Journal of Medical Society

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 33  |  Issue : 1  |  Page : 20--27

A comparative study of ropivacaine versus ropivacaine plus dexmedetomidine under epidural anesthesia in lower limb surgeries


Ashem Jack Meitei, Tikendrajit Ningombam, Takhelmayum Hemjit Singh, Gojendra Rajkumar, N Anita Devi, Yumnam Arunkumar Singh 
 Department of Anaesthesiology and Critical Care, Regional Institute of Medical Sciences, Imphal, Manipur, India

Correspondence Address:
Takhelmayum Hemjit Singh
Department of Anaesthesiology and Critical Care, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
India

Abstract

Background: Adjuvants are being used with local anesthetics for prolongation of intra- and post-operative analgesia. The aim is to compare epidural ropivacaine alone and ropivacaine with dexmedetomidine on block characteristics, hemodynamics, and postoperative analgesia. Materials and Methods: Following Institutional Ethical Committee approval and written informed consent from all the patients. This study was conducted on 50 patients of American Society of Anesthesiologists Grade I and II, age between 20 and 65 years of either sex undergoing lower limb surgeries under epidural anesthesia. The patients were randomly allocated into two groups. Group R (n = 25) received 150 mg of 0.75% ropivacaine diluted to 22 ml normal saline (NS), and Group RD (n = 25) received 150 mg of 0.75% ropivacaine plus dexmedetomidine 1 μg/kg diluted to 22 ml of NS. Two groups were compared with respect to hemodynamic changes, block characteristics, time to regression at S1 dermatome and time to the first dose of rescue analgesia for 24 h, sedation score, and side effects. Data were analyzed statistically using the Chi-square test, Fisher's exact test, and Student's t-test.P < 0.05 was considered to be statistically significant andP < 0.001 as highly significant. Results: Significant difference was observed in relation to the duration of sensory block (391.68 ± 33.404 min in Group R and 529.36 ± 58.125 min in Group RD [P = 0.000]), duration of motor block (264.96 ± 30.788 min in Group R and 390.44 ± 37.994 min in Group RD [P = 0.000]), duration of postoperative analgesia (368.40 ± 52.366 min in Group R and 512.36 ± 55.815 min in Group RD [P = 0.000]), and consequently low doses of rescue analgesia in Group RD (1.96 ± 0.455) as compared to Group R (2.80 ± 0.418) (P = 0.000). Sedation score was significantly more in Group RD in the postoperative period. Conclusion: Addition of dexmedetomidine to ropivacaine provides stable hemodynamics, prolonged sensory and motor block, prolonged postoperative analgesia, and reduced demand for rescue analgesics when compared to plain ropivacaine.



How to cite this article:
Meitei AJ, Ningombam T, Singh TH, Rajkumar G, Devi N A, Singh YA. A comparative study of ropivacaine versus ropivacaine plus dexmedetomidine under epidural anesthesia in lower limb surgeries.J Med Soc 2019;33:20-27


How to cite this URL:
Meitei AJ, Ningombam T, Singh TH, Rajkumar G, Devi N A, Singh YA. A comparative study of ropivacaine versus ropivacaine plus dexmedetomidine under epidural anesthesia in lower limb surgeries. J Med Soc [serial online] 2019 [cited 2019 Nov 21 ];33:20-27
Available from: http://www.jmedsoc.org/text.asp?2019/33/1/20/269104


Full Text



 Introduction



Epidural anesthesia for lower limb surgery is a well-accepted technique for various advantages such as better intra- and post-operative pain management and greater patient satisfaction.[1],[2],[3]

Ropivacaine, a new amide local anesthetic, has minimal cardiovascular and central nervous system toxicity as well as a lesser propensity of motor block during postoperative epidural analgesia compared to bupivacaine.[4]

The addition of opioid as an adjuvant provides a dose-sparing effect of local anesthetic and superior analgesia.[5]

Dexmedetomidine, a new α2-agonist, has evolved as a panacea for various applications and procedures in the perioperative and critical care settings.[6]

It acts on both pre- and post-synaptic sympathetic nerve terminal, thereby decreasing sympathetic outflow and norepinephrine release. This action is responsible for sedative, anxiolytic, analgesic, sympatholytic, and hemodynamic effects.[7] Dexmedetomidine produces a manageable hypotension and bradycardia, but the striking feature of this drug is the lack of opioid-related side effects such as respiratory depression, pruritus, nausea, and vomiting. Dexmedetomidine has been evaluated epidurally without any report of neurological deficit in the human being.[8],[9] It was found earlier that dexmedetomidine produces prolonged postoperative analgesia with minimal side effects when added to ropivacaine in epidural and caudal anesthesia.[10],[11],[12],[13] Only a few studies[11],[12],[13] have been carried out using dexmedetomidine as an adjuvant with ropivacaine, so we planned a randomized double-blind study to further explore the efficacy of dexmedetomidine as an adjuvant to ropivacaine in terms of duration of sensory and motor block, postoperative analgesia, and side effects of epidural anesthesia for lower limb surgeries.

 Materials and Methods



The study was a double-blind, randomized comparative study done in a tertiary care center. By taking “α” = 0.05 and “β” power as 1.00, the sample size was calculated at 25 in each group by a web-based calculation. The patients were allocated into two groups of 25 each using computer-generated randomization method. After approval from the Institutional Ethical Committee, written informed consent was obtained from each patient for the performance of epidural anesthesia. A total of 50 patients of either sex with age between 20 and 65 years and the American Society of Anesthesiologists (ASA) Physical Status I and II undergoing lower limb surgeries under epidural anesthesia were randomly allocated into two groups of 25 patients in each. Patients with any contraindication to regional anesthesia, coagulation or neurological disorders, morbid obesity, pregnancy, deformity or previous surgery of the spine, anticipated difficulty in regional anesthesia, cardiac disease, hypertension, chronic obstructive respiratory disease, and psychiatric patients were excluded from the study.

One day before the surgery, a detailed preanesthetic checkup was carried out. The patients were asked to restrict fluids and solids by mouth at least 6 h before the operation. Interpretation of visual analog scale (VAS) was explained to determine the level of analgesia in the postoperative period.[14] All the patients were given tablet ranitidine 150 mg and tablet alprazolam 0.5 mg, a night before the surgery. On the day of surgery in the preoperative room, intravenous (IV) access was secured using a large bore cannula, and the patients were preloaded with Ringer lactate solution 10 ml/kg bodyweight over 15–20 min before administering epidural block along with injection ondansetron 4 mg IV as premedication. Multipara monitor was attached and baseline pulse rate, systolic (SBP) and diastolic (DBP) blood pressure, oxygen saturation (SpO2), and electrocardiogram (ECG) were recorded and monitoring was initiated.

On the operating table, the patients were placed in the lateral decubitus position. Under aseptic precautions, skin wheal was raised with 2% lignocaine, and lumbar epidural space was identified with an 18G Tuohy needle using the loss of resistance technique. Epidural block was performed through midline approach in L3–L4 (in case of difficulty in L2–L3) intervertebral space. Epidural catheter was threaded, and thereafter, it was secured 3–5 cm into the epidural space, and the patients were turned supine position. A test dose of 2–3 ml of lignocaine with epinephrine 1:200,000 after negative aspiration for blood and cerebrospinal fluid was given to rule out intravascular or intrathecal injection. The study drugs were injected through epidural catheter according to the group allocation. Group R (n = 25) patients received 20 ml of 0.75% ropivacaine hydrochloride diluted to 22 ml with normal saline and Group RD (n = 25) patients received 20 ml of 0.75% ropivacaine hydrochloride plus dexmedetomidine (1 μg/kg bodyweight) diluted to 22 ml with normal saline.

All durations were calculated considering the time of epidural injection as zero. Continuous monitoring of pulse rate, noninvasive SBP and DBP, SpO2, and ECG were done. Readings were recorded preoperatively and then intraoperatively every 5 min for the first 30 min and thereafter every 15 min–90 min and every 30 min till the end of surgery.

Heart rate <60 beats/min (bradycardia) was treated with IV atropine 0.6 mg. SBP <20% of baseline value or <90 mmHg (hypotension) was treated with additional Ringer's lactate solution intravenously or if needed injection mephentermine hydrochloride 3 mg titrated according to blood pressure. Oxygen at 6 liters/min was given in all the patients through face mask.

Sensory block was assessed by loss of sensation to pinprick in the midline using a 22Gneedle every 2-min interval until T10 dermatome was reached and then every 5-min interval until no change in level occurred. Onset of sensory block to T10 dermatome level, maximum level of sensory block achieved, time taken to achieve maximum sensory level, and duration of sensory block were noted. The operation was started on achieving adequate sensory block at T8 dermatome.

Motor block was assessed every 5 min for the first 30 min and then every 15 min till the completion of surgery by the Modified Bromage Score (MBS). Grade 0 – patients able to move the hip, knee, and ankle; Grade 1 – inability to move the hip but is able to move the knee and ankle; Grade 2 – inability to move the hip and knee but can move the ankle; and Grade 3 – no movement at all and unable to move the hip, knee, and ankle.[14]

Maximum motor block achieved, time required to reach maximum motor block, and total duration of motor block were noted.

Analgesia was recorded by using VAS score at 5 min before epidural, at the start of surgery, and then, every 15-min interval till the surgery was over. Postoperatively, VAS was recorded ½ hourly for first 1 h, then 1 hourly for 12 h, and then 3 hourly for next 12–24 h.

Patient with VAS score of >3, rescue analgesia in the form of epidural analgesic top-up, or injection diclofenac sodium 75 mg intramuscular or if needed injection tramadol 50 mg slow intravenously was given. Time to first dose of rescue analgesia was recorded in both groups. The time at which patient demanded the first dose of rescue analgesia was the primary end point of this study because at this time, the effect of epidural block had weaned off.

Sedation was recorded every 10-min interval for the first 30 min and then every 15-min interval till the completion of surgery. The following sedation scores were used: 0 – no sedation, 1 – patient somnolent but responding to verbal commands, 2 – patient somnolent, not responding to verbal commands but responding to manual stimulation, and 3 – patient somnolent, not responding to verbal commands and manual stimulation.[15]

After completion of surgery, the patients were monitored for sensory and motor block, postoperative analgesia (VAS score), and hemodynamic parameters.

The incidences of adverse events such as hypotension, bradycardia, headache, dry mouth, nausea and vomiting, local anesthetic toxicity, backache, urinary retention, and sedation were noted in these 24 h. The results of the present study were decoded and tabulated in Microsoft Excel worksheet. Statistical analysis of data was done using Student's t-test for parametric data and Chi-square test for nonparametric data. P < 0.05 was considered as statistically significant and P < 0.01 as highly significant. The statistical software SPSS version 21.0 (IBM, Software for windows 2017, USA) was used for the analysis of the data, and Microsoft Word and Excel had been used to generate graphs, tables, etc., Results thus obtained were discussed and compared with the available literature. Conclusions were drawn keeping in mind the limitations of the study.

 Results



Demographic data of the two study groups [Table 1] were comparable and found statistically not significant (P > 0.05).{Table 1}

[Table 2] shows that the mean onset time of sensory block at T10 dermatome level in Group RD (11.16 ± 2.135 min) was significantly shorter than Group R (15.36 ± 2.481 min) P = 0.00; the mean time to reach maximum sensory level in Group R and Group RD was 24.36 ± 2.177 min and 20.48 ± 3.417 min, respectively, which was highly significant (P = 0.000); the mean time to reach complete motor block in Group R and Group RD was 27.24 ± 3.126 min and 23.76 ± 3.908 min, respectively, which was statistically significant (P < 0.05); and the mean value for total number of rescues doses in Group R was 2.80 ± 0.418 more than the Group RD (1.96 ± 0.455), which was statistically highly significant (P = 0.000).{Table 2}

VAS score recorded intraoperatively remained <3 in both the groups and post operatively during the first 24 h, at the time of rescue analgesia with epidural top up, the mean VAS score value in group R (6.08 ± 0.987) as compared to group RD (5.60 ± 0.118) was shown insignificant (P > 0.05).

The mean time taken for the regression of sensory block to T10 dermatome in Group RD (408.80 ± 44.246 min) was prolonged when compared to Group R (282.24 ± 30.343 min) with (P = 0.000). Further regression of sensory block to L5 was also significantly delayed in Group RD (505.16 ± 54.205 min) as compared to Group R (371 ± 32.911) with P = 0.000.

Total duration of sensory block, which was taken as the time required for the regression of sensory block to S1 dermatome, was again prolonged in Group RD (529.36 ± 58.125 min) comparing to Group R (391.68 ± 33.404 min (P = 0.000) as shown in [Table 2].

The mean time duration of motor block in Group RD (390.44 ± 37.994 min) was longer than Group R (264.96 ± 30.788) with P = 0.000.

[Figure 1] shows the maximum sensory level achieved in Group R was T4 and Group RD was T3. Fifteen (60%) samples in Group R show a maximum sensory level of T6, whereas 15 (60%) samples in Group RD attained the maximum sensory level of T5. Group R did not attained any T3 block level, whereas 3 (12%) in Group RD attained T3 block level. There was highly statistical significant difference between the two groups in attaining the maximum sensory level (P = 0.000) using the Chi-square test.{Figure 1}

In [Figure 2]a, 1 (4%) patient in Group R and 5 (20%) patients in Group RD developed bradycardia, which were treated with injection atropine 0.6 mg. The increase in pulse rate at 90 min might be due to sudden arousal of the patient, but it remained below the baseline. Moreover, the difference was nonsignificant (P > 0.05) at all varied time intervals, showing the hemodynamic stability of the adjuvant, dexmedetomidine.{Figure 2}

The changes were well below the baseline, which showed the hemodynamic stability in both the groups and the difference was found to be insignificant (P > 0.05) [Figure 2]b.

[Table 3] shows that the sedation score was more in Group RD as compared to Group R throughout the intraoperative period, and there was statistically highly significant difference (P = 0.000).{Table 3}

[Table 4] shows the comparative incidence of various side effects in both the groups, which were observed in the intra- and post-operative period. The incidence of hypotension and mephentermine consumption was significantly higher in RD Group on comparison (P < 0.05). The incidence of other side effects such as bradycardia, dry mouth, nausea, vomiting, shivering, and use of atropine was comparable in both the groups and statistically nonsignificant. We did not observe the respiratory depression in any patient from either group.{Table 4}

 Discussion



Epidural anesthesia with catheter in situ is one of the most commonly used standard techniques in lower limb surgeries. The use of dexmedetomidine (α2-adrenergic agonists) has been studied as an epidural adjuvant by various authors who have observed its synergism with local anesthetics without any additional morbidity.[10],[11] Its use as an adjuvant has gained popularity and tends to replace opioids as the former is devoid of respiratory depression, nausea, vomiting, or urinary retention. It also offers various benefits such as suppression of stress response by sympatholytic action, stable hemodynamics, early mobilization, reduced blood loss, and decrease in thromboembolic complications following surgery and is useful for long surgical procedures and helpful to provide postoperative analgesia.[16],[17],[18] α2-adrenoreceptor agonists produce analgesia by depressing release of C-fiber transmitters and by hyperpolarization of postsynaptic dorsal horn neurons of the spinal cord.[13],[19],[20] The complementary action of local anesthetics and α2-adrenoreceptor agonists explained their profound analgesic properties. The prolongation of the motor block of local anesthetics may be the result of binding of α2-adrenoreceptor agonists to the motor neurons in the spinal dorsal horn.[13],[20]

The demographic profile in the present study was comparable and did not show any significant difference [Table 1].

Time to onset of sensory block to T10 in Group RD (11.16 ± 2.135 min) was faster than Group R (15.36 ± 2.481 min), which was statistically highly significant (P < 0.05) in our study [Table 2]. These results were consistent with Thimmappa et al.[21] who observed that the mean time to onset of sensory block to T10 dermatome was 8.90 ± 0.99 min in dexmedetomidine group and 12.33 ± 1.56 min in ropivacaine group (P < 0.001). Our results were also supported by the findings of Bajwa et al.[6] that addition of dexmedetomidine to ropivacaine as an adjuvant resulted in an earlier onset (8.52 ± 2.36 min) of sensory analgesia at T10 as compared to the addition of clonidine (9.72 ± 3.44 min; P = 0.032). This was also similar to the findings of Kaur et al.[14] who showed a comparable time of onset of sensory block to T10 dermatome in dexmedetomidine group (12.53 ± 4.17 min) versus ropivacaine group (14.18 ± 6.02 min; P > 0.05).

In this study, Group RD attained maximum sensory level of T3 as compared to T4 in Group R. The maximum number of patients (60%) in Group RD achieved T5 as compared to T6 in Group R (60%). Moreover, the difference was highly significant between the two groups (P = 0.000). Muhammed et al.[22] achieved T2–T5 in dexmedetomidine group and T4–T6 in ropivacaine group (P < 0.01). They attained higher dermatomal spread, which may be due to higher dose of dexmedetomidine (1.5 μg/kg) given at the first or second lumbar interspace. Pratibha et al.[23] observed the highest level of sensory block achieved was T5–T6 in dexmedetomidine group. Comparable results were obtained by Vasupalli and Prakash[24] with T4 as the maximum level of sensory block in dexmedetomidine group. Kaur et al.[14] also observed the median maximum sensory level reached was higher in dexmedetomidine Group (T5) than in plain ropivacaine Group (T6) which supports our findings.

The mean time taken to reach maximum sensory level in Group R (T4) was 24.36 ± 2.177 min as compared to 20.48 ± 3.417 min (T3) in Group RD (P = 0.000) which was comparable to Kaur et al.,[14] where the mean time taken to reach maximum sensory level in ropivacaine group was 23.24 ± 5.971 min and in dexmedetomidine group was 21.63 ± 4.172 min (P > 0.05). Bajwa et al.[11] in their study also observed that the time to reach maximum sensory level was 13.14 ± 3.96 min when dexmedetomidine was used as an adjuvant to ropivacaine (P < 0.05). The shorter onset time might be due to higher dose of dexmedetomidine (1.5 μg/kg) used by Bajwa et al.[11] Sarkar et al.[25] also observed comparatively shorter onset time to reach maximum sensory block in dexmedetomidine group compared to ropivacaine group (12.61 ± 1.45 min vs. 15.55 ± 1.80 min, respectively; P < 0.05) which could be attributed to the use of higher dose of dexmedetomidine (2 μg/kg) in their study.

In the present study, the regression of sensory block to T10 dermatome was earlier in Group R (282.24 ± 30.343 min) when compared to Group RD (408.80 ± 44.246 min, P = 0.000), which is in concordance to the findings by Kaur et al.[14] with ropivacaine group (277.58 ± 17.66 min) when compared to dexmedetomidine group (404.18 ± 17.93 min, P = 0.000). Similarly, comparable time (237 ± 65 min) was observed by Brown et al.[26] using 20 ml of 0.5% ropivacaine as in our study.

Regression of sensory block to L5 was prolonged significantly in Group RD (505.16 ± 54.205 min) as compared to Group R (371.00 ± 32.911 min, P = 0.000) in our study which is in consistent with the findings by Kaur et al.[14] (504.68 ± 20.642 min in dexmedetomidine group vs. 354.56 ± 16.446 min in ropivacaine group, P = 0.000) and supports our results.

The total duration of sensory block in our study was significantly prolonged in Group RD (529.36 ± 58.125 min) as compared to Group R (391.68 ± 33.404 min). Kaur et al.[14] observed the total duration of sensory block in dexmedetomidine group (535.18 ± 19.85 min) was significantly prolonged as compared to ropivacaine group (375.20 ± 15.97 min, P = 0.000). Brown et al.[26] also obtained total duration of sensory block was 333 ± 54 min, using 20 ml of 0.5% ropivacaine which was comparable with the present study.

The onset of complete motor block in Group RD (23.76 ± 3.908 min) was earlier than Group R (27.24 ± 3.126 min), which was highly significant (P = 0.001). Comparable results were observed by Kaur et al.,[14] that is, 25.73 ± 4.172 min in dexmedetomidine group versus 27.34 ± 5.970 min in ropivacaine group (P > 0.05). Thimmappa et al.[21] observed faster establishment of complete motor blockade in dexmedetomidine group (15.77 ± 1.25 min) when compared to ropivacaine group (21.37 ± 2.13 min; P < 0.001) by using a fixed dose of 75 μg of dexmedetomidine.

Total duration of motor block was significantly prolonged in Group RD (390.44 ± 37.994 min) as compared to Group R (264.96 ± 30.788 min). The above results were in concordance with the results of Kaur et al.[14] (385.92 ± 17.719 min in dexmedetomidine group and 259.80 ± 15.486 min in ropivacaine group), and the difference was highly significant (P = 0.000). The time of motor regression in the dexmedetomidine group was 259.62 ± 21.38 min in the study by Bajwa et al.,[12] while it was 390.44 ± 37.994 min in our study. This apparent discrepancy might be due to the assessment of motor block regression, which is MBS Grade 1 in their study while MBS 0 was the criteria in our study.

In this study, the time to first rescue analgesia was significantly prolonged in Group RD (512.36 ± 55.815 min) as compared to Group R (368.40 ± 52.366 min, P = 0.000). Group RD had prolonged pain-free period and reduced 24-h analgesic requirement as compared to Group R (1.96 ± 0.455 in Group RD vs. 2.80 ± 0.418 in Group R, P = 0.000), which is in conformity to the findings of Kaur et al.,[14] where pain-free period was 496.56 ± 16.08 min in dexmedetomidine group and 312.64 ± 16.21 min in ropivacaine group (P = 0.000) with reduced 24-h analgesic requirement (1.44 ± 0.501 in dexmedetomidine group vs. 2.56 ± 0.67 in ropivacaine group, P < 0.001). The prolongation of motor block may be the result of binding α2-adrenergic agonists to the motor neurons in the spinal dorsal horn.[13],[19] This might be due to the complementary action of local anesthetics and α2-adrenergic agonists, resulting in the profound analgesic properties. VAS score at the time of rescue analgesia was more in Group R (6.08 ± 0.997) than Group RD (5.60 ± 0.118), which was comparable but not statistically significant (P > 0.05). In contrast to our studies, Kaur et al.[14] observed mean VAS score in ropivacaine group was 2.86 ± 0.78 and dexmedetomidine group was 2.40 ± 0.17 (P = 0.03 at the end of 24 h, which could be attributed to the epidural top-up administered in our study.

There was no incidence of shivering in Group RD. Dry mouth in our study accounts for 4% in both the groups and is comparable and quite less to the observations of other studies administering dexmedetomidine, which may be due to smaller sample size and was comparable to the findings observed by Routray et al.[27] The incidence of urinary retention could not be evaluated as all the patients were catheterized in our study. The incidence of hypotension and mephentermine requirement was significant in Group RD as compared to Group R (P < 0.05). Atropine requirement for bradycardia was comparable in both the groups (P > 0.05). This might be due to the effect of dexmedetomidine mediated by its central and peripheral sympatholytic action.[17] Even though there was a significant incidence of hypotension in dexmedetomidine group, it was easily manageable with IV fluids and injection mephentermine. Thereafter, all the patients remained hemodynamically stable, which reaffirms the established effects of α2-agonists in providing a hemodynamically stable perioperative period.[28],[29]

The sedation score was observed throughout the procedure and was found more in Group RD in our study. There was no incidence of sedation score of 2 and 3 in Group R, whereas the incidence of sedation score of 2 and 3 was 32% and 8%, respectively, in Group RD, which was statistically significant (P = 0.000) [Table 3]. These findings are in accordance with the findings by various authors.[14],[21],[30]

Limitations and future references of the study

The need for studies with other ASA physical status, namely, needs to be evaluatedWe could not measure the plasma concentration of dexmedetomidine level, which could have ruled out any possible link with inter-individual variabilityECG or nerve conduction velocity after the offset of motor or sensory block for actual duration needs to be assessed in the near futureThe level of sedation was not assessed with Bispectral Index monitor. Further, studies to assess the sedative and analgesic effects of dexmedetomidine in extensive surgeries need evaluation.

 Conclusion



Epidural dexmedetomidine supplementation to ropivacaine in lower limb surgeries provides early onset of sensory and motor block and prolonged duration of sensory and motor block with adequate postoperative analgesia in terms of VAS score without significant hemodynamic alterations, thereby delaying the postoperative first rescue analgesic top-up. There were minimal side effects, optimal intraoperative sedation, as well as better patient comfort when 1 μg/kg of dexmedetomidine was used as an adjuvant to ropivacaine. Hence, it can be concluded that dexmedetomidine is better than plain ropivacaine and can be a safe and effective agent for epidural blockade in lower limb surgeries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Oremus K, Safaric Z. The role of epidural anesthesia and analgesia in surgical practice. Ann Surg 2004;240:561-2.
2Moraca RJ, Sheldon DG, Thirlby RC. The role of epidural anesthesia and analgesia in surgical practice. Ann Surg 2003;238:663-73.
3Mulroy MF, Larkin KL, Hodgson PS, Helman JD, Pollock JE, Liu SS, et al. Acomparison of spinal, epidural, and general anesthesia for outpatient knee arthroscopy. Anesth Analg 2000;91:860-4.
4McClellan KJ, Faulds D. Ropivacaine: An update of its use in regional anaesthesia. Drugs 2000;60:1065-93.
5Lorenzini C, Moreira LB, Ferreira MB. Efficacy of ropivacaine compared with ropivacaine plus sufentanil for postoperative analgesia after major knee surgery. Anaesthesia 2002;57:424-8.
6Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol 2011;27:297-302.
7Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000;59:263-8.
8Maroof M, Khan SA, Jain D, Khan RM, Maroof SM. Evaluation of effect of dexmedetomidine in reducing shivering following epidural anesthesia. Anesthesiology 2004;101:A495.
9Anand VG, Kannan M, Thavamani A, Bridgit MJ. Effects of dexmedetomidine added to caudal ropivacaine in paediatric lower abdominal surgeries. Indian J Anaesth 2011;55:340-6.
10Salgado PF, Sabbag AT, Silva PC, Brienze SL, Dalto HP, Módolo NS, et al. Synergistic effect between dexmedetomidine and 0.75% ropivacaine in epidural anesthesia. Rev Assoc Med Bras (1992) 2008;54:110-5.
11Bajwa SJ, Bajwa SK, Kaur J, Singh G, Arora V, Gupta S, et al. Dexmedetomidine and clonidine in epidural anaesthesia: A comparative evaluation. Indian J Anaesth 2011;55:116-21.
12Bajwa SJ, Arora V, Kaur J, Singh A, Parmar SS. Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries. Saudi J Anaesth 2011;5:365-70.
13Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7.
14Kaur S, Attri JP, Kaur G, Singh TP. Comparative evaluation of ropivacaine versus dexmedetomidine and ropivacaine in epidural anesthesia in lower limb orthopedic surgeries. Saudi J Anaesth 2014;8:463-9.
15Mausumi N, Dhurjoti PB, Satrajit D, Nilay C. A Comparative study between clonidine and dexmedetomidine used as adjuncts to ropivacaine for caudal analgesia in paediatric patients. J Anaesth Clin Pharmacol 2010;26:149s-53.
16Villela NR, Nascimento Júnior PD. Dexmedetomidine in anesthesiology. Rev Bras Anestesiol 2003;53:97-113.
17Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res 2011;5:128-33.
18Sudheesh K, Harsoor S. Dexmedetomidine in anaesthesia practice: A wonder drug? Indian J Anaesth 2011;55:323-4.
19Al Ghanem SM, Massad IM, Al-Mustafa MM, Al-Zaben KR, Qudaisat IY, Qatawneh AM, et al. Effect of adding dexmedetomidine versus fentanyl to intrathecal bupivacaine on spinal block characteristics in gynecological procedures: A double blind study. Am J Appl Sci 2009;6:882-7.
20Lawhead RG, Blaxall HS, Bylund DB. Alpha-2A is the predominant alpha-2 adrenergic receptor subtype in human spinal cord. Anesthesiology 1992;77:983-91.
21Thimmappa M, Madhusudhana R, Potli S, Karthick D. A comparative study of epidural ropivacaine 0.75% Alone with ropivacaine plus clonidine and ropivacaine plus dexmedetomidine for lower abdominal and lower limb surgeries. World J Pharm Pharm Sci 2014;3:1218-30.
22Muhammed RO, Alex S, Asif MP, Ramadas CK. Comparative study of epidural dexmedetomidine with clonidine as adjuvant to isobaric ropivacaine in abdominal hysterectomy. J Med Sci Clin Res 2017;5:19971-6.
23Pratibha JS, Rashmi N, Chandrapal B, Kunal T. Dexmedetomidine V/S fentanyl with 0.75% ropivacaine for epidural anaesthesia in lower abdominal surgeries – A comparative study. J Anesth Intensive Care Med 2017;3:555611.
24Vasupalli R, Prakash TS. A comparative study of dexmedetomidine and fentanyl combined with ropivacaine for epidural anaesthesia in lower limb orthopaedic surgeries. J. Evid Based Med Healthc 2016;3:3878-84.
25Sarkar S, Chattopadhyay S, Bhattacharya S, Mandal M, Chakrabarti P, Pal S. Dexmedetomidine as an adjuvant to epidural ropivacaine in lower limb surgeries – A randomised control trial. J Evol Med Dent Sci 2017;6:1473-8.
26Brown DL, Carpenter RL, Thompson GE. Comparison of 0.5% ropivacaine and 0.5% bupivacaine for epidural anesthesia in patients undergoing lower-extremity surgery. Anesthesiology 1990;72:633-6.
27Routray SS, Raut K, Mishra DB, Pradhan K, Mishra D. Comparative evaluation of clonidine and dexmedetomidine used for epidural analgesia in lower abdominal and lower limb surgeries. Sch J Appl Med Sci 2015;3:2416-21.
28Taittonen MT, Kirvelä OA, Aantaa R, Kanto JH. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth 1997;78:400-6.
29Cortinez LI, Hsu YW, Sum-Ping ST, Young C, Keifer JC, Macleod D, et al. Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 2004;101:1077-83.
30Shaikh SI, Mahesh SB. The efficacy and safety of epidural dexmedetomidine and clonidine with bupivacaine in patients undergoing lower limb orthopedic surgeries. J Anaesthesiol Clin Pharmacol 2016;32:203-9.