Introduction
Strabismus surgery is one of the common procedures in ophthalmology, often performed under general anesthesia [
1]. Patients frequently experience postoperative delirium, postoperative nausea and vomiting (PONV), and postoperative pain following strabismus surgery. According to the literature, the incidence rates of these complications can be as high as 40%-84%, 37%-80%, and 65% respectively [
2]. Postoperative delirium can even lead to patients removing intravenous catheters or causing self-harm [
3]. Severe postoperative vomiting can affect patients’ ability to eat and drink, potentially leading to electrolyte imbalances, which in turn can hinder recovery and result in prolonged hospital stays or unplanned readmissions [
4]. Postoperative pain can also affect oral intake, sleep, and may prolong hospitalization [
4]. Hence, complications following strabismus surgery not only increase patients' distress and discomfort but also add to the workload and stress of medical or nursing staff [
2,
4].
Dexmedetomidine is a highly selective α2-adrenoceptor agonist, known for its sedative, analgesic, and anti-anxiety effects, making it widely used in clinical anesthesia [
5]. Dexmedetomidine can be used for the prevention or treatment of delirium in intensive care units [
6,
7], and can also be used to prevent postoperative delirium in adults undergoing cardiac or other non-cardiac surgeries [
8]. Furthermore, literature reports that dexmedetomidine can alleviate pain and delirium in children undergoing adenoidectomy without significant side effects [
9]. Moreover, a meta-analysis reported that the use of dexmedetomidine reduced the incidence of postoperative nausea and vomiting in children undergoing various types of surgery [
10]. However, there are limited and somewhat outdated meta-analyses on whether dexmedetomidine can reduce the incidence of postoperative delirium, nausea, vomiting, and pain in patients undergoing strabismus surgery. Additionally, as intranasal administration of dexmedetomidine becomes increasingly utilized in clinical settings, literature analyzing this method of administration remains scarce. Also, existing studies often have small sample sizes, and the results are frequently contradictory [
11,
12], which is confusing. Therefore, there is still a need for high-quality meta-analyses to evaluate the efficacy of dexmedetomidine in preventing anesthesia-related complications in strabismus surgery.
In this study, we conducted a comprehensive and systematic review and meta-analysis of randomized controlled trials (RCTs) concerning dexmedetomidine and strabismus surgery, to assess the efficacy of dexmedetomidine in preventing anesthesia-related complications in strabismus surgery.
Materials and methods
Search strategy and inclusion criteria
The report of this article was followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (
PRISMA) statement guidelines [
13]. The protocol of this systematic review was registered in the International prospective register of systematic reviews (PROSPERO), National Institute for Health research (ID: CRD42023438847). In adherence to the principles of Cochrane, three researchers independently searched PubMed, Medline, Embase, Ovid, Cochrane Library, ISI Web of Science, Clinical Trials, and Chinese databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Biomedical Literature Database (SinoMed), to retrieve eligible studies published up until May 2022 since the inception of these databases. Keywords used in the search included "dexmedetomidine," "α2 agonist," "children," "strabismus," "eye surgery," and "ophthalmic surgery." After generating a list of potentially eligible studies, the researchers conducted manual review and verification to determine the final selection for inclusion in the analysis.
This study only included Randomized Controlled Trials (RCTs) related to strabismus surgery that compared the use of dexmedetomidine with a placebo or other anesthetic agents, without restrictions on the route of administration or dosage of the drug. Studies that were of types such as reviews, cohort studies, or case reports, and other non-RCT studies were excluded. We only included the studies written in English or Chinese. The three independent researchers then screened the retrieved literature, removed duplicates that arose during database integration, and read the titles and abstracts of the articles for initial selection. The full texts of the preliminarily selected articles were obtained and thoroughly read to determine if they met the inclusion criteria. Any discrepancies during the process were resolved through consultation and discussion.
The primary outcomes of interest in this study were the incidence of postoperative delirium, postoperative nausea and vomiting (PONV), and postoperative pain as well as the number of patients requiring additional analgesics postoperatively. Additionally, the study also assessed the incidence of the oculocardiac reflex (OCR).
Two independent researchers extracted the necessary information from the included studies, including author, publication year, patient recruitment period, inclusion criteria, sample size, baseline data, comparison groups, intervention duration, primary anesthetic agents, and data on primary and secondary outcomes. A third researcher was involved in information verification and data cross-checking to ensure the accuracy and reliability of the information and data.
Literature quality assessment
Two researchers assessed the bias and risk of the eligible studies using the Cochrane Risk of Bias tool [
14]. This tool includes the following sections: selection bias due to random sequence generation or allocation concealment; performance bias due to participants or personnel being aware of the assigned interventions; detection bias due to blinding deficiencies when obtaining outcomes; reporting bias due to selective reporting of outcomes, and other biases. Each risk of bias level is categorized as low, high, or unclear, and the results are represented with different colored blocks and corresponding risk of bias graphs. In case of discrepancies in the evaluation, the assessment of a third researcher is adopted for the final evaluation.
Statistical analysis
For dichotomous variables, this study employs the risk ratio (RR) along with the corresponding 95% confidence intervals (CI) for outcome analysis. The heterogeneity of the studies is assessed using the I2 statistic and the chi-square test, and if substantial heterogeneity is observed, subgroup analyses are conducted to explore the reasons. I2 value is more than 50%, which means the high heterogeneity and the random model should be used. I2 value is less than 50%, which means the low heterogeneity and fixed model should be used. Egger's test are employed to assess publication bias. Forest plots and funnel plots are created using Review Manager software (Version 5.4, The Nordic Cochrane Centre, Copenhagen, Denmark). Statistical analyses are performed using STATA (Version 14.0, Stata Corp, College Station, TX, USA). A difference is considered to be statistically significant when P < 0.05.
Discussion
This study is the most up-to-date and comprehensive systematic review and meta-analysis of RCT studies to date. In contrast to other studies that only compare the intravenous administration of dexmedetomidine [
26], this study also includes the relatively new method of intranasal administration of dexmedetomidine. After searching multiple databases and screening literature, 13 studies with a total of 1018 patients were included for analysis. The meta-analysis of this study shows that the use of dexmedetomidine in strabismus surgery can significantly reduce the incidence of postoperative delirium, severe postoperative delirium, postoperative nausea and vomiting, and the need for supplemental analgesia. It was also found that intravenous dexmedetomidine can reduce the incidence of the oculocardiac reflex postoperatively.
Postoperative delirium is a common adverse complication after general anesthesia surgery, and strabismus surgery is one of the risk factors for postoperative delirium [
27]. Possible risk factors for postoperative delirium include rapid awakening after anesthesia, use of short-acting volatile anesthetics, postoperative pain, age, and type of surgery [
28]. Previous literature analysis found that dexmedetomidine reduced the incidence of postoperative delirium in non-cardiac surgeries [
29]. However, there is still controversy regarding whether dexmedetomidine can reduce the incidence of postoperative delirium in strabismus surgery, and the results are inconsistent [
17,
19]. This study did not conduct subgroup analysis for age and anesthesia methods, so the results have a certain degree of generalizability. Our results suggest that dexmedetomidine can reduce the incidence or severity of postoperative delirium. Therefore, it is recommended that anesthesiologists consider using dexmedetomidine to reduce the occurrence of postoperative delirium in patients undergoing high-risk surgeries, such as strabismus surgery.
Postoperative nausea and vomiting are common phenomena after general anesthesia and can lead to electrolyte imbalances, aspiration pneumonia, delayed discharge, and increased unplanned admissions, which significantly increase patient discomfort and medical costs [
30]. There are reports that dexmedetomidine has a prophylactic antiemetic effect during general anesthesia [
31], but this analysis lacks research on strabismus surgery. In this study, our results demonstrate that dexmedetomidine has a prophylactic antiemetic effect in strabismus surgery. However, there are few RCT studies comparing the antiemetic effects of dexmedetomidine with other preoperative prophylactic antiemetic drugs, and further research is needed to compare the antiemetic effects of dexmedetomidine.
Postoperative pain is the main cause of discomfort after anesthesia, and patients undergoing strabismus surgery are at high risk for postoperative pain [
32]. Postoperative pain is associated with pediatric postoperative delirium, and therefore the European Society for Paediatric Anaesthesiology recommends pain management for six common pediatric surgeries, but strabismus surgery is not currently included in the guideline [
33]. Dexmedetomidine has analgesic effects and is widely used in various surgeries. It can effectively relieve pain, prolong the pain-free period, and reduce the use of opioids during the recovery period after general anesthesia [
34]. Our study confirms this, showing that dexmedetomidine can reduce the number of patients requiring supplemental analgesia after strabismus surgery.
Regarding other adverse events after strabismus surgery, the oculocardiac reflex is of current interest. The oculocardiac reflex is related to triggering stimuli, most commonly caused by the traction of the extraocular muscles [
35]. There has been much clinical debate about the relationship between dexmedetomidine and the oculocardiac reflex, with no definitive results [
36]. Interestingly, the comprehensive analysis of all the literature included in this study revealed high heterogeneity between results. Subgroup analysis by administration method showed that intravenous administration can reduce the incidence of the oculocardiac reflex, which is consistent with previous meta-analyses [
26]. However, the relationship between intranasal administration and the oculocardiac reflex is still unclear, possibly due to the small number of studies on intranasal administration. More research is needed to evaluate the relationship between intranasal administration and the oculocardiac reflex.
This study has some limitations. Firstly, although the study has made efforts to include more comprehensive RCT studies, the number of studies is still small, with small sample sizes, and all studies are single-center, which may introduce bias. Secondly, there are differences in the timing and dosages of dexmedetomidine administration among different studies, but due to the small number of control experiments, intergroup analysis cannot be performed, which may affect the generalizability of the results. Additionally, postoperative management and interventions differ among studies, which may affect the heterogeneity of the results.
In summary, our study found that in patients undergoing strabismus surgery, the use of dexmedetomidine can alleviate postoperative delirium and reduce the incidence of postoperative nausea, vomiting, and pain. In addition, intravenous administration of dexmedetomidine can reduce the incidence of the oculocardiac reflex.
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