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ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 4  |  Page : 620-624  

A comparative study of tramadol and clonidine as an additive to levobupivacaine in caudal block in pediatric patients undergoing perineal surgeries


1 Department of Anaesthesiology, King George Medical University, Lucknow, Uttar Pradesh, India
2 Department of Geriatric Intensive Care Unit (Anaesthesiology), King George Medical University, Lucknow, Uttar Pradesh, India

Date of Submission10-Sep-2019
Date of Decision02-Oct-2019
Date of Acceptance21-Oct-2019
Date of Web Publication16-Dec-2019

Correspondence Address:
Radhey Shyam
Associate Professor, Department of Geriatric Intensive Care Unit, DGMH (Anaesthesiology), King George's Medical University, Lucknow - 226 003, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_127_19

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   Abstract 

Background: Caudal block is a simple, safe procedure with fewer side effects to provide intraoperative and postoperative analgesia in pediatric patients. Many drugs were used as an additive to local anesthetics in caudal block. All these drugs had their own side effects. Aims: In this study, we compare the effects of tramadol and clonidine as an additive to levobupivacaine in caudal block in children undergoing perineal surgeries regarding hemodynamic changes, analgesic effects, and side effects. Settings and Design: This is a prospective, double-blind randomized, controlled study, conducted in Department of Paediatric Surgery, at King George's Medical University, Lucknow, Uttar Pradesh during 2017–2018. Materials and Methods: After informed consent and ethical clearance from institutional ethics committee, King Georges Medical University, Lucknow. Total 66 patients aged 1–10 year, planned for perineal surgery were randomly allocated according to computer-generated random number, into three groups. Group I - 0.25% levobupivacaine (1 mL.kg-1) alone, Group II - 0.25% levobupivacaine (1 mL.kg-1) with tramadol 1 mL.kg-1, and Group III - 0.25% levobupivacaine (1 mL.kg-1) with clonidine 1 μg.kg-1. Perioperative pain was the primary outcome. Hemodynamic parameters: heart rate, mean arterial pressure, and peripheral oxygen saturation were recorded. Postoperative pain assessed by Children and Infants Postoperative Pain Scale (CHIPPS), sedation by Ramsay sedation score and requirement of rescue analgesia were recorded at predetermined time intervals. Statistical Analysis: The values were represented in number (%) and mean ± standard deviation. Comparison of quantitative variables between the study groups was done using ANOVA test and Mann–Whitney U-test. Categorical data were analyzed using Chi-square test. Results: Postoperative analgesic effect was significantly longer in levobupivacaine with clonidine group as compared to tramadol with levobupivacaine group and levobupivacaine alone group. Conclusion: Clonidine in a dose of 1 μg.kg-1 when added to levobupivacaine in caudal block significantly prolongs the duration of analgesia as compared to tramadol with levobupivacaine and levobupivacaine alone without any clinically significant side effects. Thus, it is better to add additive like clonidine to enhance the effect of analgesia.

Keywords: Caudal block, clonidine, levobupivacaine, tramadol


How to cite this article:
Rawat J, Shyam R, Kaushal D. A comparative study of tramadol and clonidine as an additive to levobupivacaine in caudal block in pediatric patients undergoing perineal surgeries. Anesth Essays Res 2019;13:620-4

How to cite this URL:
Rawat J, Shyam R, Kaushal D. A comparative study of tramadol and clonidine as an additive to levobupivacaine in caudal block in pediatric patients undergoing perineal surgeries. Anesth Essays Res [serial online] 2019 [cited 2020 Sep 28];13:620-4. Available from: http://www.aeronline.org/text.asp?2019/13/4/620/272973


   Introduction Top


Caudal analgesia is reliable, safe, and commonly performed regional blocks in pediatric patients. Reliability and ease of performance make caudal block the most suitable block in pediatric surgical patients in perioperative period.[1]

The major drawback is the duration of action is relatively short even with the use of long-acting local anesthetics with single-shot injection. Epidural catheter placement into the caudal epidural space adds to the risk of infection and tends to prevent early postoperative mobilization and hence is not very popular,[2] so usually not recommended. To prolong duration of action, several adjuvants such as adrenaline, opioids, ketamine, and neostigmine have been added to the local anesthetics. All these agents have their own potential side effects.[3]

The goal of postoperative pain relief is to reduce or eliminate pain with minimum side effects and as cheaply as possible.

Tramadol, a synthetic opioid, acts by inhibiting serotonin uptake resulting in analgesia almost equivalent to that of pethidine in potency while lacking the depressant effect on respiratory.[4] Dogra et al. showed that a combination of tramadol and levobupivacaine- if administered caudally it provide long-lasting analgesia without any adverse effects.[5]

Clonidine, an alpha 2-adrenergic agonist, produces analgesia without causing significant respiratory depression after caudal administration in children.[6] Using clonidine as an adjuvant enables us to use a lower concentration of the local anesthetic to achieve the same level of analgesia with the advantages of prolonged duration of analgesia, reduced residual motor blockade, and increased margin of safety.[7] Thus, this study was planned to compare the relative analgesic efficacy of clonidine and tramadol when added with levobupivacaine in pediatric patients undergoing perineal surgeries and to evaluate side effects of combination therapy.


   Materials and Methods Top


Study design and settings

It is a prospective, randomized, double-blind, controlled study, conducted in Department of Anaesthesiology in collaboration with Department of Paediatric Surgery at King George's Medical University, Lucknow, Uttar Pradesh, India, for 1-year duration during 2017–2018.

Methods

Ethical approval was obtained from institutional ethical committee, Research Cell (Ref. No. 87th ECM IIB-Thesis/P4) King George's Medical University, Lucknow, Uttar Pradesh. After written informed consent from parents/guardian of the children aged 1–10 years of either sex, as per American society of Anaesthesiologist physical Status I–II with ±20% of ideal body weight and height, planned for elective perineal surgeries, were enrolled in this study. Parent's refusal, contraindication for caudal block, and history of allergic reaction to levobupivacaine, clonidine, or tramadol were excluded from the study.

All children were kept nil orally according to standard fasting guidelines. After obtaining intravenous (i.v.) access, infusion of Ringer's lactate was started, and premedication midazolam 0.05 mg.kg-1 i.v. was given. All the monitors were attached, and after recording the baseline hemodynamic parameters, patients were induced with propofol 2 mg.kg-1 and then intubated using rocuronium 0.4 mg.kg-1. Caudal block was done using 23 G hypodermic needle in the left lateral decubitus position under full aseptic conditions and the drugs were given according to allocation of groups and effects were recorded by another observer for blinding of study.

Patients were randomly assigned to three groups according to a computer-generated list. Group I received 0.25% of levobupivacaine (1 ml.kg-1) alone, Group II received 0.25% levobupivacaine (1 ml.kg-1) with tramadol (1 ml.kg-1), and Group III received 0.25% levobupivacaine (1 ml.kg-1) with clonidine (1 μg.kg-1).

Heart rate (HR), mean arterial pressure (MAP), and peripheral oxygen saturation (SpO2) were recorded before performing caudal block (baseline) and then at 5, 10, 20, 30, 45, 60, and 90 min intraoperatively and also at immediate postoperative period and then at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h postoperatively.

Various other measured parameters were Children and Infants postoperative Pain Scale (CHIPPS) (Score 0–3 = No requirement for treating pain, Score 4–10 = progressively greater need for analgesia) [Table 1] and postoperative Ramsay sedation score (1 = awake and anxious, agitated, or restless, 2 = awake, cooperative, accepting ventilation, oriented, or tranquil, 3 = awake, responds only to commands, 4 = a sleep, brisk response to light, glabella tap, or loud noise, 5 = asleep, sluggish response to light, glabella tap, or loud noise, and 6 = asleep, no response to light, glabella tap, or loud noise) [Table 1].
Table 1: Children and infants postoperative pain score

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Sample size estimation

The sample size of 22 patients was required in each group which was determined using a power calculation from the data obtained from earlier similar study,[3] where α = 0.05 and β = 0.8. P < 0.05 was considered as statistically significant.

N = (Z1-a/2) 2 × SD2/d2

Z1-a/2= Two-tailed α error

=1.96 at 5% alpha error (two tailed),

SD = Standard deviation - 4.7

D = Acceptable deviation - 2

N = 1.96 × 1.96 × 4.7 × 4.7/2 × 2

=21.2.

Statistical analysis

The statistical analysis was done using SPSS Version 21 (IBM's Corporation, Privacy Office, Armonk, NY, U.S.A.). The values were represented in number (%) and mean ± standard deviation. Comparison of quantitative variables between the study groups was done using ANOVA test and Mann–Whitney U-test. Categorical data were analyzed using Chi-square test.


   Results Top


Both the groups were comparable regarding age, sex, gender, weight, and duration of surgery. Hemodynamic parameters: Heart Rate (HR), Mean Arterial pressure (MAP), and oxygen saturation (SpO2)were found to be more stable in Group III > Group II > Group I and were ranged within 20% of the baseline [Table 2].
Table 2: Demographic and hemodynamic parameters in three groups (n=22)

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Ramsay sedation scores during all the periods from immediate postoperative to 8 h postoperatively were higher among the patients of Group III followed by Group II and were minimum among the patients of Group I. The difference among the three groups was statistically significant at all the time period of observation (P< 0.05) except at 10 h and 12 h postoperatively between Group I and Group II [Figure 1].
Figure 1:Comparison of Ramsay Sedation Score at different time intervals

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CHIPPS score for all periods of observation from immediate postoperative to 12 h postoperatively was maximum among the patients of Group I and was minimum among the patients Group III throughout period of observation (P< 0.05; between Group I vs. Group II and III and Group II vs. Group III) [Figure 2].
Figure 2:Comparison of pain. CHIPPS: Children's and Infants Postoperative Pain Scale

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The requirement of first dose of postoperative analgesic was significantly delayed in Group III (17.14 ± 1.32 h) as compared to Group I (15.55 ± 1.50 h) (P< 0.05) and Group II (15.09 ± 1.48 h) (P< 0.05; Group III vs. Group I and II). No motor block was observed in patients of any group [Table 3].{Table 3}

No side effects or complications were seen in any patient in our study.


   Discussion Top


The results of our study demonstrated that use of clonidine, as an adjuvant levobupivacaine in caudal epidural block, significantly prolonged the duration of analgesia with reduced requirement of postoperative rescue analgesics following perineal surgeries as compared to levobupivacaine alone or with tramadol in pediatric patients.

Inadequate pain relief in childhood may have long-term negative effects including harmful neuroendocrine responses disrupting eating and sleep cycles and increased pain perception during subsequent painful experiences. Postoperative pain may have several effects on pediatric patient in terms of emotional and psychological disturbances and can result in an uncooperative and restless child. Hence, it is preferable to prevent the onset of pain rather than to relieve its existence.[8] Various multimodal techniques have been designed for pain relief in pediatric patients. These include both systemic and regional analgesia. The easy, effective, and better choice for prolonging the duration of analgesia in postoperative period is use of various adjuvants. The most common regional technique used in pediatric patient is caudal epidural block.[9]

Caudal epidural anesthesia is one of the safest and simplest types of block used in pediatric group during lower abdominal surgeries with high success rate. Caudal block not only provide satisfactory postoperative analgesia but also decreases the intraoperative requirement of inhalation anesthetic drug as well as muscle relaxants to attenuate the stress response of the surgery.[10] Relatively shorter duration of analgesia is a major limitation of single-shot caudal block.[11] Use of placement of caudal epidural catheter is not popular due to the risk of infection.

Various local anesthetic agents such as bupivacaine, ropivacaine, and levobupivacaine are available which can be given in caudal block for intraoperative and postoperative analgesia, but side effects and complications of all these should be kept in mind before using, especially in pediatric patients. Mortality due to cardiovascular toxic side effect after regional anesthesia with bupivacaine has been reported in the past.[12] The cardiotoxicity is infrequently observed with mainly racemic form of bupivacaine.[13] In view of this, we have used levobupivacaine in place of bupivacaine as it is observed in many studies that levobupivacaine has wide margin of safety without any side effects and complications which were seen with bupivacaine.

Various adjuvants such as clonidine, fentanyl, dexamethasone, magnesium sulfate, and dexmedetomidine were added to local anesthetic agent to prolong the duration of analgesia. In a study, the efficacy of ketamine, midazolam, and neostigmine coadministered with bupivacaine in caudal epidural to provide intraoperative and postoperative pain relief, was compared, and the results showed that single-shot caudal coadministration of bupivacaine–neostigmine and bupivacaine–midazolam was associated with an extended duration of postoperative pain relief.[14] The effects of dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in pediatric patients during perineal surgeries have also been studied, and it was concluded that dexmedetomidine as adjuvant to bupivacaine increases duration of caudal analgesia and improves hemodynamic stability without an increase in adverse effects in children.[15] A study was performed on 60 children aged 6 months to 6 years to evaluate the effects of addition of clonidine or dexmedetomidine to caudal bupivacaine, and it was found that addition of clonidine or dexmedetomidine to caudal bupivacaine significantly prolongs the analgesia in pediatric patients undergoing infra-abdominal surgeries.[16]

The lower lipid solubility and greater intrinsic vasoactivity of levobupivacaine decrease its absorption and therefore produce differential neural blockade with decreased motor block.[17],[18] In past studies, it has been demonstrated that patients who received 0.125% levobupivacaine caudally were free from postoperative motor block.[4],[19] In our study, we also did not observe motor block with caudal 0.125% levobupivacaine.

Clonidine is an alpha-2 adrenoreceptor agonist, when administered caudally it prolong the duration of analgesia and also provide prolonged motor and sensory block effects of local anesthetic agents. Epidural clonidine exerts its analgesic effect through suppression of nociceptive neurons in the spinal cord. However, the precise mechanism of action has not been clarified.[3] The efficacy and safety of the combined use of clonidine and local anesthetics in comparison with caudal local anesthetics alone have also been assessed, and it was concluded that caudally administered clonidine in addition to local anesthetics provides extended duration of analgesia with a decreased incidence for analgesic rescue requirement and little adverse effects compared to caudal local anesthetics alone.[20] The effects of caudal and i.v. clonidine on postoperative analgesia produced by caudal levobupivacaine in children undergoing perineal surgery was assessed in another study, and clonidine in a dose of 1 μg.kg-1 added to 0.25% levobupivacaine for caudal analgesia significantly prolonged the duration of analgesia, without any side effect.[3]

Tramadol is a synthetic opioid with affinity for μ receptor and weak kappa and delta activity. It also has serotonin and norepinephrine reuptake inhibiting effects and does not cause significant respiratory depression,[21] and it was found superior to caudal bupivacaine in analgesic efficacy.[22] In our study, the combination of levobupivacaine and tramadol was found superior to levobupivacaine alone with regard to duration of postoperative analgesia. It can be suggested from the findings of the previous studies that there could be a synergistic effect between the local anesthetics and the adjuvants rather than simply an additive effect.[5] Duration of analgesia of <12 h has been demonstrated in some studies with levobupivacaine and tramadol.[4],[8]

We did not observe any complication or side effect intraoperatively or in the postoperative period neither with levobupivacaine nor with adjuvants (clonidine and tramadol) used in our study.

Limitations of our study were small sample size. Thus, we recommend large studies to assess the side effects. Our study is a single-center study; so, it is not feasible to validate our results as the sample size was small. It was an observational study; so, findings could have an observer bias. Multiple observers have recorded the findings which could have a subjective bias in this study. It is better if only one blinded observer records the result.


   Conclusion Top


We conclude that both clonidine and tramadol when used with levobupivacaine as adjuvants in caudal block prolonged the duration of analgesia. Clonidine was found more effective in terms of hemodynamic stability and duration of analgesia without clinically relevant side effects or complications. Clonidine in a dose of 1 μg.kg-1 when added to levobupivacaine in caudal block significantly prolongs the duration of analgesia as compared to tramadol with levobupivacaine and levobupivacaine alone without any clinically significant side effects. Thus, it is better to add additive like clonidine to enhance the effect of analgesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Vetter TR, Carvallo D, Johnson JL, Mazurek MS, Presson RG Jr. A comparison of single-dose caudal clonidine, morphine, or hydromorphone combined with ropivacaine in pediatric patients undergoing ureteral reimplantation. Anesth Analg 2007;104:1356-63.  Back to cited text no. 2
    
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