Efficacy of Intraoperative Intravenous Dexmedetomidine on Postoperative Analgesia among Patients following Gynecological Surgeries – A Comparative Observational Study

Abstract

Context:

Dexmedetomidine has been used as an adjuvant to minimize the adverse effects associated with opioids, either in the form of intravenous injection or intravenous infusion.

Aim:

The present study aimed to compare the efficacy of dexmedetomidine when administered via intravenous infusion and intravenous bolus injection.

Materials and Methods:

A comparative observational study was conducted among 1000 participants aged 35–65 years with American Society of Anesthesiologists physical status I/II, scheduled to undergo elective gynecological surgeries. Participants were divided into Group D (received a loading dose of bolus 0.5 µg/kg, followed by 0.3 µg/kg/h intravenous infusion of dexmedetomidine) and Group C (control group) 15 min before the induction of anesthesia. Hemodynamic variables, recovery time, rescue analgesia, pain scores, and any adverse events were recorded.

Results:

Participants in Group D had lower hemodynamic parameters (after 1 h till the end of surgery) (P < 0.05). Participants in Group D took fewer rescue analgesics compared to Group C (P = 0.001), and recovery time was prolonged in Group D (P = 0.001). Pain scores were lower in Group D compared to Group C (P = 0.001).

Conclusion:

A loading dose of intravenous bolus followed by intravenous infusion of dexmedetomidine is a valuable adjunct in the perioperative management of such patients, offering potential benefits in enhancing recovery and reducing the need for postsurgical analgesia.

INTRODUCTION

Postoperative pain is an undesirable and expected byproduct of surgical procedures.[1] It is estimated that about 4.7%–95.2% of women undergoing gynecological surgeries experience at least one episode of pain in the first 24 h.[,3,4] Proper pain control not only improves patient satisfaction but also facilitates faster recovery, reduces hospital stays, and lowers the risk of complications such as chronic pain syndromes and reduced mobility.[5] Postoperative pain management should be one of the top priorities of any healthcare setting where surgical procedures are carried out.

Various drugs and techniques, such as intravenous opioids, nonsteroidal anti-inflammatory drugs, epidural analgesia, and patient-controlled intravenous analgesia, have been used to manage postoperative pain. However, according to reports, in a large cohort study, about 86% of participants already on multimodal analgesia required opioids.[6] Higher doses of opioids are associated with unwanted side effects. Therefore, identifying adjunct therapies that enhance analgesia while minimizing side effects continues to be a primary goal in the field of anesthesiology.

Dexmedetomidine is one such agent that is commonly and increasingly being used in a wide variety of clinical contexts. It is a potent, highly selective, and specific α₂-adrenoreceptor agonist that has sedative, hypnotic, analgesic, and sympatholytic properties with minimum changes in respiratory variables.[7,8] It lowers the tachycardic response to endotracheal intubation and assures greater hemodynamic stability during the intraoperative period.[7] The incorporation of dexmedetomidine as an adjunct in perioperative care is well-established, yet its application in gynecological surgeries remains a relatively underexplored area.

Intravenous infusion of dexmedetomidine is routinely used in anesthesia for achieving a deeper plane of anesthesia. Numerous studies regarding injection dexmedetomidine have been conducted either in the form of intravenous infusion or intravenous injection, but this study will lay its focus on combining both intravenous infusion and intravenous bolus for postoperative analgesia and recovery. Hence, the primary aim of our study was to compare the effect of intraoperative infusion of dexmedetomidine on postoperative analgesic requirement and recovery.

Aim

To study the efficacy of intraoperative dexmedetomidine on postoperative analgesia and recovery in patients undergoing gynecological procedures.

Objectives

• To study the analgesic requirement and sedative score between the two groups

• To compare the recovery time between the two groups

• To study the adverse effects of dexmedetomidine.

MATERIALS AND METHODS

Study design and setting

A hospital-based comparative study was conducted at a tertiary care providing teaching hospital in South India from January 2023 to December 2024.

Study participants

Female patients in the age range of 35–65 years, belonging to the American Society of Anesthesiologists (ASA) – physical status I to II.

Inclusion criteria

Those who provided consent and were scheduled to undergo elective gynecological surgeries under general anesthesia of <3 h of duration were included as study participants.

Exclusion criteria

Patients who did not provide consent, with severe systemic disease, and those requiring emergency gynecological surgeries were excluded from the study.

Sample size

The sample size was calculated for comparison of two independent means, assuming a two-sided α error of 5% and 80% power. A clinically expected difference in pain scores of 13.7 with a standard deviation of 24.34 was considered. The sample size per group was calculated using the formula:

Where Z_α/2 = 1.96, Z_β = 0.84, σ = 24.34, and Δ = 13.7

Sample size per group: 50 participants

Total Sample Size: 100 participants.

Outcome variables

Primary

1. Postoperative analgesic requirement

2. Recovery time.

Secondary

1. Hemodynamic variables

2. Intraoperative blood loss.

Method

The study was initiated following approval from the Institutional Ethics Committee and after obtaining written informed consent during a thorough preanesthetic workup. On the day of surgery, the participants were shifted to the operating theatre and monitored with electrocardiography, pulse oximetry, and noninvasive blood pressure measurement using ASA standard monitors. The participants were conveniently divided into two groups (Group D and Group C) at the discretion of the attending anesthesiologist. Randomization was performed using a computer-generated sequence, and the study was conducted in a double-blind manner, with both participants and investigators unaware of group assignments. About 15 min before the induction of anesthesia, participants in Group D received intravenous bolus dexmedetomidine 0.5 µg/kg over 15 min, followed by 0.3 µg/kg/h infusion of dexmedetomidine. Participants in Group C did not receive dexmedetomidine and acted as the control group.

This was followed by intravenous administration of 0.02 mg/kg midazolam, 2 µg/kg fentanyl, and 0.2 mg glycopyrrolate. Patients were preoxygenated with 100% oxygen using an appropriately sized face mask. Induction of anesthesia was then initiated by injection of Propofol 2 mg/kg in a titrated dose. Intubation was facilitated with an injection of Vecuronium 0.1 mg/kg. Participants were intubated after 90 s with an appropriately sized endotracheal tube, after confirming the bilateral equal air entry, and it was ensured that the endotracheal tube was fixed. Participants were maintained with oxygen: nitrous (50:50) and an appropriate amount of sevoflurane to maintain an MAC of 1. At the end of surgery, the neuromuscular blockade was reversed with 0.05 mg/kg intravenous neostigmine and 0.01 mg/kg of glycopyrrolate. After the completion of the surgery, study participants were shifted to the postoperative recovery room for observation for 24 h. During this period, rescue analgesia of injection paracetamol 15 mL/kg was administered if the Visual Analog Scale (VAS) score was more than 3.

Study tool and parameters assessed

A predesigned semistructured pro forma [Annexure A] was used to collect the data by the investigator. The hemodynamic parameters (heart rate, blood pressure, mean arterial pressure, and oxygen saturation) were recorded at baseline, after injecting the drug, after intubation, and every 15 min till the end of the surgery. In addition, the dose of anesthetic drug required, intraoperative blood loss, recovery time after cutting all the anesthetic drugs, and postoperative analgesic requirement were noted. Pain was assessed using the VAS with scores ranging from 0 “no pain” to 10 “the worst imaginable pain”, and side effects such as hypotension, bradycardia, hypertension, and tachycardia were also noted. The data of various outcome measures were recorded by another resident who was not a part of the study.

Statistical analysis

The data were analyzed using SPSS for Windows (SPSS ver. 26, IBM Corp., Armonk, NY, USA). Quantitative data were presented as mean (standard deviation) or median (interquartile range) based on normality. Continuous data between the groups were compared using the unpaired t-test, and categorical data were summarized as frequency (%) and compared using the Chi-Square test. The data were presented using graphs and tables. P < 0.05 was considered statistically significant.

RESULTS

Patient enrollment

We included female patients aged 35–65 years belonging to the ASA physical status I and II, who were scheduled to undergo elective gynecological surgeries under general anesthesia of <3 h duration, and were enrolled in the study.

Demographic characteristics

Basic demographic characteristics are shown in Table 1. A total of 100 patients who fulfilled the study criteria were included, with 50 patients in each group. The majority of participants in both groups belonged to the 41–50 years’ age group, followed by the 30–40 and 51–60 years’ age groups. The age distribution between the two groups was comparable, with no statistically significant difference observed (P = 0.33) [Table 1].

Table 1.

Distribution of participants according to age groups

Age group	Group D, n (%)	Group C, n (%)	P
30–40	14 (28.0)	20 (40.0)
41–50	26 (52.0)	19 (38.0)	0.33
51–60	10 (20.0)	11 (22.0)	NS
Total	50 (100.0)	50 (100.0)

NS using the Chi-square test. NS=Not significant

Intraoperative hemodynamic changes

Participants in Group D demonstrated a significantly higher heart rate following administration of the study drug (P = 0.04) and after intubation (P = 0.02) compared to Group C. Heart rate values remained comparable between the groups during the early intraoperative period at 15 and 30 min. From 45 min onward, heart rate in Group D showed a progressive and significant reduction compared to Group C, which persisted from 1 h up to 2 h intraoperatively (P = 0.001 at most time points). A subsequent rise in heart rate was observed in Group D toward the later part of surgery, with statistically significant differences at 2 h 15 min and 2 h 30 min (P = 0.001) [Table 2]. Systolic blood pressure was significantly higher in Group D at baseline (P = 0.01) and following drug administration (P = 0.05). After intubation, systolic blood pressure was significantly lower in Group D compared to Group C (P = 0.01). From 1 h onward until the end of surgery, systolic blood pressure remained consistently and significantly lower in Group D compared to the control group (P < 0.01 at most time points). Diastolic blood pressure followed a similar pattern, with significantly higher values in Group D at baseline (P = 0.01) and after drug administration (P = 0.001). During the intraoperative period, diastolic blood pressure was significantly lower in Group D at several later time points, particularly from 45 min onward [Table 3].

Table 2.

Comparison of mean heart rate between the groups

	Group D, mean±SD	Group C, mean±SD	P
Baseline	84.7±9.0	84.9±12.4	0.92
After the injection of drug	86.2±6.9	81.9±12.9	0.04*
After induction	85.5±4.7	72.7±11.3	0.001**
After intubation	94.3±6.6	89.8±12.0	0.02*
15 min	88.8±3.9	85.8±14.3	0.14
30 min	81.0±3.5	81.2±12.7	0.92
45 min	74.9±3.9	72.1±6.8	0.01*
1 h	70.3±3.4	77.4±11.9	0.001**
1 h 15 min	67.9±2.2	77.7±10.9	0.001**
1 h 30 min	67.4±2.8	77.9±9.1	0.001**
1 h 45 min	66.7±3.7	78.4±8.5	P0.001**
2 h	67.5±5.7	79.6±9.3	0.001**
2 h 15 min	90.6±16.1	78.0±10.9	0.001**
2 h 30 min	92.2±13.2	70.4±6.6	0.001**

*Statistically significant at P<0.05, **P<0.01 using Unpaired t-test. SD=Standard deviation

Table 3.

Comparison of mean systolic and diastolic blood pressure between the groups

Time interval	SBP (mmHg)		P	DBP (mmHg), mean±SD		P
	Group D, mean±SD	Group C, mean±SD		Group D, mean±SD	Group C, mean±SD
Baseline	128.8±8.8	122.9±14.5	0.01*	84.3±9.4	79.0±11.2	0.01*
After injection of drug	120.0±9.6	115.3±14.1	0.05*	80.1±7.4	73.0±9.5	0.001**
After induction	115.6±8.5	111.5±13.3	0.06	75.8±5.0	76.3±10.7	0.75
After intubation	124.2±8.0	131.3±17.9	0.01*	81.0±8.2	87.3±12.4	0.003**
15 min	119.4±8.1	118.8±12.4	0.74	78.1±5.7	75.2±10.6	0.10
30 min	119.2±4.1	119.4±9.4	0.89	78.5±5.6	80.6±12.5	0.29
45 min	116.4±3.7	117.7±9.1	0.34	73.3±5.5	75.9±7.4	0.04*
1 h	113.7±3.8	119.8±10.6	0.001**	72.2±6.0	83.2±12.6	0.001**
1 h 15 min	111.0±4.5	120.5±10.3	0.001**	74.9±4.6	73.4±9.4	0.32
1 h 30 min	110.8±4.5	123.5±8.6	0.001**	72.8±4.0	76.1±9.7	0.03*
1 h 45 min	109.8±5.4	112.0±12.8	0.26	75.7±4.1	72.3±7.7	0.006**
2 h	109.3±3.7	125.1±8.6	0.001**	75.6±3.5	75.5±9.3	0.93
2 h 15 min	107.7±6.3	120.4±9.2	0.001**	88.4±31.9	74.0±9.0	0.002**
2 h 30 min	109.3±3.7	116.9±8.6	0.001**	75.6±3.5	76.6±7.3	0.40

*Statistically significant at P<0.05, **P<0.01 using unpaired t-test. SD=Standard deviation, SBP=Systolic blood pressure, DBP=Diastolic blood pressure

Peripheral oxygen saturation remained comparable between the two groups throughout the intraoperative period. The time to recovery was significantly prolonged in Group D compared to Group C (13.3 ± 3.9 min vs. 5.3 ± 2.9 min; P = 0.001). Participants in Group C required rescue analgesia more frequently and earlier than those in Group D, with statistically significant differences observed at all assessed postoperative time points, including immediately postoperatively and up to 24 h (P = 0.001). Furthermore, postoperative pain scores assessed using the VAS were significantly lower in Group D at all time intervals when compared to Group C (P = 0.001), indicating superior postoperative analgesia in Group D [Table 4].

Table 4.

Comparison of recovery time, frequency of rescue analgesia, and pain scores between the groups

	Group D	Group C	P
Time to recovery, mean±SD	13.3±3.9	5.3±2.9	0.001*
Rescue analgesia, n (%)
Immediately	0	16 (32)	0.001†
2 h	0	28 (56)	0.001†
4 h	6 (12)	22 (44)	0.001†
6 h	20 (40)	34 (68)	0.001†
12 h	5 (10)	35 (70)	0.001†
24 h	0	14 (28)	0.001†
VAS (pain) scores, mean±SD
Immediately	2.2±0.7	3.5±0.9	0.001*
2 h	3.0±0.8	4.1±1.2	0.001*
4 h	2.5±0.9	3.7±1.3	0.001*
6 h	1.9±0.8	3.4±1.0	0.001*
12 h	1.3±0.6	3.2±1.0	0.001*
24 h	1.2±0.4	2.5±0.7	0.001*

*Statistically significant using Unpaired t-test, ^†Chi-square test. SD=Standard deviation, VAS=Visual Analog Scale

DISCUSSION

The present study was conducted to determine the efficacy of dexmedetomidine in reducing postoperative pain after intraoperative administration of dexmedetomidine among women undergoing gynecological procedures. The findings from the study revealed that an intraoperative intravenous administration of 0.5 µg/kg of bolus dexmedetomidine over 15 min, followed by an infusion of dexmedetomidine at 0.3 µg/kg/h, was effective in reducing postoperative pain up to 24 h after surgery. In addition, participants in Group D reported reduced consumption of rescue analgesia, had a prolonged recovery time, and had stable hemodynamic parameters. Furthermore, the results were independent of any age-based variations.

In the present study, intravenous administration of dexmedetomidine was associated with reduced rescue analgesia at all intervals when compared to the control group. The beneficial effect of dexmedetomidine was also reported by Vora et al., who reported a significant reduction in intraoperative consumption of fentanyl among participants receiving dexmedetomidine when compared to participants in the control group.[9] In addition, McQueen-Shadfar et al. reported that participants in the dexmedetomidine group received significantly lower doses of opioids during their stay in the postanesthesia care unit.[10] In addition, the present study also reported a significant reduction in subsequent postoperative pain, indicating a lasting beneficial effect after surgery and during recovery. Our findings are in line with the reports from studies conducted by Li et al.,[11] Vora et al.,[9] Wu et al.,[12] and Patel et al.[13] All the abovementioned studies reported lower pain scores when compared to control groups. The prolonged analgesic effect of dexmedetomidine can largely be attributed to its highly selective α-2 agonist adrenoceptor located on the pre- and postsynaptic membranes within the locus ceruleus, thereby modulating the nociceptive signals by disrupting the functional connectivity with higher-order brain centers. However, the reduction in pain scores could also be attributed to rescue analgesia that was administered to participants for elevated pain.

In the present study, we observed relatively stable hemodynamic parameters among our participants who received dexmedetomidine, and none of the participants experienced any adverse effects. Overall, we observed an initial rise and subsequent decrease in heart rate and blood pressure. The reduction in heart rate and blood pressure began after 1 h till the end of surgery. This finding of a subsequent reduction in hemodynamic parameters was supported by many studies reported in the literature. Wang et al. and Chavan et al. reported a significant decrease in heart rate,[14,15] while Li et al. reported a significant reduction in heart rate and blood pressure.[11] Vora et al. reported a significant reduction in heart rate and mean arterial pressure,[9] while Nishit et al. reported an intraoperative decrease in diastolic blood pressure compared to the control group.[16] These findings suggest that dexmedetomidine had a more significant effect on reducing blood pressure during surgery, thereby contributing to better intraoperative cardiovascular stability. Ideally, dexmedetomidine induces hemodynamic changes, such as hypertension, hypotension, and bradycardia, especially after a loading dose. It has been demonstrated that dexmedetomidine has a biphasic response with a tendency to initially elevate the blood pressure by increasing the peripheral vascular resistance. This, in turn, leads to an increased parasympathetic tone, leading to a reduction in heart rate and blood pressure.[17,18] The present study did not reveal any significant difference in oxygen saturation between the groups.

The mean recovery time was found to be significantly prolonged among participants in the dexmedetomidine group. The prolonged recovery time highlights the potent sedative effect of dexmedetomidine, which contributes to deeper anesthesia and prolonged postoperative sedation. Patel et al., in their study, reported better postanesthesia recovery scores in the control group when compared to the test group 30 min after extubation.[13] Chavan et al. found similar recovery from participants in both the control and test groups.[15] This difference may be due to variations in dexmedetomidine dosage, infusion duration, and anesthetic protocols, as higher doses prolong sedation and delay recovery. Patient factors such as comorbidities and metabolism could also influence anesthetic clearance. The compared studies used the modified Aldrete’s score, which assesses broader recovery parameters, leading to differing conclusions.

The dosage of dexmedetomidine used in the present study was kept at 0.5 µg/kg, which provided stable hemodynamic parameters, reduced postoperative requirement of rescue analgesia, lower pain scores postoperatively, but a slightly prolonged recovery time. Ye et al. reported similar results with a dosage of 0.6 µg/kg when compared to 0.8 µg/kg. The latter dose was associated with delayed respiratory recovery, extubation, and increased incidence of bradycardia.[19] It proves that a dose of 0.5 µg/kg dexmedetomidine was sufficient in reducing postoperative pain.

This study had a clear comparison between two groups, a well-controlled hospital setting, and the inclusion of multiple outcome variables enhances the comprehensiveness of the evaluation. However, limitations include the use of convenience sampling and a lack of a randomized study design, which may not place the results at a higher hierarchy of evidence. In addition, the study’s single-institution focus and potential reporting biases may affect the results’ generalizability.

CONCLUSION

Within the parameters of the present study, it can be concluded that an intraoperative intravenous bolus administration of 0.5 µg/kg dexmedetomidine, over 15 min, followed by an infusion of 0.3 µg/kg/h dexmedetomidine, not only enhances cardiovascular stability but also improves postoperative pain control and accelerates recovery in patients undergoing gynecological procedures. Therefore, dexmedetomidine may be considered a valuable adjunct in the perioperative management of such patients, offering potential benefits in enhancing recovery and reducing the need for postsurgical analgesia.

Informed consent statement

Informed consent was taken by the investigator after explaining the purpose of the study. The freedom to withdraw from the study at any time during the study was also explained before taking the informed consent.

Data availability statement

The data that support the study are available on request from the corresponding author of the study (can be contacted via e-mail).

Ethical consideration

The study was approved by the Institutional Scientific and Ethics Committee [Protocol number: IECKMCMLR-03/2023/86] and registered in the Clinical Trials Registry (CTRI/2024/04/065270). The study was conducted in accordance with the Helsinki Declaration.

Conflicts of interest

There are no conflicts of interest.

ANNEXURE A

PROFORMA

• Age/Sex:

• Phone number:

• Patient identification:

• Address:

• Date of admission:

• Date of surgery:

• Provisional diagnosis:

• Proposed surgery:

• Study group:

• PREOPERATIVE EXAMINATION:

1. General Physical Examination:

Height: Weight: BMI:

Pulse: BP: RR: SpO2:

Airway Examination:

•Mallampati Grading:

3. ASA-PS:

4. Systemic examination: Cardiovascular system Respiratory system Central nervous system

• INVESTIGATIONS:

• Hemoglobin:

• Total count,

• Differential count

• Platelet count

• Random blood sugar

• Serum electrolytes (if indiacted)

• Blood urea (if indicated)

• Serum creatinine (if indicated)

• PT/INR (If indicated)

• ECG (if indicated)

• ECHO (if indicated)

MONITORING CHART

Parameters	Heart rate	Systolic bp	Diastolic bp	Mean arterial bp	Oxygen saturation
Base line vitals
After injection of dexmeditomidine
After the induction
After laryngoscopy and intubtion

Intraoperative hemodynamic parameters:

Time	Heart rate	Systolic bp	Diastolic bp	Mean arterial bp	Oxygen saturation
15 Min
30 Min
45 Min
1 Hour
1 Hour 15 min
1 Hour 30 min
1 Hour 45 min
2 Hours
2 Hour 15 min
2 Hour 30 min
2 Hour 45 min
3 Hours

Dexmedetomidine infusion stopped at:

Time of recovery:

Intraoperative opioids:

Intraoperative blood loss:

Postoperative analgesic requirement:

Drug	Immediate post-op	2 Hour	4 Hour	6 Hour	12 Hour	24 Hour

	Immediate post-op	2 Hour	4 Hour	6 Hour	12 Hour	24 Hour
Vas score

Ramsay sedation score (1 to 6):

Other drugs given:

Adverse effects:

Funding Statement

Nil.