Randomized clinical study comparing safety and efficacy of adjuvant intrathecal clonidine versus normal saline along with bupivacaine anaesthesia in lower limb surgery patients

Brijesh Kumar, Kiran Shetty, Vijaya Kiran Shetty, Suresha K. R.


Background: Various adjuvants have been used in intrathecal anesthesia to avoid intraoperative visceral and somatic pain and prolong postoperative analgesia. Clonidine, partially selective α2-agonist, is being evaluated as a neuraxial adjuvant with intrathecal bupivacaine. The objective of the study was to evaluate and compare safety and efficacy of intrathecal clonidine as adjuvant to bupivacaine with control normal saline.

Methods: American Society of Anesthesiologist grade 1 and 2 patients (60 patients) were randomly divided into two groups of 30 patients each for lower limb surgeries. Study group injected with intrathecal 3ml of 0.5% Bupivacaine heavy (15mg) + 1µg/kg of clonidine and control group injected with 3ml of 0.5% Bupivacaine heavy (15mg) + equivalent dose of normal saline. The onset and duration of sensory and motor block, duration of analgesia, and the incidence of side effects in both groups were observed and compared.

Results: Time for 2 segment regressions in study group was 186.17±25.92 minutes compared to control was 103.20±19.15 minutes (p value<0.001). Total duration of analgesia in control was 226.50±35.69 minutes and in the study group was 465.67±100.37 minutes (p value<0.001). The average duration of motor block in control group was 181.17±26.12 minutes compared to study group was 217.80±41.51 minutes (p value<0.001). The small dose of intrathecal clonidine is not significantly associated with systemic side effects such as bradycardia and hypotension.

Conclusions: Clonidine added to bupivacaine for intrathecal anesthesia effectively increases the duration of sensory block, duration of motor block and duration of analgesia and does not produce any significant hemodynamic changes. No significant side effects are associated with it.


Bupivacaine, Clonidine, Intrathecal anesthesia, Lower limb surgeries

Full Text:



Mallikarjuna, Bindu, Davan KR, Mammen S, Sabreen S, Pooja P. Synergistic effects of intrathecal magnesium sulphate to the combination of bupivacaine and fentanyl spinal anaesthesia in patients undergoing lower abdominal surgeries Technology 2016;20(1):46-8.

Heavner JE. Pharmacology of local anesthetics. In D.E. Longnecker et al (eds) Anesthesiology. New York: McGraw-Hill Medical; 2008.

Zaric D, Leon N. Pace Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics. Cochrane Database Syst Rev: 2009;(2):CD003006.

Balakrishnan K, Ebenezer V, Dakir A, Kumar S, Prakash D. Bupivacaine versus lignocaine as the choice of locall anesthetic agent for impacted third molar surgery a review. Journal of Pharmacy & Bioallied Sciences. 2015;7(1):230-3.

Kaur M. Adjuvants to Local Anesthetics: Combination Wisdom. Anesthesia, Essays and Researches. 2010:122-123.

Mercier FJ, Dounas M, Bouaziz H, Des Mesnards-Smaja V, Foiret C, Vestermann MN, et al. The effect of adding a minidose of clonidine to intrathecal sufentanil for labor analgesia. Anesthesiology: The Journal of the American Society of Anesthesiologists. 1998 Sep 1;89(3):594-601.

Missant C, Teunkens A, Vandermeersch E, Van de Velde M. Intrathecal clonidine prolongs labour analgesia but worsens fetal outcome: a pilot study. Can J Anaesth. 2004;51:696.

Rochette A, Raux O, Troncin R, Dadure C, Verdier R, Capdevila X. Clonidine prolongs spinal anesthesia in newborns: a prospective dose-ranging study. Anesthesia & Analgesia. 2004 Jan 1;98(1):56-9.

Graham AC, McClure JH. Quantitative assessment of motor block in labouring women receiving epidural analgesia. Anaesthesia. 2001 May 2;56(5):470-6.

Pederson H, Santos AC, Seinberg ES. Effects of varying doses of 0.5% hyperbaric bupivacaine on visceral pain during operations. Anaesthesiology. 1989;65:380-4.

Eisenach JC, De Kock M, Klimscha W. Alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anaesthesiology 1996;85(3):655-74.

Harada Y, Nishioka K, Kitahata LM, Kishikawa K, Collins JG. Visceral antinociceptive effects of spinal clonidine combined with morphine, enkephalin, or U50, 488H. Anesthesiology. 1995;83:344-52.

Giovannitti Jr JA, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesthesia progress. 2015 Mar;62(1):31-8.

Mandal SK, Biswas MR, Mondal SK, Das A, Das K. Intrathecal Clonidine Co-Administered with Hyperbaric Bupivacaine in Infra-Umbilical Surgery- A Dose Response Study. Ann. Int. Med. Den. Res. 2016;2(6):27-32.

Eisenach J, Detweiler D, Hood D. Hemodynamic and analgesic actions of epidurally administered clonidine. Anaesthisiology. 1993:78;277-87.

Sethi BS, Samuel M, Sreevastava D. Efficacy of Analgesic Effects of Low Dose Intrathecal Clonidine as Adjuvant to Bupivacaine. Indian J of anaesthesia. 2007;51(5):415-9.

Strebel S, Gurzeler JA, Schneider MC, Aeschbach A, Kindler CH. Small-dose intrathecal clonidine and isobaric bupivacaine for orthopedic surgery: a dose-response study. Anesthesia & Analgesia. 2004 Oct 1;99(4):1231-8.

Dobrydnjov I, Axelsson K, Thorn SE, Matthiesen P, Klockhoff H, Olmstrom B, et al. Clonidine combined with small dose bupivacaine during spinal anesthesia for inguinal herniorrhaphy: A randomized double-blinded study. Anesth Analg. 2003;96:1496-503.

Singh RB, Chopra N, Choubey S, Tripathi RK, Mishra A. Role of Clonidine as adjuvant to intrathecal bupivacaine in patients undergoing lower abdominal surgery: A randomized control study. Anesth Essays Res. 2014;8:307-12.

Eisenach JC, De Kock M, Klimscha W. α2-Adrenergic Agonists for Regional Anesthesia. A Clinical Review of Clonidine (1984-1995). The J of the American Society of Ane. 1996 Sep 1;85(3):655-74.

Gecaj-Gashi A, Terziqi H, Pervorfi T, Kryeziu A. Intrathecal clonidine added to small-dose bupivacaine prolongs postoperative analgesia in patients undergoing transurethral surgery. Canadian Urological Association Journal. 2012 Feb;6(1):25.

Jyothi VH, Safiya S. Prospective randomised study of combination of epidural bupivacaine with clonidine and bupivacaine for postoperative analgesia. Internet J Anaesth. 2012;30:2.

Benhamou D, Thorin D, Brichant JF, Dailland P, Milon D, Schneider M. Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean section. Anesthesia & Analgesia. 1998 Sep 1;87(3):609-13.

Chiari A, Lorber C, Eisenach JC, Wildling E, Krenn C, Zavrsky A, et al. Analgesic and Hemodynamic Effects of Intrathecal Clonidine as the Sole Analgesic Agent during First Stage of Labor A Dose-Response Study. Anesthesiology: The Journal of the American Society of Anesthesiologists. 1999 Aug 1;91(2):388-96.