|Year : 2014 | Volume
| Issue : 1 | Page : 36-41
Addition of Clonidine or Dexmedetomidine to Ropivacaine prolongs caudal analgesia in children
Shobhana Gupta1, Virendra Pratap2
1 Department of Anaesthesiology, Gujarat Medical Education and Research Society Medical College, Gandhinagar, Gujarat, India
2 M. P. Shah Medical College, Jamnagar, Gujarat, India
|Date of Web Publication||15-Mar-2014|
Block No.105, Sector 8B, Gandhinagar - 382 010, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Caudal block is a common technique for pediatric analgesia, but with the disadvantage of short duration of action after single injection. We compared the analgesic effects and side-effects of dexmedetomidine and clonidine added to ropivacaine in pediatric patients undergoing lower abdominal surgeries. Materials and Methods: A study was conducted among 60 pediatric patients undergoing lower abdominal surgeries. A total of 60 American Society of Anesthesiologists (ASA) status I and II pediatric patients between the age of 1 and 6 years were enrolled in this study. The caudal block was administered with inj. ropivacaine 0.2% with clonidine 2 μg/kg (group A) and inj. ropivacaine 0.2% with dexmedetomidine 2 μg/kg (group B) after induction with general anesthesia. Hemodynamic parameters were observed before, during, and after the surgical procedure. Postoperative analgesic duration, total dose of rescue analgesia, pain scores, and any side effects were looked for and recorded. Results: Addition of dexmedetomidine or clonidine to caudal ropivacaine significantly promoted analgesic time. Also, there was statistically significant difference between dexmedetomidine and clonidine as regard to duration of analgesia. No significant difference was observed in incidence of hemodynamic changes or side effects. Conclusions: Addition of dexmedetomidine or clonidine to caudal ropivacaine significantly promoted analgesia in children undergoing lower abdominal surgeries with significant advantage of dexmedetomidine over clonidine and without an increase in incidence of side-effects.
Keywords: Caudal analgesia, clonidine, dexmedetomidine
|How to cite this article:|
Gupta S, Pratap V. Addition of Clonidine or Dexmedetomidine to Ropivacaine prolongs caudal analgesia in children. Indian J Pain 2014;28:36-41
| Introduction|| |
Caudal epidural block is one of the most popular, reliable, and safe technique in pediatric analgesia that can provide analgesia for a variety of infraumbilical surgical procedures. The main disadvantage of caudal analgesia is the short duration of action after a single injection.  The use of caudal catheters to administer repeated doses or infusions of local anesthetics is not popular, partly because of concerns about infection. Prolongation of caudal analgesia using a single-shot technique has been achieved by addition of various adjuvants, such as epinephrine, opioid, ketamine, and alpha 2 agonists. 
Clonidine action, similar to local anesthetic action, and its interaction with local anesthetics have been explained by three possible mechanisms. First, clonidine blocks A-delta and C fibers as a consequence of an increase in potassium conductance in isolated neurons, thus intensifying local anesthetic conduction block.  Secondly, clonidine may cause local vasoconstriction, thus decreasing local anesthetic spread and removal around neural structures. This effect is mediated by drug action on postsynaptic alpha 2 receptors, although there is little evidence of this mechanism with clinical doses.  Thirdly, clonidine combined with spinal local anesthetic or used in peripheral blocks intensifies and prolongs analgesia.  Spinal alpha 2 adrenergic agonists may also induce analgesia by activating spinal cholinergic neurons resulting in acetylcholine release. 
Dexmedetomidine has an eight fold greater affinity for alpha 2 adrenergic receptors than clonidine and much less alpha 1 effect. A major advantage of dexmedetomidine is its higher selectivity compared with clonidine alpha 2a receptors, responsible for the hypnotic and analgesic effects of such drugs. 
This study was designed to compare the analgesic effects and side effects of dexmedetomidine and clonidine when added to ropivacaine for caudal analgesia in children undergoing lower abdominal surgeries.
| Materials and Methods|| |
After obtaining informed parental consent, 60 American Society of Anesthesiologists (ASA) status I and II patients, aged 1-6 year undergoing lower abdominal surgeries, like circumcision, Lord's plication, hypospadias repair, and suprapubic cystolithotomy (SPCL) for bladder stone removal, were prospectively enrolled in this study. Study exclusion criteria included a history of developmental delay or mental retardation, which could make observational pain intensity assessment difficult a known or suspected coagulopathy; a known allergy to any of the study drugs and any signs of infection at the site of proposed caudal block.
The subjects were assigned in to two groups: A and B. All healthcare personnel providing direct patient care, the subjects, and their parents or guardians were blinded to caudal medications administered. All medications were prepared by a senior resident of Anesthesiology Department.
Patients were given oral midazolam (0.5 mg/kg) as premedication approximately 30 min prior to anesthetic induction. All the baseline parameters like the pulse rate (PR), mean arterial pressure (MAP), and peripheral oxygen saturation (SpO 2 ) were observed and recorded. A good intravenous (IV) access was secured, an induction of anesthesia was achieved with inj. sodium thiopentone (4 mg/kg), and inj. succinylcholine IV (1.5 mg/kg) intubation was done with appropriate sized endotracheal tube. After securing the endotracheal tube, patients were turned to left lateral position for the administration of caudal anesthesia which was achieved with 23 gauge hypodermic needle under all aseptic conditions and the patients were turned supine immediately after the injection. Group A (n = 30) received 0.2% ropivacaine 1 ml/kg + clonidine 2 μg/kg and group B (n = 30) received 0.2% ropivacaine 1 ml/kg + dexmedetomidine 2 μg/kg via caudal route with a total volume being constant at 1 ml/kg in both the study groups. After providing caudal block, patient was turned supine and maintenance of anesthesia was subsequently done with sevoflurane-oxygen-N 2 O and patients were mechanically ventilated with Jackson-Rees circuit. Hemodynamic parameters, respiratory rate (RR), end tidal CO 2 concentration (EtCO 2 ) and SpO 2 were recorded before induction, after intubation and then after caudal anesthesia and at 10 min interval thereafter. Any increase in MAP or PR of more than 15% from the baseline observations and values during the surgical procedure was taken out of the purview of hemodynamic stability attributable to caudal analgesia. An increase in PR or MAP within the 10-15 min of start of surgical procedure was adjudging as failure of caudal anesthesia, and rescue analgesia in the form of fentanyl was administered (2 μg/kg). IV fluids in the form of Isolyte-P solution were administered according to body weight and the fasting status.
At the end of surgical procedure all the anesthetic gases were turned off and the patients were extubated in a fully awake condition. MAP,PR,SpO 2 pain and sedation scores (opening of eyes: 3 = spontaneously, 2 = to verbal command,1 = to physical shaking, and 0 = not arousable) were recorded at a 10 min interval after extubation and thereafter at intervals of 1, 2, 4, 6, 8, 12,18 and 24h.A modified objective pain scale (OPS) was employed to assess the postoperative pain and duration of analgesia which was based on behavioral objectives that included crying, facial expression, position of legs, position of torso and generalized motor restlessness. A score of 0 was considered as excellent analgesia, while a score of 10 signifies completely ineffective analgesia. Children who had a pain score of more than 3 were administered 5 mg/kg of inj.paracetamol IV slowly. The total amount of analgesic dose and any complications or side effects were looked for and recorded. All the patients were observed for next 24 h in the special room and the recordings of all parameters were done by a senior resident of anesthesiology. All the observations were recorded half hourly for the first 6 h and thereafter hourly till the next 18 h. The patients were discharged the next day and the parents were given phone numbers to contact in case of any untoward incident. During the follow-up of 1 week, none of the parents complained of any side effects or untoward incident.
SPSS release 12.0.1 was used for statistical analysis. Data are presented as mean and standard deviation (SD). To estimate differences in normally distributed continuous outcome variables, the student's t-test for independent samples was used. A P-value of <0.05 was considered statistically significant.
| Results|| |
We enrolled 60 children (30 children in each group) in our study profile. No difference could be detected from the data of 60 children regarding the patient profile. Demographic data of patients are given in [Table 1]. There were no significant difference in the groups in terms of age, bodyweight gender distribution, and duration of surgery.
[Table 2] conveys the comparison of various vital parameters of the patients of both the groups. Intraoperative heart rate (HR), noninvasive blood pressure (NIBP), EtCO 2 , and SPO2 showed no statistical significant difference between the two groups (P > 0.05). There was no statistically significant difference between the two groups regarding the time to extubation from cessation of anesthesia (P > 0.05). No significant hypotension or bradycardia was observed in any patient. SpO 2 (> 98%) was always within the clinically acceptable range in both the groups throughout the procedure (P > 0.05).
As shown in [Figure 1] and [Figure 2], the mean PR in both the groups were comparable and no significant difference between the two groups can be made out from below bar diagram.
|Figure 2: Intraoperative changes in mean arterial pressure (MAP) in both groups|
Click here to view
It is quite clear from the [Table 3] that first analgesic requirement time was statistically prolonged in group B (17.6 ± 2.9 h) when compared to group A (10.1 ± 3.2 h) (P <0.05). Total analgesic consumption was statistically lesser in group B (60 ± 47 mg) when compared with group A (100 ± 76 mg) (P < 0.05). Four children in group B required paracetamol administration once, while in group A nine children required it once and two children twice (P < 0.05). Sixteen patients in group B and 11 patients in group A required no additional pain medication during the first 24 h study period, which was statistically significant.
The postoperative sedation scores showed no statistically significant difference (P > 0.05) which is clearly evident from description in [Table 4]. No motor impairment was seen in either group on awakening and during the next 24 h period.
As evident from [Figure 3], the mean OPS score in both the groups were comparable and no significant difference between the two groups can be made out from the line diagram given below.
|Figure 3: The comparison of mean objective pain scale (OPS) scores in groups A and B|
Click here to view
[Table 5] depicts the comparative incidence of side effects in both the groups. Two patients in group A and one in group B had episode of vomiting which is not significant on statistical analysis (P > 0.05). No any other untoward side effects were observed in either of the groups.
| Discussion|| |
The analgesic action of intrathecal or epidural clonidine was first demonstrated clinically in 1984.  The successful use of epidural clonidine in adults led to its evaluation in pediatric caudal block. The resulting studies have consistently shown caudal clonidine to increase the duration of postoperative analgesia. , On the other hand, dexmedetomidine, although currently available for IV use only, has been administered epidurally for postoperative analgesia in humans in clinical trials. ,, Nevertheless, there are still some concerns regarding its safety. 
Clonidine is being increasingly used now a day for potentiating the analgesic action of various local anesthetics administered regionally. The main interest of our study was to evaluate the efficacy of caudal dexmedetomidine over caudal clonidine when combined with the 0.2% solution of ropivacaine. The main finding of the present study is that a caudal bolus injection of combination of ropivacaine 0.2% with dexmedetomidine 2 μg/kg provides better postoperative analgesia compared to ropivacaine 0.2% with clonidine 2 μg/kg.
The quest for finding ideal combination of drugs for caudal anesthesia in children is never ending, but the efforts to use relatively safer drugs and too in lower concentration is growing day by day. Ropivacaine is one such drug that appears to be associated with greater safety margin and reduced systemic toxicity, although such toxicity has been reported in adults following various regional anesthetic technique. , Clonidine produces analgesia via a nonopioid mechanism.  Klimscha et al., had studied the effectiveness of caudal clonidine in potentiating the postoperative analgesic effect and found that in small children with a mean age of 3 years who underwent an elective lower abdominal day care surgeries, the addition of clonidine 1-2 μg/kg to ropivacaine 0.25% significantly prolonged the median duration of analgesia and reduced the total dose of postoperative analgesic compared with ropivacaine alone or ropivacaine plus epinephrine 5 μg/ml (P < 0.05).  The findings of our study are almost similar with observations of Klimscha et al., as postoperative analgesia was significantly prolonged in the patients receiving dexmedetomidine or clonidine as an adjuvant to ropivacaine.
Clonidine given by neuraxial route decreases the impulse generation by preganglionic sympathetic nerves. Similarly, the dominance of parasympathetic nervous system results in an increased vagal tone which causes bradycardia.  We did observe a fall in MAP and decrease in heart rate in groups A and B patients, but it got stabilized to normal within 20-30 min. of the caudal injection.
Clonidine causes dose-dependent post-operative sedation in children as demonstrated by Lund and his colleagues in their study on adding 2 μg/kg clonidine to caudal ropivacaine .In our study, the difference in sedation scores was not statistically significant as the all patients were easily arousable in all the three groups which is consist ant with the findings of other studies. ,,
Ropivacaine produces lesser postoperative motor blockade as compared to bupivacaine when used in lower concentration.There was no apparent motor deficit in our patients probably due to lower concentration of ropivacaine used.
The analgesic activity of alpha 2 agonist dexmedetomidine is mediated by both supraspinal and spinal mechanisms. It is assumed that central alpha 2 adrenoceptors in the locus cerulus (a supraspinal) and in the dorsal horn of the spinal cord are involved in this activity.  After addition of dexmedetomidine 2 μg/kg to caudal ropivacaine, the magnitudes of hemodynamic changes between the groups were similar. There was no significant difference in the incidence of side effects like pruritus and nausea and vomiting. No episodes of respiratory depression or urinary retention were noted. Sedation scores were comparable between the groups.
Neogi et al compared the efficacy of clonidine and dexmedetomidine as adjuvant to ropivacaine for caudal analgesia. Seventy-five patient undergoing elective inguinal herniotomy were included in one of the following three groups. Group R patients received 1 ml/kg of 0.25% ropivacaine caudally. Group C patients received 1 ml/kg of 0.25% ropivacaine and 1 μg/kg clonidine. Patients of group D were given 1 ml/kg of 0.25% ropivacaine and 1 μg/kg dexmedetomidine. They found that addition of both clonidine and dexmedetomidine with ropivacaine administered caudally significantly increases the duration of analgesia. 
| Conclusions|| |
We conclude that single caudal injection of dexmedetomidine (2 μg/kg) added to ropivacaine 0.2% offers an advantage over clonidine (2 μg/kg) added to ropivacaine 0.2% for postoperative pain relief in children undergoing lower abdominal surgery, without increasing the incidence of adverse effects. 
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]