A comparative evaluation of intranasal α2-adrenoceptor agonists and intranasal midazolam as premedication in pediatric sedation: A meta-analysis of randomized controlled trials

Abstract

Background Midazolam and α2-adrenoceptor agonists have been widely used off-label as intranasal sedatives for children. The present meta-analysis aimed to evaluate the effects of two interventions in pediatric sedation. Methods PubMed, Embase, and Cochrane Library were searched from inception to April 2022. All randomized controlled trials used intranasal α2-adrenoceptor agonists and midazolam as sedatives in children were enrolled. Parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as outcomes. Results Totally 21 studies with 1,495 patients were included. Only one study reported comparison between midazolam and clonidine met the inclusion criteria, and patients in clonidine group had significantly better mask acceptance compared to midazolam group. Compared with midazolam, using of dexmedetomidine was associated with higher rate of satisfactory parental separation (52.88% vs 75.18%, RR = 0.70, with 95%CI [0.55, 0.90]), anesthesia induction or facemask acceptance (60.92% vs 81.47%, RR = 0.76, 95% CI [0.68, 0.84]) and less incidence of postoperative pain and nasal irritation. Conclusion Compared with midazolam, dexmedetomidine should be considered as the preferred intranasal sedative option for pediatric patients, since it provides more satisfactory sedative level with less incidence of several side effects. But insufficient evidences about effects of intranasal clonidine and overall low and moderate quality evidences evaluated by GRADE system indicate that superiority of intranasal α2-adrenoceptor agonists in pediatric sedation needs to be validated by more studies with high quality and large sample size in future.

Evaluating the Quality of Systematic Reviews on Pediatric Sedation in Dentistry: An Umbrella Review

“…High: Dexmedetomidine provides effective sedation [ 36 ], associated with more satisfactory separation from parents [ 11 , 18 , 23 , 34 , 35 , 41 , 43 , 47 ] and mask acceptance [ 11 , 34 , 35 , 41 , 43 , 47 ]. It leads to a lower incidence of agitation, postoperative delirium, and tremors, reduces the need for analgesia [ 11 , 23 , 34 , 35 , 41 , 43 , 47 ], and has a prolonged onset of sedation [ 11 , 34 , 35 , 41 , 43 , 47 ]. It also decreases heart rate, systolic blood pressure [ 11 ], and nasal irritation [ 35 ].…”

“…It leads to a lower incidence of agitation, postoperative delirium, and tremors, reduces the need for analgesia [ 11 , 23 , 34 , 35 , 41 , 43 , 47 ], and has a prolonged onset of sedation [ 11 , 34 , 35 , 41 , 43 , 47 ]. It also decreases heart rate, systolic blood pressure [ 11 ], and nasal irritation [ 35 ]. However, the studies also report that there are no significant differences at the time of separation from parents [ 34 , 41 , 43 , 48 ], mask acceptance [ 18 , 23 , 34 , 41 , 43 , 48 ], incidence of agitation, postoperative delirium, tremors, need for analgesia [ 34 , 41 , 43 , 48 ], onset of action, and sedation [ 18 ].…”

“…Most SRs reported adverse effects [ 2 , 4 , 11 , 15 , 16 , 18 , 19 , 21 , 22 , 23 , 27 , 28 , 29 , 33 , 34 , 35 , 36 , 38 , 39 , 41 , 42 , 43 , 44 , 49 ], while twelve did not [ 1 , 12 , 13 , 17 , 20 , 24 , 25 , 26 , 30 , 32 , 37 , 40 ]. We have summarized the most common and the least common adverse effects ( Table 4 ).…”

“…Other events were reported less frequently, namely drowsiness, respiratory events, diplopia [ 2 , 21 ], hypoxia, coughing [ 2 , 19 ], dysphoria [ 21 ], apnea, stridor, laryngospasm [ 19 ], hallucinations, amnesia, hiccups, enuresis, bronchospasm, hypersalivation, otalgia, epistaxis, hyperexcitation, uncontrollable behavior, malaise, irritability, crying, and sneezing [ 2 ]. Adverse effects, such as nasal irritation [ 4 , 11 , 23 , 34 , 35 , 41 , 43 ] and teary eyes [ 4 , 11 , 23 , 34 , 35 , 41 , 43 ], have been associated with the administration of intranasal midazolam.…”

“…High: Children showed signs of nasal irritation [11,23,36,47]. Ketamine Moderate: The administration is well tolerated and without serious adverse effects [38].…”