Abstract
Purpose
To evaluate the effects of dexmedetomidine nasal spray on preoperative anxiety, perioperative sleep, and intraoperative haemodynamic stability in patients undergoing laparoscopic hysterectomy or myomectomy.
Methods
This is a prospective, randomised, double-blind, placebo-controlled, single-centre clinical trial. Between October 2025 and February 2026, female patients scheduled for laparoscopic hysterectomy or myomectomy who, prior to surgery, had a HAMA score of ≥14 and a VAS-A anxiety score of ≥5 were rigorously screened and enrolled. Eligible patients were randomly assigned (1:1) to receive either intranasal dexmedetomidine 50 μg or 0.9% saline placebo on the night before surgery.A double-blind design was adopted for both patients and outcome assessors throughout the study. The primary outcome measure was the Visual Analogue Scale for Anxiety (VAS-A) score recorded at 7:00 on the day of surgery (V3). Secondary endpoints included changes in the coefficient of variation of heart rate (HR) and the coefficient of variation of mean arterial pressure (MAP) during surgery; VAS-A at various perioperative time points; The number of vasoactive drug administrations and opioid usage in two patient groups during surgery; Assessment of sleep changes before and after pharmacological intervention using Athens Insomnia Scale (AIS) scores; Recording of adverse reaction incidence post-intervention and post-operatively.
Results
Group D had a significantly lower VAS-A score at 7:00 on the day of surgery than Group C (Group C; 5.92±0.89 VS Group D:4.77±0.82, 90% CI:0.885∼1.405, P < 0.0001). The coefficients of variation for both intraoperative MAP and HR were significantly lower in Group D than in Group C (MAP-CV: 7.02±2.88% vs 13.12±4.75%, P < 0.001; HR-CV: 6.29±2.79% vs 10.81±3.86%, P < 0.001).The overall Postoperative adverse reactions rate was lower in Group D than in Group C (60% vs 80%, P < 0.05). Ciprofol consumption was markedly lower than in Group C (P < 0.0001). There was no significant difference in complications following drug intervention between the two groups (3.33% vs 8.33%, P=0.413).
Conclusion
The use of a 50-microgram dexmedetomidine nasal spray on the evening prior to surgery reduces anxiety scores on the day of surgery in patients undergoing gynaecological procedures, improves perioperative sleep quality, and maintains haemodynamic stability during the operation.
Keywords: general anaesthesia, dexmedetomidine, preoperative anxiety, hysterectomy, myomectomy, sleep disorders
Introduction
Preoperative anxiety constitutes a common psychological stress response among perioperative patients, potentially adversely affecting both physiological and psychological states. This may stem from uncertain anticipations of threatening events.1,2 Studies indicate a higher prevalence among females than males.3,4 Among Chinese patients undergoing elective surgery, the incidence of preoperative anxiety ranges from 15.8%,5 rising to 30.3% in those undergoing laparoscopic gynaecological surgery.6 Failure to alleviate preoperative anxiety effectively increases the likelihood of adverse outcomes such as delayed postoperative recovery, depression, and nausea/vomiting.7,8 Consequently, exploring safe, effective, and convenient strategies for managing preoperative anxiety has become a significant research focus in perioperative medicine. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor agonist with sedative, anxiolytic, analgesic, and sympatholytic effects; it does not significantly increase the risk of respiratory depression and has become a promising and widely used treatment option for the management of perioperative anxiety.9,10 In recent years, the intranasal administration route has gained prominence in preoperative medication research due to its non-invasive nature, convenience, and high patient compliance. Studies have reported that administering dexmedetomidine nasal spray the night before surgery effectively improves sleep disturbances without causing daytime fatigue or somnolence, unlike traditional benzodiazepines such as alprazolam.11 Regarding safety, previous clinical studies have demonstrated that low-dose intranasal dexmedetomidine is generally well tolerated, with a favorable hemodynamic profile.12 Common adverse effects, such as bradycardia and hypotension, are usually mild and transient, and rarely require clinical intervention when used at recommended doses. By administering the drug the night before surgery, any potential hemodynamic effects (eg, mild reduction in heart rate or blood pressure) can be closely monitored and resolved before anesthesia induction, reducing the risk of adverse interactions with anesthetic agents. Although there is growing evidence that dexmedetomidine effectively alleviates preoperative anxiety, improves sleep quality and stabilises haemodynamics, several key knowledge gaps remain. For example, high-quality evidence is primarily derived from paediatric population,11,13 whilst data on adult and elderly patients, as well as those undergoing gynaecological surgery, are relatively limited. There is currently insufficient evidence regarding the efficacy and safety of this intervention in treating acute anxiety on the day of surgery when administered the night before the procedure. The day of surgery is a critical moment when patients’ anxiety reaches its peak, and managing anxiety at this juncture directly impacts the smooth induction of anaesthesia and the patient’s overall experience. This study hypothesises that administering 50 micrograms of demetazodine intranasally the night before surgery to patients scheduled for laparoscopic hysterectomy or myomectomy can effectively reduce preoperative anxiety scores.
Data and Methods
Ethical Approval
This study was approved by the Research Ethics Committee of Weifang People’s Hospital (KYLL20250924-1) and registered with the China Clinical Trial Registry (CHCTR2500109960). The research protocol was conducted in accordance with the Declaration of Helsinki. Between October 2025 and February 2026, 120 patients undergoing hysterectomy or myomectomy were enrolled. All eligible adult patients provided written informed consent.
Study Population
A total of 496 patients undergoing hysterectomy or myomectomy were assessed for inclusion. Of these, 120 subjects met the criteria and were randomised to the appropriate group, whilst 376 patients were excluded from the study; reasons for exclusion included failure to meet the anxiety score threshold, age outside the specified range, the presence of psychiatric or neurological disorders, severe bradycardia or atrioventricular block, refusal to participate, and failure to complete the assessment as per the protocol. Ultimately, this study included 120 patients who underwent general anaesthesia.
Inclusion and Exclusion Criteria
The trial was completed in February 2026 at Weifang People’s Hospital (Weifang, China). Inclusion criteria were as follows: Patients classified as American Society of Anesthesiologists (ASA) physical status grades I to III (I indicating healthy patients, II indicating patients with mild systemic disease, III indicating patients with severe systemic disease); aged 18–65 years; body mass index (BMI) between 18–29 kg/m2; presence of preoperative anxiety (HAMA anxiety scale score ≥14 and VAS-A score≥5). Exclusion criteria were as follows: refusal to participate in the study; history of allergy to dexmedetomidine or other α2-adrenergic receptor agonists; diagnosed or suspected sleep apnoea syndrome; history of alcohol dependence or substance abuse (particularly sedative-hypnotics, opioids, etc); psychiatric or neurological disorders; severe bradycardia; Patients with second-degree type II or third-degree heart block; abnormal nasal anatomy or nasal/sinus inflammation/infection; refusal to participate in the trial; failure to use anaesthetic agents according to the trial anaesthesia protocol; surgical duration less than 1 hour.
Randomisation and Blinding
Shaojie Zhang used Random.org (https://www.random.org/sequences/) to generate a computer-generated random sequence to randomise patients into the dexmedetomidine group and the control group in a 1:1 ratio. Allocation was concealed using sequentially numbered, sealed, light-proof envelopes. Before assessment, all assessors underwent standardised training on the use of the scales, covering the meaning of each HAMA item, scoring criteria, VAS-A marking standards and standardised questioning protocols. Assessors were only permitted to participate in the assessment after passing a post-training examination. The assessment process employed an independent double-blind assessment, with assessors unaware of patient group allocation to minimise subjective bias; if the difference between two assessors’ scores exceeded 10%, the results were reviewed and finalised by Chief Physician Bao Lang. Ning Liu, Jinfeng Liu, Weiqiang Li et al assessed patients’ anxiety levels the evening prior to surgery; the envelope was only opened and the preoperative nasal spray administered once it had been confirmed that the patient met the inclusion criteria. The study drug (50 μg dexmedetomidine or 0.9% saline) was prepared and labelled by Yaopeng Zhang. Both formulations were dispensed into nasal spray bottles that were visually indistinguishable to maintain blinding. On the day of surgery, anaesthesia was administered by Yajuan Zhao and Jun Hu, who were unaware of the group allocation, following standardised anaesthetic protocols; all data collectors and statisticians remained blinded throughout the study. Personnel involved in the preoperative assessment had undergone training prior to the commencement of the study. In emergencies, physicians or researchers may unblind a patient’s group assignment to ensure patient safety; such patients would be excluded from further study participation.
Preoperative Anxiety and Sleep Disorder Assessment
The Hamilton Anxiety Rating Scale (HAMA) serves as a classic tool for evaluating anxiety severity across clinical psychiatry, anaesthesiology, and psychology. Widely employed for preoperative anxiety screening, assessing treatment efficacy in anxiety disorders, and monitoring perioperative psychological states, it remains one of the most frequently used scales in preoperative anxiety assessment.14 The HAMA is a classic observer-rated anxiety scale comprising 14 assessment items. It evaluates anxiety across two dimensions—psychic and somatic—using a five-point rating scale (0–4) to determine symptom severity. A total score ≥14 indicates clinically significant anxiety of moderate severity or higher. Furthermore, as our outcome measure was the Visual Analogue Scale for Anxiety (VAS-A), patients meeting HAMA criteria still underwent VAS-A assessment. Previous research indicates a VAS-A score of approximately 5 cm represents a reliable threshold for clinically significant preoperative anxiety. We selected VAS-A≥5 cm as the threshold for determining anxiety status.15 Therefore, we included patients with HAMA scale scores ≥14 and VAS-A scores ≥5cm as study subjects. We assessed anxiety levels using the HAMA scale in patients scheduled for myomectomy or hysterectomy. Where scores were greater than or equal to 14, we subsequently administered the VAS-A scale; if the score was ≥5cm, the patient was enrolled in the study.
Reoperative Pharmacological Intervention and Anaesthesia Administration
On the evening prior to surgery, pharmacological intervention was administered to study participants in their hospital rooms, with adjustments made according to individual sleep patterns. The standard bedtime was maintained between 21:00 and 23:00. A computer-generated randomisation table was employed to allocate patients in a 1:1 ratio to either the experimental group or the control group. The experimental group received intranasal administration of dexmedetomidine, with one spray administered into each nostril (two sprays total, 50μg). The placebo group received two intranasal sprays of saline solution. Following administration, patients maintained a head-up position for 30 seconds while gentle nasal pressure facilitated absorption, with the entire procedure completed within 2 minutes. Patients did not require supplemental oxygen via nasal cannula during this study. Concurrent routine monitoring included mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2). Patients underwent VAS-A assessment 20 minutes post-intervention. Neither patients, nurses, nor investigators were aware of group assignments. Following intranasal administration of demetazoxine, continuously monitor the patient’s vital signs, including heart rate (HR), mean arterial pressure (MAP), and oxygen saturation (SpO2). Manage any adverse events using the following standardised interventions: 1. Hypotension (MAP >20% below baseline): intravenous injection of 2–4 μg of norepinephrine. 2. Bradycardia (HR < 50 beats/min): Intravenous injection of 0.2–0.4 mg of atropine. 3. Hypoxaemia (SpO2 < 95%): Administer supplemental oxygen via a nasal cannula at a flow rate of 2–3 L/min until SpO2 returns to normal. 4. Dizziness, headache or drowsiness: Place the patient in the supine position and monitor them until symptoms resolve spontaneously. Rescue medication (alprazolam) was administered only when patients experienced severe insomnia that could not be alleviated by conservative treatment. To avoid potential confounding effects, patients receiving rescue medication were excluded from the per-protocol sensitivity analysis. The use of rescue medication was balanced across groups and did not influence the primary outcome measures.All interventions are performed in accordance with standard clinical anaesthesia guidelines to ensure patient safety.
Both groups of patients were required to fast for 8 hours prior to surgery. Patients’ anxiety levels were assessed using the VAS-A scale at 7:00 on the day of surgery. Upon entering the operating theatre, both groups received 30mL of 0.3% ropivacaine (Shijiazhuang No.4 Pharmaceutical Co., Ltd., China; Batch No. 25049051) (15mL per side) for ultrasound-guided bilateral transverse abdominis plane block, concurrently with establishment of venous access. Induction commenced 10 minutes later, with a repeat VAS-A anxiety assessment performed immediately prior to induction initiation. Preoxygenation was administered via a face mask at an oxygen flow rate of 5 L/min. Monitored patient HR, MAP, SpO2, temperature, and end-tidal carbon dioxide pressure (PETCO2). At induction onset, administered intravenous Anesthesia was induced intravenously with ciprofol (Shenyang Hisun Pharmaceutical Co., Ltd., China, Batch No. 33251131) at 0.3–0.4 mg/kg, sufentanil (Yichang Renfu Pharmaceutical Co., Ltd., China, Batch No. AB507000711) at 0.2–0.3 μg/kg, rocuronium bromide (Hangzhou Hongyou Pharmaceutical Co., Ltd., China, Batch No. H20213778) at 0.6 mg/kg, dexamethasone (Henan Runhong Pharmaceutical Co., Ltd., China, Batch No. H41020330) at 5 mg,and flurbiprofen axetil (YuanDa Medical Nutrition Science (Wuhan) Co., Ltd., Batch No. 62509133–1) at 50 mg.Anesthesia was maintained with propofol (China JiaBo Pharmaceutical Co., Ltd., Batch No. H20.051842) at 6–8 mg·kg−1·h−1 and remifentanil (Sinopharm Group Industrial Co., Ltd., Batch No. 25037034) at 0.1–0.25 μg·kg−1·min−1,titrated to maintain a bispectral index (BIS) between 40 and 60. In all patients, intraoperative blood pressure fluctuated within ±20% of baseline values, with vasoactive agents administered as required. In all patients, intraoperative blood pressure fluctuated within ±20% of baseline values, with vasoactive agents administered as required. Intraoperative vital signs were continuously monitored, and rescue medications were administered according to the following standardized protocols:1. Hypertension (defined as systolic blood pressure > 160 mmHg or mean arterial pressure > 110 mmHg persisting for ≥5 minutes): In accordance with current anaesthetic guidelines on the management of intraoperative hypertension, administer 0.2–0.5 mg of nicardipine intravenously, repeating the dose as required. 2. Hypotension (defined as systolic blood pressure < 90 mmHg or mean arterial pressure < 60 mmHg lasting ≥ 5 minutes): Administer 40–80 μg of norepinephrine intravenously; if the response is inadequate, ephedrine 6–12 mg may be administered as a follow-up dose. 3. Bradycardia (defined as a heart rate <50 beats per minute persisting for ≥3 minutes, with or without hypotension): Administer 0.3–0.5 mg of atropine intravenously; if the heart rate does not improve, switch to 6–12 mg of ephedrine.4.Tachycardia (defined as heart rate > 100 bpm lasting ≥5 minutes):If associated with hypotension, fluid resuscitation and additional analgesia (remifentanil 0.25–0.5 μg/kg) were prioritized; if persistent despite adequate analgesia and volume status, esmolol 10–20 mg was administered intravenously with continuous monitoring of blood pressure and heart rate.Propofol infusion pumps were discontinued approximately 10 minutes prior to surgical completion. Remifentanil infusion was ceased at the conclusion of surgery, with oxygen flow increased to 5 L/min. Reversal of neuromuscular blockade was initiated 5 minutes before the end using 2 mg/kg Sugammadex (Jiangsu Coastal Pharmaceutical Co., Ltd., Batch No. 25072821). Extubate the patient upon restoration of regular spontaneous breathing and voluntary body movements. Subsequently transfer the patient to the post-anaesthesia care unit (PACU) when meeting the following criteria: - Alertness with ability to perform directed movements - Orientation restored, recognising time and location - Adequate muscle strength recovery, maintaining head-up position for ≥5 seconds in supine position cough and swallowing reflexes restored; normal respiratory function with RR 12–20 breaths/min; SpO2 ≥ 95%, PaO2 ≥ 70 mmHg, PaCO2 within normal range or at preoperative level while breathing room air; haemodynamic stability; ECG showing no significant arrhythmia, ST segment or T wave abnormalities. Patients may then be transferred from the PACU to the ward. Document the occurrence of adverse reactions within 24 hours postoperatively (eg, nausea and vomiting, Postoperative pain (NRS score > 4), Sleep disorder, Dizziness or headache).
Primary Indicator
Assess the patient’s VAS-A score at 7:00 am on the day of surgery.
Secondary Outcome Measures
Record VAS-A scores prior to administration, 20 minutes post-administration, and before anaesthetic induction. Heart rate variability coefficient (HR-CV) and mean arterial pressure variability coefficient (MAP-CV) were measured at multiple time points during the perioperative period, including: 07:00 on the day of surgery (T1), upon entering the operating theatre (T2), 10 minutes after induction of anaesthesia (T3), at the time of skin incision (T4), 30 minutes after the start of surgery (T5), 1 hour after the start of surgery (T6) and at extubation (T7), were used to assess intraoperative haemodynamic stability. Concurrently, record the number of vasoactive drug boluses administered in both groups and the consumption of Ciprofol during induction when patients failed to respond to verbal stimuli. The incidence of adverse reactions following drug intervention (eg, respiratory depression, hypotension, sinus bradycardia) and postoperative adverse reactions (postoperative pain, nausea and vomiting, somnolence, impaired consciousness, sleep disturbance) was assessed. The overall incidence of postoperative adverse events was used as a secondary outcome measure. Record changes in AIS scores in study participants before and after drug intervention. The 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) was used, with items rated from “Strongly disagree/Very dissatisfied” (1 point) to “Strongly agree/Very satisfied” (7 points). Higher scores indicate greater treatment satisfaction; a total score of ≥5 points indicates high treatment satisfaction.16 To evaluate patient satisfaction pre- and post-intervention. In addition, we collected demographic and clinical data, including age, BMI, educational attainment, ASA physical status classification, and history of previous anaesthesia or surgery.
Statistical Analysis
Normally distributed quantitative data are presented as mean±standard deviation (Mean±SD). Between-group comparisons employed independent samples t-tests, whilst within-group comparisons utilised repeated measures analysis of variance. Non-normally distributed quantitative data were presented as median (interquartile range) [M(Q1, Q3)]. Between-group comparisons employed the Mann–Whitney U-test (Wilcoxon rank-sum test). Whilst intragroup comparisons utilised non-parametric tests. Categorical data were expressed as [n(%)] and analysed using χ2-tests or Fisher’s exact probability test. P < 0.05 was considered statistically significant.
Sample Size Calculation
The primary outcome measure is the difference in VAS anxiety scores between the two groups at 7:00 on the day of surgery (V3).Based on the findings of the preliminary study, the expected difference in the mean of the primary outcome measures between the experimental group and the control group (μ1−μ2) =−0.7, with a standard deviation (SD) = 1.067. Assuming a two-tailed α = 0.05 and a power level of 90%, using PASS 15 software, the sample size for the experimental group was calculated as n1 = 50 subjects, and for the control group as n2 = 50 subjects. Accounting for a 20% attrition rate due to loss to follow-up or refusal to participate, the final minimum sample size required is 60 subjects per group, for a total of at least 120 subjects.
Results
Primary Outcome
A total of 496 patients scheduled for hysterectomy or myomectomy were initially enrolled; Of these, 376 patients did not meet the trial criteria, including 81 patients aged over 65, 263 patients who did not meet the criteria for an anxious state (HAMA score < 14), 15 patients who refused to participate in the trial, 3 patients who were unable to participate properly, and 14 patients with bradycardia. Ultimately, 120 patients (60 per group) completed the trial (Figure 1). No statistically significant differences existed between groups regarding demographic and clinical characteristics, including educational attainment, prior surgical history, ASA classification, and preoperative anxiety scores (Table 1).
Figure 1.
Trial Patient Screening Flowchart.
Table 1.
Comparison of General Patient Characteristics Between the Two Groups
| Group C (n=60) | Group D (n=60) | |
|---|---|---|
| Age (years) | 48 (43.25–51.75) | 49 (45–54) |
| BMI (kg/m2) | 23.95 (22.50–26.00) | 24.60 (22.80–26.00) |
| Level of education, n (%) | ||
| Primary school, n (%) | 5 (8.33%) | 3 (5.00%) |
| Junior high school, n (%) | 31 (51.67%) | 31 (51.67%) |
| High school, n (%) | 22 (36.67%) | 23 (38.33%) |
| ≥University, n (%) | 2 (3.33%) | 3 (5.00%) |
| Past surgical history, n (%) | ||
| None, n (%) | 30 (50.00%) | 28 (46.67%) |
| Surgery under local or regional anesthesia, n (%) | 15 (25.00%) | 19 (31.67%) |
| General anesthesia surgery, n (%) | 15 (25.00%) | 13 (21.67%) |
| Type of Surgery | ||
| Uterine fibroid removal surgery, n (%) | 15 (20.00%) | 10 (16.68%) |
| Hysterectomy, n (%) | 45 (80.00%) | 50 (83.32%) |
| HAMA Score | 18.00 (16.00–19.00) | 17.00 (16.00–18.00) |
| VAS-A Score | 5.350 (5.10–5.80) | 5.500 (5.13–5.80) |
| Surgery duration | 2.20 (1.83–2.65) | 2.56 (2.00–3.22) |
Note: Data are presented as the number of cases (n) or median (25th percentile-75th percentile).
Abbreviations: Group C, control group; Group D, dexmedetomidine group; BMI, body mass index; HAMA, Hamilton Anxiety Scale; VAS-A, Visual Analog Scale for Anxiety.
There was no statistically significant difference in preoperative anxiety levels between the two groups of patients. In terms of temporal trends, VAS-A scores in both groups reached their lowest point 20 minutes after drug administration, after which they gradually increased. However, at 20 minutes post-intervention, at 07:00 on the day of surgery, and prior to induction of anaesthesia, anxiety levels in Group D remained significantly lower than those in Group C (P < 0.05). This indicates that dexmedetomidine intervention effectively alleviated postoperative anxiety (Figure 2 and Table 2).
Figure 2.
VAS-A scores for both patient groups at different time points.
Notes: ns: P>0.05, *P<0.05, **P<0.01, ****P<0.0001.
Table 2.
VAS-A Scores for Both Patient Groups at Different Time Points
| Group C (n=60) | Group D (n=60) | P value | |
|---|---|---|---|
| V1 | 5.53±0.45 | 5.50±0.53 | >0.999 |
| V2 | 4.69±0.83 | 2.87±1.02 | <0.0001 |
| V3 | 5.92±0.89 | 4.77±0.82 | <0.0001 |
| V4 | 7.12±0.74 | 6.44±0.75 | 0.0499 |
Note: Data are presented as mean ± standard deviation.
Abbreviations: Group C, control group; Group D, dexmedetomidine group; V1, Prior to drug intervention; V2, Twenty minutes after the intervention; V3, 7:00 on the day of the operation; V4, During anesthesia induction.
Secondary Outcome
The coefficient of variation (CV) of mean arterial pressure (MAP-CV) and heart rate (HR-CV) was calculated for each patient to assess individual hemodynamic stability. The mean values of MAP-CV and HR-CV in the dexmedetomidine group (Group D) were significantly lower than those in the control group (Group C) (13.12±4.75% vs 7.02±2.88%, P<0.001; 10.81±3.86% vs 6.29±2.79%, P<0.001, respectively) (Table 3). These results indicated that dexmedetomidine effectively reduced the amplitude of hemodynamic fluctuations and significantly improved the individual stability of patients during surgery.To further characterize the variability within each group, the overall CV of the entire dataset was calculated for MAP and HR. Interestingly, the overall CV of MAP data was 36.21% in Group C and 40.96% in Group D; similarly, the overall CV of HR data was 35.69% in Group C and 44.40% in Group D (Table 4).This finding suggests that although dexmedetomidine improved the average hemodynamic stability of individual patients, the relative dispersion of the entire cohort of data in Group D was slightly larger. This discrepancy may be attributed to a higher degree of inter-individual variability in patients’ responses to dexmedetomidine administration.
Table 3.
Comparison of Individual Hemodynamic CV Values Between the Two Groups
| Index | Group C (n=60) | Group D (n=60) | P value |
|---|---|---|---|
| MAP-CV (%) | 13.12±4.75 | 7.02±2.88 | <0.001 |
| HR-CV (%) | 10.81±3.86 | 6.29±2.79 | <0.001 |
Note: Data are presented as mean ± standard deviation.
Abbreviations: Group C, control group; Group D, dexmedetomidine group; MAP-CV, coefficient of variation of mean arterial pressure; HR-CV, coefficient of variation of heart rate.
Table 4.
Overall Variability Within Each Group: Coefficient of Variation (CV) of All Data
| Index | Group C (n=60) | Group D (n=60) |
|---|---|---|
| CV of MAP data (%) | 36.21 | 40.96 |
| CV of HR data (%) | 35.69 | 44.40 |
Note: Data are presented as a percentage (%).
Abbreviations: Group C, control group; Group D, dexmedetomidine group; CV, coefficient of variation; MAP, mean arterial pressure; HR, heart rate.
Patients in Group D showed a statistically significant reduction in the amount of Ciprofol consumed (P<0.0001) (Figure 3B) and the number of intraoperative vasoactive drug boluses compared with Group C (P<0.01) (Table 5 and Figure 3A).
Figure 3.
The number of intraoperative vasoactive drug boluses (A) and the consumption of ciprofol at loss of responsiveness during anesthesia induction (B).
Notes: ns: P>0.05, *P<0.05, **P<0.01, ****P<0.0001.
Table 5.
The Dose of Ciprofol Administered at Loss of Consciousness During Anesthesia Induction and the Number of Intraoperative Vasoactive Drug Boluses
| Group C (n=60) | Group D (n=60) | P value | |
|---|---|---|---|
| Consumption of ciprofol (mg/kg) | 0.38±0.03 | 0.34±0.02 | <0.0001 |
| AVDA (times) | 1.63±1.54 | 0.92±0.81 | <0.01 |
Note: Data are presented as mean ± standard deviation.
Abbreviations: Group C, control group; Group D, dexmedetomidine group; AVDA, number of additional vasoactive drug administrations.
Regarding sleep improvement, patients in Group D had significantly lower AIS scores than those in Group C (P < 0.0001) (Table 6 and Figure 4A). Furthermore, patients in Group D reported significantly higher TSQM-9 satisfaction scores than those in Group C, which was statistically significant (P < 0.0001) (Table 7 and Figure 4B).
Table 6.
Comparison of Athens Insomnia Scale (AIS) Scores Between the Two Groups Before and After Pharmacological Intervention
| Group | Before | After | P value |
|---|---|---|---|
| Group C | 4.12±1.76 | 4.03±1.83 | 0.362 |
| Group D | 3.93±1.44 | 2.60±0.978 | <0.0001 |
| P-value | 0.765 | <0.0001 | – |
Note: Data are presented as mean ± standard deviation.
Abbreviations: Group C, control group; Group D, dexmedetomidine group; Before, AIS score before pharmacological intervention; After, AIS score following pharmacological intervention.
Figure 4.
Comparison of AIS scores (A) and TSQM-9 scores (B) between the two groups of patients.
Notes: ns: P>0.05, *P<0.05, **P<0.01, ****P<0.0001.
Table 7.
Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Scores of the Two Groups After Pharmacological Intervention
| Measure | Group C (n=60) | Group D (n=60) | P value |
|---|---|---|---|
| TSQM-9 | 4.13±0.86 | 5.04±0.69 | <0.0001 |
Note: Data are presented as mean ± standard deviation.
Abbreviations: Group C, control group; Group D, dexmedetomidine group; TSQM-9, Treatment Satisfaction Questionnaire for Medication – 9-item.
Adverse Reactions
There was no statistically significant difference in the incidence of postoperative adverse events between the two groups. However, the overall incidence of postoperative adverse events in Group D was significantly lower than that in Group C (60% vs 80%, P < 0.05) (Table 8). Although the incidence of adverse reactions following drug intervention was slightly higher in Group D, this difference was not statistically significant (8.33% vs 3.88%, P > 0.05). All adverse reactions following drug intervention remained within safe and manageable limits and did not affect the subsequent progress of the study. This indicates that low-dose dexmedetomidine significantly reduced the overall incidence of postoperative adverse reactions whilst maintaining safety (P > 0.05) (Table 9). All adverse reactions remained within safe and manageable limits and did not affect the subsequent progress of the study. This indicates that low-dose dexmedetomidine significantly reduced the overall incidence of postoperative adverse reactions whilst maintaining good safety.
Table 8.
Comparison of Postoperative Complication Rates Between the Two Patient Groups
| Postoperative Complications | Group C (n=60) | Group D (n=60) | P value |
|---|---|---|---|
| Nausea and vomiting | 11 (18.33%) | 8 (13.33%) | 0.476 |
| Postoperative pain (NRS score > 4) | 22 (36.67%) | 15 (25.00%) | 0.135 |
| Sleep disorder | 13 (21.67%) | 12 (20.00%) | 0.828 |
| Dizziness or headache | 2 (3.33%) | 1 (1.67%) | 0.617 |
| Overall incidence rate | 48 (80%) | 36 (60%) | 0.019 |
Notes: Data are presented as the number of cases (n) and the percentage (%). Some patients presented with multiple complications, with the overall incidence rate expressed as a cumulative rate. All of the above adverse reactions were recorded within 24 hours of surgery. Overall incidence: the proportion of patients who experienced at least one of the above adverse reactions within 24 hours of surgery.
Abbreviations: Group C, control group; Group D, dexmedetomidine group; NRS, numerical rating scale.
Table 9.
Comparison of the Incidence of Adverse Reactions Between the Two Groups Following Drug Intervention
| Post-Interventional Complications of Pharmacotherapy | Group C (n=60) | Group D (n=60) | P value |
|---|---|---|---|
| Bradycardia | 1 (1.67%) | 2 (3.33%) | 1.000 |
| Hypotension | 0 | 0 | |
| Hypoxemia | 0 | 1 (1.67%) | 1.000 |
| Dizziness or headache | 1 (1.67%) | 2 (3.33%) | 1.000 |
| Overall incidence rate | 2 (3.33%) | 5 (8.33%) | 0.413 |
Notes: Data are presented as the number of cases (n) and percentage (%). Some patients presented with multiple complications, with the overall incidence rate expressed as a cumulative rate. Incidence of adverse reactions following drug intervention: the proportion of patients who experience adverse reactions between the end of the drug intervention and the preoperative period.
Abbreviations: Group C, control group; Group D, dexmedetomidine group.
Discussion
The results of this study indicate that the use of demetazodine hydrochloride nasal spray on the evening prior to hysteroscopic surgery reduces patients’ anxiety scores whilst maintaining more stable haemodynamic parameters. Anxiety is a common preoperative symptom, frequently manifesting as sweating, urinary urgency and frequency, restlessness, and insomnia.17 Surgery involving the uterus often gives rise to a range of anxieties, including concerns about loss of fertility, changes to female characteristics, and a decline in quality of life following the procedure. This complex psychological stress involving “organ function-social role-self-perception” constitutes the core mechanism underpinning preoperative anxiety in these patients.6,18,19 Research indicates that female patients are more prone to anxiety than male patients, and excessive anxiety is often associated with a higher rate of postoperative adverse reactions.6,20,21 Therefore, alleviating preoperative anxiety in gynaecological patients is of paramount importance.
This study found that, compared with Group C, Group D had lower preoperative anxiety scores at all three time points, suggesting that intranasal dexmedetomidine administered the night before surgery effectively alleviates preoperative anxiety in gynaecological patients. Dexmedetomidine hydrochloride nasal spray is a highly selective α2-adrenergic receptor agonist administered nasally, with a drug half-life of approximately 3.09–4.28 hours. However, our study suggests its anxiolytic effects may persist longer, potentially through underlying mechanisms. Preoperative anxiety may arise from excessive excitation of noradrenergic (NE) neurons in the central locus coeruleus (LC) region. Dexmedetomidine, by activating α2 receptors, inhibits adenylate cyclase (AC) activity and reduces intracellular calcium signalling, thereby persistently suppressing excessive discharge of LC-NE neurons.22,23 Following suppression of LC-NE neuronal activity, noradrenaline release in the medial prefrontal cortex (mPFC) diminishes, concurrently reducing serum cortisol (a stress marker) levels, ultimately alleviating anxiety behaviours.24,25 The high selectivity of dexmedetomidine for α2 adrenergic receptors (α2/α1 = 1600:1) enables precise activation of LC α2 receptors at low doses, thereby inhibiting sympathetic activity and producing sustained sedative and anxiolytic effects. This allows maintenance of neural circuit stability without requiring high doses.26,27 Jiang et al found that a single low dose of dexmedetomidine produced an anxiolytic effect lasting ≥3 days in an anxious mouse model, accompanied by reduced serum cortisol (a stress marker) levels. Dexmedetomidine maintained anxiety relief by suppressing the LC-NE-mPFC circuit via α2 receptor mediation, with circuit excitability taking several days to recover, highlighting its potential as a novel long-acting therapeutic strategy for anxiety disorders.24 The dexmedetomidine group demonstrated significantly greater haemodynamic stability during surgery, as evidenced by lower coefficients of variation for mean arterial pressure (MAP) and heart rate (HR). This antisympathetic effect helps to mitigate marked fluctuations during anaesthetic induction, skin incision and extubation, consistent with dexmedetomidine’s role as an adjunctive anaesthetic agent that stabilises circulation without significantly impairing cardiac function. This mitigates perioperative haemodynamic fluctuations that damage organs,28 providing peripheral support for its central long-acting anxiolytic effects. Concurrently, prolonged suppression of sympathetic excitation reduces postoperative agitation and the incidence of postoperative cognitive dysfunction (POCD). As it operates independently of the GABA system, it does not induce significant respiratory depression, further lowering the risk of postoperative respiratory complications. This characteristic facilitates widespread use for short-term sedation in the ICU, with its protective effects on circulatory and neurological function persisting even after discontinuation.29 Upon binding to α2 adrenergic receptors, inhibits adenylate cyclase (AC) activity via G protein-coupled signalling pathways, thereby reducing intracellular cAMP levels and decreasing calcium channel opening. This process forms a “negative feedback regulation” that suppresses noradrenaline (NE) release, diminishes pain signal transmission, and indirectly weakens the “pain-anxiety” vicious cycle.30,31 At the spinal level, it inhibits the release of noxious neurotransmitters (such as substance P), further reducing patients’ analgesic requirements for opioids and thereby lowering the incidence of postoperative adverse reactions associated with opioid use (eg, respiratory depression, nausea, and vomiting),32 Li observed that preoperative administration of dexmedetomidine to patients undergoing thoracic surgery resulted in decreased postoperative cardiac troponin I (cTnI) levels, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and enhanced intraoperative haemodynamic stability, demonstrating the cardiovascular protective effects of dexmedetomidine.33 Our study observed similar findings. Specifically, the incidence of adverse events following drug intervention showed no significant difference compared to the placebo group, with adverse reactions remaining within manageable limits. However, the incidence of postoperative adverse reactions was markedly lower than in the placebo group, accompanied by greater haemodynamic stability and reduced anaesthetic consumption. These results are consistent with the pharmacological properties of dexmedetomidine.
This study employed a combined assessment of anxiety using the VAS-A and HAMA scales; these two complementary methods provide a more comprehensive and accurate reflection of the anti-anxiety effect. The results indicate that preoperative dexmedetomidine hydrochloride significantly reduced VAS-A scores at all time points, effectively alleviating preoperative anxiety, and thus provides a reliable basis for optimising perioperative management and enhancing anaesthetic safety and patient satisfaction. However, it should be noted that the VAS-A is merely a subjective self-assessment tool and is susceptible to factors such as mood and the environment; therefore, the clinical significance of a decrease in its score must be interpreted with caution, as a modest reduction does not necessarily equate to genuine relief from anxiety or improved clinical benefits.
Our study has certain limitations that must be acknowledged. Firstly, the research was conducted at a single centre, and the sample size was limited. A total of 496 patients were screened, but only 120 were ultimately randomised; this may introduce potential selection bias and limit the statistical power to detect clinical differences. Secondly, the study was limited to women who underwent hysterectomy or myomectomy at a single centre, resulting in poor external validity; it remains uncertain whether the findings can be generalised to other surgical populations or settings.Consequently, the statistical results for some indicators may not fully reflect genuine clinical differences. Furthermore, we did not conduct a more detailed exploration of the optimal dose of dexmedetomidine hydrochloride. We believe that future clinical studies with larger sample sizes and more comprehensive monitoring will provide a more systematic and thorough basis for evaluating the safety and efficacy of dexmedetomidine hydrochloride nasal spray in gynaecological surgery patients.
Conclusion
In this single-center randomized controlled trial, preoperative intranasal administration of 50 μg dexmedetomidine was associated with lower preoperative anxiety scores and favorable perioperative trends, including improved sleep quality, more stable intraoperative hemodynamics, and reduced postoperative adverse events in patients undergoing hysterectomy or myomectomy. These findings should be interpreted with caution, given the single-center design, selected study population, and small sample size. Further large-scale, multicenter studies are required to confirm the generalizability and long-term efficacy of this approach.
Funding Statement
This clinical research was fully supported by The Bethune Charitable Foundation’s Enze Medical Research Project on Pain Management (Grant No. ezmr2023-026), which provided important financial and technical support throughout the whole study.
Data Sharing Statement
The datasets used and/or analyzed in the current study are available from the corresponding author Bao Lang upon reasonable request.
Disclosure
The authors report no conflicts of interest in this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed in the current study are available from the corresponding author Bao Lang upon reasonable request.