|Year : 2015 | Volume
| Issue : 3 | Page : 164-168
A comparative study of analgesic effects of intrathecal hyperbaric ropivacaine with dexmedetomidine and hyperbaric ropivacaine with clonidine in lower abdominal surgery
Manohar Singanahalli Krishnappa1, Nongthombam Ratan Singh1, Khulem Maniram Singh1, Dhananjaya Bangalore Doddaiah1, Prasad Vijayashankar Narasimha2, Nirmeen Fatima1
1 Department of Anesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
2 Department of Pharmacology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||1-Dec-2015|
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Local anesthetics are often combined with adjuvants such as opioids and α2 agonists to improve or prolong the anesthetic effect. This study was taken up to compare the duration of postoperative analgesia between ropivacaine with clonidine and ropivacaine with dexmedetomidine. Materials and Methods: In this prospective, randomized, double-blinded study, 50 adult patients of both sexes undergoing lower abdominal surgeries under spinal anesthesia were allocated to two groups, C and D, by a computer-generated randomization table. Group C (clonidine group) received 2.5 mL of 0.75% hyperbaric ropivacaine with 50 μgm of clonidine (0.5 mL) and Group D (dexmedetomidine group) received 2.5 mL of 0.75% hyperbaric ropivacaine with 5 μgm of dexmedetomidine in 0.5 mL of normal saline. The spinal block characteristics, duration of surgery, duration of postoperative analgesia, first 24 h analgesic consumption, hemodynamic parameters, and adverse effects (if any) were recorded. Results: The time to S2 regression was significantly more with Group D (Group D vs Group C: 448.78 ± 41.52 vs 392.68 ± 38.72 min (P < 0.001). There was significant difference between Groups C and D in duration of analgesia (269.20 ± 51.61 vs 303.20 ± 48.65 min; P = 0.020) respectively. Analgesic consumption (in mg) in the first 24 h was statistically less in the dexmedetomidine group than in the clonidine group (248.00 ± 58.59 vs 312.00 ± 60 min; P < 0.001). The incidence of hypotension and bradycardia was: Group D vs Group C: 12 vs 10, 5:4, respectively. Conclusion: Dexmedetomidine as an adjuvant to ropivacaine spinal anesthesia, provided excellent quality of postoperative analgesia with minimal side effects in prolonged surgeries compared to clonidine.
Keywords: Clonidine, dexmedetomidine, postoperative analgesia, ropivacaine, spinal anesthesia
|How to cite this article:|
Krishnappa MS, Singh NR, Singh KM, Doddaiah DB, Narasimha PV, Fatima N. A comparative study of analgesic effects of intrathecal hyperbaric ropivacaine with dexmedetomidine and hyperbaric ropivacaine with clonidine in lower abdominal surgery. J Med Soc 2015;29:164-8
|How to cite this URL:|
Krishnappa MS, Singh NR, Singh KM, Doddaiah DB, Narasimha PV, Fatima N. A comparative study of analgesic effects of intrathecal hyperbaric ropivacaine with dexmedetomidine and hyperbaric ropivacaine with clonidine in lower abdominal surgery. J Med Soc [serial online] 2015 [cited 2021 Dec 8];29:164-8. Available from: https://www.jmedsoc.org/text.asp?2015/29/3/164/170799
| Introduction|| |
Spinal anesthesia has widespread popularity, and adequate postoperative pain control is essential to prevent adverse consequences of surgical insult. The ideal spinal anesthesia would provide rapid and adequate surgical anesthesia, enabling early ambulation and the ability to void to allow early discharge.
Bupivacaine is a widely used amide local anesthetic. Its long duration of action and tendency to provide more sensory than motor block has made it a popular drug for providing prolonged analgesia. However, the main disadvantage of bupivacaine is its cardiotoxic effects. 
On the other hand, ropivacaine is a long-acting amide local anesthetic structurally related to bupivacaine. Ropivacaine has consistently demonstrated a higher safety profile than bupivacaine, with reduced central nervous system (CNS)-toxic and cardiotoxic potential, together with wide clinical utility at different doses and for a wide range of indications. , The concept of using adjuvants with local anesthetics has progressed through the practice of administering opioids such as morphine, fentanyl, sufentanil, and alfentanil; α2 agonists such as clonidine; and a more selective α2 agonist, dexmedetomidine. α2 agonists do not have side effects such as nausea, vomiting, urinary retention, pruritus, or respiratory depression, which are all commonly associated with opioids. ,
Clonidine, a partial agonist of the α2 adrenoreceptor, acts as an analgesic, a sedative, and as a sympatholytic with potent antinociceptive properties. Dexmedetomidine is the d- enantiomer of medetomidine, a substance that provides sedation, anxiolysis, hypnosis, analgesia, and sympatholysis. It has analgesic effect if it is injected intrathecally. It shows a high ratio of specificity for the α2 receptor (α2 /α1 1600:1) compared with clonidine (α2 /α1 200:1), making it a complete α2 agonist. 
Several studies have shown that these drugs, when administered intrathecally, enhance the analgesia provided by subtherapeutic doses of local anesthetics such as ropivacaine due to synergistic effects with minimal hemodynamic effects.
This study was taken up to compare the duration of postoperative analgesia between ropivacaine with clonidine and ropivacaine with dexmedetomidine.
| Materials and Methods|| |
After obtaining institutional Ethical Committee approval and written informed consent, 50 adult patients of the American Society of Anesthesiologists (ASA)  grade I and II, aged 18-60 years, of both sexes, and scheduled to undergo elective lower abdominal surgeries under spinal anesthesia were included in this randomized, prospective, double-blinded study.
Based on previous studies, , a sample size of 24.96 in each group was determined with an alpha error of 0.05 and power of 0.95, and rounded to 25 patients in each group. The patients were allocated into two groups of 25 patients each by a computer-generated randomization table to receive the study drugs as follows:
Group C (Clonidine group), received 2.5 mL of 0.75% hyperbaric ropivacaine with 50 μgm of clonidine (0.5 mL.)
Group D (Dexmedetomidine group), received 2.5 mL of 0.75% hyperbaric ropivacaine with 5 μgm of dexmedetomidine in 0.5 mL of normal saline.
Patient with neurological deficit, bleeding disorders, psychiatric disorders, chronic pain, and/or spinal deformity, neurological disorders, and patients on antihypertensive medication were excluded.
Hyperbaric ropivacaine was prepared by adding 2 mL of 0.75% plain ropivacaine with 0.5 mL of 25% glucose, which gave a volume of 2.5 mL containing 15 mg of the drug with 4.1% glucose.  The study was double-blinded and the randomization was based on a computer-generated table.
After preanesthetic evaluation, all the patients received alprazolam 0.5 mg and ranitidine 150 mg orally as premedication on the night before surgery; on arrival in the operation room, they were preloaded with Ringer's lactate (RL) solution at 15 mL/kg body weight about 15 min before the intrathecal drug administration and monitored with pulse oximetry (SpO 2 ), noninvasive blood pressure (NIBP), and electrocardiogram (ECG).
Under aseptic and antiseptic precaution, lumbar puncture was performed at L 3-4 intervertebral space using midline approach with a 25G Quincke spinal needle in the lateral decubitus position and either of the study drugs was administered intrathecally using the randomization table. The study solution was prepared by a colleague not involved in the study to achieve blinding.
The hemodynamic parameters such as heart rate (HR), NIBP and SpO 2 were recorded at 2 mininterval for the first 10 min and thereafter at 5 min interval until the end of the surgery. The spinal block characteristics, duration of surgery, duration of postoperative analgesia, first 24 h analgesic consumption, and any adverse effects were recorded.
Hypotension, defined as a fall in systolic blood pressure (SBP) of >20% from the baseline, was treated with rapid infusion of 500 mL of RL and inj. mephentermine intravenously (IV) and bradycardia defined as HR <50 beats per minute (bpm) were treated with inj. atropine sulfate 0.6 mg IV.
All the patients were observed in the postanesthetic care unit for the first 2 h and thereafter in the ward for 24 h. Rescue analgesia was provided by inj. tramadol hydrochloride 100 mg IV.
The data collected were analyzed using Statistical Package for Social Sciences for Windows, version 15 (SPSS Inc. Chicago, IL, USA). Descriptive and inferential statistical analysis was carried out in the present study, and data on continuous measurements are presented as either mean ± SD or number and percentages. Significance was assessed at 5% level of significance.
Student's t-test (two-tailed, independent) was used to find the significance of study parameters on continuous variables and the chi-square and Fisher's exact tests were used to find the significance of the study parameters on categorical data.
| Results|| |
The groups were comparable with respect to age, sex, and ASA physical status. There was no significant difference in the type and duration of surgery [Table 1].
There was statistical significant difference between Groups C and D in the highest level of block (T 5 and T 4 , respectively; P = 0.028) and in the time to reach peak level (11.20 ± 1.45 and 10.70 ± 1.27 min, respectively; P = 0.021), but not clinically significant [Table 2]. Block regression was significantly slower with Group D as compared to Group C, that is, time to two segment regressions (148.16 ± 14.42 vs 102.16 ± 14.69 min; P < 0.001), and time to S2 regression (448.78 ± 41.52 vs 392.68 ± 38.72 min; P < 0.001) were significantly greater with Group D. As shown in [Table 3], there was significant difference between the clonidine and dexmedetomidine groups in duration of analgesia (269.20 ± 51.61 vs 303.20 ± 48.65 min; P = 0.020), respectively. There was also significance in time to mobilization (315.20 ± 5057 vs 347.80 ± 50.89 min; P = 0.028) and time to mituration (380.00 ± 61.95 vs 410.20 ± 62.77 min; P = 0.093) between Group C and Group D. The amount of analgesic consumption (in mg) in the first 24 h was statistically much lower in the dexmedetomidine group than the clonidine group (248.00 ± 58.59 vs 312.00 ± 60 min; P < 0.001).
Ten (40%) patients in Group C and 12 (48%) patients in Group D developed hypotension (SBP <20% of baseline), needing treatment with inj. mephenteramine. Four patients (16%) in Group C and 5 (20%) patients in Group D had bradycardia (HR <50 bpm) that was successfully treated with inj. atropine sulfate 0.6 g IV. Most of the patients in both the groups were sedated but easily arousable [Table 4].
| Discussion|| |
Various workers have used different doses of clonidine for intrathecal blockade, starting from 15 μg to 300 μg along with local anesthetics, , and different doses of dexmedetomidine for intrathecal blockade starting from 3 μg to 15 μg along with local anesthetics. ,, In most of these studies, 5 μg of dexmedetomidine was used. Hence, we selected a 5 μg dose of preservative-free dexmedetomidine for our study. Asano et al.  showed that binding affinity to spinal α2 receptors of dexmedetomidine when compared with clonidine is approximately 1:10. In our study, we selected 10× the dose of dexmedetomidine as clonidine, i.e., 50 μg or 1 μg/kg, whichever was smaller.
In our study, it was observed that the analgesic effect of intrathecal ropivacaine was potentiated by intrathecal dexmedetomidine and clonidine. The addition of 5 μg of intrathecal dexmedetomidine and clonidine (50 μg or 1 μg/kg, whichever was smaller) prolonged the postoperative analgesic effect of ropivacaine by 303.20 ± 48.65 and 269.20 ± 51.61 h (P = 0.020), respectively. Clonidine with ropivacaine when used intrathecally in three different doses-15 μg, 45 μg, and 75 μg-showed that clonidine 15 μg significantly improved the quality of anesthesia without delaying sensory and motor recovery and 45 μg prolonged the sensory blockade without any influence on motor blockade, but a dose of 75 μg was associated with delayed sensory and motor recovery as well as detectable side effects such as hypotension and sedation,  These findings may be favorably compared with the findings of our study. Gupta et al.  demonstrated that the duration of analgesia in Group D (dexmedetomidine 5 μg) was 478.4 ± 20.9 min and in Group R (isobaric ropivacaine) was 241.7 ± 21.7 min. The duration of analgesia was longer in their study compared to the present study, which could be possibly due to their higher dose of ropivacaine. Moreover, their study was carried out on lower limb surgeries compared to our study, which was on lower abdominal surgeries. In their study, the dexmedetomidine group required less postoperative analgesic in the first 24 h compared to the clonidine group, which is in agreement with the findings of our study (P < 0.001).
The use of dexmedetomidine was associated with a decrease in HR and blood pressure in a study by Al-Ghanem et al.  Similarly, in the present study, 9 cases of bradycardia and 22 cases of hypotension were observed. This could be due to the combination of α2 agonists with ropivacaine, even though ropivacaine has been shown to be a better drug in terms of cardiovascular and hemodynamic control. ,
Intrathecal dexmedetomidine and clonidine prolonged the analgesic effect of ropivacaine by approximately 5-6 h and the analgesic demand in the first 24 h was lower in the dexmedetomidine group postoperatively, which may be compared with the findings of Gupta et al.  Even though the exact mechanism for the prolongation of the sensory and motor blockade of the local anesthetic by intrathecal α2 agonists is not known, α2 agonists act by binding to the presynaptic C fibers and postsynaptic dorsal horn neurons, whereas local anesthetics act by blocking the sodium channels. At the same time, intrathecal α2 -adrenoceptor agonist produces analgesic action by depressing the release of C fiber transmitters and by hyperpolarization of postsynaptic dorsal horn neurons.  Salgado et al.  opined that the antinociceptive effect of α2 -adrenoceptor agonist could have produced the prolongation of the sensory block when added to spinal anesthetics. Moreover, the binding of α2 -adrenoceptor agonists to motor neurons in the dorsal horn may have produced the prolongation of the motor block of spinal anesthetics. ,
There was no incidence of shivering observed in either of the groups, which might be due to the antishivering property of the α-2 adrenergic agents, and similar findings were observed by Talke et al.  We did not observe any side effect other than a few cases of bradycardia (HR <50 bpm) in both groups, which were successfully managed with atropine 0.6 mg IV. The reason may be due to the fact that we had used small doses of intrathecal dexmedetomidine (5 μg) and clonidine (50 μg or 1 μg/kg), which was supported by the findings of various studies. ,,
Varied doses of the two adjuvants with the same dose of local anesthetic were not assessed. Different doses of the local anesthetic with equivalent doses of the adjuvant should be evaluated.
| Conclusion|| |
Dexmedetomidine, as an adjuvant to ropivacaine spinal anesthesia, provided better and excellent quality of postoperative analgesia with minimal side effects in prolonged surgeries compared to clonidine.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Catterall W, Mackie K. Local anesthetics. In: Gilman AG, Hardman JG, Limbird LE, editors. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 10 th
ed. USA: McGraw Hill; 2001. p. 375.
Wille M. Intrathecal use of ropivacaine: A review. Acta Anaesthesiol Belg 2004;55:251-9.
Kuthiala G, Chaudhary G. Ropivacaine: A review of its pharmacology and clinical use. Indian J Anaesth 2011;55:104-10.
Gutstein HB, Akil H. Opioid analgesics. In: Gilman AG, Hardman JG, Limbird LE, editors. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 10 th
ed. USA: McGraw Hill; 2001. p. 595-6.
Bajwa SJ, Bajwa SK, Kaur J, Singh A, Singh A, Parmar SS. Prevention of hypotension and prolongation of postoperative analgesia in emergency cesarean sections: A randomized study with intrathecal clonidine. Int J Crit Illn Inj Sci 2012;2:63-9.
Reves JG, Glass PS, Lubarsky DA, McEvoy MD, Martinez-Ruiz R. Intravenous anesthetics. In: Miller RD, Eriksson LL, Fleisher LA, Wiener-Kronish JP, Young WL, editors. Miller's Anesthesia. 7 th
ed. Philadelphia: Churchill Livingstone; 2010. p. 751-7.
Fischer SP, Bader AM, Sweitzer B. Perioperative evaluation. In: Miller RD, editor. Miller's Anesthesia. 7 th
ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 1002.
Sagiroglu G, Sagiroglu T, Meydan B. The effects of adding various doses of clonidine to ropivacaine in spinal anesthesia. Eurasian J Med 2009;41:149-53.
Gupta R, Bogra J, Verma R, Kohli M, Kushwaha JK, Kumar S. Dexmedetomidine as an intrathecal adjuvant for postoperative analgesia. Indian J Anaesth 2011;55:347-51.
McLeod GA. Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose. Br J Anaesth 2004;92:547-51.
Benhamou D, Thorin D, Brichant JF, Dailland P, Milon D, Schneider M. Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during caesarean section. Anesth Analg 1998,87:609-13.
Kanazi GE, Aouad MT, Jabbour-Khoury SI, AI Jazzar MD, Alameddine MM, AI-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.
Shukla D, Verma A, Agarwal A, Pandey HD, Tyagi C. Comparative study of intrathecal dexmedetomidine with intrathecal magnesium sulfate used as adjuvants to bupivacaine. J Anaesth Clin Pharmacol 2011;27:495-9.
Asano T, Dohi S, Ohta S, Shimonaka H, Iida H. Antinociception by epidural and systemic alpha(2)-adrenoreceptor agonists and their binding affinity in rat spinal cord and brain. Anesth Analg 2000;90:400-7.
De Kock Mc, Gautier P, Fanard L, Hody JL, Lavand'homme P. Intrathecal ropivacaine and clonidine for ambulatory knee arthroscopy: A dose-response duty. Anesthesiology 2001;94:574-8.
Al-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 controlled study. American J Appl Sci 2009;6:882-7.
Yamashita A, Matsumoto M, Matsumoto S, Itoh M, Kawai K, Sakabe T. A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits. Anesth Analg 2003;97:512-9, table of contents.
McNamee DA, Convery PN, Milligan KR. Total knee replacement: A comparison of ropivacaine and bupivacaine in combined femoral and sciatic block. Acta Anaesthesiol Scand 2001;45:477-81.
Eisanach JC, De Kock M, Klimscha W. alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology 1996;85:655-74.
Salgado 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 2008; 54:110-5.
Harada Y, Nishioka K, Kitahata LM, Kishikawa K, Collins JG. Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H. Anesthesiology 1995;83:344-52.
Yaksh TL, Reddy SV. Studies in primate on the analgesic effects associated with intrathecal actions of opiates, alpha-adrenergic agonists and baclofen. Anesthesiology 1981;54:451-67.
Talke P, Tayefeh F, Sessler DI, Jeffrey R, Noursalehi M, Richardson C. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology 1997;87:835-41.
[Table 1], [Table 2], [Table 3], [Table 4]