|Year : 2015 | Volume
| Issue : 11 | Page : 733-738
Comparison of clonidine and dexmedetomidine as adjuncts to intravenous regional anaesthesia
Shalini Pravin Sardesai, Kalyani Nilesh Patil, Adnanali Sarkar
Department of Anesthesiology, Srimati Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India
|Date of Web Publication||20-Nov-2015|
Shalini Pravin Sardesai
D4/204, Laketown, Katraj, Pune - 411 046, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Aims: Intravenous regional anaesthesia (IVRA) provides reliable and rapid analgesia with good muscular relaxation of the extremity distal to the tourniquet, but tourniquet pain and absence of post-operative analgesia are major drawbacks. α2 agonists, clonidine and dexmedetomidine are known to potentiate peripheral nerve blocks. The aim of this study was to compare clonidine and dexmedetomidine as adjuvants to IVRA with respect to block characteristics, tourniquet pain and post-operative analgesia. Methods: A prospective, randomised, double-blind study was conducted on 60 adult patients of American Society of Anesthesiologists physical status grades I and II, in two groups of 30 each, to receive either clonidine 1 μg/kg or dexmedetomidine 1 μg/kg added to 40 ml 0.5% preservative-free lignocaine. Independent samples t-test was used for analysing demographic data, haemodynamic data and block characteristics and Mann-Whitney U-test for skewed data. Results: Sensorimotor block onset was significantly faster and recovery delayed with dexmedetomidine as compared to clonidine. Intra-operative visual analogue scale (VAS) at 10 min, 15 min and 40 min and post-operative VAS at 30 min and 2 h were significantly higher with clonidine. Fentanyl consumption and sedation were comparable. Duration of analgesia was significantly longer with dexmedetomidine. Haemodynamic parameters were comparable. Conclusions: Dexmedetomidine significantly facilitates onset, prolongs recovery of sensory as well as motor block and also prolongs duration of analgesia as compared to clonidine. Both decrease tourniquet pain satisfactorily and have comparable intra-operative fentanyl requirement . Patient satisfaction is better with dexmedetomidine.
Keywords: Clonidine, dexmedetomidine, fentanyl, intravenous regional anesthesia
|How to cite this article:|
Sardesai SP, Patil KN, Sarkar A. Comparison of clonidine and dexmedetomidine as adjuncts to intravenous regional anaesthesia. Indian J Anaesth 2015;59:733-8
|How to cite this URL:|
Sardesai SP, Patil KN, Sarkar A. Comparison of clonidine and dexmedetomidine as adjuncts to intravenous regional anaesthesia. Indian J Anaesth [serial online] 2015 [cited 2020 Feb 21];59:733-8. Available from: http://www.ijaweb.org/text.asp?2015/59/11/733/170034
| Introduction|| |
Intravenous regional anaesthesia (IVRA) or Bier's block is an ideal technique for short operative procedures on extremities, performed on day-care basis. The advantages of IVRA are high indices of reliability, rapid onset of analgesia and good muscular relaxation. The disadvantage is application of a pneumatic tourniquet throughout the procedure. The duration of surgery is limited by time during which the tourniquet could be safely inflated. Another drawback is the absence of post-operative analgesia.  Advancements in this field have been primarily aimed at increasing tourniquet tolerance, improving overall quality of intra-operative, post-operative analgesia and reducing drug-related adverse effects. In an attempt to improve peri-operative analgesia, various methods have been used, which include supplementation by narcotics and non-steroidal anti-inflammatory drugs, either systemically or as adjuvants to IVRA. However, none of them has been proven as ideal. , Clonidine enhances peripheral nerve blocks of local anaesthetics by selectively blocking Ad and C fibres. Dexmedetomidine, a potent α2 receptor agonist, is approximately 8 times more selective toward α2 receptors than clonidine.  In the present study, we have evaluated and compared the effects of adding clonidine or dexmedetomidine to lignocaine for IVRA in upper limb orthopaedic surgeries.
| Methods|| |
After Institutional Ethics Committee approval, a double-blind, prospective, randomised study was carried out over a period of 8 months on 60 patients in the age group of 18-60 years and American Society of Anaesthesiologists physical status I and II, undergoing elective upper limb orthopaedic surgeries. Patients with coagulation disorder, peripheral vascular disease, sickle cell anaemia and allergy to study drug and patients on adrenoceptor agonist or antagonist therapy and those unwilling for the study were excluded. At pre-operative visit, the visual analogue scale (VAS) scoring system was explained along with the nature and safety of the procedure. Written, valid, informed consent was obtained.
The patients were randomly recruited to one of the following groups of 30 each, using a computer generated random number list, depending on the study drug used: Group C: 0.5% lignocaine (preservative-free) 40 ml + clonidine 1 μg/kg, Group D: 0.5% lignocaine (preservative-free) 40 ml + dexmedetomidine 1 μg/kg. Lignocaine 0.5% was constituted by adding 30 ml normal saline to 10 ml of 2% preservative-free lignocaine.
On arrival to operating room, starvation was confirmed. No premedication was given. Patients' baseline pulse rate, electrocardiogram and non-invasive blood pressure were recorded, and a wide bore intravenous (IV) line was established on unaffected limb and infusion was started with lactated Ringer's solution.
A 22-gauge IV cannula was inserted into distal vein of the extremity to be operated. Cotton pad was applied to the arm. Two tourniquets were placed over the cotton pad. The arm was exsanguinated using Esmarch bandage. Proximal tourniquet was inflated to 100 mm Hg above the patient's systolic blood pressure. The absence of radial artery pulsations and failure of pulse-oximetry tracing in ipsilateral index finger was confirmed. 40 ml of test solution was injected over 10 s by an anaesthesiologist who was blinded to the study drug. The sensory block was assessed by pinprick with a 22-gauge short-bevelled needle every 30 s. Patient response was evaluated in dermatomal sensory distribution of medial and lateral cutaneous, ulnar, median and radial nerves. Motor function was assessed by asking the patient to flex and extend the wrist and fingers, and complete motor block was noted when no voluntary movement was possible. Sensory block onset time was noted as time elapsed from injection of study drug to sensory block achieved in all dermatomes, and motor block onset time was noted as time elapsed from injection of study drug to complete motor block.
After sensory and motor block were achieved, distal cuff was inflated to 250 mm Hg, followed by release of proximal tourniquet and surgery started. Mean arterial pressure (MAP), heart rate (HR) and arterial oxygen (O 2) saturation were monitored before tourniquet application and at 5, 10, 15, 20 and 40 min after the injection of anaesthetic. Hypotension (>25% decrease in MAP from baseline) was treated with IV ephedrine (3 to 9 mg bolus) and bradycardia (>25% decrease from baseline) was treated with IV atropine 0.6 mg. O 2 supplementation was done via a face mask when arterial oxygen saturation dropped below 91%. Assessment of tourniquet pain scores was made by VAS between 0 and 10 (0 - "no pain" and 10 - "worst pain imaginable") and sedation was assessed by Ramsay sedation score before tourniquet application and at 5, 10, 15, 20 and 40 min after the injection of anaesthetic. Intra-operatively, intravenous boluses of 1 μg/kg fentanyl were given for tourniquet pain when required (VAS >3), and total fentanyl consumption was recorded.
The tourniquet was not deflated before 30 min and was not inflated for more than 1 h 30 min. At the end of surgery, tourniquet deflation was performed by cyclic deflation technique. Sensory recovery time (time elapsed after tourniquet deflation up to recovery of sensation in all dermatomes) was determined by pinprick test. Complete recovery of motor power was assessed by asking the patient to flex and extend the wrist and fingers at 30 s interval. Complete motor recovery was recorded when all voluntary movements were shown at the end of surgery and after removal of the tourniquet.
MAP, HR, VAS and degree of sedation values were recorded 30 min after tourniquet deflation and at 2, 4, 6, 12 and 24 h after tourniquet deflation. Patients were instructed to receive 75 mg intra-muscular diclofenac once they complained of pain in the post-anaesthesia care unit. The duration of analgesia was the time elapsed between tourniquet release and the first intra-muscular intake of diclofenac. If no diclofenac was necessary within 24 h, the duration of analgesia was considered 1440 min.
Patient satisfaction score was recorded post-operatively after 24 h as: 5 - very satisfied, 4 - satisfied, 3 - neutral, 2 - dissatisfied and 1 - very dissatisfied. It was based on patients' subjective assessment of the quality of anaesthesia.
During the study period, any local or systemic complications were recorded. All the measurements were performed by an anaesthesiologist who was blinded to the medication administered.
The software used was Statistical Package for Social Sciences version 20.0 (IBM Corp., Armonk, NY, USA). The sample size was estimated from data of previous studies, using alpha level of 0.05 and beta level of 0.90 to establish a desired power of 90% using two-sample means test (Satterthwaite's t-test) assuming unequal variance. Enrolment of at least 28 patients in each group was required. Independent samples t-test was used for evaluation of demographic data, haemodynamic data, block characteristics, duration of surgery and tourniquet, onset of tourniquet pain, duration of analgesia and intra-operative analgesic requirement. Mann-Whitney U-test was used for VAS, sedation scores and patient satisfaction score. P < 0.05 was considered statistically significant.
| Results|| |
Both groups were comparable with respect to age, sex, weight, baseline haemodynamic vitals, duration of surgery, duration of tourniquet inflation [Table 1] and intra-operative and post-operative haemodynamic variables.
|Table 1: Distribution of subjects according to demographic profile vital signs and surgical characteristics|
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There was a significant difference in both groups with respect to mean onset and recovery of sensory and motor block. Sensory block onset and recovery were 6.18 ± 1.07 min and 5.1 ± 1.12 min, respectively in Group C and 4.28 ± 1.23 min and 7.3 ± 1.49 min, respectively in Group D (P < 0.001). Motor block onset and recovery were 11.27 ± 1.66 min and 6.9 ± 0.84 min, respectively in Group C and 8.63 ± 1.86 min and 9.53 ± 1.07 min, respectively in Group D (P < 0.001) [Figure 1] and [Figure 2].
The intra-operative VAS score was significantly higher in Group C at 10 min, 15 min and 40 min than in Group D (P = 0.001) [Figure 3]. During post-operative period, VAS score was significantly higher at 30 min and at 2 h in Group C [Figure 4]. However, the fentanyl consumption in both groups was comparable. The consumption in Group C was 72.22 ± 17.70 μg and in Group D was 65 ± 25.98 μg (P = 0.59905). There was no statistically significant difference in the two groups with respect to intra-operative and post-operative sedation as assessed by Ramsay sedation score. The maximum sedation score achieved was 2, that is, awake but drowsy at around 15-20 min in both groups.
The mean duration of analgesia, based on time for request of first dose of supplemental analgesic, in Group C was 571 ± 627.48 min while in Group D was 1224 ± 446.11 min, which was significantly longer in Group D (P < 0.001) [Figure 5]. The patient satisfaction was significantly higher in Group D (P = 0.003).
None of the patients had significant bradycardia or hypotension so as to require any intervention.
| Discussion|| |
IVRA provides analgesia in the distal part of a limb by intravenous injection of a local anaesthetic solution into the vein of the same limb, while circulation to the limb is occluded by application of tourniquet. The duration of surgery is limited by the time during which the arterial tourniquet could be kept safely inflated. Tourniquet pain, described as a dull and aching pain sensation, is a well-known limitation. Skin compression, tourniquet size and inflation pressure have been implicated, but the exact mechanism remains unclear. Another drawback with this technique is the absence of post-operative analgesia. Different agents are used as additives to local anaesthetic for IVRA, including phencyclidines, non-steroidal anti-inflammatory drugs, opioids, muscle relaxants, neostigmine and magnesium; , however, none of them have demonstrated a clear advantage.
The pharmacological properties of α2 agonists, which include sedation, analgesia, anxiolysis, peri-operative sympatholysis, cardiovascular stabilising effects, reduced anaesthetic requirements and preservation of respiratory function, have been extensively studied and clinically employed in regional anaesthesia. , Dexmedetomidine is 8-10 times more selective toward α2 adrenergic receptors and is 3.5 times more lipophilic than clonidine. It thus prolongs the duration of both sensory and motor blockade induced by local anaesthetics, irrespective of the route of administration. ,,
Gupta et al. conducted a study with two different doses of dexmedetomidine as an adjunct in IVRA and concluded that addition of dexmedetomidine 1 μg/kg to lignocaine improves quality of anaesthesia and post-operative analgesia in comparison to 0.5 μg/kg.  We used 1 μg/kg dexmedetomidine and compared it with 1 μg/kg clonidine in our study.
Kol et al. suggested that addition of 0.5 μg/kg dexmedetomidine had more potent effect, shortening sensory block onset time and prolonging sensory block recovery time more than lornoxicam in IVRA. 
In our study, the onset of sensory as well as motor block was significantly shortened and recovery was prolonged by addition of dexmedetomidine to lignocaine as compared to clonidine. The duration of analgesia, assessed by time for requirement of rescue analgesic, was significantly longer in the dexmedetomidine group. This could be attributed to more selective action of dexmedetomidine on α2 adrenergic receptors and its lipophilic nature as compared to clonidine. Clonidine is a partial agonist and dexmedetomidine is a full agonist at the α2 adrenergic receptors. 
Addition of dexmedetomidine to lignocaine for IVRA has been shown to improve quality of anaesthesia in previous studies. , Dexmedetomidine enhances the local anaesthetic action of lignocaine via α2A adrenoceptors.  Peri-operative dexmedetomidine administration decreases the requirements for opioid or non-opioid analgesics both intra- and post-operatively.  Intravenous dexmedetomidine as a premedication was effective because it reduced patient anxiety, sympathoadrenal responses and opioid analgesic requirements, but it did not reduce tourniquet pain. , Even in our study, the patient satisfaction score was significantly better with dexmedetomidine than with clonidine.
Tourniquet pain and lack of post-operative analgesia are major drawbacks of IVRA. Many studies have shown that addition of clonidine to IVRA decreases tourniquet pain and improves post-operative analgesia. , Clonidine has also been reported to depress nerve action potentials, especially in C fibres by a mechanism independent of the stimulation of α2 adrenergic receptors.  Memis et al. concluded that addition of dexmedetomidine to lignocaine attenuated tourniquet pain and reduced the fentanyl consumption.  In our study, the intra-operative and post-operative differences in VAS scores in the two groups could be attributed to the pharmacokinetic differences between clonidine and dexmedetomidine. Dexmedetomidine is 3.5 times more lipophilic and has 8 times more specificity for α2 receptors as compared to clonidine.  Moreover, there was no significant difference in the fentanyl consumption in the two groups.
In the present study, we recorded the time for demand of rescue analgesic as a measure of post-operative analgesia. The duration of post-operative analgesia was significantly higher with dexmedetomidine as an adjuvant as compared to clonidine. Most of the patients who received dexmedetomidine did not demand analgesic or complain of pain for 24 h post-operatively. α2 adrenergic receptors located at nerve endings may have a role in the analgesic effect of the drugs by preventing norepinephrine release. The effect is more pronounced with dexmedetomidine as it is more selective and a complete agonist at these receptors.  Clonidine and dexmedetomidine have been compared in various studies as adjuvants to local anaesthetics. ,, Swami et al. concluded that dexmedetomidine prolongs duration and enhances quality of sensorimotor block as compared with clonidine as an adjuvant to bupivacaine in peripheral nerve block. 
Both the adjuvants did not cause significant sedation in the present study. This is in accordance with study conducted by Memis et al.  Other studies have shown significant sedation with dexmedetomidine. , Also, we did not observe any side effects in both the study groups. Dexmedetomidine administration produces abrupt hypertension and bradycardia till the central sympatholytic effect dominates, resulting in moderate decrease in both MAP and HR from baseline.  In our study, no such haemodynamic changes were observed with the use of dexmedetomidine or clonidine in IVRA. This could be explained by the cyclical deflation of tourniquet done in our study, which prevented sudden release of drugs in the systemic circulation.
The limitation of our study is a small sample size, but it had significantly important results.
| Conclusions|| |
Dexmedetomidine when added to lignocaine for IVRA significantly facilitates onset and prolongs the recovery of sensory as well as motor block as compared to clonidine. Both α2 adrenergic agonists decrease the pain associated with the inflation of pneumatic tourniquet, without any associated haemodynamic instability or other significant side effects. Block quality, duration of post-operative analgesia and patient satisfaction were better with dexmedetomidine.
Financial support and sponsorship
Department of Anesthesiology, Srimati Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]