The effect of dexmedetomidine on emergence agitation and pain in post-anesthesia recovery of patients undergoing upper limb elective orthopedic surgery: a double-blind randomized clinical trial

Abstract

Background and objective

Emergence agitation is a common complication following anesthesia, particularly impacting recovery in patients undergoing elective orthopedic surgeries. This study aimed to test the hypothesis that dexmedetomidine would reduce the incidence of emergence agitation and postoperative pain in patients undergoing upper limb orthopedic surgery under general anesthesia.

Methods

This prospective, randomized, double-masked, placebo-controlled clinical trial was conducted at Fatemi Hospital in Ardabil, Iran. Patients scheduled for elective upper limb orthopedic surgeries were randomly assigned to receive either dexmedetomidine (0.4 µg/kg/hr) or a placebo during surgery. The primary outcome was the incidence of emergence agitation, assessed using the Riker Sedation-Agitation Scale. Secondary outcomes included: the severity of emergence agitation, postoperative pain intensity measured with the Visual Analog Scale, hemodynamic parameters, recovery time, and adverse events.

Results

A total of 150 patients were enrolled, with 75 in each group. Regarding the primary outcome, the dexmedetomidine group exhibited a significantly lower incidence of emergence agitation (14.7% vs. 48.0%, p = 0.001). Among secondary outcomes, the dexmedetomidine group reported lower pain scores (Visual Analog Scale: 2.32 ± 1.14 vs. 4.77 ± 0.79, p = 0.001) and showed significant differences in heart rate and systolic blood pressure, with lower values in the dexmedetomidine group (p = 0.022 and p = 0.008, respectively).

Conclusion

The intraoperative infusion of dexmedetomidine significantly reduces the incidence of emergence agitation and is associated with improved postoperative pain management in adults undergoing elective upper limb orthopedic surgery. These findings support the use of dexmedetomidine as a beneficial adjunct in anesthetic practice to enhance recovery outcomes.

Introduction

The recovery phase following general anesthesia is a crucial period during which patients are particularly susceptible to various complications [1]. Among these, emergence agitation (EA) emerges as a notably challenging condition to address in the post-anesthesia care unit (PACU) [2, 3]. While extensive research has been conducted on EA in pediatric populations [4], its presentation and management in adults remain less clearly defined [5]. This oversight is concerning, given EA’s potential to cause patient distress, self-harm, prolonged recovery times, and increased healthcare costs [6, 7].

Emergence agitation is characterized by a range of symptoms, including restlessness, disorientation, hyperactivity, and inconsolability [8]. Its incidence varies significantly, ranging from 0.25% to 90.5% across different surgical populations [9]. This variability is influenced by several factors, including anesthetic techniques [10], the type of surgery performed [11], and individual patient characteristics [12]. In adult patients, specific risk factors have been identified, including younger age [13], specific surgical procedures [14], the use of inhalational anesthetics [15], and postoperative pain [16].

Current strategies for the prevention of EA include various pharmacological interventions [17], among which dexmedetomidine, a selective alpha-2 adrenergic agonist, has shown particular promise due to its unique combination of sedative and analgesic properties [18–20]. Its mechanism of action, primarily through central sympatholytic [21], results in hemodynamic stabilization [22], reduced opioid requirements [23], and an attenuated stress response [24], all while maintaining a favorable cognitive profile [25].

Despite this promise, a clear gap in the existing literature persists. Specifically, most research on the effect of dexmedetomidine on EA has been conducted exclusively in children [26], and only a limited number of studies have examined its effectiveness in adults undergoing orthopedic procedures [27]. More importantly, to the best of our knowledge, no previous study has specifically investigated the role of intraoperative dexmedetomidine infusion on EA in adults undergoing upper limb orthopedic surgery, a distinct surgical population that may experience unique pain patterns, positioning challenges, and early postoperative mobilization requirements. Therefore, the present study aimed to fill this gap by investigating the impact of intraoperative dexmedetomidine infusion on EA in adults undergoing upper limb orthopedic surgery. Through a randomized, double-blind, placebo-controlled trial design, we sought to evaluate whether dexmedetomidine reduces the incidence and severity of emergence agitation while improving postoperative recovery outcomes in this specific adult surgical population [28]. The findings of this study may significantly contribute to the understanding and management of EA in adult patients, for whom evidence-based preventive strategies remain notably underrepresented in the literature.

Methodology

Study design

This research was conducted as a prospective, randomized, double-masked, placebo-controlled clinical trial, adhering to the CONSORT guidelines to guarantee a thorough evaluation and transparent reporting. The study was prospectively registered with the Iranian Registry of Clinical Trials (IRCT20230819059181N1; registered on September 10, 2023). A completed CONSORT checklist is included as an accompanying file with this revised manuscript.

Setting and duration

The study was conducted at Fatemi Hospital, a tertiary referral and academic medical center affiliated with Ardabil University of Medical Sciences in Ardabil, Iran. Participant recruitment spanned from September 10, 2023, to May 21, 2024.

Study population and sampling

The study enrolled adult patients (ASA physical status I or II) scheduled to undergo elective upper-limb orthopedic surgery under general anesthesia. While emergence agitation (EA) is well documented in pediatric populations and individuals undergoing upper airway surgery, its prevalence in adults undergoing limb procedures remains less well defined. This study, therefore, has significant potential to contribute to the fields of anesthesia and orthopedic surgery. Key inclusion criteria required participants to be 18 years or older and scheduled for elective upper limb surgery. Exclusion criteria included chronic barbiturate use, substance or alcohol abuse, significant renal or hepatic impairment, major psychiatric or intellectual disorders, known hypersensitivity to the study medications, and any major intraoperative complications.

Sample size calculation and randomization

The sample size was calculated a priori using G*Power software (version 3.1) for a two-proportion comparison. Based on previous literature [29], the anticipated incidence of emergence agitation was 28% in the control group and 8% in the dexmedetomidine group. To detect this difference with a statistical power of 80% (β = 0.2) and a two-sided alpha error of 5% (α = 0.05), a minimum of 62 patients per group was required. Accounting for a potential 20% dropout rate, the final target sample size was increased to 75 patients per group, resulting in a total of 150 participants. Eligible patients who provided informed consent were randomly assigned to one of two parallel groups: Group D (Dexmedetomidine, n = 75) or Group C (Control, n = 75). The randomization sequence was generated by an independent statistician using a computer-based random number generator. Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes (SNOSE) to eliminate selection bias.

Blinding (double-blind procedure)

The study used a double-blind design in which both participants and the healthcare providers directly involved in patient care and outcome assessment were unaware of group assignments. Patients were blinded to whether they were receiving dexmedetomidine or a placebo (normal saline). Similarly, the anesthesiologists responsible for administering the drugs and evaluating postoperative outcomes in the post-anesthesia care unit (PACU) were also blinded to group allocation. The statistician performing the data analysis was also blinded. To maintain this blinding, the study drugs were prepared in identical 50 ml syringes by an independent anesthesiologist or nurse who was not involved in any other aspect of the patient’s perioperative care or data collection.

Anesthetic protocol

Before surgery, all patients were instructed to fast for a minimum of 8 h, and routine oral medications were withheld. Intraoperative management adhered to a standardized induction protocol for all patients, which included intravenous (IV) administration of Midazolam (0.03 mg/kg for anxiolysis and amnesia), Fentanyl (2 µg/kg for analgesia), Lidocaine (1 mg/kg to minimize hemodynamic responses during laryngoscopy), Propofol (1–2.5 mg/kg for inducing loss of consciousness), and Atracurium (0.5 mg/kg as a muscle relaxant to facilitate endotracheal intubation). Following induction, a continuous intravenous infusion of Dexmedetomidine was initiated at a rate of 0.4 µg/kg/hour for Group D, continuing until extubation at the conclusion of surgery. A loading dose was not administered to avoid the potential risk of intraoperative bradycardia and hypotension, which are known dose-dependent side effects of dexmedetomidine, particularly during the loading phase. Given that our study population consisted of adults undergoing upper limb orthopedic surgery, many of whom were normotensive and without significant cardiovascular comorbidities, we prioritized hemodynamic stability over rapid achievement of therapeutic plasma levels. Furthermore, a loading dose was considered unnecessary because the continuous infusion at 0.4 µg/kg/hour alone has been previously reported to provide adequate sedation and analgesia without the increased risk of adverse hemodynamic events. Group C received an equivalent volume of 0.9% Normal Saline as a placebo, administered via a continuous IV infusion at the same rate and duration. Anesthesia was maintained with Isoflurane, titrated to achieve a minimum alveolar concentration (MAC) of 1.0, combined with a balanced oxygen/air mixture. Mechanical ventilation was adjusted to sustain normocapnia, with end-tidal CO₂ levels maintained between 35 and 40 mmHg.

Data collection and outcome measures

Data were collected using a pre-designed checklist. The primary outcome was the incidence of emergence agitation, defined as a Riker Sedation-Agitation Scale (SAS) score of 5 or more at any time during the stay in the post-anesthesia care unit (PACU) [30]. The Riker SAS was chosen due to its validation in adult critical care and post-anesthesia settings, high inter-rater reliability (r = 0.91), and its ability to differentiate between levels of sedation and agitation using clearly defined behavioral descriptors. The SAS is a validated tool that ranges from 1 to 7, where a score of 1 represents an “unarousable” state, scores of 1–3 indicate varying levels of sedation, a score of 4 denotes a calm and cooperative state, and scores of 5–7 represent increasing levels of agitation (with 7 indicating “dangerous agitation”). In this study, a SAS score of 5 or greater was not treated as a purely numerical cutoff; rather, a score of 5 corresponds to “agitated” behavior defined as “fussy, but not requiring restraint” and a score of 6 corresponds to “very agitated” defined as “requiring restraint.” A score of 7 indicates “dangerous agitation” defined as “pulling at tubes, trying to climb out of bed.” Therefore, SAS ≥ 5 consistently captured patients exhibiting clinically meaningful agitation, ranging from fussiness requiring close observation to behaviors necessitating active nursing intervention or physical restraint, rather than transient or subclinical restlessness. This threshold was selected to identify patients whose agitation had the potential to compromise patient safety, disrupt monitoring, or increase nursing workload. The Persian version of the scale used in this study was culturally adapted through a process that included expert panel review, pilot testing, and back-translation, demonstrating good internal consistency with a Cronbach’s alpha of 0.89. Agitation was assessed upon arrival at the Post-Anesthesia Care Unit (PACU) and at 15-minute intervals thereafter to capture its time course systematically.

Postoperative pain intensity was assessed using the Visual Analog Scale (VAS), where a score of 0 represents “no pain” and a score of 10 signifies “the worst pain imaginable,” recorded at predetermined intervals in the PACU [31]. Secondary outcomes included: (1) severity of emergence agitation (distribution of Ricker SAS scores), (2) postoperative pain intensity (VAS scores), (3) hemodynamic parameters (heart rate and systolic blood pressure), (4) surgery duration, (5) recovery time, (6) need for rescue analgesics, (7) extubation time, and (8) adverse events. Hemodynamic parameters were recorded at baseline (preoperatively), every 5 min during surgery, and at 15-minute intervals during the PACU stay. Surgery duration was measured from skin incision to final dressing application. Recovery time was defined as the interval from PACU admission until discharge criteria were met. The PACU discharge criteria used in this study were based on a modified Aldrete score ≥ 9, which includes assessments of consciousness, activity, respiration, circulation, and oxygen saturation. Additionally, patients were required to have stable vital signs for at least 15 min, minimal nausea or vomiting, adequate pain control (VAS ≤ 4 or patient comfort with available analgesia), and absence of active bleeding or surgical complications. Regarding sedation levels at discharge, all patients in both groups achieved a Riker Sedation-Agitation Scale (SAS) score of 4 (calm and cooperative) prior to PACU discharge. No patient was discharged with a SAS score < 4 (sedated) or > 4 (agitated). Therefore, sedation levels did not differ between groups at the time of discharge, and the observed difference in recovery time cannot be attributed to residual sedation alone. Rescue analgesics (Meperidine 1 mg/kg IV) were administered if VAS exceeded 4. VAS assessments were conducted at predetermined intervals: upon PACU admission, at 30 min, at 60 min, and before PACU discharge. Extubation time was measured from cessation of anesthesia to extubation. Adverse events included bradycardia, hypotension, hypoxia, nausea, and vomiting.

We acknowledge that testing multiple secondary outcomes without statistical adjustment for multiplicity increases the risk of type I error (false-positive findings). However, a formal multiplicity correction, such as the Bonferroni or Holm adjustment, was not applied in this study for the following reasons. First, the secondary outcomes were predefined as exploratory rather than confirmatory, with the primary outcome (incidence of emergence agitation) serving as the sole confirmatory endpoint. Second, the secondary outcomes are clinically distinct and conceptually independent (e.g., hemodynamic parameters, recovery time, and adverse events); adjusting for multiplicity across such heterogeneous measures could obscure clinically relevant signals and increase the risk of type II error (false-negative findings). Third, the results of the secondary analyses are explicitly reported as hypothesis-generating and are interpreted with caution, emphasizing effect sizes and confidence intervals rather than relying solely on p-values. This approach is consistent with prior recommendations for reporting secondary outcomes in randomized controlled trials where the primary endpoint is clearly defined.

To ensure accurate pain assessment in agitated patients, the Visual Analog Scale (VAS) was administered once patients were calm and cooperative enough to reliably use the scale. In cases where self-reporting was initially impossible due to significant agitation, the Riker Sedation-Agitation Scale (SAS) score served as the primary distress indicator. VAS assessment was conducted as soon as agitation subsided (typically at an SAS score ≤ 4), ensuring that pain scores accurately reflected subjective experience without being influenced by the communication challenges associated with agitation.

We acknowledge that this methodological approach introduces a potential timing bias, as VAS scores measured after the resolution of agitation may not fully capture the intensity of pain experienced during the peak of agitation. Specifically, pain scores obtained at SAS ≤ 4 could underestimate the true pain level present at the moment of agitation, given that effective analgesia might have been administered or that agitation itself may have subsided spontaneously over time. However, this approach was deemed necessary because VAS requires active patient participation, including visual fixation, motor coordination, and verbal or gestural communication—all of which are compromised in agitated patients (SAS ≥ 5). Thus, attempting VAS during active agitation would have produced invalid or unreliable pain scores. The potential timing bias was partially mitigated by the standardized timing of VAS assessment (immediately upon reaching SAS ≤ 4) and by the concurrent use of SAS as an immediate behavioral distress indicator in all patients. This limitation was considered in the interpretation of the results.

Statistical analysis

Data were analyzed using IBM SPSS Statistics (Version 25). Descriptive statistics included mean ± SD for normally distributed continuous variables and frequency (percentage) for categorical variables. Normality was assessed using the Shapiro-Wilk test. Continuous variables were compared using an Independent Samples t-test, while categorical variables were compared using the Chi-square test (or Fisher’s exact test). The Spearman’s rank correlation coefficient assessed relationships between non-parametric variables. Statistical significance was set at p < 0.05.

Results

Table 1 Hemodynamic data collected at predefined intervals during the intraoperative and recovery periods are summarized in Table 2. The analysis revealed that patients in Group D (Dexmedetomidine) exhibited statistically significant lower heart rates and systolic blood pressure compared to those in Group C (Control) throughout the perioperative period (p < 0.05 for both parameters) (Fig. 1).

Table 1.

Baseline and Demographic Characteristics of the Study Participants

Variable	Group D (Dexmedetomidine) (n = 75)	Group C (Control) (n = 75)	p-value
Age (years)	24.19 ± 12.80	26.48 ± 13.46	0.442
Sex
- Male, n (%)	57 (76.0%)	58 (77.3%)	0.851
- Female, n (%)	18 (24.0%)	17 (22.7%)
Duration of Surgery (minutes)	61.25 ± 10.59	62.20 ± 11.01	0.414

Data are presented as mean ± standard deviation or number (percentage), as applicable. Group D received dexmedetomidine; Group C served as the control. The p-values for age, duration of surgery, and sex were derived from independent t-tests, Chi-square tests, or Fisher’s exact tests, as appropriate. A p-value < 0.05 was considered statistically significant

Table 2.

Comprehensive summary of primary and secondary outcomes

Outcome Measure	Group D (Dexmedetomidine) (n = 75)	Group C (Control) (n = 75)	p-value
Primary Outcome
Emergence Agitation (SAS ≥ 5), n (%)	11 (14.7%)	36 (48.0%)	< 0.001
Secondary Outcomes
Pain & Recovery
Postoperative Pain (VAS, 0–10)	2.32 ± 1.14	4.77 ± 0.79	< 0.001
Need for Rescue Analgesic, n (%)	15 (20.0%)	42 (56.0%)	< 0.001
Recovery Time (minutes)	45.2 ± 8.3	52.7 ± 9.1	< 0.001
Extubation Time (minutes)	8.5 ± 2.1	7.9 ± 1.8	0.065
Hemodynamic Parameters
Mean Heart Rate (beats/min)	72.22 ± 4.02	74.95 ± 2.57	0.022
Mean Systolic BP (mmHg)	106.15 ± 11.63	118.64 ± 9.45	0.008
Adverse Events
Bradycardia, n (%)	8 (10.7%)	2 (2.7%)	0.049
Hypotension, n (%)	6 (8.0%)	1 (1.3%)	0.117
Nausea/Vomiting, n (%)	9 (12.0%)	23 (30.7%)	0.005
Correlation Analysis in Group D	Spearman’s rho	p-value
Age vs. Agitation Score	-0.565	< 0.001
Surgery Duration vs. Agitation Score	-0.449	< 0.001

Data presented as mean ± standard deviation or number (percentage). SAS Riker Sedation-Agitation Scale, VAS Visual Analog Scale, BP Blood Pressure

Fig. 1.

CONSORT flow diagram

The primary and secondary outcomes are comprehensively summarized in Table 2. Administration of dexmedetomidine was associated with statistically significant and clinically relevant improvements in both primary and secondary outcomes. For the primary outcome, the incidence of emergence agitation was significantly lower in the dexmedetomidine group than in the control group (14.7% vs. 48.0%, p < 0.001), representing a more than 3-fold reduction. Among secondary outcomes, patients receiving dexmedetomidine reported substantially lower postoperative pain scores (2.32 vs. 4.77, p < 0.001) and demonstrated reduced need for rescue analgesics (20.0% vs. 56.0%, p < 0.001). The recovery time was significantly shorter in the dexmedetomidine group (45.2 vs. 52.7 min, p < 0.001), whereas extubation time did not differ significantly between groups.

Hemodynamic parameters revealed significantly lower heart rates and systolic blood pressure in the dexmedetomidine group, consistent with its known pharmacological profile. Regarding adverse events, bradycardia was more frequent with dexmedetomidine (10.7% vs. 2.7%, p = 0.049), while nausea and vomiting were significantly less common (12.0% vs. 30.7%, p = 0.005). Correlation analysis within the dexmedetomidine group revealed significant negative correlations between patient age, surgical duration, and agitation scores (rho = -0.565 and − 0.449, respectively; p < 0.001 for both), suggesting enhanced efficacy in older patients and in those undergoing longer procedures.

Discussion

This randomized, double-blind, placebo-controlled clinical trial demonstrated that a continuous intraoperative infusion of 0.4 µg/kg/hr dexmedetomidine significantly reduced the incidence of emergence agitation (EA) in adult patients undergoing elective upper-limb orthopedic surgery under general anesthesia. In our study, the dexmedetomidine group exhibited a substantially lower incidence of EA than the placebo group (14.7% vs. 48.0%, p = 0.001), representing a more than 3-fold reduction in risk. This finding supports our primary hypothesis and confirms the effectiveness of dexmedetomidine in this specific adult surgical population [3, 12].

The neuropharmacological basis for this observed effect lies in dexmedetomidine’s highly selective alpha-2 adrenoceptor agonist properties [32]. In our patients, the action of dexmedetomidine on the locus coeruleus likely modulated arousal pathways and attenuated the stress response, thereby reducing the likelihood of agitation during emergence [32, 33]. This mechanism explains why our dexmedetomidine group experienced significantly lower EA rates despite receiving the same anesthetic protocol as the control group [34, 35].

A key finding of our study was the substantial analgesic benefit associated with dexmedetomidine. We observed significantly lower postoperative pain scores in the dexmedetomidine group (2.32 vs. 4.77, p < 0.001) and a reduced need for rescue analgesics (20.0% vs. 56.0%, p < 0.001) [36, 37]. By providing both sedation and analgesia simultaneously, dexmedetomidine addresses two major contributors to emergence agitation in our patients [38, 39].

Regarding hemodynamic effects in our trial, we observed higher rates of bradycardia (10.7% vs. 2.7%, p = 0.049) and hypotension (8.0% vs. 1.3%, p = 0.117) in the dexmedetomidine group [40, 41]. Importantly, all events in our patients were self-limited or readily managed with standard interventions, and no patient required discontinuation of the infusion. These clinically manageable hemodynamic changes support the safety of our protocol [42].

An unexpected but important finding in our study was that recovery time was significantly shorter in the dexmedetomidine group (45.2 vs. 52.7 min, p < 0.001). This contrasts with some previous reports of delayed recovery with dexmedetomidine [43]. We attribute this difference to our moderate infusion protocol (0.4 µg/kg/hr without a loading dose), which provided adequate sedation without excessive residual effects [44].

Our correlation analyses revealed two additional insights. First, we found that older age was associated with lower agitation scores (rho = -0.565, p < 0.001), suggesting enhanced dexmedetomidine efficacy in older patients. Second, longer surgical duration correlated with reduced agitation scores (rho = -0.449, p < 0.001), which may reflect cumulative drug effects during prolonged procedures [44, 45].

Although dexmedetomidine has been reported to exert neuroprotective and anti-inflammatory effects in critically ill patients with sepsis [45], extrapolating these mechanisms to explain the reduced vulnerability to emergence agitation observed in our older patients undergoing elective surgery remains speculative and requires dedicated investigation in similar surgical populations.

Taken together, our findings add to the increasing evidence that dexmedetomidine is effective in preventing emergence agitation in adults. Based on our results, we emphasize the importance of proper dosing (0.4 µg/kg/hr continuous infusion without a loading dose) and careful patient selection, particularly avoiding patients at high risk for bradycardia or hypotension. Future research should aim to optimize protocols tailored to specific surgical populations and to explore the long-term neurocognitive outcomes associated with dexmedetomidine use.

In the present study, bradycardia (10.7% vs. 2.7%, p = 0.049) and hypotension (8.0% vs. 1.3%, p = 0.117) occurred more frequently in the dexmedetomidine group, consistent with the alpha-2 agonist profile. All events were self-limited or readily managed: bradycardia (heart rate < 50 bpm) with glycopyrrolate (0.2 mg) and hypotension (SBP < 90 mmHg or 20% decrease) with ephedrine (5–10 mg). No patient required infusion discontinuation. These findings align with previous reports that dexmedetomidine-associated hemodynamic changes are typically mild to moderate and responsive to conventional measures without drug withdrawal [46, 47]. Nevertheless, the higher event rate underscores the need for continuous hemodynamic monitoring during dexmedetomidine administration [48].

Limitations

Several limitations of our study must be acknowledged. First, although the sample size was calculated a priori, the power calculation was based on emergence agitation (EA) incidence data derived from pediatric and nasal surgery populations, where baseline EA rates differ substantially from those in adult upper limb orthopedic surgery. Given that EA incidence varies significantly by surgical type and patient age, the assumed effect size may not perfectly correspond to our specific population, potentially affecting the precision of our sample size estimation.

Second, we acknowledge that testing multiple secondary outcomes without statistical adjustment for multiplicity increases the risk of type I error (false-positive findings). A formal multiplicity correction, such as the Bonferroni or Holm adjustment, was not applied in this study for the following reasons: the secondary outcomes were predefined as exploratory rather than confirmatory, with the primary outcome (incidence of EA) serving as the sole confirmatory endpoint; the secondary outcomes are clinically distinct and conceptually independent (e.g., hemodynamic parameters, recovery time, and adverse events); and adjusting for multiplicity across such heterogeneous measures could obscure clinically relevant signals and increase the risk of type II error (false-negative findings). The results of the secondary analyses are explicitly reported as hypothesis-generating and are interpreted with caution, emphasizing effect sizes and confidence intervals rather than relying solely on p-values. The absence of multiplicity adjustment is explicitly noted as a limitation herein.

Third, the lack of Bispectral Index (BIS) monitoring means we cannot objectively confirm equal depth of anesthesia between groups, although a standardized minimum alveolar concentration (MAC) of isoflurane was maintained at 1.0. MAC alone may not fully capture anesthetic depth, particularly in the presence of adjuvant medications such as dexmedetomidine, which has anesthetic-sparing effects.

Fourth, intraoperative opioid administration was not strictly standardized beyond the induction dose of fentanyl (2 µg/kg). Although additional fentanyl boluses were permitted based on clinical judgment, this variability may have influenced postoperative pain levels and emergence agitation, potentially confounding the observed treatment effect.

Fifth, although the study was double-blinded, post-anesthesia care unit (PACU) staff may have become inadvertently unblinded due to the recognized side effect profile of dexmedetomidine, particularly bradycardia and hypotension. The higher prevalence of these hemodynamic events in the dexmedetomidine group could have signaled group assignment to attentive clinical staff, thereby introducing detection bias despite formal blinding procedures.

Sixth, the study was conducted exclusively on American Society of Anesthesiologists (ASA) class I–II patients undergoing elective upper limb orthopedic surgery, all of whom were relatively young and healthy. Caution should therefore be exercised when extrapolating these results to patients with significant comorbidities (ASA class III or higher), elderly populations, emergency surgeries, or different surgical types (e.g., lower limb, abdominal, or thoracic procedures).

Finally, the sample size, though calculated a priori, was moderate. A larger, multi-center trial would strengthen the generalizability of our findings across diverse patient populations and clinical settings.

Conclusion

The results of our study provide compelling evidence that an intraoperative infusion of dexmedetomidine at 0.4 µg/kg/hr is a highly effective strategy for reducing the incidence of emergence agitation and improving pain management in adults recovering from general anesthesia for orthopedic surgery. These findings are in strong agreement with the established literature, including systematic reviews in pediatric populations, and highlight the drug’s dual benefit of providing hemodynamic stability alongside enhanced recovery quality. Despite predictable bradycardia and hypotension, the favorable safety profile and significant clinical benefits position dexmedetomidine as a valuable adjunct in modern balanced anesthetic practice. Future research should focus on optimizing dosing regimens for different surgical populations and further elucidating its long-term benefits on patient satisfaction and recovery trajectories.

Authors’ contributions

- Dr. Khaterah Eisazadeh: Conceptualization, methodology, data collection, and manuscript writing. - Dr. Ali Abitrapi: Data analysis, interpretation of results, and manuscript editing. - Dr. Masoud Entezari: Supervision, critical review of the manuscript, and project administration. - Dr. Mahzad Yousofian: Responsible for the overall project, coordination between authors, and final approval of the manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The Ethics Committee of Ardabil University of Medical Sciences approved this study (IR.ARUMS.REC.1402.127), which was prospectively registered with the Iranian Registry of Clinical Trials (IRCT20230819059181N1; registered 2023-09-10,1402/06/19). This randomized controlled trial (RCT) was conducted in accordance with the principles set forth in the Declaration of Helsinki, which underscores the ethical treatment of human subjects in research.

Written informed consent was obtained from all participants following a thorough explanation of the study’s procedures, associated risks, and potential benefits. Participants were made aware that their involvement was entirely voluntary and that they could withdraw from the study at any time without any impact on their medical care. The consent process ensured that participants fully understood the nature of the study and the implications of their participation. Throughout the research, stringent measures were implemented to safeguard the confidentiality of patient data, ensuring both privacy and security. Data were anonymized, and access was limited to authorized personnel only. These ethical considerations were vital in maintaining the integrity of the research and protecting the rights of all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.