Comparison between caudal bupivacaine and bupivacaine with ketamine for postoperative analgesia in children: A prospective randomized clinical study.

BACKGROUND: Efficacy of caudal bupivacaine plus ketamine on postoperative pain in children. AIMS: The aim of this study was to compare the analgesic efficacy and safety of caudal block with mixture of bupivacaine and ketamine to bupivacaine alone for postoperative analgesia in pediatric patients undergoing infraumbilical surgery. SETTINGS AND
DESIGN: A prospective randomized study was conducted in a tertiary care teaching hospital. STATISTICAL ANALYSIS: Data were collected; mean value and standard deviation were computed for age, weight, duration of surgery, and duration of analgesia. Then, the mean values of the two groups were compared using ANOVA. P < 0.05 was considered statistically significant.
MATERIALS AND METHODS: A total of 60 American Society of Anesthesiologists I and II pediatric patients of either sex, aged 1-10 years, undergoing herniotomy, orchidopexy, and urethroplasty were randomly allocated to receive one of the two analgesic regimens. Group A (30 patients) received caudal bupivacaine 0.25% in a dose of 1 ml/kg, and Group B received caudal block with 0.25% bupivacaine 1 ml/kg and preservative-free ketamine 0.5 mg/kg; duration of analgesia was recorded by objective pain scale to equate pain and discomfort in young children with changes in standardized behavioral and physiological parameters.
RESULTS: Mean duration of analgesia in Group A was 5.63 ± 0.98 h while the mean duration of analgesia in Group B was 10.18 ± 2.24 h with P < 0.001. There were no differences between groups in the incidence of motor block and side effects.
CONCLUSION: On the basis of results derived from this study, it is concluded that addition of ketamine 0.5 mg/kg to caudal bupivacaine 0.25% in a dose of 1 ml/kg significantly prolonged the postoperative analgesia compared with administration of caudal bupivacaine 0.25% in a dose of 1 ml/kg alone.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Pain is perhaps the most feared symptoms of disease, which a human being is always trying to alleviate and conquer since ages. Children are special in this regard because in them, it is a very complex phenomenon. It is very difficult to differentiate restlessness or crying due to pain from that of hunger or fear in children. Caudal analgesia is the most useful and popular pediatric regional block used today. It is one of the regional anesthetic techniques frequently used for operations below the diaphragm in children. The main disadvantage of caudal anesthesia is the short duration of action after a single injection of local anesthetic solution. Even long-acting local anesthetic drug such as bupivacaine provides only 4–8 h of analgesia. The use of caudal catheter to administer repeated doses of infusion of local anesthetic solution is not popular, partly because of concerns about infections. Ketamine is an anesthetic and analgesic agent with a wide range of applications in pediatric anesthesia.[12] Therefore, epidurally administered ketamine exerts profound analgesic actions at spinal cord level without exerting any systemic side effects. Hence, addition of ketamine (preservative free drug which is safe for epidural administrations) to caudal bupivacaine has been shown to prolong the duration of postoperative analgesia in children undergoing orchidopexy and inguinal herniotomy.[3] There are few studies in which an attempt was made to determine the optimal dose of ketamine for caudal epidural blockade in children. Semple et al.[4] concluded that the optimum dose of ketamine for caudal epidural blockade is 0.5 mg/kg. Hence, this study was designed to compare the efficacy of caudal block with bupivacaine and mixture of bupivacaine with ketamine for postoperative analgesia in pediatric patients undergoing surgery below the level of the umbilicus.

MATERIALS AND METHODS

After obtaining approval from the Local Ethical Committee and parental consent, 60 American Society of Anesthesiologists (ASA) I and ASA II children between 1 and 10 years of age, who were undergoing surgery of the urogenital region (herniotomy, orchidopexy, and urethroplasty), were included in the present study. The children having allergy or sensitivity to bupivacaine and ketamine or having any contraindication to caudal injection, i.e., infection at the site, bleeding disorder, and caudal vertebral anomalies, etc., were excluded from the study. In this randomized trial, patients were randomly allocated to either Group A (n = 30) where bupivacaine was used or Group B (n = 30) where bupivacaine and ketamine were used by drawing slips from a sealed envelope before induction of anesthesia.

Group A (30 patients)The children received caudal bupivacaine 0.25% in a dose of 1 ml/kg, just after induction of general anesthesia

Group B (30 patients)The children received caudal bupivacaine 0.25% in a dose of 1 ml/kg and caudal ketamine preservative free 0.5 mg/kg, just after induction of general anesthesia.

The parents were instructed to keep the children nil orally up to 6 h before surgery, and clear fluid orally was allowed only up to 3 h before surgery. General anesthesia was induced with thiopentone 5–6 mg/kg via a 22–24 gauze intravenous (IV) cannula in a dorsal vein on hand or by inhalational induction with N2O, oxygen, and halothane according to age and preference. Before surgery, every child received caudal injection according to its allocated groups. The surgery was allowed to perform, and anesthesia was maintained with N2O, oxygen, halothane, and muscle relaxant through either Bain coaxial system or Jackson-Rees modification of Ayre's T-piece. Routine monitoring of each and every child included precordial stethoscope, electrocardiogram, noninvasive blood pressure, SpO2 through pulse oximeter, and temperature. After surgery, the children were transferred to recovery ward and were observed up to 1 h in recovery ward and then in postoperative ward for 24 h, and observations were recorded at 1, 4, 6, 12, and 24 h. In postoperative ward, anesthetist on duty, the person who was blinded to analgesic technique observed the patient for the following parameters.

Duration of analgesia was recorded by objective pain scale (OPS) [Table 1] to equate pain and discomfort in young children with changes in standardized behavioral and physiological parameters.[567] Each criterion scores from 0 to 2 to give a total score of 0–10. Duration of analgesia was defined as the time between caudal injection of the drug and first administration of postoperative analgesia. End of adequate analgesia means that pain score was four or more than four. If the analgesia was not required within the 24-h observation period, duration of analgesia was counted as 24 h. Analgesia was given to children when their OPS reached four or more and consist of paracetamol syrup 15 mg/kg by mouth every 4 h as required. The timing of micturition and any evidence of nightmares, hallucinations, or odd behavior were noted. The total requirement of postoperative analgesia in the 24-h period was noted.

Table 1

Objective pain scale

Motor block was assesed by Bromage scale[8]

0 - Full flexion of knees and feet possible, able to lift extended legs

1 - Unable to lift extended legs, but able to flex knees and feet

2 - Unable to flex knees but flexion of feet possible

3 - Unable to move legs and feet at all.

Sedation was assessed using an objective score based on eye opening:

Eye open spontaneously = 0

Eye open in response to verbal stimulation = 1

Eye open in response to physical stimulation = 2.

Statistical analysis

Data were collected separately from both the groups and fed in a Microsoft Excel Worksheet. Mean value and standard deviation were computed for age, weight, duration of surgery, and duration of analgesia. Then, the mean values of the two groups were compared using ANOVA. P < 0.05 was considered statistically significant.

RESULTS

The two groups were comparable for age and weight as well as in surgical procedures as shown in Tables 2 and 3, respectively. Table 4 shows the duration of surgery in both groups. The mean duration of surgery in Group A was 45.6 ± 15.42 min and in Group B was 45.67 ± 17.35 min. P < 0.05 was considered statistically insignificant. Table 5 shows the objective pain score during 1, 4, 6, 12, and 24 h of postoperative period. Satisfactory analgesia was achieved in both the groups in the immediate postoperative period (1, 4 h). However, in the late postoperative period (6, 12, and 24 h), additional analgesia was given in patients in Group A, whereas in Group B, only one patient needed additional analgesia at 6 h of observation. Similarly, in 12, 24 h, all the patients in Group A required additional analgesia, while in Group B there were few patients, who did not require any additional analgesia. Table 6 shows that duration of analgesia in Group A and Group B patients. Majority of patients in Group A, i.e., 53.33% of patients had duration of analgesia 3–5 h, and mean duration of analgesia in Group A was 5.63 ± 0.98 h. While the majority of patients in Group B, that is, 63.33% of patients had duration of analgesia in the range of 9–11 h and mean duration of analgesia was 10.18 ± 2.24 h. P < 0.001 which is highly significant, so the duration of analgesia is statistically comparable. As shown in Table 7, duration of motor block was insignificant in both the groups. Time taken to void urine after surgery (in h) is shown in Table 8.

Table 2

Demgraphic data

Table 3

Distribution according to type of surgery

Table 4

Distribution of duration of surgery - Groups A and B

Table 5

Pain score (objective pain scale)

Table 6

Distribution of duration of postoperative analgesia - Group A and B patients

Table 7

Duration of motor block

Table 8

Time taken to void urine after surgery (in h)

DISCUSSION

Caudal epidural is one of the most popular and commonly performed regional blocks in pediatric anesthesia. The limitation of the single-shot caudal blockade is its finite and short duration, which reduces its utility as postoperative analgesic. Even long-acting local anesthetic drug such as bupivacaine provides only 4–6 h of analgesia. Therefore, there is a continuous search for an ideal adjuvant to prolong the duration of analgesia.

Another concern is regarding caudal block analgesia is whether to give light general anesthesia or not? In our study, we induced the children either with IV pentothal or with gaseous inhalation agent before caudal block and found that this allows caudal block to be performed with more ease and intraoperative surgical conditions also remain satisfactory.[9]

We have opted for bupivacaine as a local anesthetic agent in the concentration of 0.25% at a dose of 1 ml/kg. Most of the authors[4910] have used bupivacaine as a local anesthetic agent of choice, though the volume and concentration may differ from study to study.

Several studies have provided evidence of the long-lasting profound analgesia, which is produced in children after administration of caudal ketamine with bupivacaine.[34] Ketamine, a derivative of phencyclidine, has a chemical structure similar to that of bupivacaine and therefore has local anesthetic effects. These local anesthetic effects are also caused by N-Methyl-D-aspirate receptor antagonism (NMDA receptors are in substantia gelatinosa in the spinal cord), opioid µ receptor agonism and voltage-sensitive sodium channel interaction.[31112] Efficacy of caudal epidural ketamine in children has been demonstrated in a number of studies.[1314] Semple et al.[4] studied the optimal dose of ketamine for caudal epidural blockade in children. The study compared the 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg dose of caudal ketamine with 1 ml/kg of 0.25% bupivacaine. They concluded that the optimum dose of ketamine for caudal epidural blockade is 0.5 mg/kg.

In our study, we have used caudal bupivacaine 0.25% 1 ml/kg in Group A and caudal bupivacaine 0.25% 1 ml/kg with ketamine (preservative free) 0.5 mg/kg in Group B that is in accordance with the study conducted by Semple et al.[415161718]

In our study, duration of analgesia after caudal block was documented using the objective pain score. The OPS is an observational pain scoring system which has been validated for use by parents. Using ANOVA, we observed that the mean duration of action with bupivacaine plain was 5.63 ± 0.98 h while its range varied between 3 and 7 h. In bupivacaine with ketamine group duration of action was in the range of 3–19 h, and its mean duration of action was 10.18 ± 2.24 h P < 0.001, which is highly significant. The results indicate that caudal bupivacaine and ketamine combined prolonged postoperative analgesia by 5–6 h and significantly reduced the need for subsequent postoperative analgesia by more than 50% compared with caudal bupivacaine alone. Naguib et al.[19] compared the analgesic effects of bupivacaine 0.25% (1 ml/kg) with and without ketamine 0.5 mg/kg in children undergoing inguinal herniotomy. Although there was no significant difference in the quality of analgesia between the groups, only 7% of patients who received the ketamine/bupivacaine combination required any further analgesia in the first 24 h after surgery, compared with 20% and 50%, respectively, of children in the ketamine-only and bupivacaine-only groups. Similarly, Cook et al.[10] demonstrated that the addition of ketamine 0.5 mg/kg to bupivacaine 0.25% (1 ml/kg) provided a longer median duration of postoperative analgesia after orchidopexy (12.5 h) than either clonidine 2 µg/kg (5.8 h, P < 0.05) or epinephrine 5 µg/ml (3.2 h, P < 0.001).

The degree of motor blockade was also comparable in both the groups. No motor blockade was seen after 6 h of observation in both the groups. Martindale et al.,[7] in 2004, compared the motor blockade using Bromage scale. Duration of motor blockade was 2.4 h, 2 h, and 1.8 h in caudal bupivacaine group, bupivacaine with ketamine, and IV ketamine group, respectively. Racemic bupivacaine is gradually being replaced by ropivacaine or levobupivacaine. This change is driven by the reduced potential for systemic toxicity and the lower risk of unwanted motor blockade.[20] There was no significant difference in the time taken to eat and drink between both the groups. There were no differences between the groups in terms of motor block, urinary retention, or postoperative sedation. One patient in Group B had urinary retention for which he was catheterized in the evening. Nausea and vomiting was not a major problem in any of the groups. In our study, success rate of caudal administration was 98%, remaining 2% of the patients, although not included in the study were due to some anatomical variation of the sacral canal.

CONCLUSION

On the basis of results derived in this study, it is concluded that ketamine in a dose of 0.5 mg/kg, added to 0.25% bupivacaine for caudal analgesia in children, for subumbilical surgery, significantly prolongs the duration of postoperative analgesia and reduced the need for postoperative analgesic supplementation when compared to 1 ml/kg of 0.25% bupivacaine reduced the need for perioperative analgesic supplementation alone, without any side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.