|Year : 2015 | Volume
| Issue : 2 | Page : 195-207
A comparative study of intrathecal clonidine and dexmedetomidine on characteristics of bupivacaine spinal block for lower limb surgeries
Jahnabee Sarma1, P Shankara Narayana2, P Ganapathi2, MC Shivakumar2
1 Department of Anesthesiology, KVG Medical College and Hospital, Sullia, Karnataka, India
2 Department of Critical Care, KVG Medical College and Hospital, Sullia, Karnataka, India
|Date of Web Publication||6-May-2015|
Department of Anesthesiology, KVG Medical College and Hospital, Kurunjibag, Sullia, Dakshina Kannada, Karnatak
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Intrathecal clonidine or dexmedetomidine has improved the quality of spinal anesthesia, this clinical study was undertaken to assess the behavior of intrathecal clonidine as an adjuvant to bupivacaine in augmenting sensory block in patients undergoing lower limb surgeries.
Materials and Methods: We studied 150 patients, between 18 and 60 years of age, patients were randomly divided into three groups of 50 each Group B: 0.5% bupivacaine 15 mg + 0.5 ml normal saline Group C: 0.5% bupivacaine 15 mg + 50 μg clonidine Group D: 0.5% bupivacaine 15 mg + 5 μg dexmedetomidine. Onset and duration of sensory block and motor block, the highest level of sensory blockade, duration of analgesia, and side-effects were assessed.
Results: The onset of motor block was faster in Group C and Group D as compared to Group B, The time to reach Bromage scale 3 was fastest in Group C followed by Group D P < 0.001. The duration of sensory, motor blockade and duration of analgesia was longer in Groups C and D as compared to Group B, longest in Group D followed by C and B. The time to regression time to S1 dermatome was. It was longest in Group D followed by Group C and then Group B. Intergroup comparison B to C, B to D and C to D was significant. Duration of analgesia was significantly prolonged in Group C and Group D (P < 0.001) with a mean duration of 309.6 ± 50.99 min in Group C and 336.8 ± 55.38 min in Group D as compared to 204.8 ± 16.81 min in Group B. Intergroup comparison B to C, B to D and Group C to D was significant. Duration was longest in Group D followed by Group C and then Group B.
Conclusion: Supplementation of bupivacaine spinal block with a low dose of intrathecal dexmedetomidine (5 μg) or clonidine (50 μg) produces a significantly shorter onset of motor and sensory block and a significantly longer sensory and motor block than bupivacaine alone.
Keywords: Bupivacaine, clonidine, dexmedetomidine, spinal anesthesia
|How to cite this article:|
Sarma J, Narayana P S, Ganapathi P, Shivakumar M C. A comparative study of intrathecal clonidine and dexmedetomidine on characteristics of bupivacaine spinal block for lower limb surgeries. Anesth Essays Res 2015;9:195-207
|How to cite this URL:|
Sarma J, Narayana P S, Ganapathi P, Shivakumar M C. A comparative study of intrathecal clonidine and dexmedetomidine on characteristics of bupivacaine spinal block for lower limb surgeries. Anesth Essays Res [serial online] 2015 [cited 2020 Aug 13];9:195-207. Available from: http://www.aeronline.org/text.asp?2015/9/2/195/153763
| Introduction|| |
Uncontrolled postoperative pain may produce a range of detrimental acute and chronic effects. The attenuation of perioperative pathophysiology that occurs during surgery through reduction of nociceptive input to the CNS and optimization of perioperative analgesia may decrease complications and facilitate recovery during the immediate postoperative period  and after discharge from the hospital. Attenuation of postoperative pain, especially with certain types of analgesic regimens, may decrease perioperative morbidity and mortality.  Uncontrolled postoperative pain may activate the sympathetic nervous system and thereby contribute to morbidity or mortality. Sympathetic activation may increase myocardial oxygen consumption, which may be important in the development of myocardial ischemia and infarction, , and may decrease myocardial oxygen supply through coronary vasoconstriction and attenuation of local metabolic coronary vasodilation.  Postoperative pain relief is a growing concern for an anesthesiologist as an uneventful postoperative period makes surgery a comfortable proposition for surgical patients. 
Spinal anesthesia was introduced into clinical practice by Karl August Bier in 1898.  Unlike spinal opioids, clonidine does not produce pruritis or respiratory depression. It also prolongs the necessary blockade , and reduces the amount or concentration of local anesthetic required to produce postoperative analgesia. ,
Spinal anesthesia is popular and commonly used worldwide. The advantages of an awake patient, minimal drug cost and rapid patient turnover has made this a method of choice for many surgical procedures. These advantages are sometimes offset by relatively short duration of action and complain of postoperative pain. Intrathecal clonidine is being extensively evaluated in last 25 years as an alternative to neuraxial opioids for control of pain and has proven to be a potent analgesic. Dexmedetomidine is a new highly selective, an alpha 2 adrenergic receptor agonist. It has an alpha 2/alpha 1 selectivity ratio which is 8 times higher than that of clonidine. The present study is aimed at evaluating the efficacy of the use of intrathecal clonidine and dexmedetomidine as an adjuvant to hyperbaric bupivacaine in providing better intraoperative and postoperative analgesia and hemodynamic stability.
| Materials and methods|| |
This clinical study was conducted on 150 adult patients of American Society of Anaesthesiologists (ASA) physical status 1 and 2 in the age group of 18 to 60 years of either sex posted for elective lower limb surgeries under spinal anesthesia after taking informed consent and ethical clearance at KVG Medical College, Sullia between December 2011 and December 2013.
Patients were randomly divided on an alternative basis into three groups of 50 each:
- Group B: 0.5% bupivacaine 15 mg + 0.5 ml normal saline
- Group C: 0.5% bupivacaine 15 mg + 50 μg clonidine (test solution was diluted with normal saline to a total volume of 3.5 ml)
- Group D: 0.5% bupivacaine 15 mg + 5 μg dexmedetomidine (test solution was diluted with normal saline to a total volume of 3.5 ml).
- Patients aged between 18 and 60 years
- ASA I-II
- Scheduled for elective lower limb surgeries.
- Patients using alpha 2-adrenergic receptors antagonists, calcium channel blockers, angiotensin-converting enzyme inhibitors
- Body weight more than 120 kg
- Height <140 cm
- Postspinal surgeries, spinal deformity
- History of allergy to study drugs
- Neurological disorder.
All patients examined properly in pre-anesthetic clinic 1 day prior to surgery. Routine investigations performed in each case including electrocardiogram (ECG), chest X-ray, serum electrolytes, blood sugar, blood urea, serum patients instructed to undergo overnight fasting after 12 midnight.
Patients premedicated with tablet ranitidine 150 mg orally the night before surgery.
All procedures explained in detail.
After arrival of patient in OT, an intravenous (IV) line secured with 18-gauge IV cannula and standard monitoring including noninvasive blood pressure (BP) cuff, ECG lead, and pulse oximetry probe attached to patient. Baseline systolic BP and heart rate (HR) recorded by taking the mean of 3 consecutive reading taken 1 min apart.
Preloading done with Ringer lactate solution at a dose of 20 ml/kg/body weight over 15 min and no premedication given. The procedure of subarachnoid block was explained to the patient. Syringes of injection ephedrine (6 mg/ml) and the injection atropine (6 mg/ml) loaded and kept ready for use. After taking all aseptic precautions and proper draping lumber interspace L3-L4 identified in sitting a position. Subarachnoid space identified by using a 25-gauge Quinke spinal needle and once free flow of cerebrospinal fluid appears, study solution injected at a rate of 1 ml/10 s with direction of bevel of the needle cephalad [Figure 1],[Figure 2] and [Figure 3]. After completion of injection, the patients immediately returned to the supine position. The drug combinations were prepared by one anesthetist, and various observations were made by a second anesthesiologist who was involved after the procedure had been performed. The following parameters were observed and recorded.
Assessment of sensory blockade
Sensory level assessed by loss of pinprick sensation using a blunt 25-gauge needle along the mid-clavicular line bilaterally every minute till it reaches the highest level. In case of discrepancy level between left and right the higher level used for statistical analysis. On achieving T10 sensory blockade level, surgery was allowed. The time from intrathecal injection to two dermatome sensory regression, sensory regression to S1 dermatome were noted. The duration of sensory blockade was taken as time from onset to time of return of pinprick sensation to S1 to S1 dermatome is (lateral aspect of the calcaneus).
Assessment of motor blockade
This was assessed by Bromage scale (Appendix 1 [Additional file 1]).
The time interval between injection of the drug into the subarachnoid space, to the patient's inability to lift the straight extended leg was taken as onset time (Bromage 3). The duration of motor block was taken from time of injection to complete regression of motor block (ability to lift the extended leg) (Bromage 0). Assessment of analgesia pain was assessed by visual analogue score (VAS) (Appendix 2). Duration of pain relief (effective analgesia) was defined as the time from the spinal injection to the first request for rescue analgesics, or VAS was >4 was recorded. Rescue analgesics consisted of intravascular injection of diclofenac sodium 75 mg and repeated after 12 h if needed with a maximum daily dose of 150 mg. Rescue doses of diclofenac were recorded. Sedation was assessed by ramsay sedation scale (Appendix 3).
All durations were calculated in relation to the time of spinal injection. All duration calculated considering the time of spinal injection as time 0. Patients discharged from postanesthesia care unit after sensory regression to S1 dermatome and Bromage score 0.
Patients were shifted to the postoperative ward and observed till the administration of rescue analgesic (diclofenac sodium 75 mg IV, as per the patient demanded or VAS >4). Occurrence of nausea and vomiting, pruritus, shivering, drowsiness, hypoxia (SO 2 <90%) dry mouth, bradycardia, hypotension or respiratory depression (respiratory rate <8/min) recorded to know undesirable side effects. The incidence of hypotension (arterial BP <20% of baseline or mean arterial pressure (MAP) <60 mmHg was treated with injection ephedrine 6 mg IV increments and bradycardia as HR <60/min was treated with atropine 0.6 mg IV stat. Nausea and vomiting were treated with injection ondansetron 4 mg IV. Shivering was treated with warm drapes and warm IV fluids. The statistical tests which were used to measure the outcome were ANOVA, Chi-square test and Turkey test.
| Results|| |
All the groups were comparable with regards to the demographic variables [Table 1]. The time required to reach T10 sensory block level was 6.92 ± 1.275 min in Group B, 6.00 ± 1.245 min in Group C and 6.32 ± 1.168 min in Group D. P <0.001 (statistically significant). Intergroup comparison B to C and B to D P < 0.05 was significant. Whereas C to D was not significant > 0.05 [Table 2]. In respect to motor all patients achieved Bromage 3 motor block. The time to reach Bromage scale 3 was 15.36 ± 3.367 min in Group B, 9.52 ± 1.876 min in Group C and 10.76 ± 1.744 min in Group D. P <0.001 (statistically significant). Intergroup comparison B to C and B to D and C to D, P < 0.05 was significant. It was fastest in Group C followed by Group D and last was Group B [Table 3]. The regression time to reach Bromage scale 0 was 175.00 ± 28.54 min in Group B, 229.00 ± 42.13 min in Group C and 253.2 ± 38.04 min in Group D. P <0.001 (statistically significant). Intergroup comparison B to C, B to D and C to D, P < 0.05 was significant. It was longest in Group D followed by Group C and then Group B [Table 4]. The two segments regression time was 99.4 ± 28.938 min in Group B, 120.00 ± 30.436 min in Group C and 139.8 ± 30.655 min in Group D. P < 0.001 (statistically significant). Intergroup comparison B to C, B to D and C to D was significant (<0.05). It was longest in group D followed by Groups C and B [Table 5]. The time to regression time to S1 dermatome was 199.8 ± 32.613 min in Group B, 278.6 ± 26.208 min in Group C and 306.6 ± 50.567 min in Group D. P < 0.001 (statistically significant). Complete recovery of sensory function was observed in all studied patients. Intergroup comparison B to C, B to D and C to D was significant (P < 0.05). It was longest [Table 6]. The time of first rescue dose requested by patient was 204.8 ± 16.81 min in Group B, 309.6 ± 50.99 min in Group C and 336.8 ± 55.38 min in Group D. P < 0.001 (statistically significant). Intergroup comparison B to C, B to D and Groups C to D was significant (<0.05). Duration was longest in Group D followed by Group C and then Group B [Table 7]. In Group B mean HR was between 121 and 81. In Group C it was between 127 and 65. In Group D it was between 125 and 63. The decrease in mean HR from 3 to 6 min until the end surgery was greater in Group C and Group D. P < 0.05. Intergroup comparison B to C and B to D was statistically significant. Between C and D it was significant only at 3, 9, 15, 18, 30, 105, 120, 150 and 180 min. None of the patients had bradycardia in Groups B and C. Decrease was more in Group D. Two patients in Group D had bradycardia. The MAP in Group B decreased from 93 mmHg (baseline) to 88 at 12 min and to 78 mmHg at 21 min, which increased gradually to 92 mmHg at the end of 2 h and to 83 mmHg at the end of 3 h. In Group C it decreased from 93 to 83 mmHg at 12 min to 76 mmHg at 21 min, which increased gradually to 93 mmHg at 2 h and was maintained at 67 mmHg at the end of 3 hrs. In Group D MAP decreased from 91 to 78 mmHg at 12 min to 70 mmHg at 21 min. At the end of 3 h it was maintained at 66 mmHg. Intergroup comparison B to C it was significant throughout except at 120 min B to C was significant throughout except at 3 and 9 min. And C to D was significant throughout except at 9, 30, 45, 60 and 165 min. Though intergroup MAP difference was significant between the three groups but mean of MAP never fell below 78 mmHg in Group B and 66 mmHg and 67 mmHg in Groups C and D. Fall was more in Group D followed by Groups C and B. Four patient in Group B and Group D, and eight patients in Group C received one dose of ephedrine. Two patients in Group D required atropine. VAS values were <3 during the whole duration of the study and none of the patients required additional analgesics. The level of sedation scores were in the range 0-1 in all three groups with a median of zero. Intra-operative or postoperative nausea or vomiting occurred in six patients in Group B and four patients in Group D [Table 8],[Table 9] and [Table 10].
| Discussion|| |
Spinal anesthesia is currently widespread popular anesthetic technique available today. It has the definitive advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anesthetic.  An ideal local anesthetic agent used in spinal anesthesia in lower limb surgeries should have rapid onset of action, intense analgesia, adequate motor blockade, long duration of action, adequate postoperative analgesia though for limited duration and minimal cardiovascular changes. Kalso et al.,  and Post et al.,  showed that a 1:10 dose ratio between intrathecal dexmedetomidine and clonidine produced a similar effect in animal models. Asano et al.,  showed that the potency of epidurally administered alpha 2-adrenoceptor agonists was well correlated with their binding affinity to spinal alpha 2-adrenoreceptors. The binding affinity of dexmedetomidine compared with clonidine is approximately 1:10. Thus, it hypothesized that 3 μg of intrathecal dexmedetomidine might be equipotent to 30 μg of intrathecal clonidine. Several studies have been done using different doses of clonidine (15-300 μg) and dexmedetomidine in order to determine the most effective intrathecal administration with minimal side effects. In our study, 50 μg of clonidine and 5 μg of dexmedetomidine were used, as it was found that the incidence of side effects increased with larger doses. In this clinical study, 150 patients in age group between 18 and 60 years, posted for various elective lower limb surgeries belonging to ASA physical status I and II selected. Highest dose of intrathecal dexmedetomidine used in animal studies was 100 μg.  Konakci et al.,  reported white matter injury in rats when high dose epidural dexmedetomidine (6 μg/kg) was used alone. In the study conducted by Kanazi et al. (2006)  reported that the mean time to reach T10 sensory block was 9.7 ± 4.2 min in the control group (bupivacaine 12 mg), 7.6 ± 4.4 min in Group C where bupivacaine supplemented with clonidine 30 μg and 8.6 ± 3.7 min in Group D where bupivacaine supplemented with dexmedetomidine 3 μg. P > 0.05 so it was statistically not significant. In the same study the time to achieve Bromage 3 motor block was significantly shorter in dexmedetomidine group (13.2 ± 5.6 min) and clonidine group (11.7 ± 5.9 min) than in bupivacaine group (20.7 ± 10.3 min, P = 0.002), whereas values C versus D was not significantly different. In the same study they also observed that observed that there was clinically and statistically significant difference between the groups in the median and range of the regression time to reach modified Bromage 0 level. It was, 163 ± 47 min in bupivacaine group, 216 ± 35 min in clonidine group and 250 ± 76 min in dexmedetomidine group. Kanazi et al.,  also observed that there was statistically significant difference between the bupivacaine group and dexmedetomidine group (P = 0.003) in the two segments regression time, but not between bupivacaine group and clonidine group. In an another study conducted by Eid and Shafie,  there was no significant difference observed in the time to reach T10 sensory block, 8.7 ± 3.3 min for Group B (15 mg hyperbaric bupivacaine), 7.7 ± 3.6 min for Group D1 (dexmedetomidine 10 μg) and 8 ± 2.5 min for Group D2 (dexmedetomidine 15 μg) with P = 0.67. 
In the study conducted by Al-Mustafa et al.,  to reach Bromage 3 motor block was significantly shorter in dexmedetomidine group (5 μg) (13.0 ± 3.4 min) compare to bupivacaine (12.5 mg) group (18 ± 3.3 min).
In the study conducted by Gupta et al.,  the time to reach the Bromage scale 3 was 11.6 ± 1.8 min in Group D (bupivacaine 12.5 mg plus dexmedetomidine 5 μg) which almost concur with control group (Group B) of present study. Two segments regression time was, 80 ± 28 min in bupivacaine group, 101 ± 37 min in clonidine group and 122 ± 76 min in dexmedetomidine group. The result of our study in regard to regression to S1 dermatome was almost similar to the studies done by different authors [Table 10]. It is concluded that the difference in the regression time to reach S1 dermatome between the groups was significant. Sethi et al.,  used clonidine 1 μg/kg with 12.5 mg 0.5% bupivacaine and compared duration of analgesia the control group received an identical volume of saline mixed with 12.5 mg 0.5% bupivacaine. Author observed that duration of analgesia was significantly longer in clonidine group (223 min) than bupivacaine group (614 min). In a study conducted by Hala E A Eid et al.  shown significant prolongation of the duration of spinal blockade by intrathecal administration of dexmedetomidine as an adjunct to hyperbaric bupivacaine. Patients in the groups that received dexmedetomidine had reduced postoperative pain scores and a longer analgesic duration than those who received spinal bupivacaine alone Eisenach et al., found that addition of a low dose of alpha 2-agonist to a high dose of local anesthetics does not further affect the near-maximal sympatholysis.  Strebel et al., observed that clonidine in the dose range 37.5-150 μg did not cause a significant decrease in BP when added to 18 mg of bupivacaine compared with bupivacaine alone.  In contrast, Klimscha et al.,  and D'Angelo et al.,  in different studies observed that more than 150 μg of clonidine added to a low dose of bupivacaine (5 mg) yielded a greater decrease in BP than bupivacaine alone. In our study the addition of dexmedetomidine or clonidine to bupivacaine did cause statistically significant decrease in the BP when three groups were compared intra-operatively or postoperatively but incidence of hypotension and bradycardia were low.
| Conclusion|| |
Acute pain following surgical procedures is unique to the clinical practice of pain medicine. It is one of the few opportunities in which the cause of pain is known before its occurrence, the pain is reliably expected to occur, and can be annulled effectively.
Despite advances in the knowledge of pathophysiology, pharmacology and the development of more effective techniques for the management of perioperative analgesia, many patients continue to experience distressing pain in the postoperative period. It is shown that relief of pain with neuraxial blockade with a local anesthetic like bupivacaine alone is limited to the initial postoperative period. When a combination of local anesthetic and an alpha 2 adrenergic agonist like clonidine is used, pain relief can be extended well into the postoperative period. In conclusion, this study shows that the supplementation of bupivacaine spinal block with a low dose of intrathecal dexmedetomidine (5 μg) or clonidine (50 μg) produces a significantly shorter onset of motor and sensory block and a significantly longer sensory and motor block than bupivacaine alone. The 50 μg of clonidine or 5 μg dose provides maximum benefit and minimum side effects. These doses have an effect on sedation level, HR and MAP which does not however require any therapeutic intervention and hence can be advocated as an adjuvant to bupivacaine in spinal anesthesia for lower limb surgeries. This approach to pain therapy may hold promise, that favorable outcomes such as successful analgesia may be achieved with minimal side-effects.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]