Co-ordinated multidisciplinary intervention to reduce time to successful extubation for children on mechanical ventilation: the SANDWICH cluster stepped-wedge RCT.

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.

Mechanical ventilation is a life-saving therapy, but may involve related risks because of the breathing tube in the mouth and throat, the sedative drugs required to reduce anxiety and remaining confined to bed. Therefore, getting off the ventilator (called weaning) is an important patient outcome. Previous studies have shown that an organised approach involving nurses, doctors and physiotherapists reduces the time that patients spend on the ventilator. Our study involved more than 10,000 patients admitted to 18 children's intensive care units. We tested a co-ordinated staff approach for managing a child's sedation and ventilator needs against usual care, which was mainly consultant led and did not involve bedside nurses. We wanted to find out if this approach improved the outcomes for children and did not cause additional harm. We first collected information in the intensive care units when children were weaned from the ventilator using usual care. Following staff training in the new approach, we compared children's outcomes between the two approaches. Compared with usual care, the new approach reduced the time that children spent on the ventilator by between 5 and 9 hours, and increased children's chances of having their breathing tube removed successfully. Some children pulled out their breathing tubes themselves before it was medically planned to do so. This happened more with the new approach, but the chance of needing the breathing tube put back in was not different from usual care. With the new approach, more children needed to use a mask ventilator than those receiving usual care, although the length of time that this was required was not different from usual care. The intensive care length of stay was the same for children receiving the new approach and usual care. However, with the new approach, children stayed in hospital 1 day longer, which resulted in higher costs (£715 per child); thus, the clinical relevance is uncertain.

A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial.

BACKGROUND: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. METHODS: This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. DISCUSSION: This trial's pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE. TRIAL REGISTRATION: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018. Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01). SPONSOR: Belfast Health and Social Care Trust. Ethics Reference Number: 17/NE/0339. Protocol version: v3.0 Final_14052018.

Sedation AND Weaning In Children (SANDWICH): protocol for a cluster randomised stepped wedge trial.

INTRODUCTION: Weaning from ventilation is a complex process involving several stages that include recognition of patient readiness to begin the weaning process, steps to reduce ventilation while optimising sedation in order not to induce distress and removing the endotracheal tube. Delay at any stage can prolong the duration of mechanical ventilation. We developed a multicomponent intervention targeted at helping clinicians to safely expedite this process and minimise the harms associated with unnecessary mechanical ventilation. METHODS AND ANALYSIS: This is a 20-month cluster randomised stepped wedge clinical and cost-effectiveness trial with an internal pilot and a process evaluation. It is being conducted in 18 paediatric intensive care units in the UK to evaluate a protocol-based intervention for reducing the duration of invasive mechanical ventilation. Following an initial 8-week baseline data collection period in all sites, one site will be randomly chosen to transition to the intervention every 4 weeks and will start an 8-week training period after which it will continue the intervention for the remaining duration of the study. We aim to recruit approximately 10 000 patients. The primary analysis will compare data from before the training (control) with that from after the training (intervention) in each site. Full details of the analyses will be in the statistical analysis plan. ETHICS AND DISSEMINATION: This protocol was reviewed and approved by NRES Committee East Midlands-Nottingham 1 Research Ethics Committee (reference: 17/EM/0301). All sites started patient recruitment on 5 February 2018 before randomisation in April 2018. Results will be disseminated in 2020. The results will be presented at national and international conferences and published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: ISRCTN16998143.