TY - JOUR
T1 - Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units
T2 - A Randomized Clinical Trial
AU - Blackwood, Bronagh
AU - Tume, Lyvonne N.
AU - Morris, Kevin P.
AU - Clarke, Mike
AU - McDowell, Clíona
AU - Hemming, Karla
AU - Peters, Mark J.
AU - McIlmurray, Lisa
AU - Jordan, Joanne
AU - Agus, Ashley
AU - Murray, Margaret
AU - Parslow, Roger
AU - Walsh, Timothy S.
AU - MacRae, Duncan
AU - Easter, Christina
AU - Feltbower, Richard G.
AU - McAuley, Daniel F.
N1 - Funding Information:
Funding/Support: This trial (HTA 15/104/01) was commissioned and funded by the National Institute for Health Research and supported by the Paediatric Critical Care Society Study Group. The Queen’s University Belfast took legal responsibility for all aspects of the research but did not provide specific funding.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/8/3
Y1 - 2021/8/3
N2 - 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.
AB - 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.
KW - Airway Extubation
KW - Child
KW - Child, Preschool
KW - Duration of Therapy
KW - Female
KW - Humans
KW - Hypnotics and Sedatives/therapeutic use
KW - Infant
KW - Intensive Care Units, Pediatric
KW - Length of Stay
KW - Male
KW - Respiration, Artificial
KW - Ventilator Weaning/methods
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UR - http://www.scopus.com/inward/citedby.url?scp=85112041462&partnerID=8YFLogxK
U2 - 10.1001/jama.2021.10296
DO - 10.1001/jama.2021.10296
M3 - Article (journal)
C2 - 34342620
AN - SCOPUS:85112041462
SN - 0098-7484
VL - 326
SP - 401
EP - 410
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 5
ER -