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Year : 2016  |  Volume : 10  |  Issue : 1  |  Page : 77-81  

Comparative evaluation of dexmedetomidine and clonidine with low dose ropivacaine in cervical epidural anesthesia for modified radical mastectomy: A prospective randomized, double-blind study

1 Department of Anaesthesiology, Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, India
2 Department of Surgery, Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, India

Date of Web Publication12-Jan-2016

Correspondence Address:
Shivakumar M Channabasappa
SSS Mansion, 3rd Cross, 3rd Stage, Basaveshvaranagar, Shimoga - 577 201, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.167844

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Context: Alpha-2 adrenergic agonists clonidine and dexmedetomidine, are well known to produce analgesia through an opioid independent mechanism. Alpha-2 agonists are used as an adjuvant to local anesthetic agents to extend the duration of spinal, epidural and brachial plexus blocks.
Aims: We compared clonidine and dexmedetomidine as an adjuvant to Ropivacaine in cervical epidural anesthesia (CEA) with respect to onset and duration of sensory block, duration of analgesia and adverse effects.
Subjects and Methods: A total 150 American Society of Anesthesiologists Class I or II adult female patients who were scheduled to undergo modified radical mastectomy were randomly allocated to the following two groups to receive CEA: Group D receive 15 mL of 0.375% ropivacaine combined with 1 μg/kg of dexmedetomidine; Group C received 15 mL of 0.375% ropivacaine combined with 1.5 μg/kg of clonidine. The onset of sensory block, duration of analgesia, mean arterial pressure (MAP), heart rate (HR), sedation scores, and the incidences of adverse effects, such as hypotension, bradycardia, and oxygen desaturation were recorded.
Results: The addition of dexmedetomidine to ropivacaine (Group D) resulted in faster onset of sensory block time compared with the addition of clonidine to ropivacaine (Group C) (95% confidence interval [CI]: 14.53 ± 2.96 vs. 16.72 ± 4.43 P = 0.032). The duration of analgesia block in Group D was significantly longer than that in Group C (95% CI: 234.65 ± 23.76 vs. 286.76 ± 34.65; P = 0.037). The Ramsay sedation score at in Group D were significantly higher between 20 and 60 min as compared to Group C (P < 0.022). MAP level and HR level in Group D and Group C were comparable.
Conclusion: The addition of dexmedetomidine to low dose ropivacaine for CEA could shorten the onset of sensory block and extend the duration of analgesia with optimum sedation without episodes of hypoxemia as compared to addition of clonidine to ropivacaine.

Keywords: Cervical epidural anesthesia, clonidine, dexmedetomidine, modified radical mastectomy, ropivacaine

How to cite this article:
Channabasappa SM, Venkatarao GH, Girish S, Lahoti NK. Comparative evaluation of dexmedetomidine and clonidine with low dose ropivacaine in cervical epidural anesthesia for modified radical mastectomy: A prospective randomized, double-blind study. Anesth Essays Res 2016;10:77-81

How to cite this URL:
Channabasappa SM, Venkatarao GH, Girish S, Lahoti NK. Comparative evaluation of dexmedetomidine and clonidine with low dose ropivacaine in cervical epidural anesthesia for modified radical mastectomy: A prospective randomized, double-blind study. Anesth Essays Res [serial online] 2016 [cited 2020 May 27];10:77-81. Available from:

   Introduction Top

Surgery for carcinoma breast is conventionally done under general anesthesia. However, there is worldwide increased interest in cervical epidural anesthesia (CEA) due to evolved surgical techniques, newer local anesthetics and adjuvant drugs. Regional anesthesia has advantages of the less postoperative stress response, superior analgesia, decreased intraoperative blood loss, early ambulation, and decreased hospitalization cost.[1],[2]

CEA with a conventional epidural dosage of local anesthetics produced moderate restrictive pulmonary syndrome with subsequent oxygen desaturation.[3],[4] To minimize these adverse effects, diluted concentration local anesthetics has been successfully studied in previous studies to conduct surgeries under epidural anesthesia.

There has always been a search for adjuvants to the epidural anesthesia with drugs that prolong the duration of analgesia but with lesser adverse effects. The search for the ideal adjuvant led us to try the novel alpha-2 adrenergic agent, dexmedetomidine.

Alpha-2 adrenergic receptor agonists have been used as sedative, analgesic, and perioperative sympatholytic. Furthermore, these drugs are used as an adjuvant in various methods of administration, such as epidural, intrathecal, and plexus blocks either alone or in combination with another drug to prolong and intensify the local anesthetic agents.[5],[6],[7]

Dexmedetomidine, a potent alpha-2 adrenoceptor agonist, is approximately 8-time more selective towards the alpha-2 adrenoceptor than clonidine.[7] There are no such studies which compared the epidural dose equivalence of clonidine, but observation of various studies have stated that epidural dose of clonidine is 1.5 times the dose of dexmedetomidine.[8],[9],[10]

Till date, no studies have compared dexmedetomidine with clonidine with respect to duration of the block and postoperative analgesia as an adjuvant to low dose ropivacaine in CEA. The current study was planned as double-blind prospective randomized clinically controlled study at our institute with an aim to compare the analgesic and sedative effects of both these drugs when used for CEA as an adjuvant to ropivacaine in patients undergoing modified radical mastectomy.

   Subjects and Methods Top

After ethical committee approval and written informed consent, a double-blind randomized prospective clinical study was carried out on 150 American Society of Anesthesiologist (ASA) grades I and II female patients, aged 18–60 years, undergoing modified radical mastectomy under CEA. The study was conducted in two groups of 75 patients each. The patients were randomly assigned using “computerized random number table” to one of the following groups:

Group C: Ropivacaine 0.0375% (15 mL) + clonidine 1.5 μg/kg

Group D: Ropivacaine 0.0375% (15 mL) + dexmedetomidine 1 μg/kg

Patients on adrenoreceptor agonist or antagonist therapy, with known hypersensitivity to local anesthetic drugs, aortic stenosis, with a history of left ventricular failure, with atrioventricular conduction block bleeding disorders, uncontrolled diabetes mellitus, were excluded from the study. Details of the anesthetic technique and study protocol were explained to the patients at the preoperative visit. Patients were not premedicated. No intravenous (IV) sedative medications were used.

On arrival in the operation room, an IV line was secured with 18-gauge cannula and ringer lactate drip was started. The patients were monitored with noninvasive blood pressure, electrocardiogram, and pulse oximeter and baseline heart rate (HR), blood pressure, and oxygen saturation were recorded. An anesthesiologist who was not involved in the data collection or intervention prepared the drug syringes. Patients were made to sit on a chair with head slightly flexed and supported on edge operation table; hands were rested on patient's thigh. The cervical epidural block was administered with loss of resistance to air with 18-gauge Tuohy needle C7-T1 space and catheter was secured 3–4 cm into epidural space and fixed to skin after tunneling the catheter, patient were made to lie supine and a test dose of 3 mL of 2% lignocaine hydrochloride solution containing adrenaline 1:200,000 was injected. After 4−6 min of administering the test dose, patients in Group C received 15 mL of 0.375% ropivacaine and 1.5 μg/kg of clonidine; and patients in Group D received 15 mL solution of 0.375% ropivacaine and 1 μg/kg of dexmedetomidine. The bilateral sensation ice cube was used to evaluate and check the sensory level at 5, 10, 15, 20, 25, and 30 min intervals after the epidural administration of the drugs.

The following epidural block characteristics were observed and recorded: Onset of analgesia; upper and lower dermatomal level of sensory analgesia, grading of sedation was evaluated by a five-point scale (1 - alert and wide awake, 2 - arousable to verbal command, 3 - arousable with gentle tactile stimulation, 4 - arousable with vigorous shaking, and 5 - unarousable). Sedation scores were recorded just before the initiation of surgery and thereafter, every 20 min during the surgical procedure. The onset of postoperative pain defined as the time from completion of surgery to the onset of visual analog scale >4 were recorded.

Statistical analysis

To calculate the required study size, we took into account the results of a previous study. Accepting a one-tailed alpha error of 5%, a beta error of 5%, and power of 90%.[11] Based on these calculations, the required study size was 60 patients per group. Assuming a dropout rate of 20%, we attempted to recruit 75 patients in each group

Statistical analysis was performed using the program GraphPad Prism software package versus 5 (GraphPad Inc., CA, USA). Numerical variables were presented as mean, and standard deviation and categorical variables were presented as frequency (%). One-way ANOVA was used for between group comparisons of numerical variables, if its assumptions were fulfilled, otherwise for nonparametric, the Kruskal–Wallis test was used. Tukey's honest significant difference test or the Mann–Whitney U-test was used, whenever appropriate, as post-hoc tests. χ2 test was used for between group comparisons between categorical variables. A P ≤ 0.05 was considered statistically significant.

   Results Top

A total of 150 patients who underwent modified radical mastectomy were enrolled for the study. The demographic profiles of the patients in both the groups were comparable with regards to age, weight and body mass index, and ASA grade and duration of surgery [Table 1]. The onset of sensory block at T4 level in Group D (14.53 ± 2.96 min) was significantly faster (P = 0.032) as compared to Group C (16.72 ± 4.43 min). Addition of dexmedetomidine to ropivacaine not only provided a maximum dermatomal spread but also helped in reducing the period of the maximum sensory level (17.43 ± 3.82 min) compared to clonidine (19.26 ± 5.32 min) [Table 2].
Table 1: Demographic profile (mean±SD)

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Table 2: Onset of sensory block characteristics (mean±SD)

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[Table 3] shows a comparison of postoperative block characteristics between the two groups. Duration of postoperative analgesia in Group D was longer as compared to Group C. Two segmental dermatomal regression in Group D (123.21 ± 8.63 min) as compared Group C (111.52 ± 7.21) that was statistically significant. The requirement of rescue analgesia was comparatively longer (286.76 ± 34.65 min) in the patients who were received dexmedetomidine (P < 0.05). The superior block characteristics by the addition of dexmedetomidine were clearly evident from the lesser dose consumption (48.67 ± 16.98 mg) of ropivacaine for postoperative analgesia for the next 24 h as compared to clonidine group (66.46 ± 18.42 mg), which was statistically significant (P < 0.05).
Table 3: Postoperative block characteristics (mean±SD)

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Mean Ramsay sedation score in Group D was significantly higher than Group C and till first 60 min after injection, maximum sedation was found at 20 and 40 min in both the groups [Figure 1]. No patient required any additional sedation in either group.
Figure 1: Graphical presentation of Ramsay sedation score during first 120 min. Sedation scores in Group D were significantly higher between 20 and 60 min as compared to Group C

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The mean values of mean arterial pressure (MAP) and HR were comparable between the two groups throughout the intraoperative and postoperative periods [Figure 2] and [Figure 3]; the mephentaramine requirement was also comparable in both groups. The mean requirement of ropivacaine for postoperative analgesia was significantly less in Group D (48.67 ± 16.98 mg) as compared to Group C (66.46 ± 18.42 mg). Nine patients in Group D, 6 patients in Group C developed bradycardia (HR < 60/min) and hypotension, which was treated as per protocol. Two patients in Group D developed a brief period of desaturation (<90%), which was corrected, with the administration of oxygen with a simple mask. No significant respiratory depression was reported in any patient in Group C, and none of the patients had a SpO2 value of <95% in Group C [Table 4].
Table 4: Incidence of adverse events

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Figure 2: Graphical presentation of the mean arterial pressure during first 180 min. Mean arterial pressure in Group D was comparable to Group C

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Figure 3: Graphical presentation of the heart rate during first 180 min. Heart rate in Group D was comparable to Group C

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   Discussion Top

Radical mastectomy for carcinoma of the breast is conventionally done under general anesthesia. However, there has been rising interest in the use of cervical and thoracic epidural anesthesia due to advances in surgical techniques, newer local anesthetics, and adjuvant drugs. Regional anesthesia has advantages of the less postoperative stress response, superior analgesia, decreased intraoperative blood loss, early ambulation, and decreased hospitalization cost.[1] CEA for modified radical mastectomy is one of the regional anesthetic techniques that can be done by using a low dose of local anesthetic in combination with epidural adjuvants for better analgesia with minimum weakness of respiratory muscle and sedation.

CEA is not used routinely in everyday anesthesia practice, mainly because routine high concentration local anesthetic drugs associated with moderate restrictive pulmonary syndrome with subsequent oxygen desaturation.[11] To minimize these adverse effects, we used 0.375% ropivacaine in combination with either clonidine or dexmedetomidine.

The pharmacologic properties of alpha-2 agonists as lumbar/thoracic epidural adjuvants have been studied vastly and been used clinically to achieve the desired effects in regional anesthesia,[12],[13] but none of the studies compared alpha-2 agonists as adjuvant to local anesthetic in CEA. The quicker onset of action of local anesthetics, rapid establishment of both sensory and motor blockade, prolonged duration of analgesia; dose-sparing action of local anesthetics and stable cardiovascular parameters makes these agents a very effective adjuvant in regional anesthesia.[14],[15],[16],[17]

This study was undertaken to compare the analgesic and sedative effects of alpha-2 agonists through CEA. The results of the study has shown that the addition of either 1 μg/kg dexmedetomidine or 1.5 μg/kg clonidine as adjuvant to low dose epidural ropivacaine not only prolongs the duration of analgesia, but also decreases concentration of local anesthetic required to produce optimum anesthesia during the surgical procedure. In comparison epidural clonidine, dexmedetomidine has shortened onset of sensory block and prolonged the duration of analgesia. Further, the epidural addition of dexmedetomidine with ropivacaine produced better sedation in comparison to clonidine. Overall the sedation scores were highly significant statistically with the administration of dexmedetomidine.

The hemodynamic parameters, as is evident from [Figure 2] and [Figure 3], remained stable throughout the study period which reaffirms the established effects of alpha-2 agonists in providing a hemodynamically stable intraoperative and perioperative.[18],[19] Although a slight decrease in HR and MAP was observed in both the groups, it never fell down to more than 30% of the baseline values.

The respiratory rate and oxygen saturation did not change significantly from baseline as we used 0.375% of ropivacaine, but the depth of respiration may be decreases if 0.5% or 0.75% of ropivacaine is given. Many studies have observed the adverse events such as bradycardia, hypotension, and acute ventilatory failure due to the administration of high concentration local anesthetics.[20],[21]

The adverse events of both these drugs was quite comparable and favorable as none of the patient in either group had profound deep sedation, and only two patients in dexmedetomidine group had oxygen desaturation <90% which was corrected with prompt oxygen administration by simple mask. Co-operation of surgical team for CEA was excellent, and patient satisfaction was optimum due to the relative ease of the procedure, early ambulation, and good postoperative analgesia.

Our results should be considered in light of several limitations. First, lack of data on patient feedback and surgeons acceptance of CEA. Further prospective studies with particular stress on patient acceptance of CEA and postoperative feedback from both patients and the surgical team needed to mitigate the shortcomings of this study.

   Conclusion Top

Use of 0.375% ropivacaine with alpha-2 agonists as adjuvants is safer for CEA for radical mastectomy. It provides good surgical anesthesia with a lesser degree of motor blockade and the respiratory effects. In comparison to clonidine, dexmedetomidine is a better adjuvant for CEA as far as patient comfort, stable hemodynamic parameters, and intraoperative and postoperative analgesia is concerned. Dexmedetomidine also provides superior sedation during the surgical procedure under regional anesthesia.

Financial support and sponsorship

Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, India.

Conflicts of interest

There are no conflicts of interest.

   References Top

Khanna R, Singh DK. Cervical epidural anaesthesia for thyroid surgery. Kathmandu Univ Med J (KUMJ) 2009;7:242-5.  Back to cited text no. 1
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Kulkarni K, Namazi IJ, Deshpande S, Goel R. Cervical epidural anaesthesia with ropivacaine for modified radical mastectomy. Kathmandu Univ Med J (KUMJ) 2013;11:126-31.  Back to cited text no. 3
Jadon A, Agarwal PS. Cervical epidural anaesthesia for radical mastectomy and chronic regional pain syndrome of upper limb – A case report. Indian J Anaesth 2009;53:696-9.  Back to cited text no. 4
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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4]

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