Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units
Authors: Bronagh Blackwood, Lyvonne N. Tume, Kevin P. Morris, Mike Clarke, Clíona McDowell, Karla Hemming, Mark J. Peters, Lisa McIlmurray, Joanne Jordan, Ashley Agus, Margaret Murray, Roger Parslow, Timothy S. Walsh, Duncan Macrae, Christina Easter, Richard G. Feltbower, Daniel F. McAuley, Nazima Pathan, Deborah White, Esther Daubney, Ben Lakin, Laura Rad, Dawn Jones, Laura O'Malley, Sean Cuddihy, Alex Taylor, Jaspreet Sodhi, Katie Price, Rachel Loughead, Mireia Garcia Cusco, Sarah Mogan, Kate Baptiste, Helen Marley, Hope Lacy, Chris MacKerness, Rachel Agbecko, Angela Woodhall, Lindsay Cooper, Dawn Metcalfe, Suzan Kakat, Lauran O'Neill, Holly Belfield, Ana Luisa Tomas, Francesca Standing, Yvonne Leonard, Helen Vander-Johnson, Deirdre O'Shea, Kirsten Beadon, Nicola Howell, Pam D'Silva, Sam Archer, Stacey Bedford, Jo Lumsden, Louise Turner, Heather Rostron, Donna Ellis, Sarah Hanson, Emily Scriven, Julie Armstrong, Siva Oruganti, Iona Buchanan, Claire Speirs, Julie Richardson, Caroline McCluskey, Becky Simpson, Carolyn Green, Rachel Anderson, Angela Aramburo, Helena Sampaio, Laura Alcantara, Laura Tous, John Alexander, Penny Percical, Claire Sidley, Rum Thomas, Samantha Burns, Jade Bryant, Amy Pickard, John Pappachan, Christie Mellish, Soumendu Manna, Elena Maccacari, Joana Queiroz, Sian Butler, David Inwald, Thomas Bycroft, Sarah Darnell
Journal: JAMA (2021)

There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit.To determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation.A pragmatic multicenter, stepped-wedge, cluster randomized clinical trial was conducted that included 17 hospital sites (18 pediatric intensive care units) in the UK sequentially randomized from usual care to the protocol intervention. From February 2018 to October 2019, 8843 critically ill infants and children anticipated to require prolonged mechanical ventilation were recruited. The last date of follow-up was November 11, 2019.Pediatric intensive care units provided usual care (n = 4155 infants and children) or a sedation and ventilator liberation protocol intervention (n = 4688 infants and children) that consisted of assessment of sedation level, daily screening for readiness to undertake a spontaneous breathing trial, a spontaneous breathing trial to test ventilator liberation potential, and daily rounds to review sedation and readiness screening and set patient-relevant targets.The primary outcome was the duration of invasive mechanical ventilation from initiation of ventilation until the first successful extubation. The primary estimate of the treatment effect was a hazard ratio (with a 95% CI) adjusted for calendar time and cluster (hospital site) for infants and children anticipated to require prolonged mechanical ventilation.There were a total of 8843 infants and children (median age, 8 months [interquartile range, 1 to 46 months]; 42% were female) who completed the trial. There was a significantly shorter median time to successful extubation for the protocol intervention compared with usual care (64.8 hours vs 66.2 hours, respectively; adjusted median difference, -6.1 hours [interquartile range, -8.2 to -5.3 hours]; adjusted hazard ratio, 1.11 [95% CI, 1.02 to 1.20], P = .02). The serious adverse event of hypoxia occurred in 9 (0.2%) infants and children for the protocol intervention vs 11 (0.3%) for usual care; nonvascular device dislodgement occurred in 2 (0.04%) vs 7 (0.1%), respectively.Among infants and children anticipated to require prolonged mechanical ventilation, a sedation and ventilator liberation protocol intervention compared with usual care resulted in a statistically significant reduction in time to first successful extubation. However, the clinical importance of the effect size is uncertain.isrctn.org Identifier: ISRCTN16998143.