Daily Sedation Interruption vs Continuous Sedation in Pediatric Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis

Abstract

Importance: The effectiveness of daily sedation interruption (DSI, defined as temporary interruption of sedation) has yet to be demonstrated in critically ill pediatric patients.

Objective: To compare the clinical outcomes of DSI vs continuous intravenous (IV) sedation in patients receiving invasive mechanical ventilation (MV) support in the pediatric intensive care unit (PICU).

Data sources: A systematic search for studies was conducted using predefined keywords and Medical Subject Headings in 5 major databases (PubMed, Embase, Web of Science, CINAHL [Cumulated Index to Nursing and Allied Health Literature], and Cochrane Central Register of Controlled Trials) from database inception to October 31, 2023.

Study selection: Retrospective and prospective observational studies, randomized clinical trials (RCTs), and systematic reviews were assessed for inclusion. Studies were eligible if they compared DSI to continuous IV sedation in patients aged 18 years or younger requiring MV in the PICU.

Data extraction and synthesis: Study characteristics, including the types of sedation, sedation protocols, and clinical outcomes, were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. A random-effects model was used to pool results from articles for the meta-analysis.

Main outcomes and measures: The primary outcomes of interest were duration of MV and length of PICU stay. Secondary outcomes included total sedative dose requirement, adverse events (eg, complications associated with MV, withdrawal, and delirium), and mortality.

Results: A total of 6 RCTs with 2810 pediatric patients (1569 males [55.8%]; mean age, 26.5 [95% CI, 15.0-37.9] months) were included in the final analysis; patients had a mean PRISM (Pediatric Risk of Mortality) score of 13.68 (95% CI, 10.75-16.61). Compared with continuous IV sedation, DSI was associated with a reduction in length of PICU stay (5 studies, n = 2770; mean difference [MD], -1.45 [95% CI, -2.75 to -0.15] days; P = .03]. There was no difference in MV duration (5 studies, n = 2750; MD, -0.93 [95% CI, -1.89 to 0.04] days; P = .06), total doses of midazolam (3 studies, n = 191; MD, -1.66 [95% CI, -3.95 to 0.63] mg/kg) and morphine used (2 studies, n = 189; MD, -2.63 [95% CI, -7.01 to 1.75] mg/kg), or adverse events (risk ratio [RR], 1.03 [95% CI, 0.74-1.42]; P = .88). There was no difference in mortality between patients exposed vs not exposed to DSI (RR, 0.89 [95% CI, 0.55-1.46]; P = .65).

Conclusions and relevance: This systematic review and meta-analysis found that use of DSI in pediatric patients was associated with reduced length of PICU stay with no increase in adverse events. Further research is needed to ascertain whether this strategy is associated with improved neurodevelopmental outcomes in PICU survivors.

Figure 1.. Systematic Review Study Selection PRISMA Flowchart

Figure 2.. Duration of Mechanical Ventilation in Daily Sedation Interruption (DSI) vs Continuous Intravenous (IV) Sedation

Square data marker sizes represent the weight of the study; error bars indicate 95% CIs. NA indicates not applicable.

Figure 3.. Length of Intensive Care Unit Stay in Daily Sedation Interruption (DSI) vs Continuous Intravenous (IV) Sedation

Square data marker sizes represent the weight of the study; error bars indicate 95% CIs. NA indicates not applicable.

Figure 4.. Risk of Bias Across All Included Studies as Assessed by Independent Reviewers