Endoscopic tumor resection is one of the most common modalities in GI tumor management. Endoscopic submucosal dissection (ESD) is considered superior to mucosal resection, given that it offers complete resection with negative histological margins irrespective of the size of the original lesion [¹]. Despite these overwhelming advantages, ESD is associated with multiple postoperative complications, including bleeding, postoperative perforation, and minor complications like abdominal pain, nausea, vomiting, and stricture, which limit its use [²]. Post-operative abdominal pain is a debilitating complication associated with ESD, which is severely underestimated and results in decreased patient satisfaction and longer hospital stays. Studies show the incidence of postoperative pain in 44.9 62.8% of patients, especially in the early post-operative period, necessitating the use of aggressive pain management [³,⁴]. Dexmedetomidine is a new α2-receptor agonist that has anxiolytic, sedative, and analgesic properties, which, when used in combination with other anesthetics, help lower their dose and also decrease postoperative opioid consumption and pain intensity [⁵,⁶]. A study by Chang et al. also shows a better cardiovascular profile of dexmedetomidine than propofol [⁷]. In our study, we reviewed the possible benefits of dexmedetomidine as an adjunct sedative perioperatively in patients undergoing ESD for GI adenomas and early-stage neoplastic lesions. We evaluated its efficacy by assessing variables like en-bloc resection, Complete resection, sedation time, procedure time, patient restlessness, and other adverse events.

Although the debilitating pain associated with ESD warrants aggressive pain management, physicians are hesitant due to the possibility of masking the pain of perforation. This not only causes patient discomfort but also increases the burden on healthcare by prolonging discharge time [³,²]. A study done by Seiichiro et al. shows an increased incidence of metachronous gastric cancer in patients who underwent curative ESD of early gastric cancer [¹⁸]. These warrant further endoscopic surveillance and possible repeat ESD. However, poorly managed post-operative pain increases apprehension in patients for further endoscopic procedures. As previously described, a few studies have been done describing the incidence of postoperative pain after ESD, but there is no consensus on the management of this pain. Studies done by Lee and Kim recommend a single dose of dexamethasone or postoperative local bupivacaine and triamcinolone [¹³,¹⁹].

Our study found a significant reduction in restlessness and bradycardia associated with dexmedetomidine, highlighting its potential as an effective sedative agent for endoscopic procedures. A study that investigated the effect of local anesthesia in ESD procedures showed that local anesthesia decreased the incidence of bradycardia (OR = 0.16, 95% CI = 0.03, 0.95) [²⁰]. We also observed a statistically significant decrease in tachycardia, which could indicate less anxiety and pain, thus providing a more comfortable sedative experience for the patients. These properties could be attributed to its selective alpha two adrenergic agonist and sympatholytic properties [²⁰]. The non-significant difference found in en bloc resection rates between dexmedetomidine, and the comparator groups alleviated concerns regarding the influence of the sedation regimen on the technical aspects of the procedure [²¹].

The subgroup analysis also revealed better outcomes, particularly regarding reduced restlessness and bradycardia, with Dexmedetomidine in combination with Midazolam compared to other combinations. Midazolam’s anxiolytic and amnestic properties, coupled with Dexmedetomidine’s sedative and analgesic effects, may offer superior patient comfort and procedural tolerance. Additionally, considering the favorable safety profile of Midazolam in terms of respiratory depression compared to Propofol, this combination presents a compelling option for optimizing sedation strategies in endoscopic settings [¹⁷].

Our review suggests that dexmedetomidine is an effective sedative agent for ESD. Lee et al. [¹⁵] on the other hand, compared the outcomes of sedation using dexmedetomidine infusion plus on-demand midazolam versus sedation using midazolam infusion plus on-demand midazolam. They concluded that the sedation effect of dexmedetomidine with midazolam was superior to the sedation effect with midazolam alone. Furthermore, four studies reported sedation time as an outcome, while five studies reported procedure time as an outcome, . The pooled results from these studies showed no statistically significant difference in sedation or procedure time between the dexmedetomidine and the control group. Despite the significant reduction in intraoperative restlessness in the dexmedetomidine group in our review, as mentioned above, this did not translate into a shorter sedation or procedure time .

Nonaka et al. [¹⁶] reported a significantly shorter procedure time in the combination group (dexmedetomidine and propofol) compared to the benzodiazepine group; nevertheless, this finding was lost after pooling with other studies in the analysis, as shown in .

In terms of safety, our findings support the use of dexmedetomidine as an adjunctive agent in procedural sedation for ESD procedures, consistent with previous studies [²²,²³]. As noted by Candiotti et al. [²²], the Dexmedetomidine group demonstrated a higher incidence of bradycardia. However, there was no statistically significant increase in the occurrence of other adverse events such as hypoxia, hypotension, bleeding, or perforation. Additionally, Dexmedetomidine’s cardiovascular and hemodynamic effects are well-known and are attributed to its strong alpha 2-adrenergic agonist effect and include bradycardia, hypotension, and hypoxia [²⁴,²²,²⁵,²³]. Kim et al. evaluated risk factors for dexmedetomidine-associated bradycardia during spinal anesthesia [²⁵] and found that a long tourniquet time and low baseline heart rate were associated with an increased incidence of bradycardia during procedures under spinal anesthesia. Notably, Alshikaria et al. [¹¹] reported that no serious adverse events were observed in patients in the dexmedetomidine group who experienced bradycardia and that their clinical outcomes were not altered due to it, which is also consistent with previous literature [²⁶,²⁷].

The use of Dexmedetomidine as an adjunctive sedative has shown promising results in our meta-analysis, yet this type of intervention needs further exploration. The included studies in this review have already explored the combination of Dexmedetomidine with the two main sedatives, propofol and midazolam. The results are extraordinary in terms of restlessness and bradycardia incidence, the latter being a good sign of less stress and discomfort during the procedure. Fewer movements (restlessness) during the ESD procedure lead to more convenient and accurate procedures for the operator. So, this therapy should be explored more to reach the best results possible for the patient.

More exploration means more multicenter randomized controlled trials and observational studies comparing this type of adjunctive therapy with other adjunctive sedatives and even other types of pain management methods, like local anesthesia in the region of intervention, to test this intervention’s safety and efficacy, to standardize its use during ESD procedures in the near future. Limitations: To our knowledge, this is the first meta-analysis to assess the safety and efficacy of Dexmedetomidine as an adjunctive sedative after ESD. Additionally, we performed subgroup analysis according to each general therapy. Most included articles (6 out of 8) did not conduct a head-to-head comparison between dexmedetomidine and other agents. Also, the limited number of published clinical trials and the number of patients included in certain subgroups limit our evidence and conclusions on some outcomes. All eight included trials were conducted in eastern Asia, including 5 in Japan, two in Korea, and one in China. Thus, the generalizability of these study results to other regions with different ethnicities and medical environments may be affected. A standardized dosage of dexmedetomidine as an adjuvant sedative has not yet been established, resulting in a wide variety of dexmedetomidine regimens.

In conclusion, our meta-analysis supports the safe use of dexmedetomidine as an adjunctive sedative in ESD procedures. Dexmedetomidine, when combined with other sedatives, appears to reduce restlessness without increasing the risk of hypoxia, hypotension, bleeding, or perforation. The increased risk of bradycardia noted with dexmedetomidine can be perceived as less physiological stress and tachycardia during procedures. However, our findings are limited by the lack of direct comparisons with other sedatives and the predominantly Eastern Asian study populations. Further research, including multicenter trials, is needed to establish optimal dosing regimens and evaluate dexmedetomidine’s efficacy compared to other sedatives and pain management methods in diverse patient populations.