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

Abstract

BackgroundStudies 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.MethodsThe 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.ResultsFifty-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.ConclusionsIn 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 registrationPROSPERO CRD42015017559.

Crossover Studies of Pediatric Dental Sedation are Inappropriate

“…It is noteworthy that there was an improvement regarding the reduction in the percentage of struggling behavior from the first to the second visit, which was remarkable in older children at G1. This is probably due to the amnestic properties of the midazolam, which is able to produce loss of memory of procedures (5). In fact, a previous study demonstrated that 0.2 mg/kg of intranasal midazolam in combination with nitrous oxide produced more anterograde amnesic effects evaluated by a recall test for children 24-28 months old during dental treatment compared with 3.7 mg/kg of hydroxyzine (21).…”

“…Although sedated children may show more controllable behavior compared to placebo (3), it is known that sedation can fail in guiding children's behavior in some cases (4). On the other side, drugs such as midazolam promote anterograde amnesia, a desirable sedative effect when dealing with pediatric patients (5).…”

“…Os dados foram analisados por ANOVA de três fatores (alfa=0,05). Midazolam [média(DP); 71,7% (16,5)] e placebo [48,6%(33,1)] resultaram em mais comportamento não cooperativo quando administrados na primeira sessão comparado com a segunda (p=0,001). Com o uso do placebo, crianças de 2-3 anos de idade exibiram mais comportamento não cooperativo [G1 54,9%(36,2); G2 80,5%(8,3)] que as de 4-5 anos de idade (p=0,04).…”

Amnesia after Midazolam and Ketamine Sedation in Children: A Secondary Analysis of a Randomized Controlled Trial

“…Ketamine, benzodiazepines, barbiturates, chloral hydrate, antihistamines, narcotics, nitrous oxide, dexmedetomidine, Propofol, and melatonin have been administered for dental sedation, with limited research for most regarding the incidence of amnesia [9]. Factors associated with amnesia include patient characteristics, level of sedation, and the method used to evaluate amnesia [10].…”

“…Factors associated with amnesia include patient characteristics, level of sedation, and the method used to evaluate amnesia [10]. Establishing memory and recall in the pediatric population is challenging, with quantitative methods most frequently employed [9,11,12].…”