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Original Investigation
August 3, 2021

Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units: A Randomized Clinical Trial

Author Affiliations
  • 1Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast, Ireland
  • 2School of Health and Society, University of Salford, Manchester, England
  • 3Alder Hey Children’s NHS Trust, Liverpool, England
  • 4Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, England
  • 5Institute of Applied Health Research, University of Birmingham, Birmingham, England
  • 6Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Ireland
  • 7Northern Ireland Clinical Trials Unit, Royal Hospitals, Belfast, Ireland
  • 8University of Birmingham, Birmingham, England
  • 9Great Ormond Street Hospital, London, England
  • 10University College London, Great Ormond Street Institute of Child Health, NIHR Biomedical Research Centre, London, England
  • 11Leeds Institute for Data Analytics, School of Medicine, University of Leeds, Leeds, England
  • 12Usher Institute of Population Health Sciences, University of Edinburgh, Edinburgh, Scotland
  • 13Royal Brompton Hospital, London, England
JAMA. 2021;326(5):401-410. doi:10.1001/jama.2021.10296
Key Points

Question  Does a sedation and ventilator liberation protocol intervention reduce duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation compared with usual care?

Findings  In this stepped-wedge, cluster randomized trial that included 8843 infants and children anticipated to require prolonged mechanical ventilation, the unadjusted median time to successful extubation was 64.8 hours for those receiving the protocol intervention compared with 66.2 hours for those receiving usual care. This difference was statistically significant but smaller than had been anticipated.

Meaning  Among infants and children anticipated to require prolonged mechanical ventilation, a sedation and ventilator liberation protocol intervention resulted in a reduction in time to first successful extubation; however, the clinical importance of the effect size is uncertain.

Abstract

Importance  There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit.

Objective  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.

Design, Setting, and Participants  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.

Interventions  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.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

Trial Registration  isrctn.org Identifier: ISRCTN16998143

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