Comparison of ropivacaine and bupivacaine with fentanyl for caudal epidural in pediatric surgery.

CONTEXT: Ropivacaine, s-enantiomer of amide local anaesthetic produces differential neural blockade with less motor blockade, cardiovascular and neurological toxicity makes it suitable for day case surgery in children. AIMS: To compare the effectiveness of Inj. Ropivacaine (0.2 or 0.25%) or Inj. Bupivacaine (0.25%) with fentanyl in caudal block for intra and postoperative analgesia. SETTINGS AND
DESIGN: Double blind retrospective randomized study.
MATERIALS AND METHODS: All the patients (n=112) varying from age group 3.02 ± 3.29 years belonging to ASA I-IV were randomly allocated to receive caudal analgesia Group BF inj. Bupivacaine (0.25%, 2 mg/kg) + Inj. Fentany1 μg/kg (n=70) and group RF: Inj. Ropivacaine (0.25% or 0.2%, 2 mg/kg) + inj. Fentanyl 1 μg/kg (n=42). We monitored vitals and requirement of inhalational gases inraoperatively and also observed pain by pain score (Visual Analogue Score in verbal group and Objective Pain Scale in nonverbal group) and vitals postoperatively. We used rescue analgesics (inj. Paracetamol 5 mg/kg iv) when VAS score ≥4. STATISTICAL ANALYSIS: Student's t-test.
RESULTS: Duration of analgesia was prolonged in both group RF and BF. Time for first rescue analgesic for group RF (6.1 ± 1.1 hr) compared to group BF (5.6 ± 0.9 hr). Haemodynamic stability and less requirement of inhalation agent intraoperatively with group RF than others.
CONCLUSIONS: Ropivacaine with Fentanyl found to be better combination for pediatric surgeries for below umbilical surgeries as an adjuvant to general anaesthesia or sole technique with chances of less complication with high success rate.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

The combination of local anesthetic with adjuvant is getting more popular for better post-operative pain control with less side effects and early discharge. Bupivacaine was a popular drug in regional anesthesia for years until toxic reactions were reported. Ropivacaine, the S-enantiomer of the amide local anesthetic, produces differential neural blockade, with less motor blockade, cardiovascular and neurological toxicity, making it suitable for day-care surgery in children. Caudal analgesia is more popular because of its simple technique, predictable level of blockade and high success rate, excellent postoperative analgesia with smooth recovery for various surgeries, for example, lower abdominal, urologic and lower limb operations. It reduces analgesic requirement and facilitates early discharge. The aim of our study, which is a double-blind, retrospective, randomized study, was to determine the efficacy of ropivacaine and bupivacane with fentanyl for caudal anesthesia in children for onset, duration, sensory and motor blockade, and postoperative analgesia.

SUBJECTS AND METHODS

After following the institutional protocol, informed and written consent was obtained from the parents of 112 children ASA I-IV aged between 1 and 12 years undergoing lower abdominal and urological surgical procedures who were selected randomly for administration of caudal analgesia. All children were given oral premedication with midazolam 0.5 mg/kg 45 min prior to surgery. After securing intravenous access, inj. glycopyrolate and inj. ondensetron were administered. All patients were induced with either an inhalational mask (younger children) of O2/NO2 (at a 50:50 ratio) with sevoflurane (2-3%) or intravenous inj. ketaminel (1-2 mg/kg) and intravenous succinyl choline (1-2 mg/kg) to facilitate tracheal intubation with a proper sized endotracheal tube. All patients were maintained with the mask, LMA (laryngeal mask airway) or endotracheal tube with assisted ventilation with inhalation gases (sevoflurane or isoflurane 2-3%) or controlled ventilation with inj. atracurium 0.5 mg/kg) or inj. vecuronium bromide (0.02 mg/kg) was used as a non-depolarizing muscle relaxant and IPPV was given with the O2/NO2–sevoflurane mixture. After establishment of anesthesia, a caudal epidural single shot block was performed in the lateral position, after proper painting and draping, with a 22-G hypodermic needle after needle testing for negative aspiration and injecting 2 cc saline and checking for no aspirate of blood or cerebrospinal fluid. All children were injected, either of the drugs (2 mg/kg) and the volume injected was 1 ml/kg. Inj. bupivacaine (0.25%) with inj. fentanyl (1 μg/kg) (Group BF, n = 70) or inj. ropivacaine (0.2% or 0.25) with inj. fentanyl (1 μg/kg) (Group RF, n = 42). Recording and monitoring of pulse, non-invasive blood pressure, requirement of inhalational gases and O2 saturation were done every 15 min starting from induction of anesthesia and until the child was discharged from the recovery room. All patients received inj. paracetamol 5 mg/kg intravenously before discharge from the hospital in case of day-care surgery. Motor weakness was determined according to modified Bromage scale and duration of postoperative analgesia using hourly observation of Visual Analogue Score in the verbal group and Objective Pain Scale in the non-verbal group. Statistical analyses were done using Student's “t” test.

RESULTS

Table no: 1 all demographic data were comparable.

Table 1

Demographic and clinical data of BF and RF groups (mean±SD or range)

Table: 2, 3, 4, 5 and Fig 1 & 2 -There were no statistically significant difference noted within or between the groups. All were comparable.

Table 2

Mean pulse of BF and RF groups (mean±SD)

Table 3

Mean systolic blood pressure of BF and RF groups (mean±SD)

Table 4

Mean diastolic blood pressure of BF and RF groups (mean±SD)

Table 5

Mean MAP of BF and RF groups (mean±SD)

Figure 1

Pulse comparison between the different groups

Figure 2

Comparison of systolic blood pressure, diastolic blood pressure and mean arterial pressure between the RF and BF groups

Table 6: The duration of analgesia was slightly more with the Ropivacaine fentanyl (6.1hr) as compared to5.6hr in bupivaacine group but difference was statistically insignificant.

Table 6

Duration of analgesia (h) in all groups

DISCUSSION

Ropivacaine produces an equivalent sensory block as compared with bupivacaine but a less intense and shorter duration of motor block.[1] The duration of action is prolonged by addition of adjuvants to the local anesthetic drug, for example, clonidine, opioids, etc.[2345] In children, 0.2% ropivacaine (1 mg/kg) produced more rapid onset of action and a prolonged duration of action as compared with 0.25% bupivacaine (2 mg/kg).[6] Use of a low concentration and large volume of the drugs is responsible for obtaining differential block in children because of smaller diameter of the A-delta and C fibers and a short distance from nodes of Ranvier.[789] Hence a single shot of 0.2% ropivacaine (1 mg/kg) is equivalent to 0.25% bupivacaine when administered in equal volumes.

Ropivacaine is a long-acting, enantiomerically pure (S-enantiomer) amide local anesthetic with a high pKa and low lipid solubility, which blocks nerve fibers involved in pain transmission (A-delta and C fibers) to a greater degree than those controlling motor function (A-beta fibers)[79] It is less cardiotoxic than equal concentrations of racemic bupivacaine, with a significantly higher threshold for central nervous system toxicity than racemic bupivacaine in healthy volunteers (mean maximum tolerated unbound arterial plasma concentrations were 0.56 and 0.3 mg/l, respectively).[8]

Ropivacaine has less cardiovascular and central nervous system toxicity than racemic bupivacaine in healthy volunteers. Epidural ropivacaine 0.2% is similar to 0.2% bupivacaine for onset, quality and duration of sensory blockade. Ropivacaine also provides effective pain relief especially in conjunction with opioids or other adjuvants. Epidural administration of ropivacaine causes a significantly less motor blockade at low concentrations. It is still controversial that the greater degree of blockade of nerve fibers involved in pain transmission (A-delta and C fibers) than those controlling motor function (A-alpha and A-beta fibers) as compared with bupivacaine is due to a lower relative potency of the drug or its physiochemical properties or stereo-selectivity.[1011] As compared with bupivacaine, ropivacaine undergoes lower systemic absorption from the caudal epidural space in children.[12]

Fentanyl causes least respiratory depression when given extra-durally because of high lipid solubility, and when added to bupivacaine for single caudal epidural injection, it provides additional post-operative analgesia up to 24 h. A bupivacaine–fentanyl mixture as a single caudal epidural injection does not change onset, quality and duration of analgesia, and sedation score.[1314] A higher dose of 2 μg/kg when added to 0.25% bupivacaine for single injection in children causes vomiting and desaturation.[14]

The sensory block produced by ropivacaine is equivalent to bupivacaine, but the motor block is less intense and shorter in duration. Low concentration and large volume of the local anesthetic agent is used to obtain the differential block in children because of the A-delta and C fibers, and the small distances between the nodes of Ranvier. The lower chances of toxicity of drug increases the safety margin in pediatric patients.[17] The lower lipid solubility of ropivacaine compared with Bupivacaine retards penetration of myelin sheaths.[71516]

Addition of caudal epidural analgesia to general anesthesia inhibits the stress responses from the lower part of the body during surgery and reduces the neurohormonal responses. It was demonstrated that small doses of a mixture of bupivacaine 0.25% alone or with fentanyl 1 μg/kg when administered through the caudal epidural does not have any beneficial effect on pain scores and catecholamine levels.[1718] Caudal ropivacaine provides effective analgesia in the post-operative period, which is similar to bupivacaine with less motor blockade in pediatric patients and so makes it more suitable for day-care surgery.[1920] We did not monitor the first micturition time but it was reported to be higher in the bupivacaine group (4 ± 2.3) as compared with ropivacaine (3.1 ± 1.6).[21] Ropivacaine (0.375%) 1 mg/kg when given as a single-shot caudal epidural block provides hemodynamic stability, sensory blockade and post-operative analgesia same as that with bupivacaine at the same concentration and volume, with a shorter duration of motor block and lower chances of toxicity, which makes it a more popular drug of choice in pediatric patients.[21] Caudal block with ropivacaine 2 mg/kg in children of age 1-8 years resulted in an unbound ropivacaine plasma concentration of 0.043 mg/l and the mean Cmax of total ropivacaine was 0.47 mg/l, below the toxic level, and a shorter duration of motor block was seen as compared with bupivacaine.[22]

In conclusion, addition of fentanyl 1 μg/kg to inj. ropivacaine (0.2% or 0.25%) and inj. bupivacaine (0.25%) in similar doses of 2 mg/kg administered through the caudal epidural route imparts no added advantage to bupivacaine except a less intense motor block in children undergoing surgery below the umbilicus probably due to the lower doses of fentanyl.