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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 2-6

Comparison of effects of 50 μg clonidine and 5 μg dexmedetomidine on characteristics of levobupivacaine spinal block


Department of Anaesthesiology and Critical Care Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission10-Apr-2018
Date of Decision01-Nov-2019
Date of Acceptance02-Nov-2019
Date of Web Publication2-Jun-2020

Correspondence Address:
M Hanumantha Rao
Dean, Senior Professor, Department of Anaesthesiology and Critical Care Medicine, Sri Venkateswara Institute of Medical Sciences, Alipiri Road, Tirupati 517 507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_2_20

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  Abstract 


Background: Various adjuvants are being used with local anaesthetics for prolongation of intra- and post-operative analgesia.
Methods: We randomly allocated and studied 60 patients, aged between 18 and 60 years into two groups. Group C received 3 mL (15 mg) of 0.5% isobaric levobupivacaine with 0.5 mL (50 μg) clonidine and Group D received 3 mL (15 mg) of 0.5% isobaric levobupivacaine with 0.5 mL (5 μg) dexmedetomidine. Onset and duration of sensory and motor blockade, haemodynamic parameters, and side effects were assessed.
Results: Onset of sensory block (seconds) was faster in Group D than in Group C (141.7 ± 84.5 Vs 152.4 ± 77.8; P = 0.48). The mean time (minutes) for regression of sensory block to S1 dermatome was earlier in Group C compared to Group D (372.3 ± 69.3 Vs 395.3 ± 63.8; P = 0.10). The time of onset of motor block was earlier in Group D compared to Group C (3.5 ± 2.1 min Vs 3.3 ± 1.8 P = 0.81). The time required to achieve complete motor block (minutes) was more in Group C compared to Group D (9.7 ± 4.0 Vs 9.1 ± 3.1; P = 0.52). The mean time (minutes) taken for resolution of motor block was longer in Group D compared with Group C (309.5 ± 60.0 Vs 338.2 ± 61.6; P = 0.07).
Conclusions: The supplementation of 50 μg clonidine and 5 μg dexmedetomidine to 0.5% isobaric levobupivacaine produced similar characteristics of the spinal block and maintained haemodynamic stability.

Keywords: Clonidine, dexmedetomidine, levobupivacaine, spinal block


How to cite this article:
Aruna P, Rao M H, Swetha PS, Srihari B, Karuturi C, Kadiyala S. Comparison of effects of 50 μg clonidine and 5 μg dexmedetomidine on characteristics of levobupivacaine spinal block. J Clin Sci Res 2020;9:2-6

How to cite this URL:
Aruna P, Rao M H, Swetha PS, Srihari B, Karuturi C, Kadiyala S. Comparison of effects of 50 μg clonidine and 5 μg dexmedetomidine on characteristics of levobupivacaine spinal block. J Clin Sci Res [serial online] 2020 [cited 2020 Jul 11];9:2-6. Available from: http://www.jcsr.co.in/text.asp?2020/9/1/2/285711




  Introduction Top


Central neuraxial blockade can provide excellent intraoperative anaesthesia, prolonged and satisfactory postoperative analgesia in many cases. The adequacy of spinal anasthesia with bupivacaine for lower limb and lower abdominal surgeries is limited by fixed duration of action. Levobupivacaine, the S (-) enantiomer of bupivacaine, recently introduced in the Indian market, has emerged as a safe alternative to bupivacaine due to its low cardiovascular and neurological toxic adverse effects.[1],[2]

Single-dose spinal anaesthesia is associated with haemodynamic instability, especially when high doses were used to achieve a longer duration of block. Several neuraxial adjuvants are used most commonly with hyperbaric bupivacaine to minimize the instability in haemodynamics.[3]

Alpha-2 agonists such as clonidine and dexmedetomidine are used as neuraxial adjuvants. They potentiate the effect of local anaesthetics and allow a decrease in required doses.[4],[5] They prolong the duration of both motor and sensory spinal blockade.[4],[5],[6] This study is designed to compare the onset, duration of sensory and motor block and haemodynamic characteristics and side effects of addition of clonidine (50 μg) and dexmedetomidine (5 μg) to intrathecal 0.5% isobaric levobupivacaine.


  Material and Methods Top


After obtaining approvals from the Institutional Research and Ethics Committees, 60 patients aged 18–60 years with American Society of Anesthesiologists (ASA)[7] physical status I/II who were scheduled for elective infra umbilical surgery (inguinal hernioplasty) under spinal anasthesia were included in this prospective, randomised, double-blind study. Patients with contraindication to the central neuraxial blockade, those with neurological and psychiatric disorders, obesity (body mass index >30 kg/m2), hypersensitivity to study drugs, pregnant and lactating women, and patients who were not willing to participate in the study were excluded. Patients were kept fasting as per the guidelines.[8] Patients were premedicated with tab alprazolam 0.5 mg and ranitidine 150 mg on the night and morning before surgery. On arrival in the operation theatre, routine monitoring with electrocardiogram, noninvasive arterial pressure, and pulse oximetry were done and preloaded with 10 ml/kg ringer's lactate after securing an intravenous (IV) access overs 20 min before surgery. The patients were randomly allocated into one of the two groups of 30 patients each using a computer-generated randomization code and sealed opaque envelope technique. The patients were given intrathecal study drug as follows: Group C (n = 30) received 3.5 mL (3 mL [15 mg] of 0.5% levobupivacaine + 0.5 mL [50 μg] of clonidine) and Group D received 3.5 mL (3 mL [15 mg] of 0.5% levobupivacaine + 0.5 mL [5 μg] of dexmedetomidine). All the drugs used in this study were preservative free. The intrathecal injections were prepared by an an anesthesiologist who was not involved in the study. The investigator performing the block and recording the observations of the study parameters was blinded to the intrathecal drug administered. Lumbar puncture was performed in lateral position at L3-L4 intervertebral space using a 25 gauge, Quincke–Babcock's spinal needle and intrathecal injection was administered after aspiration of cerebrospinal fluid. Patients were administered oxygen with a face mask at the rate of 6 L/min. Crystalloid solutions were administered during anasthesia and the rate was adjusted depending on the haemodynamic response.

The haemodynamic parameters, such as, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure (MAP) were recorded at baseline (at the time of injection of study drug), 2 min, 3 min, 6 min, 10 min, 15 min, 30 min, 45 min, 60 min, 2 h, 3 h, 6 h, 8 h after injection of study drug. Hypotension was defined as a drop in SBP below 90 mmHg or more than 30% of the baseline and initially treated with 200 mL IV fluid bolus over 10 min, if not corrected then was treated with IV ephedrine 0.06 mg/kg bolus. Bradycardia was defined as decrease in HR below 50 beats per minute and was treated with IV atropine 0.04 mg/kg bolus. The number of incidences of hypotension and bradycardia of each patient was used for statistical analysis.

The subarachnoid block characteristics were assessed such as sensory onset time (time between the injections of intrathecal anaesthetic to loss of cold sensation at T10 dermatome), maximum height of sensory block attained, time to reach maximum height and regression to S1. The motor level was assessed according to the modified Bromage score: (0 = no motor loss; 1 = inability to flex hip; 2 = inability to flex the knee joint; and 3 = inability to flex the ankle).[9] The onset of motor block (modified Bromage score I), time to achieve complete motor block (modified Bromage score III), and time to regression (modified Bromage score 0) from the completion of intrathecal injection were assessed.

Statistical analysis

Data are presented as mean (standard deviation), or frequencies as appropriate. Normality was tested by the Shapiro–Wilk test. Continuous variables between the groups were compared using Student's t-test or Mann–Whitney U-test as appropriate. Categorical data between the groups were compared using the Chi-square test. A P value < 0.05 was considered statistically significant.


  Results Top


The patient screening and treatment allocation are showin [Figure 1]. The groups were comparable with respect to age, weight, height, gender, and ASA status [Table 1].
Figure 1: Study plan

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Table 1: Comparison of demographic characteristics

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The mean times of onset of sensory block (loss of cold sensation at T10), maximum height of block, time to reach maximum height, and regression time to S1 were comparable in between the two groups. The motor block onset and duration of block were comparable between the two groups [Table 2].
Table 2: Comparison of block characteristics

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Haemodynamic parameters were well maintained in both the groups. HR [Figure 2] was compared between the groups at regular intervals. The results did not show any statistically significant difference.
Figure 2: Comparison of heart rate
Group C = Intrathecal clonidine; Group D = Intrathecal dexmedetomidine + bupivacaine


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MAP compared between the two groups. A statistically significant difference was observed at 2 min, 60 min, and 3 h [Figure 3].
Figure 3: Comparison of mean arterial pressure
Group C = Intrathecal clonidine; Group D = Intrathecal dexmedetomidine + bupivacaine


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Hypotension was observed in 4 out of 30 patients in Group C and 6 out of 30 in Group D. Bradycardia was observed in 4 out of 30 patients in both Group C and D. No statistically significant difference is observed between two groups [Table 3].
Table 3: Comparison of adverse effects

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The mean doses of ephedrine and atropine and total amount of IV fluid given to the patients were comparable between the groups [Table 4].
Table 4: Comparison of ephedrine and atropine doses required

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  Discussion Top


Adjuvants for spinal anasthesia are intended to improve the success of regional anasthesia by prolonging the analgesia of local anesthetics and preventing the deleterious clinical effects of their toxic doses. Interest in the alpha-2 agonists has been rising in the field of regional anasthesia given their ability to enhance neuraxial analgesia without the respiratory depression and pruritus common to opioids. Intrathecal α2-adrenoceptor agonists bind and depresses the release of presynaptic C-fiber neurotransmitters and also hyperpolarize the postsynaptic dorsal horn neurons thereby producing analgesia.[10] This antinociceptive effect may explain the elongation of the sensory block while the elongation of motor block may be due to the binding of α2-adrenoceptor agonists to motor neurons in the dorsal horn. Limited studies till now have been undertaken to compare the efficacy of the addition of dexmedetomidine and clonidine intrathecally to levobupivacaine.

Our study showed the addition of dexmedetomidine resulted in the mean onset of sensory block in 141.7 s and motor block in 3.283 min that is comparable to 2.3 min and 3.4 min reported in another study[11] in which 5 μg dexmedetomidine is added to 0.5% hyperbaric bupivacaine. Similarly, the addition of clonidine resulted in sensory blockade within 152.4 s and motor block in 3.5 min that is comparable to 2.0 min and 3.3 min reported in another study[12] by addition of 50 μg clonidine to 0.5% hyperbaric bupivacaine.

Times for the complete sensory and motor block in clonidine group were 5.4 ± 2.6 min and 9.7 ± 4.0 min respectively and in dexmedetomidine are 5.95 ± 2.82 min and 9.1 ± 3.1 min. The times for complete sensory and motor block wereless in Group D when compared to Group C, but the difference is not statistically significant. The present study has been undertaken to compare the effects of the addition of clonidine or dexmedetomidine intrathecally to levobupivacaine.

In a study[13] it was reported that dexmedetomidine (3 μg) and clonidine (30 μg) in a dose ratio1:10 produced an equipotent effect on the characteristics of the block. 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.[13] The current pharmacodynamics evidence from animal and human studies suggests that levobupivacaine has a potentially greater margin of safety than the racemic bupivacaine. Our results were compared with studies that used dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine as in literature we found very few studies[14],[15] on levobupivacaine.

In a study.[16] different doses of dexmedetomidine were added to spinal bupivacaine for urological procedures and the authors reported that the mean time taken for sensory block to reach T10 dermatome was 6.3 ± 2.7 min with the addition of 5 μg dexmedetomidine. The time of onset of peak in clonidine group was comparable with results reported in another study[17] conducted in below-knee orthopedic surgeries where the addition of 50 μg clonidine to 12.5 mg hyperbaric bupivacaine resulted in peak sensory block within 4.7 ± 1.3 min. The time of onset of complete motor block can be comparable with that reported in another study,[18] where the addition of 50 μg clonidine to hyperbaric bupivacaine resulted in complete motor block within 9.52 ± 1.87 min and addition of 5 μg, dexmedetomidine to bupivacaine resulted in motor block in 10.7 ± 1.7 min.

The time for the regression of sensory block to S1 dermatome was 372.3 ± 69.3 min in the clonidine group and 395.3 ± 63.8 min with dexmedetomidine. The time for regression of sensory block was less in Group C than in Group D, but the difference was not significant. In a study[18] the addition of similar doses of clonidine and dexmedetomidine to 0.5% bupivacaine resulted in sensory block time of 278.60 ± 26.20 min in clonidine group and 306.60 ± 50.56 min in dexmedetomidine group. This may be because of levobupivacaine that produced a prolonged block than bupivacaine in our study. The time taken to the resolution of motor block (to the modified Bromage score 0) in the clonidine group is 309.5 ± 60 min and in dexmedetomidine group is 338.2 ± 61.6 min. The duration of motor block was more in the dexmedetomidine group than the clonidine group but the difference is statistically not significant.

In our study, patients remained haemodynamically stable both in dexmedetomidine and clonidine groups. Few patients required therapeutic interventions but it was not statistically significant. Similar results were also observed in another study[11] which compared 3 μg dexmedetomidine with 30 μg clonidine intrathecally with hyperbaric bupivacaine in patients undergoing transurethral resection of prostate/transurethral resection of bladder tumour under spinal anasthesia. The MAP and HR were comparable in all three groups – control, clonidine, and dexmedetomidine groups in this study.

The adverse effects observed in the study are bradycardia, hypotension, and nausea and vomiting. None of the patients complained of nausea and vomiting. The incidence of hypotension and bradycardia did not show any statistically significant difference between the groups. The total IV fluid given to the patient intraoperatively and postoperatively up to 8 h after giving the spinal drug was comparable in between the groups.

The limitations of the present study are the small sample size and absence of control group presence of which would have been useful to evaluate the effectiveness of dexmedetomidine and clonidine.

The addition of 50 μg clonidine and 5 μg dexmedetomidine to 0.5% isobaric levobupivacaine produced effective sensory and motor block in all the patients participated in our study. In our study, we concluded that the addition of clonidine 50 μg or 5 μg dexmedetomidine produced similar characteristics of sensory and motor block with the maintenance of haemodynamic stability.



Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



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



 

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