Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis

Abstract

Objectives: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). Data Sources: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. Study Selection: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. Data Extraction: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. Data Synthesis: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 μg/kg (range, 30–232.7 μg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5–525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0–0.92), tachycardia 0.26 (range, 0.0–0.87), and agitation 0.26 (range, 0.09–0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, –0.47; p = 0.048) and tachycardia (correlation coefficient, –0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. Conclusions: On review of the 2000–2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.