|ORIGINAL RESEARCH REPORT
|Year : 2017 | Volume
| Issue : 4 | Page : 157-161
A randomized double-blinded comparison between dexmedetomidine and clonidine as an adjuvant to caudal ropivacaine in children for below umbilical surgery
Ganapathi Mavuri, Priyanka Jain, Swastika Chakraborty, Sandeep Kumar Mucherla, Ashok Jadon
Department of Anaesthesia, Tata Motors Hospital, Jamshedpur, Jharkhand, India
|Date of Web Publication||8-Nov-2017|
Duplex-63, Vijaya Heritage Phase-6, Kadma, Jamshedpur - 831 005, Jharkhand
Source of Support: None, Conflict of Interest: None
Background: Alpha-2 adenoreceptors as an adjuvant to local anesthetic during caudal analgesia in children prolongs the duration of analgesia. This study was designed to compare the analgesic efficacy and adverse effects of dexmedetomidine and clonidine when added to ropivacaine for caudal analgesia in children undergoing lower abdominal surgeries. Methods: In a prospective study, Seventy-eight children received block with either 0.2% ropivacaine 1.5 mg/kg (Group R; n = 26) or 0.2% ropivacaine 1.5 mg/kg + 1 mcg/kg clonidine (Group RC; n = 26) or 0.2% ropivacaine 1.5 mg/kg + dexmedetomidine 1 mcg/kg (Group RD; n = 26). Results: Duration of analgesia was 7.15 ± 1.00 h in Group R, 11.57 ± 1.27 h in Group R + C, and 14.73 ± 1.53 h in Group R + D (P < 0.0001). One patient in Group R + D had vomiting and 1 patient in Group R had urinary retention which was not statistically significant (P > 0.05). Conclusion: Addition of clonidine and dexmedetomidine to caudal ropivacaine significantly prolongs the duration of analgesia without adverse effects.
Keywords: Analgesia, caudal, clonidine, dexmedetomidine, face, leg, activity, cry and consolability score, postoperative period, ropivacaine, sevoflurane
|How to cite this article:|
Mavuri G, Jain P, Chakraborty S, Mucherla SK, Jadon A. A randomized double-blinded comparison between dexmedetomidine and clonidine as an adjuvant to caudal ropivacaine in children for below umbilical surgery. J Clin Sci 2017;14:157-61
|How to cite this URL:|
Mavuri G, Jain P, Chakraborty S, Mucherla SK, Jadon A. A randomized double-blinded comparison between dexmedetomidine and clonidine as an adjuvant to caudal ropivacaine in children for below umbilical surgery. J Clin Sci [serial online] 2017 [cited 2017 Dec 11];14:157-61. Available from: http://www.jcsjournal.org/text.asp?2017/14/4/157/217812
| Introduction|| |
Caudal analgesia in combination with general anesthesia is well established as a safe and reliable technique for providing analgesia in pediatric patients undergoing infraumbilical surgeries. While excellent pain relief, minimal side effects, and high patient satisfaction are the advantages; short duration after a single injection is the single main disadvantage  even with long-acting local anesthetics such as bupivacaine. Although caudal catheters can administer repeated doses or continuous infusions, infection is a major concern. Therefore, various adjuvants have been added to prolong the duration of single-shot technique.
Although a variety of adjuvants have been tried, the search for an ideal agent continues. Epinephrine prolongs the effect of lidocaine but has no effect with bupivacaine. The addition of opioids (particularly morphine) significantly prolongs the analgesic duration but is associated with several adverse effects, particularly the risk of late respiratory depression. Therefore, caudal opioids have been superseded by alpha2 agonists, namely, clonidine and dexmedetomidine.
The analgesic effect of epidural or intrathecal clonidine results from direct stimulation of pre- and post-synaptic alpha2 adenoreceptors in the dorsal horn of the spinal cord thereby inhibiting the release of nociceptive neurotransmitters. When combined with local anesthetics, it intensifies and prolongs the duration of analgesia, however, causes bradycardia and hypotension. Dexmedetomidine is an alpha2 agonist with an 8-fold greater affinity for alpha2 receptors and much less alpha1 effect. This higher selectivity of dexmedetomidine is advantageous and has less adverse effects compared to clonidine.,,
This study was designed to compare the analgesic efficacy and adverse effects of dexmedetomidine and clonidine when added to ropivacaine for caudal analgesia in children undergoing lower abdominal surgeries.
| Materials and Methods|| |
Seventy-eight ASA Status I and II patients aged 6 months to 6 years admitted for lower abdominal surgeries (during October 2014 – November 2016) were enrolled in this prospective double-blind randomized study after obtaining Ethical Committee approval and informed consent. Patients with a history of developmental delay or mental retardation, anomalies of the central nervous system and spine, coagulopathy, allergy to any of the study drugs and patients with infection at the injection site were excluded from the study.
The subjects were randomly allocated to receive caudal block with either 0.2% ropivacaine 1.5 mg/kg (Group R; n = 26) or 0.2% ropivacaine 1.5 mg/kg + 1 mcg/kg clonidine (Group RC; n = 26) or 0.2% ropivacaine 1.5 mg/kg + dexmedetomidine 1 mcg/kg (Group RD; n = 26) using a table of random numbers. All the subjects, their parents, and the health-care personnel providing patient care and collecting data were blinded to the medications administered. A total volume of 1 ml/kg to a maximum of 20 ml was given. The group allocation sequence and medications were prepared by an observer not participating in the study, however, having 3-year experience in department. This information was concealed in sealed envelopes that were opened only after obtaining informed consent from the subjects.
All patients received oral midazolam (0.3 mg/kg) 1 h before the start of surgery. All the subjects were induced with a standard technique using sevoflurane 8% and a mixture of 60% N2O in 40% oxygen after recording vital signs (pulse, blood pressure [BP], SpO2). A peripheral intravenous (IV) access was obtained following which the patient was turned to the left lateral position and taking all aseptic precautions using a 23 gauge sterile needle; the caudal space was identified using the loss of resistance technique. Once localization was successful, drug was injected following negative aspiration for cerebrospinal fluid or blood. The patient was turned back to supine position and anesthesia was maintained with a mixture of 1% sevoflurane and 60% nitrous oxide in 40% oxygen. The inhaled concentrations were adjusted so as to maintain hemodynamic changes within 20% of the baseline values. Inability to maintain vital parameters within 20% of the baseline and movement on surgical stimulation even after 15–20 min after block with increased depth of anesthesia was considered as block failure. Heart rate (HR), BP, and SpO2 were monitored every 5 min during the entire length of the surgery. No other narcotics, analgesics, sedatives were administered during the surgery. Any episodes of hypotension and bradycardia were noted and were treated appropriately with a bolus of IV fluid (2 ml/kg every 5 min) and atropine (10 μg/kg every 2–5 min), respectively. At the end of the surgery, the patient was awakened breathing spontaneously, receiving oxygen by mask, and transferred to the postanesthesia care unit.
All the subjects were monitored postoperatively for pain using the Face, Leg, Activity, Cry and Consolability (FLACC) pediatric observational pain scale [Table 1] at 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 16 h, and 24 h. A FLACC score ≥4 was treated with rescue analgesia. Patients complaining of pain within 2 h of surgery were given IV fentanyl 1 μg/kg with close continuous monitoring for desaturation/respiratory depression and were removed from the study. Patients complaining of pain after 2 h of surgery were given oral paracetamol syrup (15 ml/kg) and the time to first request to analgesia after caudal block was noted. Sedation was assessed using sedation score of 1 through 3 where 1 opens eyes spontaneously, 2 opens eyes on verbal commands, and 3 opens eyes on painful stimulation. The duration of sedation, i.e., the time elapsed between end of anesthesia to spontaneous eye opening was noted. All the patients were also monitored for vital parameters (pulse, BP, SpO2) and sedation at all points during the study. The occurrence of postoperative desaturation (SpO2≤95%), hypotension (systolic BP >20%), bradycardia (pulse <80/min for children aged <1 year and <60/min for children >1 year of age), postoperative nausea and vomiting (PONV) (present/absent), pruritus (present/absent), urinary retention (present/absent) were also recorded.
|Table 1: Face, Leg, Activity, Cry and Consolability pain assessment score|
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The primary measure of outcome was the time to first request of rescue analgesia. The secondary outcome measures were the total number of analgesic doses required in 24 h, sedation scores, and adverse events such as PONV, pruritus, desaturation, and urinary retention.
Calculation of sample size revealed that at least twenty subjects in each group were required to detect an average difference in the meantime to first analgesic request as small as 1.5 times the standard deviation (SD) with a power of 80% and a significance level of 0.05. The sample size was increased by 30% (i.e., 26 patients in each group) to allow for attrition. Data were analyzed using SPSS software version 17 (SPSS Inc., 233 South Wacker Drive, 11th Floor, Chicago, IL 60606-6412) and presented as mean and SD. A P < 0.05 was considered statistically significant.
| Results|| |
Eighty-four subjects were enrolled in the study once they satisfied the inclusion criteria and an informed consent was obtained. They were then randomized into three groups using a computer-generated table of random numbers. A total of 78 patients (26 per group) were analyzed in the study. The three groups were comparable on most parameters [Table 2]. No significant difference was seen in the intraoperative [Table 2] and postoperative vital parameters (HR, BP, SpO2) between the three groups (P > 0.05). No significant hypotension or bradycardia requiring treatment was observed in any patient during the entire study.
The time to first analgesic request, i.e., the duration of analgesia was 7.15 ± 1.00 h in Group R, 11.57 ± 1.27 h in Group R + C, and 14.73 ± 1.53 h in Group R + D (P < 0.0001) [Table 3]. The number of analgesic doses required in 24 h was highest in Group R that is 2.73 ± 0.45 compared to Groups R + C 1.96 ± 0.19 and Group R + D 1.73 ± 0.53; this difference was statistically significant (P < 0.0001) [Table 3]. The duration of sedation, i.e., the time elapsed between the end of anesthesia to spontaneous eye opening was 57.69 ± 16.07 min in Group R, 122.88 ± 16.38 min in Group R + C and 147.11 ± 10.78 min in Group R + D (P < 0.0001) [Table 3]. Duration of postoperative analgesia was significantly longer in the Group RD (14.73 ± 1.53 h) compared to the Group RC (11.57 ± 1.27 h) (P < 0.0001) [Table 4].
One patient in Group R + D had vomiting and 1 patient in Group R had urinary retention which was not statistically significant (P > 0.05) [Table 5]. No other untoward effects were observed in any of the three groups [Table 5].
| Discussion|| |
This study was conducted to compare the analgesic efficacy of clonidine and dexmedetomidine as adjuvants to ropivacaine in caudal epidural block. Our study showed that the duration of analgesia was significantly prolonged when either clonidine or dexmedetomidine was added to ropivacaine in caudal block [Table 3]. However, the duration of analgesia was the longest in the dexmedetomidine group compared to the other two groups (P < 0.0001) [Table 3] and [Table 4]. This was also supported by the observation that the least number of rescue analgesics was required in the dexmedetomidine group compared to clonidine or plain ropivacaine group and this difference was statistically significant; P < 0.001 [Table 3] and [Table 4].
In a similar study conducted by El-Hennawy et al., the analgesic effects of clonidine and dexmedetomidine added to bupivacaine were compared in sixty pediatric patients undergoing lower abdominal surgeries. They found that addition of clonidine or dexmedetomidine significantly prolonged the duration of analgesia when compared to bupivacaine alone. However, no difference was seen between clonidine and dexmedetomidine as regards the analgesia time. We are not sure the reason for this outcome; however, we speculate that this is probably due to lower dose of clonidine used and differences in mean age group.
In a more recent study conducted by Jinjil et al., the analgesic efficacy of caudal clonidine (1 μg/kg) and dexmedetomidine (1 μg/kg) as adjuvants to 0.2% ropivacaine was compared in 100 children aged 2–8 years undergoing lower abdominal surgeries. They found that the duration of postoperative analgesia was significantly longer in the dexmedetomidine group compared to the clonidine group. These findings are similar to the observations made in our study as we also observed that duration of postoperative analgesia was significantly longer in the dexmedetomidine group (14.73 ± 1.53 h) compared to the clonidine group (11.57 ± 1.27 h) (P < 0.0001).
Clonidine and dexmedetomidine are alpha2 agonists and are known to cause adverse effects such as hypotension and bradycardia due to uninhibited increase in parasympathetic tone. We therefore also evaluated the effects of these drugs on HR and BP intraoperatively and postoperatively. Although a decrease in HR [Figure 1] and BP [Figure 2] was seen intraoperatively with caudal clonidine and dexmedetomidine, none of the subjects required therapeutic intervention for these changes and the parameters returned to normal within 20–30 min of caudal injection. The possible reason could be use of lower doses of clonidine and dexmedetomidine that is (1 μg/kg) in our study compared to other studies.
Our study showed a significantly prolonged duration of sedation with clonidine and dexmedetomidine when compared to plain ropivacaine, with dexmedetomidine showing the longest duration of sedation. The duration of sedation was 56.69 ± 16.07 min in Group R, 122.88 ± 16.38 min in Group RC, and 147.11 ± 10.78 min in Group RD, respectively (P < 0.0001) [Table 3]. However, none of the subjects showed delayed emergence at the end of surgery. All the subjects were calm and rousable postoperatively indicating that sedation at this dose of clonidine and dexmedetomidine is not clinically significant. Similar findings were observed in the trial conducted by Reddy and Gangadharaiah  which evaluated the effects of clonidine and dexmedetomidine added to caudal ropivacaine in sixty patients undergoing circumcision. They found that the duration of sedation was significantly prolonged in the dexmedetomidine group as compared to the clonidine group. However, two other studies have failed to show any such difference in sedation with clonidine and dexmedetomidine.,
Finally, the addition of clonidine or dexmedetomidine in this study did not result in an increase in adverse effects or delay in recovery from general anesthesia [Table 5]. There was no detectable difference in the incidence of nausea, vomiting, or urinary retention between the groups. No episodes of clinically significant respiratory depression were identified. A similar conclusion was drawn from the studies conducted by Gupta and Pratap  and Neogi et al. They observed that addition of caudal clonidine and dexmedetomidine significantly prolonged the duration of analgesia without an increase in the incidence of adverse effects.,
Our study, however, is limited by a small sample derived from a single institution. Furthermore, the patients were followed up postoperatively for a brief duration of time.
| Conclusion|| |
We conclude that addition of clonidine (1 μg/kg) and dexmedetomidine (1 μg/kg) to 0.2% caudal ropivacaine significantly prolongs the duration of analgesia without an increase in the incidence of adverse effects. Our study showed the longest duration of analgesia with dexmedetomidine when compared to the other groups. The addition of clonidine and dexmedetomidine also caused statistically significant sedation.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]