Title: Sedation and weaning in children: the SANDWICH trial
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: DESIGN: Cluster-randomised stepped wedge clinical and cost-effectiveness trial with an internal pilot and a process evaluation. SETTING: PICUs in the UK with a case mix typical of UK critical care practice. TARGET POPULATION: Invasively mechanically ventilated children admitted to UK PICUs. HEALTH TECHNOLOGY BEING ASSESSED: A protocol-based intervention incorporating co-ordinated care with greater nursing involvement; patient-relevant sedation plans linked to regular assessment using the COMFORT sedation tool; regular assessment of ventilation parameters with a higher than usual trigger for undertaking an extubation readiness test; a spontaneous breathing trial (SBT) on low levels of respiratory support to test extubation readiness. COMPARATOR: Usual care that is non-protocol-based and primarily medically-driven. Sedation levels are assessed using the COMFORT tool. Ventilator weaning generally involves slow, gradual reduction of pressure support to very low levels to test readiness for extubation. MEASUREMENT OF COSTS AND OUTCOMES: The primary outcome is duration of IMV. Secondary outcomes are: accidental self-extubations; extubation failures; reintubation; post-extubation use of non-invasive ventilation; any adverse events (e.g. unplanned removal of any invasive tube, post-extubation stridor); new tracheostomy; PICU and hospital length of stay; mortality (PICU and hospital); cost/life-year saved at 28-days; cost/adverse event avoided at 28-days. Outcomes will be measured from patient admission to discharge or maximum 28-days after the trial ends. The process evaluation will evaluate dose, fidelity and reach of the intervention, acceptability of staff delivering the intervention and factors promoting sustainability. HEALTH ECONOMIC EVALUATION: A within-trial economic evaluation will be undertaken to measure cost-effectiveness of the intervention with standard care. The perspective of the analysis will be the hospital. The incremental cost-effectiveness ratio (ICER) is a measure of the additional cost per additional unit of effect produced by one intervention compared with another. We will calculate two ICERs; the cost per life year saved and cost per adverse event avoided at 28-days. SAMPLE SIZE: Using data from the Paediatric Intensive Care Audit Network (PICANet) (2011-13) the mean number of eligible children admitted/month/site is 53, average time to extubation is 5.5 days and Intra-cluster Correlation Coefficient (ICC) is estimated to be 0.007 (95% CI 0.001, 0.01). Using power calculations for stepped wedge cluster trials for a survival outcome we aim to recruit 13-15 PICUs in order to have 90% power to detect a hazard ratio between 0.8 and 0.9 (0.8 equates to a reduction of 1-day in duration of ventilation). Assuming 13-15 PICUs are recruited, the study will have a total patient sample size of circa 11,024 or 14,310. PROJECT TIMETABLE: The trial duration is 36 months that includes a 9-month start-period, 20-month trial period and 7-month close-down period to allow for follow-up, cost effectiveness, data analysis and reporting. EXPERTISE IN TEAM: The team comprises multi-professionals with relevant skills to successfully conduct and complete the trial. Expertise includes: PICU clinical experience; conduct of multi-centre clinical trials, stepped wedge design and statistics; health economics; epidemiology; and ethnography.

Lay abstract: AIMS: The aims of this study are to find out if a coordinated approach using guidelines with greater involvement of nurses in getting children off the ventilator compared with usual care which is uncoordinated with no guidelines: (1) reduces duration of time spent on the ventilator; (2) reduces length of stay in the PICU and the hospital; (3) does not cause additional harm; (4) is cost effective in the NHS; and (5) is acceptable to staff delivering care and can be sustained. BACKGROUND TO THE RESEARCH: Mechanical ventilation is a common lifesaving therapy, but the longer a child remains on the ventilator, the more risk they have of developing problems because of the breathing tube in their mouth, the drugs needed to reduce anxiety and remaining immobile and confined to bed. For this reason, getting off the ventilator (called weaning) is an important patient outcome. Sedative drugs are necessary when the child is on the ventilator so the child can tolerate the breathing tube, but too much can make them sleepy and delay coming off the ventilator. In adults, studies of sedation and ventilator weaning guidelines showed they reduced the time needed on the ventilator, but there are very few studies in children. We visited 23 PICUs to see what they usually do about weaning. We found out that weaning is usually done by the doctors and occasionally some senior nurses, but they do not always wean the same way and because not everyone is involved it is often disjointed. We want to study if a coordinated approach using guidelines provides benefits, is cost effective and is acceptable and can be continued by the staff in PICU. DESIGN AND METHODS USED: This study will be done in 15 PICUs. We will include all children except those who will only need a ventilator for a very short time or those who will not come off a ventilator. From the beginning of the study until the end research nurses will collect information on the child’s length of time on the ventilator, PICU length of stay, any harms and costs. Each month, one PICU at a time will be randomly chosen and we will train the PICU staff to use the new guidelines. Then that PICU will continue to use the new guidelines until the end of the study while the others continue as they usually did until their time comes to be chosen. By the end of the study all PICUs will be using the guidelines. We will compare the information collected during the usual care period with the new guidelines period. During the study, we will check how the coordinated approach is introduced and how it is working in the PICU. To do this we will interview staff and ask their views. PATIENT AND PUBLIC INVOLVEMENT: This study idea was reviewed by parents, a 15-year old child who had been in the PICU and a young person’s group. They agreed it was important and a small number volunteered to help us with writing the information sheets, providing advice and helping us to tell parents and children about the results of the study afterwards. DISSEMINATION: When the study is completed, we will write a report explaining what we found. The report will be made publically available online on the website of the organisation funding this study. We will also publish the report in a journal that is highly regarded and read by a large number of doctors and nurses who work in PICU. In addition, we will present the findings at relevant medical and nursing conferences and we will provide a summary for support groups such as ‘Baby Steps'.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: RESPIRATORY