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

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.