|Year : 2021 | Volume
| Issue : 3 | Page : 233-239
Comparison of the safety and efficacy of dexmedetomidine with midazolam for the management of paediatric dental patients: A systematic review
Mousumi Goswami, Aayushi Sangal, Bushra Rahman, Sakshi Chawla
Department of Paediatric and Preventive Dentistry, I.T.S Dental College, Hospital and Research Centre, Greater Noida, Uttar Pradesh, India
|Date of Submission||08-Dec-2020|
|Date of Decision||23-Mar-2021|
|Date of Acceptance||20-May-2021|
|Date of Web Publication||22-Nov-2021|
Dr. Mousumi Goswami
Flat 104, Tower 30, Lotus Panache, Sector 110, Noida - 201 304, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Pain, fear, and anxiety have long been associated with pediatric dentistry. A child's cooperation with a dental.procedure.usually requires various behavioral management strategies conveyed by the entire dental team. The use of sedatives in dental clinics for providing analgesia and anxiolysis allows the patient to respond appropriately to verbal commands and light tactile stimulation., thus making dental treatment more patient friendly and effective. Aim: The aim of this study was to compare the safety and efficacy of dexmedetomidine versus midazolam for the management of pediatric patients in the dental clinic. Materials and Methods: This systematic review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six articles were selected for this systematic review. Of them, only in four articles, homogeneous data were available which were subjected to meta-analysis. Results: When compared with midazolam, premedication with dexmedetomidine resulted in much lower incidence of emergence delirium (odds ratio = 0.07, 95% confidence interval: 0.01–0.54, P = 0.01). No significant difference was observed with respect to satisfactory behavior of the child, successful parental separation, and satisfactory mask acceptance following sedation. Conclusion: Both dexmedetomidine and midazolam are equally effective for the management of pediatric patients in the dental clinic. In addition, dexmedetomidine premedication is associated with lower incidence of emergence delirium and has a better margin of safety.
Keywords: Dentistry, dexmedetomidine, midazolam, pedodontics, premedication
|How to cite this article:|
Goswami M, Sangal A, Rahman B, Chawla S. Comparison of the safety and efficacy of dexmedetomidine with midazolam for the management of paediatric dental patients: A systematic review. J Indian Soc Pedod Prev Dent 2021;39:233-9
|How to cite this URL:|
Goswami M, Sangal A, Rahman B, Chawla S. Comparison of the safety and efficacy of dexmedetomidine with midazolam for the management of paediatric dental patients: A systematic review. J Indian Soc Pedod Prev Dent [serial online] 2021 [cited 2021 Dec 7];39:233-9. Available from: https://www.jisppd.com/text.asp?2021/39/3/233/330716
| Introduction|| |
Most of the pediatric patients experience preoperative anxiety in the dental clinic. They can become uncooperative at the time of separation from their parents, during the administration of local anesthesia or even while undergoing a simple noninvasive dental procedure. Untreated anxiety can lead to unwanted movement of the child during dental procedures, increased postoperative pain, complications, greater analgesic requirements, emergence agitation, and further aggravation of postoperative psychological effects and behavioral issues.,,
If, therefore, nonpharmacological behavior management strategies prove to be inadequate in minimizing dental anxiety, then some form of pharmacological sedation is indicated so as to optimize the course of successful provision of efficient dental treatment to uncooperative children.
A plethora of sedative agents are used in pediatric dental settings such as midazolam, ketamine, propofol, chloral hydrate, and nitrous oxide. Each of these has its own set of limitations, the deep sedation state being provided by them requiring a high dosage of these sedatives; which may often lead to potential complications such as nausea, vomiting, hallucinations, hypoxemia, and even catastrophe during the period of pediatric sedation.
Dexmedetomidine is a recently introduced sedative agent in pediatric dentistry. It was approved by the Food and Drug Administration in 1999 for the sedation of intensive care unit patients and for premedication. In 2005, it was introduced in dentistry. It is a highly selective α2 adrenergic receptor agonist with sedative, anxiolytic, and mild analgesic properties. The sedation produced by dexmedetomidine is compliant and semi-arousable, similar to natural sleep, indicating that it has minimal influence on respiration. It maintains spontaneous respiration during sedative action and reactivity to CO2 increase, reduces dose of anesthetic drug required, and inhibits tachycardia. It causes preoperative sympatholytic effects and hypotension, due to stimulation of central α2 and imidazoline receptors.
Unlike midazolam, dexmedetomidine does not have an affinity for gamma-aminobutyric acid or opioid receptors and does not result in respiratory depression. Furthermore, dexmedetomidine can be administered by various routes including oral, buccal, intranasal, intravenous, and intramuscular and it has a quick onset of action. Therefore, sedation with dexmedetomidine may be optimal for dental procedures in children as it provides easy and rapid control of sedative and conscious levels, amnesia, and rapid recovery after sedation.
Despite its advantages, there are only limited data that are available till date on its use as a safe and effective sedative agent for dental procedures in the pediatric age group, when compared to other drugs. Therefore, in this systematic review, we aim to compare the safety and the efficacy of sedation provided by dexmedetomidine versus midazolam for the management and dental treatment of pediatric patients.
| Materials and Methods|| |
This systematic review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration number: CRD42020209203).
To be eligible for this systematic review and meta-analysis, publications were required to meet the following inclusion criteria:
- Studies published between the year 2009 and 2020
- Studies comparing the effectiveness and safety of sedation with dexmedetomidine to that with midazolam in pediatric patients undergoing dental procedures
- Studies in which the age of the participants was between 2 and 14 years
- Disclosure of at least one of the following outcome measures: quality of separation from parents, effect on behavior management, success rate of sedation, effect on vital parameters following sedation, postoperative nausea and vomiting, shivering, and other possible untoward events.
Studies with any of the following characteristics were not included:
- Studies carried out in animals
- Studies not available in English language
- Free, full text not available
- Studies in which the age of the participants was >14 years
- Studies not involving any dental procedures
- Reviews, editorials, letters, and case reports.
Information sources and search strategy
Searching of electronic databases as well as hand searching for relevant articles was carried out until May 20, 2020. Electronic database searched included PubMed (Medline), Google Scholar, Cochrane Library databases, SCOPUS, and LILACS. Medical Subject Headings terms used were “(dexmedetomidine OR adrenergic alpha-2 agonists) AND (sedation) AND (paediatric dentistry OR dentistry in children OR dentistry). Filters were applied during the search, so as to access only those articles published from January 1, 2009, to October 20, 2020.
A total of 634 articles were recorded from electronic databases. The articles provided by Google Scholar were 502, PubMed (Medline) provided 120, and Cochrane Library databases provided 12 articles. SCOPUS and LILACS provided no articles. Five articles were identified from hand searching of references. Duplicate articles were identified and removed manually.
Two hundred and sixty-three articles were left after removal of the duplicate articles. Their titles and abstracts were evaluated thoroughly, and full manuscripts were carefully assessed according to the inclusion and exclusion criteria to finalize eligibility. Only the articles fulfilling all eligibility criteria were selected. Finally, six articles,,,,, were selected to be included in this systematic review. A PRISMA flow diagram depicting the trial selection process is shown in [Figure 1].
The following data from the included studies were extracted and tabulated: author, year of publication, sample size, age range of the participants, drug administered for sedation along with its route of administration and dosage, type of procedure, and any outcome that met the inclusion criteria. The characteristics of these six studies are summarized in [Table 1].
When outcomes of interest were reported by two or more studies, the included articles were pooled and weighted using Review Manager (version 5.4, 2020; the Nordic Cochrane Center, the Cochrane Collaboration). Categorical outcomes are reported as odds ratios (ORs) and 95% confidence intervals (CIs), while continuous outcomes are reported as weighted mean differences (WMDs) and 95% CI. Heterogeneity, which was assessed using I2 statistics, describes the percentage variability in effect estimates (OR or WMD) that is due to heterogeneity rather than sampling error. I2 was used to identify the statistical heterogeneity: an I2 value above 50% was considered obvious heterogeneity. A random-effect model was applied when I2 was >50%. A fixed-effect model was used applied when I2 <50%.
Risk of bias (ROB) was assessed using Risk of Bias in Systematic Reviews (ROBIS) tool by Whiting P et al. (2015). ROBIS Phase 2, domains 1, 2, and 3 were associated with low concern while the concern for domain 4 was unclear [Table 2]. In Phase 3 of ROBIS, the overall ROB for the systematic review was assessed by answering the signaling questions [Table 3] and it was found to be low. The assessment was done by two trained and calibrated reviewers (AS and SC). Any disagreements were resolved by discussion with the third reviewer (MG).
|Table 2: Risk of bias in systematic Phase 2: Identifying concerns about bias in the review process|
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| Results|| |
Out of the six studies that compared the safety and the sedation efficacy of dexmedetomidine versus with midazolam for the management of pediatric patients in the dental clinic, only four studies were selected for meta-analysis. Homogeneous data from these studies were extracted and pooled into subgroups. Effect of dexmedetomidine versus midazolam premedication was assessed with respect to the following outcomes:
Meta-analysis for satisfactory behavior of the child following sedation with intranasal dexmedetomidine versus intranasal midazolam showed that there was no significant difference between the groups (OR = 1.17, 95% CI: 0.39–3.48, P = 0.78) [Figure 2]. This analysis was influenced by heterogeneity (I2 = 46%).
|Figure 2: Meta-analysis of satisfactory behavior of the child following sedation with dexmedetomidine versus with midazolam|
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Successful parental separation
Meta-analysis for successful parental separation following sedation with intranasal dexmedetomidine versus oral midazolam showed that again there was no significant difference between the groups (OR = 1.36, 95% CI: 0.29–6.39, P = 0.70) [Figure 3]. No significant heterogeneity (I2 = 0%) was detected in this analysis.
|Figure 3: Meta-analysis of successful parental separation of the child following sedation with dexmedetomidine versus with midazolam|
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Satisfactory mask acceptance
Meta-analysis for satisfactory mask acceptance following sedation with intranasal dexmedetomidine versus oral midazolam showed that again there was no significant difference between the groups (OR = 1.00, 95% CI: 0.24–4.21, P = 1.00) [Figure 4]. No significant heterogeneity (I2 = 0%) was detected in this analysis.
|Figure 4: Meta-analysis of satisfactory mask acceptance by the child following sedation with dexmedetomidine versus with midazolam|
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Presence of emergence delirium
Meta-analysis for presence of emergence delirium following sedation with intranasal dexmedetomidine versus oral midazolam revealed that the occurrence of emergence delirium was significantly lower in dexmedetomidine group as compared to midazolam group (OR = 0.07, 95% CI: 0.01–0.54, P = 0.01) [Figure 5]. No significant heterogeneity (I2 = 0%) was detected in this analysis.
|Figure 5: Meta-analysis of presence of emergence delirium following sedation with dexmedetomidine versus with midazolam|
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| Discussion|| |
Premedication is the most common way to minimize distress for children entering the dental clinic and to facilitate the smooth induction of anesthesia. It can be accomplished using various sedative drugs. Midazolam, which is an anxiolytic, sedative, hypnotic, and amnesic drug, has been widely used for premedication via several routes. But studies have shown that midazolam was ineffective in preventing emergence delirium when compared to other drugs such as propofol, ketamine, α2 agonist, and fentanyl. Therefore, different drugs, including α2 adrenoceptor agonists, which allow the child to remain cooperative or arousable and do not cause “clouding of consciousness,” are considered as alternatives for premedication in pediatric anesthesia.
Dexmedetomidine is a highly selective α2 adrenoceptor agonist that provides sedation, anxiolysis, and analgesic effects without causing deleterious respiratory depression. Recently, it has been extensively explored in pediatric patients for premedication.
The meta-analysis revealed that there was no significant difference between dexmedetomidine and midazolam premedication of pediatric patients in the dental clinic with regards to the behavior of the child, successful parental separation, and mask induction following sedation. However, the occurrence of emergence delirium was significantly lower with dexmedetomidine than with midazolam.
Meta-analysis could not be carried out for other outcomes due to lack of homogeneity. However, the results of individual studies that were included in this systematic review were compared and it was observed that in the study conducted by Waly in 2019, in which both dexmedetomidine and midazolam were administered by intravenous route, as well as in the study conducted by Surendar in 2014, in which both dexmedetomidine and midazolam were administered by intranasal route, the time of onset of sedation following administration of midazolam was shorter than that following administration of dexmedetomidine. This difference was statistically significant in the study conducted by Surendar in 2014 (P < 0.001). This explains why intranasal dexmedetomidine is commonly administered 45–60 min before induction of surgery, because of the relatively slow onset of maximal sedation.
In the study conducted by Waly in 2019, both dexmedetomidine and midazolam were administered intravenously and recovery time was significantly shorter following administration of dexmedetomidine than following administration of midazolam, but when administered by intranasal route as in the study conducted by Surendar in 2014, the recovery time was significantly shorter for midazolam than for dexmedetomidine.
In respect to the faster recovery time with intravenous dexmedetomidine than with intravenous midazolam, these results agreed with the results obtained by Koroglu et al. and Al Taher et al. Faster recovery time following sedation with intranasal midazolam was in accordance with the previous results that suggest faster recovery after midazolam administration when used orally, and intranasally.
Hemodynamics must be closely monitored following premedication with dexmedetomidine as it produces a dose-dependent decrease in blood pressure and heart rate (HR) resulting from its sympatholytic effect. Dexmedetomidine acts by binding to α2 receptors presynaptically and postsynaptically in the locus ceruleus and in the spinal cord resulting in decreasing norepinephrine release and inhibiting sympathetic activity which may lead to bradycardia and hypotension.
In a study conducted by Sundaram and Mathian in 2011, systolic blood pressure (SBP) decreased significantly with 1 μg/kg intranasal dexmedetomidine administration, when compared with 0.2 mg/kg intranasal midazolam (P = 0.004). In the studies conducted by Surendar in 2014, there was a significant reduction in pulse rate (P ≤ 0.001) and SBP (P ≤ 0.05) among D1 (intranasal dexmedetomidine 1 μg/kg) and D2 (intranasal dexmedetomidine 1.5 μg/kg) groups as compared to M1 (intranasal midazolam 0.2 mg/kg) group. However, the changes in vital parameters following sedation did not need any clinical intervention in any of the studies. In the remaining four studies,,, that compared premedication with dexmedetomidine versus with midazolam, no significant differences were found in HR, oxygen saturation, and respiratory rate on administration of either of the two drugs.
However, whether dexmedetomidine causes hypotension, bradycardia, and hypoxia depends on the dose and route of administration, these side effects being seldom observed following nonintravenous administration. In addition, it has been shown to have minimal effects on respiration, which is its key advantage over other sedatives like midazolam. Furthermore, unlike conventional sedatives, the site of action of dexmedetomidine is the central nervous system, primarily the locus ceruleus, in which it induces sedation that parallels natural sleep. Therefore, external stimulation facilitates arousal.
No adverse effects were observed in any of the included studies following premedication with dexmedetomidine irrespective of the dose and the route of administration. Moreover, in the study conducted by Sheta in 2014, the incidences of postoperative agitation and shivering were significantly lower with dexmedetomidine compared with midazolam.
In the same study, 36.1% of children showed signs of nasal irritation with intranasal midazolam premedication. This sensation of burning, nasal irritation, and crying of a child could be deterrents to the use of intranasal midazolam premedication and has been reported in several studies.,,, On the other hand, this sign was not seen in any of the children when intranasal dexmedetomidine was used. Moreover, dexmedetomidine being odorless, colorless, and tasteless had greater acceptability by most children compared to midazolam due to its poor palatability and bitter taste. Midazolam has also been shown to be associated with other disadvantages such as cognitive dysfunction, staged behavioral abnormalities, hiccups, and respiratory depression.
These results suggest that both dexmedetomidine and midazolam provide adequate sedation to control anxiety and unwanted movements in children undergoing dental procedures. Moreover, dexmedetomidine shows a wider margin of safety when compared to midazolam.
The main limitation of this systematic review was that the sample sizes were highly variable among the included studies.
Furthermore, as the number of studies for each outcome variable was not more than two, publication bias could not be assessed using funnel plot.
| Conclusion|| |
Midazolam is now commonly being used in pediatric dentistry for the sedation and behavior management of uncooperative patients. However, it is associated with respiratory depression and other adverse effects unlike dexmedetomidine. Although dexmedetomidine has comparable sedative efficacy to midazolam, it is difficult to find a lot of studies dealing with its use in children as it was approved by the Food and Drug Administration agency as a sedative for nonintubated patients only in late 2008. This systemic review provides pediatric dentists with a comprehensive comparison between dexmedetomidine and midazolam premedication to provide optimal and efficient dental treatment to uncooperative patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]