Efficacy and Safety of Midazolam Oral Solution for Sedative Hypnosis and Anti-anxiety in Children: A Systematic Review and Meta-Analysis

Abstract

Background: Midazolam is recommended by health guidelines for sedation and hypnosis in children. Oral solution is a suitable dosage form for children. But there is no conclusive evidence for sedative-hypnosis and antianxiety effects by midazolam oral solution in children.Methods: Relevant studies were identified through searching PubMed, Embase, Cochrane Library, CINAHL, International Pharmaceuticals, four Chinese electronic databases, and relevant lists. Two reviewers independently selected trials, assessed trial quality, and extracted the data.Results: Eighty-nine randomized controlled trials (RCTs) comparing midazolam oral solution with placebo or blank (n = 33), dexmedetomidine (n = 15), ketamine (n = 11), different midazolam doses (n = 10), midazolam injection (n = 8), chloral hydrate (n = 7), diazepam (n = 5), N 2 O (n = 5), triclofos (n = 4), butorphanol (n = 2), fentanyl (n = 2), hydroxyzine (n = 1), and thiopental (n = 1) were identified. Meta-analysis showed no significant difference in the success rate and duration of sedation and hypnosis between midazolam oral and injectable solution (P > 0.05). The success rate of sedation and hypnosis of midazolam was higher than that of ketamine [risk ratio (RR) = 1.32, 95% CI (1.07, 1.62), I 2 = 0%, P < 0.01]. No significant difference was found in the success rate of sedation and hypnosis, mask acceptance, and parental separation between midazolam oral solution and dexmedetomidine (P > 0.05), and the result of one cohort study was consistent. The results of RCTs and a prospective cohort study showed that the incidence of adverse drug reactions (ADR) was 19.57% (189/966). Incidence of adverse reactions between dose groups of (0.25, 0.5] and (0.5, 1.0] mg/kg was similar [Pf (95% CI) = 0.10 (0.04, 0.24) and Pf (95% CI) = 0.09 (0.02, 0.39), respectively], higher than that of the dose group of (0, 0.25] mg/kg [Pf (95% CI) = 0.01 (0.00, 0.19)].Cheng et al. Efficacy and Safety of Midazolam Oral SolutionConclusions: Available evidence suggests that midazolam oral solution is as good as midazolam injection and dexmedetomidine and is better than ketamine. Based on efficacy and safety results, an oral midazolam solution dose of 0.5-1 mg/kg is recommended for children.

Efeitos Adversos Associados ao Uso de Benzodiazepínicos no Controle de Ansiedade na Prática Odontológica: uma Revisão de Literatura

“…Cheng et al 14 realizou uma revisão sistemática com casos seriados de sedação em pacientes pediátricos com midazolam em solução oral. Nesta, revelou-se 106 casos alterações mentais incluindo 74 casos de choro, 9 casos de agitação, 6 casos de mordida labial, 6 casos de letargia, 5 casos de alucinações, 4 casos de excitação anormal, 1 caso de gritos e desorientação.…”

Anesthesia management experience for pediatric day-case PDA ligation under thoracoscopy assisted by a robot: a retrospective study

“…Pediatric patients are prone to fear and anxiety before surgery, which can lead to prolonged anesthesia induction time, longer stay in the PACU, increased consumption of analgesics, more complications, and prolonged wound healing time [ 18 ]. Oral administration of 0.5 mg/kg midazolam has good anxiolytic and amnestic effects, with a short duration of action, high acceptance by pediatric patients, and helps with the separation of the child from their parents [ 19 ].…”

“…Currently, experts agree on the following recommendations: fasting solid food 6 h before surgery, fasting breast milk 4 h before surgery, refraining from clear fluids 2 h before surgery, and consuming liquid rich in carbohydrates (surgical energy) within 2 h before surgery is beneficial for the patient’s postoperative recovery [ 18 ]. Studies have shown that drinking a carbohydrate drink 2 h before surgery does not cause delayed gastric emptying and reduces postoperative insulin resistance, which can improve patient satisfaction and clinical outcomes [ 19 – 23 ]. Preoperative consumption of Outfast 5 ml/kg (Yichang Humanwell Pharmaceutical Co., ltd. China) within 2 h before surgery in this study, can relieve preoperative hunger, thirst, and anxiety, without increasing the risk of reflux or aspiration during surgery, thus, accelerating patient recovery, and shortening hospital stay.…”

The application of drug behavior management methods in the treatment of dental fear and oral diseases in children: A review

“…Drug efficacy can be achieved within 20 minutes, with a half-life of approximately 2.2 to 6.8 hours, significantly the drug effect does not seem to continue until 24 hours after surgery. [ 30 ] A study found that oral administration of 0.5 and 0.75 mg/kg MID provides equally good sedative and anti-anxiety effects in children. [ 31 ] Considering that the effectiveness and safety of MID are related to drug dosage, oral administration of 0.5 mg/kg MID solution is often chosen.…”