Efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients: a meta-analysis of randomized controlled trials

Abstract

Background Intranasal midazolam and ketamine have been widely used as sedative premedication in children. It is difficult to determine which one yields better sedative effects for clinical practice. We conducted the present meta-analysis by summarizing the evidences to evaluate the efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients. Methods We searched PubMed, Embase, and Cochrane Library from inception to April 2022. All randomized controlled trials (RCTs) used intranasal midazolam and ketamine as sedatives in children were enrolled. The risk of bias in RCTs was assessed by Cochrane risk of bias tool. Condition of parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as the outcomes in our study. Results A total of 16 studies with 1066 patients were enrolled. Compared with midazolam, administration of intranasal ketamine might be associated with severer changes in hemodynamics parameters including mean blood pressure (SMD = -0.53, with 95% CI [-0.93, -0.13]) and heart rate (HR) (SMD = -1.39, with 95% CI [-2.84, 0.06]). Meanwhile, administration of intranasal midazolam was associated with more satisfactory sedation level (61.76% vs 40.74%, RR = 1.53, with 95%CI [1.28, 1.83]), more rapid onset of sedation (SMD = -0.59, with 95%CI [-0.90, -0.28]) and more rapid recovery (SMD = -1.06, with 95%CI [-1.83, -0.28]). Current evidences also indicated that the differences of various adverse effects between two groups were not significant. Conclusions Given that administration of midazolam via intranasal route provides more satisfactory sedative level with less fluctuation of hemodynamics parameters and more rapid onset and recovery, it might be considered as the preferred sedative premedication for pediatric patients compared to ketamine. However, the widespread evidences with low or moderate quality indicated that superiority of intranasal midazolam in pediatric sedation needs to be confirmed by more studies with high quality and large sample size in future. Trial registration The protocol of present study was registered with PROSPERO (CRD42022321348).

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

“…High: Both are considered safe and effective in moderate sedation [ 14 ]. Intranasal midazolam provides more rapid onset and recovery; however, it has only sedative properties.…”

“…Intranasal midazolam provides more rapid onset and recovery; however, it has only sedative properties. Meanwhile, ketamine provides better sedation, anxiolysis and analgesia when used for premedication [ 14 ].…”

“…This was undertaken in order to investigate safety and sedation efficacy. It has been reported to have an increased level of sedation when compared with chloral hydrate [ 21 ] and is equally safe and effective when compared with ketamine [ 14 ]. Additionally, when compared with dexmedetomidine, the results are inconsistent; there is not exactly a consensus.…”

“…Although studies compare adverse effects that are generally very minimal, it is notable that the most common general adverse effects were nausea [ 14 , 19 , 21 , 23 , 34 , 35 , 41 , 43 ], vomiting [ 2 , 4 , 15 , 19 , 23 , 35 ], tremor [ 23 , 34 , 35 , 41 , 43 ], and desaturation [ 15 , 19 , 23 ]. 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 ].…”

Effects of ketamine‐induced H3K9 hypoacetylation during pregnancy on cardiogenesis of mouse offspring

“…Ketamine, commonly known as “K‐powder”, has been widely used as an analgesic, sedative, and antidepressant (Kohtala, 2021; Nowacka & Borczyk, 2019; Zanos et al, 2018), as well as a drug of abuse (Chang et al, 2019; Ma, Mu, Bao, & Liu, 2018; Morgan & Curran, 2012; Stewart et al, 2021). As an anesthetic, ketamine has been used in obstetric and pediatric operations for decades (Downing, Mahomedy, Jeal, & Allen, 1976; Grunwell et al, 2016; Kidd, Lyons, & Lloyd, 2016; Liang et al, 2022) and produces cardiovascular and respiratory adverse reactions such as tachycardia, hypertension (Hayes, Aljuhani, De Oliveira, & Johnston, 2021; Lang et al, 2022), and laryngospasm (Bellolio et al, 2016; Lee & Tham, 2022; Melendez & Bachur, 2009). Due to its hallucinogenic property, ketamine has become a popular club drug (Corkery et al, 2021; Palamar, Rutherford, & Keyes, 2021).…”