European Journal of Cardiovascular Medicine

During the anesthesia practice, management of anxiety and intraoperative tension pose a significant challenge as these factors have various negative results on various systems of the body. With the use of only local anesthetic agents for neuraxial analgesia usually result in increased side-effects and inadequate analgesia. However, spinal anesthesia provides efficacious pain management postoperatively which is vital for reducing the adverse outcomes linked with the surgical trauma. It also helps in ensuring the sufficient and rapid surgical anesthesia making it a globally accepted technique for orthopedic surgeries, urological procedures, cesarean sections, and abdominal surgeries.¹

Ropivacaine is a newer local anesthetic agent which has combined long lasting effects and potency of bupivacaine and offer a toxicity profile which is intermediate between lidocaine and bupivacaine. It also has added benefits of faster and better recovery. On its intrathecal use, 1.5mg ropivacaine has 3 times more efficacy compared to 10mg bupivacaine and produce comparable hemodynamic and motor effects and slightly strong anesthesia. Owing to its lower risk of central nervous system and cardiotoxicity, reduced tendency for motor block, and safety, ropivacaine is a significant agent for regional anesthesia. Also, it has differential blockade which is characterized by increased separation between motor and sensory blockade.² 

To attain prolonged postoperative analgesia following subarachnoid block, adjuvants are usually added to intrathecal local anesthetic agents. In these, intrathecal clonidine has been widely used as an adjuvant for various surgical procedures with it being selective partial α2-adrenergic agonist. Clonidine increases postoperative analgesia by hypo polarization of C and A-delta fibers in the spinal cord and inhibition of high-voltage gated sodium channels. It has depicted potent analgesia without typical adverse effects linked to opioids. Also, clonidine strengthens motor and sensory blockade of local anesthetics.³

Clonidine, when used systemically, can induce the sedation owing to bradycardia and central action. It has various clinical applications including postoperative analgesia and premedication when added to the local anesthetic agents.⁴ Considering these benefits, the present study was aimed to comparatively assess the clinical efficacy of two different doses of 30 µg and 30 µg intrathecal clonidine as an adjuvant to the hyperbaric ropivacaine in subjects undergoing lower limb surgeries.

The present observational clinical study was aimed to comparatively assess the clinical efficacy of two different doses of 30 µg and 30 µg intrathecal clonidine as an adjuvant to the hyperbaric ropivacaine in subjects undergoing lower limb surgeries. The study subjects were from Department of Surgery of the Institute. Verbal and written informed consent were taken from all the subjects and school authorities before study participation.

The inclusion criteria for the study were subjects aged 18 to 65 years, in ASA grade I and II, no known history of allergy, no history of reaction to amide or ester type local anesthesia, and subjects willing to participate in the study. The exclusion criteria for the study were subjects that did not give consent for study participation, had spinal anesthesia contraindication as requiring supplementation with general anaesthesia, known allergy to the study drugs, pregnant females, lactating females, ASA grade III or higher, respiratory diseases, cardiovascular diseases, hepatic diseases, renal diseases, arrythmias, or did not give consent for study participation. Subjects that met the inclusion criteria were finally included.

For preoperative assessment, detailed history was recorded for all the subjects followed by general examination for assessing edema, clubbing, lymphadenopathy, cyanosis, icterus, and pallor along with vital signs as respiratory rate, SpO2, blood pressure, pulse rate, and temperature. Systemic examination assessed central nervous system, respiratory, and cardiovascular system along with per abdomen examination. Routine preoperative assessment included chest X-ray, electrocardiography, serology, renal and liver function tests, random blood sugar, and complete blood count. Subjects were kept NPO (mil per oral) for 6 hours for solids and 4 hours for liquids. Subjects were assessed concerning VAS (visual analogue scale) for pain assessment and IV lines were secured.

Ringer’s lactate was used for preloading and premedication was given with ondansetron and glycopyrrolate. For 180 subjects included, they were randomly divided into two groups of 90 subjects each where Group I subjects were given 3ml of 0.75% hyperbaric ropivacaine along with 30µg clonidine which was diluted with normal saline for total of 3.5mL volume. Group II subjects were given 50 µg clonidine with 3ml of 0.75% hyperbaric ropivacaine diluted with normal saline for total of 3.5mL volume.

Pinprick method was used for assessment of sensory blockade. Data assessed were time to sensory block onset assessed as time from spinal injection to the loss of sensation at the L1 level, total sensory block duration from spinal injection to the return of sensation at the L1 level, the time for regression by two segments, and time to achieve the highest sensory block level. Motor block was assessed with bromage scale and data assessed were total motor block duration (from spinal injection to the return to grade, time to achieve the highest motor block level (grade III), and time to motor block onset (from spinal injection to Bromage grade I).⁵

Adverse effects assessed in study subjects were respiratory depression, hypotension, and bradycardia were managed and monitored. Bradycardia (<60 beats/minute) was managed with 0.6mg intravenous atropine sulphate, respiratory depression (<10 breaths/minute) was managed with 100% oxygen, and hypotension was defined as 20% or more decrease in blood pressure from baseline and was managed with 6mg intravenous mephentermine.

4-point Likert scale was used to evaluate the sedation and sedation scores were assessed every 5 minutes for first 15 minutes followed by every 15 minutes till end of the surgery. Scale depicted following 4 scores as 1 for spontaneous eye opening, 2 for verbal stimuli response, 3 for physical stimuli response, and 4 for no response.⁶

Adverse effects were recorded as ADR (Adverse Drug Reaction) and any complication which emerged were accordingly managed. Postoperatively, vital signs were monitored in all the subjects along with duration of motor and sensory block. Postoperative pain was assessed using VAS scores and both effective and absolute analgesia duration was recorded. Number of rescue analgesia needed in 24 hours was recorded.

Vital signs were assessed postoperatively and duration of motor and sensory block was recorded. VAS was assessed for pain measurement. Duration of absolute analgesia was recorded as time from intrathecal injection to when VAS ≥ 1, whereas, effective analgesia duration was time from intrathecal injection to when VAS ≥ 4. Total number of rescue analgesia dose needed in 24 hours was noted with each dose comprising of 1.5mg/kg diclofenac sodium.

The collected data underwent statistical evaluation using the chi-square test, Fisher’s exact test, Mann Whitney U test, and SPSS (Statistical Package for the Social Sciences) software version 24.0 (IBM Corp., Armonk. NY, USA) using ANOVA, chi-square test, and student's t-test. The significance level was considered at a p-value of <0.05.

The present observational clinical study was aimed to comparatively assess the clinical efficacy of two different doses of 30 µg and 30 µg intrathecal clonidine as an adjuvant to the hyperbaric ropivacaine in subjects undergoing lower limb surgeries. The present study assessed 180 subjects that were randomly divided into two groups of 90 subjects each where Group I subjects were given 3ml of 0.75% hyperbaric ropivacaine along with 30µg clonidine which was diluted with normal saline for total of 3.5mL volume. Group II subjects were given 50 µg clonidine with 3ml of 0.75% hyperbaric ropivacaine diluted with normal saline for total of 3.5mL volume. The mean age of the study subjects in two groups was statistically comparable in two groups with p=0.243. The gender distribution in two groups was statistically non-significant with p=0.643. The ASA status was also statistically comparable in two groups of study subjects with p=0.538 (Table 1).

Table 1: Demographic characteristics in two groups of study subjects

Table 2: Spinal blockade characteristics in two groups of study subjects

Table 3: Duration of spinal blockade in two groups of study subjects

Table 4; Number of rescue analgesia needed in 24 hours postoperative in two groups of study subjects

It was seen that for spinal blockade characteristics in two groups of study subjects, onset of Grade III motor blockade bromage, the results were statistically comparable with two doses of clonidine with p=0.944. Time to achieve highest level was significantly higher with 30µg clonidine (group I) compared to 50µg clonidine (group II) with p=0.003. Onset of Grade I motor blockade bromage was non-significantly higher in Group I with p=0.236. Simialr non-signiifcant difference was seen for sensory blockade onset at L1 with p=0.483 (Table 2).  

The study results showed that concerning duration of spinal blockade in two groups of study subjects, effective analgesia duration waas significatly higher in Group I comapred to Group I with p<0.001. Absolute analgesia duration was significantly higher in Group II with p<0.001. Simialr highly statistical difference with higher values was seen for Group II compared to Group I for sensory blockade duration, motor blockade duration, and two segments regression with p<0.001 (Table 3).

Concerning the number of rescue analgesia needed in 24 hours postoperative in two groups of study subjects, 1 rescue analgesia was needed in 52 subjects that were given 30µg clonidine and 44 subjects from Group II that were given 50 µg clonidine. Two rescue analgesia were needed in 38 subjects from Group I and 46 subjects from Group II. The difference was statistically non-significant between the two groups with p=0.307 (Table 4).

The present study assessed 180 subjects that were randomly divided into two groups of 90 subjects each where Group I subjects were given 3ml of 0.75% hyperbaric ropivacaine along with 30µg clonidine which was diluted with normal saline for total of 3.5mL volume. Group II subjects were given 50 µg clonidine with 3ml of 0.75% hyperbaric ropivacaine diluted with normal saline for total of 3.5mL volume. The mean age of the study subjects in two groups was statistically comparable in two groups with p=0.243. The gender distribution in two groups was statistically non-significant with p=0.643. The ASA status was also statistically comparable in two groups of study subjects with p=0.538. These data were comparable to the previous studies of Thakur A et al⁷ in 2013 and Adlakha N et al⁸ in 2022 where authors assessed subjects with demographic data comparable to the present study in their respective studies.

The study results showed that for spinal blockade characteristics in two groups of study subjects, onset of Grade III motor blockade bromage, the results were statistically comparable with two doses of clonidine with p=0.944. Time to achieve highest level was significantly higher with 30µg clonidine (group I) compared to 50µg clonidine (group II) with p=0.003. Onset of Grade I motor blockade bromage was non-significantly higher in Group I with p=0.236. Simialr non-signiifcant difference was seen for sensory blockade onset at L1 with p=0.483. These results were consistent with the findings of Sri Hyndavi K et al⁹ in 2013 and Anusha T et al¹⁰ in 2021 where spinal blockade characteristics with clonidine similar to the present study were also reported by the studies of the authors.  

It was seen that concerning duration of spinal blockade in two groups of study subjects, effective analgesia duration waas significatly higher in Group I comapred to Group I with p<0.001. Absolute analgesia duration was significantly higher in Group II with p<0.001. Simialr highly statistical difference with higher values was seen for Group II compared to Group I for sensory blockade duration, motor blockade duration, and two segments regression with p<0.001. These findings were in agreement with the results of Ganesh M et al¹¹ in 2018 and Munnoli T et al¹² in 2016 where authors reported comparable duration of spinal blockade in their study subjects as in the present study.

The study results also showed that concerning the number of rescue analgesia needed in 24 hours postoperative in two groups of study subjects, 1 rescue analgesia was needed in 52 subjects that were given 30µg clonidine and 44 subjects from Group II that were given 50 µg clonidine. Two rescue analgesia were needed in 38 subjects from Group I and 46 subjects from Group II. The difference was statistically non-significant between the two groups with p=0.307. These results were in line with the findings of Zhang C et al¹³ in 2016 and Kakunje R et al¹⁴ in 2016 where number of rescue analgesia needed in 24 hours simialr to the present study was also reported by the authors in their respective studies.

Within its limitations, the present study concludes that50µg of intrathecal clonidine provides higher analgesic effects in comparison to 30µg clonidine. However, it is linked with a higher risk of hypotension and bradycardia. Timely interventions and careful watch and monitoring are vital when clonidine is used in higher dose compared to a low dose.

1. Mahendru V, Tewari A, Katyal S, Grewal A, Singh MR, Katyal R. A comparison of intrathecal dexmedetomidine, clonidine, and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: A double blind controlled study. J Anaesthesiol Clin Pharmacol. 2013;29:496–502.
2. Gautier P, De Kock M, Huberty L, Demir T, Izydorczic M, Vanderick B. Comparison of the effects of intrathecal ropivacaine, levobupivacaine, and bupivacaine for Caesarean section. Br J Anaesth. 2003;91:684–9.
3. Krishnappa MS, Singh N, Singh K, Doddaiah D, Narasimha P, 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.
4. Sharan R, Verma R, Dhawan A, Kumar J. Comparison of clonidine and fentanyl as adjuvant to ropivacaine in spinal anesthesia in lower abdominal surgeries. Anesth Essays Res. 2016;10:526–31.
5. Kanazi 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.
6. Lee SC, Kim TH, Choi SR, Park SY. No difference between spinal anesthesia with ropivacaine and intravenous dexmedetomidine sedation with and without intrathecal fentanyl: A randomized noninferiority trial. Pain Res Manag. 2022;2022:3395783.
7. Thakur A, Bhardwaj M, Kaur K, Dureja J, Hooda S, Taxak S. Intrathecal clonidine as an adjuvant to hyperbaric bupivacaine in patients undergoing inguinal herniorrhaphy: A randomized doubleblinded study. J Anaesthesiol Clin Pharmacol. 2013;29:66–70.
8. Adlakha N, Chaudhary S, Jain M. Evaluation of two doses of intrathecal clonidine on analgesia and haemodynamic profile in elderly patients undergoing endoscopic bladder surgeries: A randomized clinical trial. J Clin Diagn Res. 2022;16.
9. Sri Hyndavi K, Patil D, Mohite A, Navale R, Paranjpe J. Clonidine as an adjuvant to bupivacaine in infraclavicular brachial plexus block for prolongation of postoperative analgesia. Sci Technol. 2016;18:3.
10. Anusha T. A comparative study between intrathecal isobaric ropivacaine 0.75% (15 mg) plus dexmedetomidine (10 µg) and isobaric ropivacaine 0.75% (15 mg) plus clonidine (30 µg) for elective lower abdominal and lower limb surgeries. Int J Med Anesthesiol. 2021;4:185–8.
11. Ganesh M, Krishnamurthy D. A comparative study of dexmedetomidine and clonidine as an adjuvant to intrathecal bupivacaine in lower abdominal surgeries. Anesth Essays Res. 2018;12:539–45.
12. Munnoli T, Singh G, Mohammad B, Gupta I, Attar J, Naveen NK. A randomised, double-blind, placebo-controlled trial comparing dexmedetomidine and clonidine as an adjuvant to intrathecal ropivacaine in lower limb surgery. J Evol Med Dent Sci. 2016;5:6680–4.
13. Zhang C, Li C, Pirrone M, Sun L, Mi W. Comparison of dexmedetomidine and clonidine as adjuvants to local anesthetics for intrathecal anesthesia: A meta-analysis of randomized controlled trials. J Clin Pharmacol. 2016;56:827–34.
14. Kakunje R, Sethuramachandran A, Parida S, Bidkar PU, Talawar P. Effects of adding low-dose clonidine to intrathecal hyperbaric ropivacaine: A randomized double-blind clinical trial. Anesth Essays Res. 2016;10:38–44.