A Comparative Clinical Study between Clonidine and Tramadol with Bupivacaine in Caudal Epidural for Postoperative Analgesia in Pediatric Surgery.

CONTEXT: Adjuvants to bupivacaine for single shot caudal block in children. AIMS: This study entitled was conducted to compare the effects of addition of tramadol to bupivacaine over addition of clonidine to bupivacaine as a single shot caudal block in children. SETTINGS AND
DESIGN: Sixty children of ASA grade I and II in the age group of 2-12 years coming for various infra-umbilical surgeries were included.
MATERIALS AND METHODS: They were divided into two groups of 30 each. Group BC received caudal bupivacaine 0.25% 0.5ml/kg with clonidine 2 mcg/kg Group BT received caudal bupivacaine 0.25% 0.5 ml/kg with tramadol 2 mg/kg. The main parameters studied were hemodynamic changes, duration of post-operative analgesia and incidence of adverse effects. STATISTICAL ANALYSIS USED: The results of continuous variables are given as mean ± SD and proportion as percentage. The difference between the two groups was assessed by student's - t test and chi-square test.
RESULTS: The mean duration of post-operative analgesia in group BT was statistically significant (P <0.001), reducing the requirement of analgesics in group BT. There was no difference in sedation score, nausea, vomiting, urinary retention.
CONCLUSIONS: The present study demonstrated that caudal administration of bupivacaine 0.25% 0.5 ml/kg with tramadol 2 mg/kg resulted in superior analgesia with longer duration of action and reduced requirement of analgesics in first 24 hours postoperatively when compared with 0.25% bupivacaine 0.5 ml/kg with clonidine 2 mcg/kg.

INTRODUCTION

Pain results in immediate physiological, humoral, immunological, and behavioral responses in a child, which are associated with increase in circulating catecholamines, cortisol, aldosterone, glucagon, and other steroid hormones leading to harmful effects.[1] Caudal epidural block has gained popularity, especially for procedures below the umbilicus, since it is a simple, safe, and reliable technique.[23]

The main disadvantage of this single-shot caudal block is its shorter duration of action even with the use of long-acting local anesthetic agents such as bupivacaine.[2] To prolong the duration and improve the quality of intraoperative and postoperative analgesia of local anesthetics, various drugs such as opioids,[456] epinephrine, midazolam,[7] ketamine,[8] neostigmine,[9] and clonidine[21011] have been used as adjuvants with various advantages, disadvantages, and adverse effects.

Clonidine is used as an adjuvant in caudal block to improve the intraoperative and post operative analgesia and to reduce the dose of local anesthetic.[12]

MATERIALS AND METHODS

This prospective study was conducted in a 750-bedded hospital between December 2012 and July 2014.

Approval from the Ethics and Standards Committee of this institution was obtained. Informed consent was obtained from the parent before including the children in the study.

The study included 60 children, of either sex, divided into two groups of 30 patients each randomly.

Inclusion criteria

Patients in the age group of 2–12 years

Patients with American Society of Anesthesiologists (ASA) Physical Status Classes I and II

Patients coming for elective lower abdominal and lower limb surgeries.

Exclusion criteria

Patients with ASA Physical Status Classes III and IV

Patients with infection at the site of injection

Patients on coagulopathy or on anticoagulation

Patients with congenital abnormalities of lower spine and meninges

Patients with active disease of the central nervous system

Patients with a history of allergy to local anesthetics, clonidine, and tramadol

Parents’ refusal

Patient posted for emergency surgery.

Methods

Preanesthetic assessment was done, and baseline investigations were sent

Preoperative fasting was followed based on pediatric fasting guidelines.

Premedication

All patients were premedicated with syrup promethazine 1 mg/kg, once on the night before the surgery and on the day 2 h before the surgery, after securing an intravenous (IV) access injection atropine 0.02 mg/kg IV was given.

Procedure

Depending on the weight of the patient, isolyte-P or normal saline IV fluids were started. All patients were preoxygenated with 100% oxygen for 3 min using Jackson–Rees circuit.

Patients were induced using injection thiopentone 5 mg/kg IV until eyelash reflex is lost. Injection succinylcholine 2 mg/kg was given, and the patients were intubated using appropriate-sized endotracheal tubes.

Caudal block was performed in the right lateral position

Group BC – received inj bupivacaine 0.25%, 0.5 ml/kg with inj Clonidine 2 mcg/kg.

Group BT – received inj bupivacaine 0.25%, 0.5 ml/kg with inj Tramadol 2 mg/kg.

After procedure, the child was placed in supine and head up position. No analgesia was given by any route preoperatively or intraoperatively. Anesthesia was maintained with O2:N2O = 33%:66%, halothane 0.5%–0.75%, and muscle relaxation with NDMR-non depolarising muscle relaxant (NDMR) injection vecuronium according to the body weight.

At the end of the surgery, the patients were reversed and extubated and shifted to the recovery room.

The child was monitored for another 1 h with SpO2, respiratory rate, noninvasive blood pressure (NIBP), and heart rate every 15 min. After that, the child was shifted to the ward and monitored thereafter.

Monitoring

Intraoperative monitoring included precordial stethoscope, pulse oximetry, NIBP, respiratory rate, and electrocardiogram. The time of caudal block and duration of surgery were noted.

Parameters studied

Hemodynamic parameters

Patient's heart rate, respiration rate, and blood pressure were monitored after the administration of caudal block at 0, 5, 10, 15, 20, 40, and 60 min.

Rescue analgesia

It is the time interval between the administration of caudal block and the first requirement of supplementary analgesia for the patient.

Post-operative analgesia is assessed by Paediatric Objective Pain Scale [Table 1]. The assessment was done for 24 h after caudal block. If the pain score was ≥6 for two consecutive intervals of 10 min, then supplementary analgesia with suppository paracetamol (20 mg/kg) was given. These assessments were made at 1, 2, 3, 4, 8, 12, and 24 h after caudal block.

Table 1

Pediatric objective pain scale

Observations	Criteria	Points
BP	±10% preoperative value	0
	>20% preoperative value	1
	>30% preoperative value	2
Crying	Not crying	0
	Crying but responds to tender loving care	1
	Crying with no response to tender loving care	2
Movement	None	0
	Restlessness	1
	Thrashing	2
Agitation	Asleep	0
	Mild	1
	Hysterical	2
Posture	No special posture	0
	Flexing legs and thighs	1
	Holding penis or groin	2

BP=Blood pressure

Side effects were monitored

Nausea and vomiting, bradycardia, hypotension, and respiratory depression, sedation score [Table 2] were noted.

Table 2

Sedation: A five point sedation score

Score	Degree of sedation
1	Fully awake and oriented
2	Drowsy
3	Eyes closed but arousable to command
4	Eyes closed but arousable to mild physical stimulation
5	Eyes closed but unarousable to mild physical stimulation

Statistical analysis

Analysis of the present study was made using the following parameters.

Percentages

The arithmetic mean (m or x)

The standard deviation (SD) (S)

Student's t-test

Proportion test.

The results of continuous variables are presented as mean ± SD and proportion as percentage. The difference between the two groups was assessed by Student's t-test and Chi-square test. For all the tests, a P ≤ 0.05 was considered statistically significant.

RESULTS

A total number of 60 children in the age group of 2–12 years were enrolled.

Age distribution of patients

Graph 1 shows the age distribution of the patients studied.

Graph 1

Age distribution

Mean age distribution

The mean age in Group BC was 8.26 ± 2.98 years whereas in Group BT was 9.03 ± 2.94 years (P = 0.320).

Mean weight of the patients

The mean weight was 22.16 ± 7.78 in group bupivacaine + clonidine and 26.76 ± 6.74 in group bupivacaine + tramadol, with P = 0.018 [Graph 2].

Graph 2

Mean weight

Mean height of the patients

The mean height in group bupivacaine + clonidine was 120.03 ± 14.95 and mean height in group bupivacaine + tramadol was 125.67 ± 7.72, with P = 0.072 [Graph 3].

Graph 3

Mean height

Sex distribution

Group BC has 26 (86.7%) males and 4 (13.3%) females, while Group BT has 27 (90.0%) males and 3 (10.0%) females [Graph 4].

Graph 4

Sex distribution

Changes in mean arterial pressure

The baseline mean arterial pressure (MAP) was 87.66 ± 7.013 mmHg in group bupivacaine + clonidine. The MAP was 85.16 ± 8.11 mmHg at 15 min and then gradually decreased to 67.5 ± 3.26 mmHg at 60 min. In group bupivacaine + tramadol, the baseline MAP was 84.46 ± 7.71 mmHg, which increased to 86.73 ± 6.09 mmHg at 15 min and then gradually decreased to 76.6 ± 4.81 mmHg at 60 min. Moreover, P value was statistically significant at 10th, 20th, 40th, and 60th min [Table 3].

Table 3

Changes in mean arterial pressure

	Bupivacaine + clonidine	Bupivacaine + tramadol	Mean difference	P
Basal BP	87.66±7.013	84.46±7.71	3.20000	0.098
5 min	76.4±6.61	76.83±9.59	−0.43333	0.839
10 min	85.16±7.90	91.8±8.20	−6.63333	0.002
15 min	85.16±8.11	86.73±6.09	−1.56667	0.401
20 min	76.43±5.69	81.73±4.68	−5.30000	0.001
40 min	71.13±4.36	78.5±5.17	−7.36667	0.001
60 min	67.5±3.26	76.6±4.81	−9.10000	0.001

BP=Blood pressure

Changes in heart rate

In group bupivacaine + clonidine, the mean baseline heart rate was 110.43 ± 13.45 beats/min. Heart rate gradually decreased to 80.66 ± 5.52 beats/min at 60 min. The mean baseline heart rate in group bupivacaine + tramadol was 109.3 ± 11.82 beats/min, which then gradually decreased to 84.56 ± 4.59 beats/min at the end of 60 min. Moreover, P value was statistically significant at 15th and 60th min [Table 4].

Table 4

Changes in heart rate

	Bupivacaine + clonidine	Bupivacaine + tramadol	Mean difference	P
Basal HR	110.43±13.45	109.3±11.82	1.13333	0.730
5 min	117.13±13.02	100.86±19.52	16.26667	0.000
10 min	123.67±13.36	119.43±13.72	4.23333	0.231
15 min	124.7±11.82	108.53±10.01	16.16667	0.001
20 min	102.4±10.91	98.43±8.18	3.96667	0.117
40 min	85.5±7.81	90.43±7.784	−4.93333	0.017
60 min	80.66±5.52	84.56±4.59	−3.90000	0.004

HR=Heart rate

Mean duration of surgery

There was not much difference in two groups. It was shown by P = 0.550 [Graph 5].

Graph 5

Mean duration of surgery

Incidence of complications

Four patients in group bupivacaine + clonidine and seven patients in group bupivacaine + tramadol had an incidence of nausea and vomiting, with P = 0.317. Moreover, two and three patients in bupivacaine + clonidine and bupivacaine + tramadol group, respectively, had a incidence of urinary retention, with P = 0.640 [Graph 6].

Graph 6

Incidence of complications

Sedation score at various time intervals

The mean sedation score was 1 in both the groups at all the time intervals [Graph 7].

Graph 7

Sedation scoring

Mean duration of postoperative analgesia

The mean duration of analgesia provided by group bupivacaine + clonidine and group bupivacaine + tramadol was 412 ± 42.68 and 851.93 ± 66.69, respectively, with P = 0.001 [Graph 8].

Graph 8

Mean duration of postoperative analgesia

Number of times analgesics given in first 24 h

Twenty-four patients in Group BT required analgesics only twice in the first 24 h and remaining six patients in Group BT required analgesics three times in the first 24 h postoperatively. However, 25 patients in Group BC required analgesics three times in the first 24 h postoperatively and remaining five patients needed it four times. P = 0.001 is considered statistically significant [Graph 9].

Graph 9

Number of times analgesics given in first 24 h

DISCUSSION

The major disadvantage of single-shot caudal anesthesia is the short duration of action. To overcome this problem, additives were used.

Drug concentration and volume

In 1989, Dalens and Hasnaoui[13] compared the efficacy of different local anesthetics and concluded that bupivacaine provides a long duration of analgesia.

Different volumes of bupivacaine were used by different studies. Cook et al.[14] in 1995 had used 1 ml/kg, and Klimscha et al.[15] in 1998 had used 0.75 ml/kg.

Concentration of bupivacaine used in different studies is also different. In 1989, Coad and Hain[16] studied 40 children posted for inguinal surgery using 0.25% and 0.5% bupivacaine. They concluded that the preferred regimen for caudal anesthesia would be 0.25% bupivacaine.

In both the groups, males were more (>85%). This could be due to inclusion of surgeries such as herniotomy, hypospadias repair, orchidopexy, and circumcision in our study.

Primary outcome

Mean duration of postoperative analgesia

If the pain score was more or equal to 6 at two consecutive intervals of 10 min, supplementary analgesic with paracetamol suppository (20 mg/kg) was given.

Constant et al.[11] in 1998 observed the duration of analgesia as 265 min in those who received clonidine 1.5 μg/kg and 287 min in those who received caudal clonidine 0.75 μg/kg with fentanyl 0.5 μg/kg as adjuvants to 0.25% bupivacaine 1 mg/kg.

In 2007, Khalid et al. studied 60 children aged from 1 to 12 years undergoing unioscrotal surgeries and they were randomly divided into two groups. Group BT was given 0.25% of 0.8 ml/kg bupivacaine and tramadol 2 mg/kg, while the other Group B was given 0.25% of 0.8 ml/kg bupivacaine through caudal route.

Addition of tramadol with bupivacaine resulted in increased postoperative analgesic period (16.06 ± 4.04 h). It was concluded that use of tramadol as an additive can prolong the postoperative analgesic period when administered caudally.[17]

Taheri et al.[18] in 2010 evaluated 60 children undergoing inguinal herniorrhaphy. They were either given 0.25% bupivacaine 1 ml/kg with neostigmine 2 μg/kg (Group BN) or tramadol 1 mg/kg (Group BT). Duration of analgesia was longer in Group BT (17.30± 8.24 h) compared with Group BN (13.98 ± 10.03 h) (P = 0.03).

However, in 2000, De Mey et al.[19] concluded that addition of clonidine to caudal bupivacaine does not offer any additional benefit over bupivacaine; in our study, the mean duration postoperative analgesia seen in Group BT was 851.9333 ± 66.69 min, which correlates with these studies.

Secondary outcome

Changes in hemodynamic parameters

Prakash et al.,[20] in their study, on addition of tramadol to bupivacaine have reported no significant changes in hemodynamic parameters between the two groups.

Initially, there was an increase in MAP in both groups, i.e., 85.16 ± 8.11 mmHg in Group BC and 86.73 ± 6.09 mmHg in Group BT at 15 min, which could be due to the use of injection atropine as a premedicant or due to surgical stimulus itself.

However, once after the commencement of action of caudal block, gradual decline in MAP was noticed, which was more pronounced in Group BC 67.5 ± 3.26 mmHg at 60 min compared to 76.6 ± 4.81 mmHg in Group BT at 60 min, which was statistically significant (P < 0.001).

Similarly, the mean baseline heart rates in two groups were 110.43 ± 13.45 beats/minute in Group BC and 109.3 ± 11.82 beats/minute in Group BT, which initially increased to 123.67 ± 13.36 beats/minute in Group BC and 119.43 ± 13.72 beats/minute in Group BT that could be due to injection atropine or because of surgical stimulus; however, later once caudal block started acting, there was gradual decline in mean heart rates. It reached to 80.66 ± 5.52 beats/ minute in Group BC and 84.56 ± 4.59 beats/minute in Group BT at 60 min. Decrease in the mean heart rate was more pronounced in Group BC which was statistically significant P = 0.004 at the end of 60 min.

Complications

In our study, 4 (13.3%) of the children in Group BC and 7 (23.3%) of them in Group BT had an episode of vomiting which was treated with injection metoclopramide (0.1–0.2 mg/kg) IV and the incidence of vomiting was comparable in both the groups.

Sabbar et al.[21] and Prakash et al.[20] have reported that addition of tramadol did not result in any significant increase in incidence of vomiting, which correlates well with our study.

In our study, we observed 2 (6.7%) cases of urinary retention in Group BC and 3 (10.0%) cases of urinary retention in Group BT, and the incidence was comparable in both the groups.

Sedation scores

The mean sedation score was 1 at all the time intervals in both the groups. Somasundran and Garasia[22] and Sabbar et al.[21] found no significant difference in sedation scores.

Strengths

The study population was uniform with respect to age, weight, height, and type of surgical procedure, i.e., infraumbilical.

Limitation

Assessment of pain is complex in children, based only on physiological, behavioral parameters

More studies are needed in this area to keep children comfortable in the postoperative period.

CONCLUSION

The present study demonstrated that caudal administration of bupivacaine 0.25% 0.5 ml/kg with tramadol 2 mg/kg resulted in superior analgesia with longer duration of action and reduced requirement of analgesics in first 24 h postoperatively when compared with 0.25% bupivacaine 0.5 ml/kg with clonidine 2 μg/kg. As compared to tramadol with bupivacaine, clonidine with bupivacaine produced significant decrease in mean heart rate and MAP without any significant increase in the incidence of side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.