European Journal of Cardiovascular Medicine

Caudal epidural is one of the most popular, commonly practiced, safe and reliable regional blocks in paediatric anaesthesia with predictable level of blockade.^[1]Amide local anaesthetics like bupivacaine and ropivacaine are commonly used in caudal analgesia. The lower incidence of cardiovascular side effects and neurotoxicity, as well as the ability to produce lesser motor blockade has made ropivacaine a safer choice as compared to bupivacaine for caudal epidural anaesthesia especially for day care surgeries.^[2] Ropivacaine, a long acting local anaesthetic has been extensively used in adults and older children and has been used safely even in the younger age group as well for caudal epidural.^[3,4] The main disadvantage of caudal is short duration of action after single shot injection.^[5] Prolongation of caudal analgesia has been achieved by addition of various adjuvants such as epinephrine, opioids, ketamine, alpha agonists.^[6] Clonidine, an alpha 2 adrenergic agonist, when given epidurally can prolong sensory block to much greater extent than motor block. This is mediated by opening of potassium channels and subsequent hyperpolarisation rather than alpha 2 agonist effect.^[7,8] Dexmedetomidine has an eight fold greater affinity for alpha 2 adrenergic receptors than clonidine and much less alpha 1 effects. A major advantage of dexmedetomidine is its higher selectivity compared with clonidine for alpha 2a receptors, responsible for hypnotic and analgesic effects of such drugs.^[9] Therefore this study has been undertaken to compare duration of sedation, duration of analgesia, hemodynamic parameters and adverse effectsof clonidine and dexmedetomidine as an adjuvant to ropivacaine in caudal block in paediatric patients.

This prospective, randomized controlled study was done after obtaining the approval of institutional ethical committee. After obtaining informed parental consent, 60 patients of ASA physical status I and II in the age group of 1 to 12 years of either genderwithin the normal weight range of 12 to 48kgundergoing elective infraumbilical surgeries under general anaesthesia were enrolled for the studybetween January 2019 to June 2020.Children withhistory of developmental delay or mental retardation that may interfere with pain intensity assessment, hemodynamic or respiratory instability,local infection at the site of proposed caudal block, congenital anomaly of lower back,known or suspected coagulopathy andskeletal deformities were excluded from the study.

Following a detailed pre-anaesthetic check-up in children undergoing infraumbilical surgeries under general anaesthesia with caudal block, demographic (age, gender), morphological (weight) and vital parameters were recorded. Patients were randomized into 2 groups:( n=30), based on computer generalized randomization table, to receive caudal block after general anaesthesia.Group Creceived ropivacaine 0.2% 0.5ml/kg + 1mcg/kg clonidine and Group D received ropivacaine 0.2% 0.5ml/kg + 1mcg/kg dexmedetomidine. On arrival to the operation theatre, patient’s nil per oral status was confirmed. All children received a preoperative dose of oral midazolam (0.5mg/kg) 20-30 minutes before induction. Baseline parameters like heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP) and peripheral oxygen saturation were monitored and recorded. Patient was induced with sevoflorane in oxygen followed by insertion of i.v line using 22G cannula and ringer lactate fluid was started. inj.glycopyrrolate 5mcg/kg,inj.midazolam 0.05mg/kg and propofol 2% 2mg/kg was given. After confirming bag and mask ventilation inj. vecuronium bromide 0.1mg/kg was given. After 3 minute ofventilation patient was intubated with adequate size endotracheal tube. Hemodynamic parameters were recorded after intubation. Anaesthesia was maintained using Oxygen:Nitrousoxide, sevoflorane and intermittent boluses of inj.vecuronium. After securing the airway, the patient was positioned in lateral position by an assistant for the caudal block and epidural space was identified with 22G hypodermic needle and drug was injected as per the group to which patient was allotted. Patient was immediately turned supine after caudal block. Hemodynamic parameters were recorded after caudal block. Surgery was started after 20minutes of the block. If any patient showed an increase in HR and MAP more than 30% at incision, it was taken as failure of caudal block and they were excluded from the study. Intraoperatively heart rate, non-invasive blood pressure, SpO2, EtCO2 were monitored continuously and following parameters like HR and MAP was recorded every 10mins till the end of surgery. At the end of surgery, patient was reversed with inj.Neostigmine 0.05mg/kg and inj.Glycopyrrolate 0.01mg/kgand extubated and was shifted to recovery room. In postoperative period following parameters were assessed,

Sedation was assessed using Ramsay sedation score every 15 minutes, Until he/she responded to oral commands when the Ramsay score of 3. Duration of sedation was taken as the time from caudal block till Ramsay score of 3.

Ramsay Sedation Score^[10]

Score Responsiveness

1. Patient is anxious and agitated or restless or both
2. Patient is co-operative, oriented and tranquil
3. Patient responds to commands only
4. Patient exhibits brisk response to light glabellar tap or loud auditory stimulus
5. Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus
6. Patient exhibits no response

Pain was assessed using FLACC pain scale at 15min, 30min, 45min, 1h, 2h, 3h until patient showed FLACC score of ≥4.

Flacc Scale^[11]

When FLACC score ≥4, rescue analgesia with inj.fentanyl 1mcg/kg was given. Duration of analgesia was taken as time from caudal block to administration of rescue analgesia. Haemodynamic parameters like heart rate, non-invasive blood pressure, oxygen saturation, respiratory rate were monitored every 15mins for first 1 hour and thereafter every 30mins until patient responded to oral commands, that is Ramsay sedation score of≥ 3. Adverse effects like bradycardia (fall by 20% from baseline heart rate) was treated with inj.Atropine 0.01mg/kg, hypotension (fall by 20% from baseline blood pressure) was treated with fluids, respiratory depression (defined as oxygen saturation <95%) was supplemented with oxygen, post-operative nausea vomiting was treated withIV Ondansetron 0.06mg/kg.

Statistical Analysis

The sample size was calculated based on the duration of sedation with clonidine as an adjuvant from the study of Reddy et al^[12] and expecting the mean difference of 15% with dexmedetomidine, taking into consideration the power of the study of 90% (β error = 10%) and 95% confidence (α error = 5% ). The sample size obtained was 26, in order to allow for dropouts and exclusions sample size of 30 was taken in each group.All characteristics were summarized descriptively. For continuous variables, the mean± standard deviations (SD) were used. For categorical data, the number and percentage were used. Chi-square (χ²) test was used for association between two categorical variables. The difference of the means between two independent groups was tested by unpaired t test.

p-value < 0.05, were considered to be statistically significant. Data were analyzed using SPSS software v.23.0 and Microsoft office 2007.

The demographic profile of patients in both groups was comparable with regard to age and weight. (Table number: 1)

The duration of sedation was 93.5 minutes in Group C and 103 minutes in Group D with p value of 0.030, which was not significant. Duration of analgesia in group C was 8.10 hours and 10.17 hours in Group D with p value of <0.001 which was significant(Table number: 2). Hemodynamic parameters were comparable in both the groups (figure number: 1). No adverse drug reactions were noted in our study.

3. Haemodynamic Parameters

1. Heart Rate

1. Mean Arterial pressure

Pediatric regional anaesthesia is commonly used with general anaesthesia (GA) and is a component in the multimodal approach for the management in pediatric patients to provide postoperative analgesia.^[8] Postoperative management of a child is a big challenge for the anaesthesiologist. Adequate sedation without respiratory depression and pain relief is an integral part of the postoperative management. Therefore in pediatric regional anaesthesia, caudal epidural block with local anaesthetics and adjuvants are used for intraoperative and postoperative management especially for sub umbilical surgeries in young children.^[3]

The efficacy of the block in providing good postoperative analgesia depends on the duration of action of the local anesthetic used. Different authors have used various local anesthetic agents like levobupivacaine, bupivacaine, ropivacaine with varying volume and concentration.^[3,10,13] The lower incidence of cardiovascular side effects and neurotoxicity as well as the ability to produce lesser motor blockade has made ropivacaine a safer choice as compared to bupivacaine for caudal epidural anaesthesia especially for day care surgeries.^[14,15,16] Ropivacaine, a long acting local anesthetic, is used in both adult and pediatric in varying concentration ranging from 0.2 to 0.75%.^[17,18] Most authors have used 0.2% ropivacaine with volume ranging from 0.5 to 2ml/kg for caudal epidural in children. Mavuri et al in their study have used 0.2% 1.5mg/kg ropivacaine and Jinjil et al have used 0.2%, 1ml/kg ropivacaine. Reddy M et al have used 0.25% 0.5ml/kg.^[8,12,17] Suresh et al have recommended the use of 0.2 % ropivacaine for the performance of caudal blocks in children and should not exceed 2mg/kg.^[16]

Clonidine, an alpha 2 agonist is commonly used as an adjuvant with ropivacaine because of its analgesic and sedative property.^[4,19] Clonidine has been used in the range of1-2mcg/kg in various studies without any significant incidence of side effects. Jjinjil et al, have used 1mcg/kg, Reddy et al have used 0.5mcg/kg and Gupta et al have used 2mcg/kg as adjuvant to caudal ropivacaine in children.^[4,8,12] Dexmedetomidine, a highly selective alpha 2 adrenergic agonist having analgesic and sedative effect has a wide pharmacological profile and doses vary depending on the route of administration. Caudal Dexmedetomidine has been used in the range of 1-2mcg/kg without any significant side effects. Neogi et al and Mavuri et al have used 1mcg/kg dexmedetomidine and Reddy M et al have used 0.5mcg/kg.^[20,21]

The demographic profile of patients regarding age and weight (Table number 1) in both the groups were similar.

Sedation is commonly monitored by using different sedation scores. Ramsay sedation score was used in our study and in the study of Arunkumar and Hosalli et al. Neogi et al have used four point scale, Gupta et al have used 1 through 3 scale.^[4,22,12,20] In the study conducted by Gupta et al the mean duration of sedation was 2.86±0.52h and 2.72±0.49h in clonidine and dexmedetomidine groups respectively with p value of 0.69 which was not significant.^[4] Mavuri et al while comparing ropivacaine alone, or combined with clonidine and dexmedetomidine the mean duration of sedation was found to be 56.6±16.07 ,122.88±16.38 and 147.11±10.78 minutes respectively with p value of < 0.0001 which was statistically significant.^[17] Reddy et al, while comparing clonidine and dexmedetomidine as adjuvant to ropivacaine found the mean duration of sedation was 132±15.62 and 152±10.52 minutes respectively (p <0.001) which was statistically significant.^[12] In the above studies, most authors have found statistical difference between the groups but clinically they are comparable. Similarly, our results concur with the above studies. The variations in the duration of sedation may be attributed to the dose of adjuvant used, different scales to assess the sedation and anaesthetic drugs used during the procedure.

Analgesia in children is assessed by using different scales, like FLACC scale, Visual Analogue Scale (VAS), Children’s hospital of eastern ontariopain scale (CHEOPS), Children and infants postoperative pain scale (CHIPPS). Nilesh et al and Mavuri et al have used FLACC scale, Jinjil et al has used VAS scale and Reddy M et al has used CHIPPSscale.^[8,12,17,20] In study conducted by Nilesh et al , 0.2mg per kg of dexamethasone and 1 mcg per kg of clonidine was used along with 0.25% bupivacaine and observed mean duration of analgesia being 18-24 hrs and 12-15 hrs respectively.^[20] Mavuri et al while comparing ropivacaine alone, or combined with clonidine and dexmedetomidine found the mean duration of analgesia was 7.15±1.00h, 11.57±1.27h and 14.73±1.53h respectively with p value of <0.0001 which is statistically significant.[17] In the study conducted by Jinjil et al while comparing 1mcg/kg clonidine and 1mcg/kg dexmedetomidine with 0.2% ropivacaine 1ml/kg caudally in children undergoing lower abdominal surgeries found the duration of analgesia in dexmedetomidine group was 14.21±1.33h and in the clonidine group was 9.56±0.85h which was significant.(p <0.01).^[8] Reddy et al found mean duration of analgesia in clonidine group was 430.52±20.58 minutes and in dexmedetomidine group was 555.6±18.22 minutes with p value of <0.001 which was statistically significant.^[12] Our results also concur with the results of the above studies. The varying duration of analgesia in different studies may be attributed to varying volume and concentration of local anaesthetic, doses of adjuvants used and various pain scales used.

Both clonidine and dexmedetomidine produce minimal haemodynamic disturbance and there was no adverse effects in our study. Similar results were observed by Neogi M et al, Mavuri et al, Reddy et al.^[12,17,23]

We conclude both clonidine and dexmeditomidine provides good sedation and hemodynamic stability, but dexmeditomidine provides increased duration of analgesia when compared to clonidine. Therefore dexmeditomidine can be used as an alternative to clonidine for postoperative sedation and as a effective adjuvant to prolong the duration of analgesia for caudal block in pediatric patients.

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