatric population.
OBJECTIVES: To determine the effect of a ventilation liberation intervention in critically ill children who are anticipated to have a prolonged duration of mechanical ventilation (primary objective) and in all children (secondary objective).
DESIGN: A pragmatic, stepped-wedge, cluster randomised trial with economic and process evaluations.
SETTING: Paediatric intensive care units in the UK.
PARTICIPANTS: Invasively mechanically ventilated children (aged < 16 years).
INTERVENTIONS: The intervention incorporated co-ordinated multidisciplinary care, patient-relevant sedation plans linked to sedation assessment, assessment of ventilation parameters with a higher than usual trigger for undertaking an extubation readiness test and a spontaneous breathing trial on low levels of respiratory support to test extubation readiness. The comparator was usual care. Hospital sites were randomised sequentially to transition from control to intervention and were non-blinded.
MAIN OUTCOME MEASURES: The primary outcome measure was the duration of invasive mechanical ventilation until the first successful extubation. The secondary outcome measures were successful extubation, unplanned extubation and reintubation, post-extubation use of non-invasive ventilation, tracheostomy, post-extubation stridor, adverse events, length of intensive care and hospital stay, mortality and cost per respiratory complication avoided at 28 days.
RESULTS: The trial included 10,495 patient admissions from 18 paediatric intensive care units from 5 February 2018 to 14 October 2019. In children with anticipated prolonged ventilation (n = 8843 admissions: control, n = 4155; intervention, n = 4688), the intervention resulted in a significantly shorter time to successful extubation [cluster and time-adjusted median difference -6.1 hours (interquartile range -8.2 to -5.3 hours); adjusted hazard ratio 1.11, 95% confidence interval 1.02 to 1.20; p = 0.02] and a higher incidence of successful extubation (adjusted relative risk 1.01, 95% confidence interval 1.00 to 1.02; p = 0.03) and unplanned extubation (adjusted relative risk 1.62, 95% confidence interval 1.05 to 2.51; p = 0.03), but not reintubation (adjusted relative risk 1.10, 95% confidence interval 0.89 to 1.36; p = 0.38). In the intervention period, the use of post-extubation non-invasive ventilation was significantly higher (adjusted relative risk 1.22, 95% confidence interval 1.01 to 1.49; p = 0.04), with no evidence of a difference in intensive care length of stay or other harms, but hospital length of stay was longer (adjusted hazard ratio 0.89, 95% confidence interval 0.81 to 0.97; p = 0.01). Findings for all children were broadly similar. The control period was associated with lower, but not statistically significantly lower, total costs (cost difference, mean £929.05, 95% confidence interval -£516.54 to £2374.64) and significantly fewer respiratory complications avoided (mean difference -0.10, 95% confidence interval -0.16 to -0.03).
LIMITATIONS: The unblinded intervention assignment may have resulted in performance or detection bias. It was not possible to determine which components were primarily responsible for the observed effect. Treatment effect in a more homogeneous group remains to be determined.
CONCLUSIONS: The intervention resulted in a statistically significant small reduction in time to first successful extubation; thus, the clinical importance of the effect size is uncertain.
FUTURE WORK: Future work should explore intervention sustainability and effects of the intervention in other paediatric populations.
TRIAL REGISTRATION: This trial is registered as ISRCTN16998143.
FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 18. See the NIHR Journals Library website for further project information.
| Original language | English |
|---|---|
| Pages (from-to) | 1-114 |
| Number of pages | 114 |
| Journal | Health Technology Assessment |
| Volume | 26 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - 31 Mar 2022 |
Bibliographical note
Funding Information:Declared competing interests of authors: Ashley Agus is a member of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) General Committee (2021 to present). Mike Clarke is a former member of the NIHR Funding Board for the Complex Reviews Research Support Unit (2014), NIHR HTA Funding Committee (General) (2016–19), and member of the HTA Prioritisation Committee: Hospital Based Care (B) Methods Group (2019 to present). Mark J Peters is a member of the HTA General Committee (2018 to present). Lyvonne N Tume is a member of the HTA General Committee (2020 to present) and a former member of the HTA Maternal, Neonatal and Child Health Panel and the HTA Prioritisation Committee C (mental health, women and children’s health) (2013–19). Daniel F McAuley is a member of the Efficacy and Mechanism Evaluation (EME) Strategy Advisory Committee, the EME Funding Committee Members, and the EME Funding Committee Sub-Group Remit and Comp Check (2019 to present), and is a former member of the NIHR and UK Research and Innovation COVID-19 Reviewing Committee (2020) and HTA General Committee (2016–18) and Commissioning Committee (2013–16). He also reports personal fees from consultancy for GlaxoSmithKline (Brentford, UK), Boehringer Ingelheim (Ingelheim am Rhein, Germany), Bayer (Leverkusen, Germany), Novartis (Basel, Switzerland) and Eli Lilly (Indianapolis, IN, USA) and from sitting on a Data Monitoring and Ethics Committee for a trial undertaken by Vir Biotechnology (San Francisco, CA, USA). In addition, his institution has received funds from grants from the NIHR, Wellcome Trust, Innovate-UK, the Medical Research Council and the Northern Ireland Health and Social Care Research and Development Division. He has a patent issued to his institution for a treatment for acute respiratory distress syndrome and is a Director of Research for the Intensive Care Society (2009–20) and NIHR EME Programme Director (2019 to present).
Funding Information:
W e wish to thank the NIHR HTA programme for funding the trial. We acknowledge the contribution of Dr Claire Kydonaki to the process evaluation.
Funding Information:
The trial was sponsored by Queen’s University Belfast, Belfast, UK. Ethics approval was granted by the National Research Ethics Committee East Midlands. The trial was co-ordinated by the Northern Ireland Clinical Trials Unit and was managed by a Trial Management Group. Independent oversight was provided through a Trial Steering Committee and a Data Monitoring Committee.
Funding Information:
The research reported in this issue of the journal was funded by the HTA programme as project number 15/104/01. The contractual start date was in April 2017. The draft report began editorial review in December 2020 and was accepted for publication in May 2021. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.
Publisher Copyright:
© 2022 Blackwood et al.
Keywords
- Airway Extubation
- Child
- Cost-Benefit Analysis
- Humans
- Intensive Care Units, Pediatric
- Noninvasive Ventilation
- Respiration, Artificial
- Ventilator Weaning/methods
ASJC Scopus subject areas
- Health Policy