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

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.

Figure 1.. Selection of Pediatric Intensive Care Units (ICUs) and Enrollment of Patients in a Stepped-Wedge, Cluster Randomized Trial of a Sedation and Ventilator Liberation Protocol Intervention in Infants and Children

IQR indicates interquartile range. ^aOne hospital site had 2 pediatric ICUs that were randomized together to avoid contamination of the intervention. ^bDiagnostic codes associated with a short duration of ventilation (<24 hours) were categorized as short and all others were categorized as prolonged. ^cThere were 3 patients excluded from the analysis because they could not be linked to the Paediatric Intensive Care Audit Network data set.

Figure 2.. Probability and Time to Successful Extubation by Observation Period in the Prolonged Invasive Ventilation Cohort

The hazard ratio (95% CI) and the median difference (interquartile range) were adjusted for cluster and calendar time. Patients were observed from initiation of ventilation until the first successful extubation (defined as still breathing spontaneously for 48 hours after extubation). The curves on the graph were created using adjusted data. The No. at risk are the absolute patient numbers and therefore will not match precisely with the covariate-adjusted curve.