What is the level of evidence for the amnestic effects of sedatives in pediatric patients? A systematic review and meta-analyses

PLoS One. 2017 Jul 7;12(7):e0180248. doi: 10.1371/journal.pone.0180248. eCollection 2017.

Abstract

Background: Studies have suggested that benzodiazepines are amnestic drug par excellence, but when taken together, what level of evidence do they generate? Are other sedatives as amnestic as benzodiazepines? The aim of this study was to assess the level of scientific evidence for the amnestic effect of sedatives in pediatric patients who undergo health procedures.

Methods: The literature was searched to identify randomized controlled trials that evaluated anterograde and retrograde amnesia in 1-19-year-olds who received sedative drugs during health procedures. Electronic databases, including PubMed, Scopus and Cochrane Library besides clinical trial registries and grey literature were searched. Two independent reviewers performed data extraction and risk of bias assessment using the Cochrane Collaboration's Tool. The meta-analyses were performed by calculating relative risk (RR) to 95% confidence intervals (CI). The quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach.

Results: Fifty-four studies were included (4,168 participants). A higher occurrence of anterograde amnesia was observed when benzodiazepines, the most well-studied sedatives (n = 47), were used than when placebo was used (n = 12) (RR = 3.10; 95% CI: 2.30-4.19, P<0.001; I2 = 14%), with a moderate level of evidence. Higher doses of alpha2-adrenergic agonists (clonidine/dexmedetomidine) produced more anterograde amnesia than lower doses (n = 2) (RR = 1.83; 95% CI: 1.03-3.25; P = 0.038; I2 = 0%), with a low level of evidence; benzodiazepines' amnestic effects were not dose-dependent (n = 3) (RR = 1.54; 95% CI: 0.96-2.49; P = 0.07; I2 = 12%) but the evidence was low. A qualitative analysis showed that retrograde amnesia did not occur in 8 out of 10 studies.

Conclusions: In children, moderate evidence support that benzodiazepines induce anterograde amnesia, whereas the evidence for other sedatives is weak and based on isolated and small studies. Further clinical trials focused on the amnesia associated with non-benzodiazepine sedatives are therefore needed.

Trial registration: PROSPERO CRD42015017559.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Amnesia, Anterograde / chemically induced
  • Amnesia, Anterograde / diagnosis*
  • Amnesia, Retrograde / chemically induced
  • Amnesia, Retrograde / diagnosis*
  • Benzodiazepines / adverse effects*
  • Child
  • Child, Preschool
  • Clonidine / adverse effects
  • Dexmedetomidine / adverse effects
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Infant
  • Male
  • Randomized Controlled Trials as Topic
  • Young Adult

Substances

  • Hypnotics and Sedatives
  • Benzodiazepines
  • Dexmedetomidine
  • Clonidine

Grants and funding

This study is partially funded by the State of Goias Research Foundation (Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG) and by the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES).). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.