We searched the PubMed, Embase, Scopus, Web of Science, Cochrane and ClinicalTrials.gov from inception to August 28, 2025. Additional studies were identified through citation chaining and searching websites. The detailed search strategies for each source are provided in Supplementary Table S1. The search string consisted of three search terms: i) Functional Endoscopic Sinus Surgery; ii) Dexmedetomidine; and iii) Esmolol.

Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Certainty was rated as high, moderate, low, or very low. The primary domains for downgrading the quality of evidence are risk of bias, inconsistency, indirectness, imprecision, and publication bias. Findings were organized and summarised using the GRADEpro software.

Statistical analyses were conducted in R (version 4.5.1) using a random-effects model. For continuous outcomes, mean differences (MD) with 95% confidence intervals (CIs) were calculated, and for dichotomous outcomes, risk ratios (RR) with 95% CIs were calculated. Heterogeneity was assessed using the χ² and I² statistics. Sensitivity analyses were performed using a leave-one-out approach, and subgroup and meta-regression analyses were conducted to explore heterogeneity. Publication bias was assessed for outcomes with ≥ 10 studies by funnel plots. For outcomes with fewer studies, publication bias was not formally evaluated due to limited statistical power.

The literature search yielded a total of 102 records through databases and registers. 39 duplicates were removed and the remaining articles were screened on the basis of title-abstracts and then full-texts. 11 studies met the eligibility criteria and were included. From other sources (website and citation searching), 109 records were screened and 7 studies met the inclusion criteria. In total, 18 studies were included in this systematic review and meta-analysis (13–30). The detailed study selection process is outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart (Fig. 1).

This systematic review and meta-analysis included a total of 18 randomized controlled trials, comprising 1,056 participants. The studies were published between the years 2013 and 2025. All studies were parallel-group, single-center trials; most were conducted in India (k = 15), followed by Egypt (k = 2) and Bangladesh (k = 1). All trials compared dexmedetomidine, administered intravenously, to esmolol, also administered intravenously, in functional endoscopic sinus surgery (FESS). The most common dosing regimen for dexmedetomidine was a loading dose of 1 µg/kg given over 10 minutes, followed by a maintenance dose of 0.4–0.8 µg/kg/hr. For esmolol, the most common regimen was a loading dose of 1 mg/kg given over 1 minute, followed by a maintenance dose of 0.4–0.8 mg/kg/hr. Mean participant ages varied from 29.24 ± 1.38 years to 40.12 ± 11.9 years. The American Society of Anesthesiologists (ASA) physical statuses of the included participants were ASA I-II. The majority of the participants were male. Table 1 summarizes the key characteristics of the included studies.

Risk of bias was assessed across five domains for seven key outcomes, with the overall risk of bias also being judged. The outcomes assessed were intraoperative blood loss, emergence time, time to first rescue analgesia, time to modified Aldrete score > 9, incidence of hypotension, incidence of bradycardia, and incidence of postoperative nausea and vomiting.

Across most outcomes, the overall risk of bias was judged as some concerns, mainly arising from issues in domain 5. For emergence time, one study was judged to be at high risk of bias, largely due to concerns in domains 4 (measurement of outcomes) and 5. Other studies reporting emergence time were judged as having some concerns overall. The risk of bias assessment per outcome is given in supplementary (Supplementary Figures SA1-SA14).

Twelve out of the eighteen included trials reported duration of surgery (N = 746). A statistically non-significant difference was seen for the surgical duration between dexmedetomidine and esmolol usage (MD -3.04 minutes, 95% CI [-6.16 to 0.08], P = 0.056, I² = 70.5%) (Fig. 2B). Omitting Shivakumara et al., 2018 in the LOO analysis reduced I² heterogeneity to 16% (Supplementary Table S2). Univariate meta-regression using the year of publication as covariate did not significantly explain variation in effect sizes. Likewise, neither raw total sample size nor log total sample size was able to explain the heterogeneity (Supplementary Figures S2A-C).

Ten trials reported emergence time. Esmolol use showed a statistically significant shorter time to emergence (MD 3.13 minutes, 95% CI [2.64 to 3.63], P < 0.001, I² = 87.7%) (Fig. 2C). Omitting Ravikumar et al., 2017 in the LOO analysis reduced I² to 68.3%, with considerable heterogeneity persisting (Supplementary Table S3). Subgroup analyses by dexmedetomidine maintenance dose or esmolol maintenance dose did not meaningfully resolve heterogeneity (Supplementary Figures S2D, S2E).

Univariate meta-regression with year of publication as covariate showed that it was not a significant predictor of the difference in emergence time between dexmedetomidine and esmolol, with residual heterogeneity remaining very high. Likewise, no evidence of association was seen between total study sample size and effect estimates, or log total study sample size and effect estimates (Supplementary Figures S2F-H).

Nine studies reported time to first rescue analgesia. Dexmedetomidine use showed a significantly higher time to first rescue analgesic administration (MD 27.83 minutes, 95% CI [26.41 to 29.26], P = 0, I² = 54.3%) (Fig. 2D). LOO analysis omitting Vasavi et al., 2024 reduced I² heterogeneity to 1.2% (Supplementary Table S4).

Two trials reported time to Aldrete score > 9. In one study (n = 60), the dexmedetomidine group reached this threshold later than those receiving esmolol (10.4 ± 2.5 minutes versus 8.5 ± 2.3 minutes). In the other study (n = 60), reported time was much longer with dexmedetomidine (180 minutes versus 150 minutes). Due to the substantial differences in reported absolute times between the two trials, likely due to different starting and ending points, meta-analysis was not performed. Both studies, however, showed a longer time to recovery in the dexmedetomidine group compared with the esmolol group.

Six studies reported time to modified Aldrete score > 9. Dexmedetomidine use showed a significantly higher time to modified Aldrete score > 9 (MD 2.68 minutes, 95% CI [2.26 to 3.11], P < 0.001, I² = 34.1%) (Fig. 2E).

Nine studies reported RSS 30 minutes postoperatively. Dexmedetomidine use showed a significantly higher RSS (MD 0.84, 95% CI [0.51 to 1.18], P < 0.001, I² = 97.4%) (Fig. 2G). Subgroups by maintenance dose of esmolol or dexmedetomidine did not resolve heterogeneity (Supplementary Figure S2K, S2L). Heterogeneity remained high across all LOO iterations (Supplementary Table S6).

Two trials reported hypotension incidence. Nonsignificant difference was seen between the two groups (RR 0.20, 95% CI [0.02 to 1.65], P = 0.135, I² = 0%) (Fig. 3B).

Two trials reported on bradycardia incidence, which was significantly higher with dexmedetomidine use (RR 3.96, 95% CI [1.62 to 9.65], P = 0.002, I² = 0%) (Fig. 3C).

Three trials reported dry mouth incidence, which was significantly higher with dexmedetomidine use (RR 4.26, 95% CI [2.10 to 8.64], P < 0.001, I² = 0%) (Fig. 3E).

Two trials reported shivering incidence. Nonsignificant difference was seen between the two groups (RR 0.39, 95% CI [0.10 to 1.42], P = 0.153, I² = 0%) (Fig. 3F).

Our analysis reveals several noteworthy points regarding the comparative effects of dexmedetomidine and esmolol. In terms of intraoperative blood loss, no significant differences were observed between the two groups, which suggests that neither drug has a clear advantage in minimizing bleeding during surgery. Similarly, duration of surgery showed a trend toward reduced time with dexmedetomidine, but this difference was not statistically significant. A more striking difference was observed in emergence time, with esmolol providing a significantly shorter recovery time compared to dexmedetomidine. This aligns with past studies which show that dexmedetomidine may delay recovery when administered with propofol (31). Dexmedetomidine provides smooth recovery by decreasing agitation associated with emergence (32, 33), and by adjusting the dose of propofol administered, the delay in recovery time can be reduced to non-significant levels (32). Conversely, time to first rescue analgesia was significantly longer in the dexmedetomidine group, indicating its role in prolonging postoperative analgesia.

Ramsay Sedation Scale is an established 6-point tool which provides a simple monitoring method to gauge the awareness level of the patient (34). Dexmedetomidine was associated with a significantly higher Ramsay Sedation Score (RSS) at 15 and 30 minutes postoperation, reinforcing its sedative properties. A nonsignificant increase in the RSS with dexmedetomidine was observed at 60 minutes postoperation as well. While sedation can be beneficial for patient comfort, it may also delay the postoperative recovery process, as evidenced by the prolonged time to modified Aldrete score > 9 with dexmedetomidine. The modified Aldrete scoring system is a post-anesthesia recovery tool used to evaluate the readiness for post-anesthesia discharge of the patient (35). It consists of five criteria including activity, respiration, circulation, consciousness, and oxygen saturation which are rated from 0 to 1 depending on the patient condition, with a score of 9–10 indicating a readiness for discharge (35). Dexmedetomidine causing prolonged time to reach modified Aldrete score of greater than 9 means that the patient has to be kept in post-anesthesia care unit (PACU) for a longer period. In contrast, esmolol’s lack of a sedative effect allows for a faster return to baseline alertness and function (36), potentially facilitating a quicker discharge from the PACU.

This review has several notable strengths that contribute to the robustness of its findings. First, it is the first to systematically evaluate the head to head efficacy and safety of dexmedetomidine and esmolol in the context of FESS, and includes only RCTs, which enhances the internal validity of the conclusions. Secondly, the search strategy was comprehensive, incorporated additional sources and citation searching, and resulted in the inclusion of 18 trials published between 2013 and 2025. This thorough approach ensured an up-to-date evidence base. The use of GRADE assessment to evaluate the certainty of evidence, along with adherence to the PRISMA guidelines in the study selection process, strengthens the transparency and methodological rigor of the review. These methodological choices collectively enhance the trustworthiness of the pooled estimates.