Controlled comparison of ropivacaine with dexmedetomidine, clonidine and magnesium sulphate as adjuvant in caudal epidural block in paediatric population for infra-umbilical surgeries

Introduction

Caudal anaesthesia and analgesia are most widely used regional block in children for post-operative pain management in below umbilicus surgeries. It is simple to perform, reliable and safe.^[1] The main limitation is duration of block is short after single administration which can be prolonged by adding various adjuvants.^[2]

Ropivacaine is long acting amide local anaesthetic providing selective sensory blockade. Lower incidence of cardiovascular side effects, neurotoxicity and ability to produce less motor blockade has made it local anaesthetic of choice for regional blocks.^[2]

Clonidine and Dexmedetomidine are alpha-2 adrenergic agonists with the later having eight times more affinity for alpha-2 adrenergic receptors than former and negligible alpha-1 effects.^[3] Both provide a substantial anti-nociceptive effect by acting on the alpha-2 receptors in the dorsal horn of spinal cord and brain stem nuclei dealing with pain sensations at spinal cord level.^[4]

Magnesium’s anti-nociceptive effects are primarily based upon the regulation of calcium influx into the cell. It blocks NMDA receptors and also acts as an agonist on central alpha-2 receptors desensitising the nociceptive stimulation.^[5], ^[6]

This study compares the effects of these drugs as adjuvants in caudal epidural block, using it as primary mode of anaesthesia.

Materials and Methods

This prospective, randomized, controlled, double blinded study was conducted following principles of Declaration of Helsinki. It was approved by Institutional ethical committee. This study was conducted in a teaching institute over a period of 1.5 years from June 2018 to November 2019 and 90 children belonging to age group of 2-8 years, weighing 8-20 kilograms(kgs), falling into American Society of Anesthesiologists’ (ASA) physical status I-II and undergoing elective below umbilical surgeries, were enrolled for the study.[Figure 1] Children with bleeding diathesis, active respiratory infection, fever, spinal deformity, neurological diseases, developmental delays, local site infections and allergies to local anesthetics, were excluded from the study. Out of 90 patients, eight patients did not consent and two had fever on the day of surgery hence dropped from the study.

In pre-anaesthetic assessment child’s age, sex, weight and baseline parameters were recorded, detailed history was taken followed by general and systemic examination. Investigations including complete blood count, kidney function tests and coagulation profile were done preoperatively. Parents were taught the use of Wong-Baker Faces Pain Score^[7] (WBFPS) for participation in the study and explained about the procedure after which written informed consent was taken.

Computer randomisation with sealed envelopes method was used and twenty patients were allocated in each group. Table of random allocation was kept with anesthesiologist who prepared drugs and was not part of the study. The drugs were given in prefilled unlabeled syringes while performing the block.

On the day of surgery children were kept fasted according to standard fasting protocols. After arriving in preoperative area, children were accompanied by their parents inside the operating room where multipara monitor was attached and baseline heart rate (HR), mean arterial pressure (MAP), oxygen saturation (spo2) recorded. Induction of anaesthesia done with oxygen and nitrous oxide (50/50) and 8% sevoflurane with spontaneous ventilation. After loss of consciousness, peripheral venous access taken and inj. glycopyrrolate 4μg/kgs, inj. ondansetron 80 μg/kgs and inj. ketamine 0.5 mg/kgs administered after which sevoflurane was switched off. All children then placed in lateral decubitus position and single dose caudal epidural block performed with 23-gauge needle by loss of resistance technique under all aseptic and antiseptic precautions by an experienced anaesthesiologist who was blinded to the group allocations. Caudal anaesthesia given with inj. Ropivacaine 0.25% in group R and with added adjuvant inj. dexmedetomidine 0.5 μg/kg in group D, inj. clonidine 1μg/kgs in group C, inj. magnesium sulphate 50 mg in group M. The drug volume was calculated according to modified Armitage formula (0.75-1ml/kg). Patients were made supine after the procedure and onset of block was checked by absence of rise in HR and Systolic blood pressure (SBP) of more than 20% from the baseline and by pinching with toothed forceps at the incision site and time for onset of block was noted. Children were administered oxygen with Hudson mask and Inj. dexmedetomidine started at rate 0.5 μg/kg/hr and Inj. Isolyte-P started at the rate of 6ml/kg/hour.

Haemodynamic parameters like ECG, HR, MAP and oxygen saturation recorded before and after induction of anaesthesia, after caudal blockade administration, every 10 minutes till completion of surgery and thereafter every 30 minutes postoperatively.

Children were assessed intraoperatively by Children’s Hospital of Eastern Ontario Pain Scale^[8] (CHEOPS) for effectiveness of blockade every 10 minutes till completion of surgery. Ten minutes before completion of surgery dexmedetomidine infusion stopped and total duration of surgery noted.

Children were shifted to PACU for continuous monitoring and assessed using WBFPS and Face Leg Activity Cry Consolability scale^[9] (FLACC) every 30 minutes till both FLACC and WBFPS were ≥4 then inj. Paracetamol 20 mg/kg was administered intravenously as rescue analgesia.

Primary objective of the study was to calculate duration of block (time interval between onset of caudal block to first recording of pain scores ≥4) and time to onset of block. Secondary objective was to study haemodynamic stability and adverse effects such as nausea, vomiting, hypotension, bradycardia and urinary retention monitored.

Study of continuous variables from independent controls and experimental subjects with 1 control per experimental subject planned. The primary endpoint being FLACC and WBFPS score ≥4 after study drug administration, 16 patients in each group would be needed to detect an intergroup difference in the meantime to first rescue analgesia of at least 20% with α = 0.05, β= 0.10 and power of 90% based on the pilot study demonstrating mean (standard deviation) time of 256 (31.78) mins in children who received caudal analgesia using ropivacaine 0.25%.We recruited 20 subjects for each group anticipating any dropouts.

Results were recorded as mean (standard deviation), median (IQR) and ratios. Normally distributed data (age, weight, HR, MAP, duration of analgesia and onset of block) were analysed with One-Way Analysis of Variance Test (ANOVA) to compare all the four groups together and within pairs of group comparisons and finding the better group done with unpaired t test. The non-normal data distributions (FLACC, WBFPS and CHEOPS) were analysed with Kruskal Wallis Test and inter group comparison done with Mann Whitney U test. Qualitative data (gender) was analysed using chi-square(χ2) test. P- value of < 0.05 was considered statistically significant. The data was analysed using institutional SPSS statistical software (version 21.0, IBM corporation NY, USA).

Results

The demographic data distribution in all four groups showed no statistically significant difference ([Table 1]). The mean duration of analgesia in group R, D, C and M were 256.75±10.91, 433±10.81, 377.6±10.91 and 326.75±13.10 minutes(mins) respectively and the difference was statistically significant in all four groups (F=855.4778 and P<0.0001) ([Table 1]). The inter group differences were highly significant. The mean duration of analgesia was highest in group D followed by C, M and finally least in group R ([Table 2]).

The time to onset of blockade in group D, C, M and R were 10.78±0.80, 10.7±0.66, 7.33±0.83 and 7.18±0.85 mins respectively and the difference was statistically not significant. ([Table 1])

The intraoperative CHEOPS scores showed no statistically significant difference between the four groups. Postoperatively there was no statistically significant difference in FLACC and WBFPS for four groups till 180 minutes. The comparison of FLACC between four Groups showed highly significant difference at 240 mins, 300 mins and 360 mins. The comparison of WBFPS showed similar findings at 240 mins, 300 mins and 360 mins. ([Table 3])

No significant difference was seen in all four groups regarding haemodynamic parameters intraoperatively and postoperatively till 180 mins. The comparison of HR between four Groups showed highly significant difference at 240 mins, 300 mins and 360 mins, whereas of MAP showed similar findings at 240 mins, 300 mins and 360 mins. ([Table 4])

No respiratory depression, haemodynamic instability, neurological deficit or any other adverse effect was noted in any study group.

Discussion

Caudal block has good recovery profile, better post-operative analgesia and early restoration of function.

Anand VG et al^[10] Gupta S et al^[11] studied 60 children divided in two groups for caudal block with Ropicavaine 0.25% with Dexmedetomidine 1μg/kgs and Ropicavaine 0.25% in former study while 0.25% ropivacaine with 2 mg/kg of tramadol (RT) and 2 μg/kg dexmedetomidine (RD) as adjuvant in later. They observed lower FLACC scores in dexmedetomidine group similar to results of our study where Group D showed longest duration of analgesia and lowest FLACC and WBFPS.

A Parmeshwari et al^[12] compared three groups, consisting of hundred patients of 1-3 years each where namely: Group A 1 ml/kg 0.25% bupivacaine, group B 1 ml/kg 0.25% bupivacaine with clonidine 1 µg/kg. The mean duration of analgesia was prolonged with lower FLACC scores in group B concluding clonidine-bupivacaine mixture provided longer duration of analgesia similar to our study, where group C had longer duration of analgesia compared to Group R.

H. Birbicer et al^[13] Studied 60 children assigned in two groups with ropivacaine 0.25% administered in Group R and ropivacaine 0.25% plus 50 mg magnesium to Group RM. Paediatric observation priority score, CHEOPS, Bromage Motor Scales, analgesia duration and adverse effects were similar in both groups showing that addition of magnesium as an adjuvant agent to local anaesthetics for caudal analgesia has no effect on postoperative pain and analgesic need, which was in contrast to our study where adding magnesium sulphate as adjuvant results in longer duration of analgesia as compared to control group similar to study by Kim E et al.^[14] who studied 80 children administered caudal block with magnesium 50 mg added to ropivacaine 0.1% compared with ropivacaine 0.1% alone.

In our study the duration of analgesia showed statistically significant difference between Group C and D with better analgesia in Group D, results are congruent with study done by S.Gupta et al^[15] where 60 children were administered caudal block with ropivacaine 0.2% and clonidine 2 μg/kg as adjuvant in group A and dexmedetomidine 2 μg/kg in group B concluding that there was a significant increase in duration of analgesia in dexmedetomidine over clonidine group without increase in incidence of side-effects. Jehan Ahmed Sayed et al^[6] allocated 120 children into four groups: group C (saline), group MG (50 mg magnesium sulphate), group D (1 µg/kg dexmedetomidine), and group MGD (same doses dexmedetomidine and magnesium sulphate) added to bupivacaine as adjuvants. When all groups were compared it showed dexmedetomidine as adjuvants to bupivacaine in caudal block had higher duration of analgesia and lower FLACC scores as compared to magnesium sulphate group, a finding similar to our study where duration of analgesia was longer in group D when compared to group M. Duration of analgesia was longer in group C compared to group M and is found to be statistically significant and These two groups were never compared before in any other study.

The onset of block when compared in all four groups showed no statistically significant difference but time to onset of block was faster in group M and R.

All studies quoted above used general anaesthesia with or without muscle relaxants while securing the airway either with laryngeal mask airway or endotracheal tube facilitating caudal epidural block unlike our study where induction agents were used to make children unaware of caudal block administration, afterwards no supplementation with anaesthetic agents were done and inj. dexmedetomidine was only used for sedation at maintenance dose along with oxygen support. The groups compared in our study have never been compared before in our knowledge. Addition of control group to the study makes it more sensitive.

The limitations of study are it does not analyze the further administration of rescue analgesia and time of administering them.

Conclusion

It can be concluded there is a definitive increase in post-operative analgesia when any of three adjuvants namely dexmedetomidine, clonidine or magnesium are added to Ropivacaine for caudal epidural block than control group. Maximum duration of analgesia seen with dexmedetomidine followed by clonidine and magnesium group while least in control group. The study also showed more rapid onset of blockade in magnesium and control group.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.