Comparison of Analgesic Efficacy of Dexamethasone versus Tramadol in Combination with Ropivacaine in Caudal Anesthesia for Children Undergoing Lower Abdominal Surgeries.

BACKGROUND: Caudal anesthesia has emerged as a reliable and effective anesthetic technique in the pediatric age group. However, the limited duration of action of the local anesthetic drugs proves to one of the major hindrances in the complete utilization of caudal block as an effective analgesic technique. To overcome this shortcoming, adjuvant drugs were introduced into clinical practice. AIM: Our aim was to determine which of the two drugs - dexamethasone and tramadol - serves as a better adjuvant for caudal analgesia in pediatric patients. SETTINGS AND
DESIGN: This was a prospective, randomized, double-blind study that comprised 90 American Society of Anesthesiologist (ASA) physical status I and II pediatric patients posted for lower abdominal surgeries.
MATERIALS AND METHODS: Ninety ASA physical status I and II children aged 5-12 years posted for lower abdominal surgeries were chosen. They were randomly divided into three groups - Group R received 0.5 ml.kg-1 of 0.2% ropivacaine plus 0.9% normal saline; Group T received 0.5 ml.kg-1 of 0.2% ropivacaine plus 2 mg.kg-1 tramadol; and Group D received 0.5 ml.kg-1 of 0.2% ropivacaine plus 0.1 mg.kg-1 dexamethasone. Postoperative pain was assessed using a modified objective pain score and time to first rescue analgesia (duration of sensory block) was recorded. Postoperative sedation and any other postoperative adverse effects were noted. STATISTICAL ANALYSIS: Student's independent t-test was employed for comparing continuous variables and Chi-square test for categorical variables. Kruskal-Wallis test was used for postoperative pain and sedation score data.
RESULTS: The duration of sensory block was significantly longer with dexamethasone than tramadol. No significant postoperative sedation or any other adverse effect was noted in any patient.
CONCLUSION: Dexamethasone is superior to tramadol as an adjuvant to ropivacaine for pediatric lower abdominal surgeries. Copyright:

INTRODUCTION

Pain has always been one of the most traumatic experiences of human psyche that becomes the foremost concern of patients posted for surgery. The necessity for providing a pain-free postoperative period can be gauged from the studies which show that intense postoperative pain not only increases the trauma of surgery but also hampers the early physiological and psychological rehabilitation of the patients.

Postoperative pain becomes an even more important concern in pediatric age group. Choosing an anesthetic approach that provides the flexibility of extending analgesia into the postoperative period without any great risk of anesthetic neurotoxicity as well as ensures optimal intraoperative sensory and motor blockade is of paramount importance. Caudal anesthesia has gained the reputation of providing a reliable anesthesia for surgery as well as affording a comfortable postoperative period which is free of pain. However, single-shot blocks have a limited duration of action which depends on the volume and concentration of the drug used. The duration of action can be prolonged either by addition of additives or by placing catheters for continuous analgesia. Placing catheters requires expertise and also greater postoperative care to prevent catheter migration intrathecally or into a blood vessel. Addition of adjuvant drugs eliminates these shortcomings and allows the anesthesiologist to exploit the full potential of caudal anesthesia without the risk of anesthetic toxicity.

A number of previous studies have evaluated the use of different adjuvants with local anesthetics in a caudal block. Naguib et al. evaluated the addition of midazolam.[1] and ketamine[2] to bupivacaine in a pediatric caudal block. Marco Valls et al.[3] studied the effect of caudal morphine in pediatric surgeries. Saadawy et al.[4] investigated the effect of dexmedetomidine on block characteristics of bupivacaine in pediatric caudal anesthesia.

Dexamethasone is a type of corticosteroid medication. It has analgesic, anti–inflammatory, and antiemetic properties. As a result, it has found common use in the prophylaxis and treatment of postoperative nausea and vomiting, reducing airway edema and as an intravenous (i.v.) analgesic in children undergoing otolaryngologic procedures. Apart from this, dexamethasone has also proven itself as an effective adjuvant in prolonging the duration of analgesia, as shown by a number of studies.[5]

Tramadol, a synthetic analog of codeine, belongs to the opioid class of drugs. It has two enantiomers – (+) and (−); (+) enantiomer has more affinity for opioid μ-receptor, thus exhibits a greater analgesic efficacy. However, tramadol typically lacks the respiratory depressant effects seen with the opioid class of drugs.

In developing countries where the resources are limited, dexamethasone and tramadol are cheap and easily available. Thus, studying their potential in caudal analgesia assumes significance in a scenario where there is limited availability of drugs which are safe and effective in pediatric population.

Hence, we decided to compare and evaluate the efficacy of dexamethasone vs tramadol in caudal analgesia in pediatric infraumbilical surgeries.

MATERIALS AND METHODS

After obtaining approval of institutional ethical committee and informed written consent from the parents/legal guardians, this prospective, randomized, double-blinded study was conducted in the department of anesthesia between May 2019 and July 2020. Ninety American Society of Anesthesiologist (ASA) Grade I and II patients aged 5–12 years scheduled for lower abdominal surgeries were enrolled for the study. The eligibility criteria were as follows.

Inclusion criteria

Written informed consent from the parent/legal guardian

ASA Grade I and II

Patients aged 5–12 years of either sex

Patients scheduled for elective lower abdominal surgeries.

Exclusion criteria

Allergy to local anesthetics

Coagulation disorder

Local infection, sepsis, and bacteremia

Vertebral deformity

Preexisting neurological diseases

Allergic to any of the drug to be used.

Using GPOWER software version 3.0.10 (Heinrich Heine University Dusseldorf, Germany), it was estimated that the least number of patients required in each group with effect size of 0.25, 80% power, and 5% significance level is 30. Since we have to compare three groups in our study, we have included 90 patients in our study.

Randomization was achieved by pulling envelops out of a partially sealed box. Blinding was done by preparation of medication according to the assigned group by one anesthesiologist while performance of the block and administration of the drug was done by another anesthesiologist who was unaware of the group allocation. Data collection was done by the second anesthesiologist.

All patients underwent a pre-anesthetic checkup and were kept fasting for 6 h prior to surgery after a light evening meal. On the morning of surgery, patients were shifted to the operating room and all the monitors, namely pulse oximetry, electrocardiogram, and noninvasive blood pressure (BP) were attached. General anesthesia was induced with injection propofol 1 mg.kg−1, injection fentanyl 1 μg.kg−1, and injection atracurium 0.5 mg.kg−1. The patients were then intubated and anesthesia was maintained with sevoflurane 0.8–1 Minimum alveolar concentration (MAC) by intermittent positive pressure ventilation.

Immediately after intubation, patients were turned into the lateral decubitus position and caudal anesthesia was given with 22-gauge cannula using a loss of resistance technique. Epidural space was confirmed by loss of resistance felt after piercing of sacrococcygeal ligament and whoosh test by injecting 0.5 ml air. Anesthesiologist blinded for the content of the drug injected the formulation according to the group allocated

Group R received 1 ml.kg−1 0.2% ropivacaine plus 0.9% normal saline

Group T received 1 ml.kg−1 of 0.2% ropivacaine plus 2 mg.kg−1 tramadol

Group D received 1 ml.kg−1 of 0.2% ropivacaine plus 0.1 mg.kg−1 dexamethasone.

The volume of drug injected would not exceed 1 ml.kg−1 in any patient.

Surgery was started 10 min after the caudal block and rise in heart rate (HR) and mean arterial pressure (MAP) more than 20% from baseline was considered a failure of the block. In such a case, the patient was excluded from the study and i.v. fentanyl (1 μg.kg−1) was given.

At the end of surgery, patients were extubated and moved to postoperative anesthesia care unit (PACU) for further monitoring.

The demographic data such as age, weight, ASA status, type, and duration of surgery were noted for all patients. Haemodynamic parameters - heart rate (HR), systolic BP (SBP), diastolic BP(DBP), mean arterial pressure(MAP) were monitored as follows- at baseline,after caudal anesthesia, 5min after skin incision and immediately post operatively. Hypotension was defined as fall in BP >20% from the baseline (to be treated with fluid bolus) and bradycardia as fall in heat rate >20% from the baseline (to be treated with atropine).

Modified Objective Pain Score (MOPS) was assessed every hourly for 3 h and then at 6 and 12 h [Table 1]. The time from administration of block to the time patient asked for rescue analgesia was taken as the duration of sensory block. Rescue analgesia was given with iv paracetamol 15 mg.kg−1.

Table 1

Modified objective pain score

Criteria	0	1	2
Crying	None	Consolable	Non consolable
Movements	None	Restless	Thrashing
Agitation	Asleep or calm	Mild	Hysterical
Posture	Normal	Flexed	Holds injury site
Verbal	Asleep or not complaint	Complaint but cannot localize	Complaint but can localize

Postoperative sedation was assessed using RAMSAY sedation scale (RSS) immediately post extubation and then at 30 min, 1 h and then every hourly for 3 h and then at 6 and 12 h [Table 2]. Duration of postoperative sedation was taken as the time from extubation till RSS score was ≤2.

Table 2

RAMSAY sedation scale

Score	Clinical response
1/	Anxiety and completely awake
2	Completely awake
3	Awake but drowsy
4	Asleep but responsive to verbal command
5	Asleep but responsive to tactile stimulus
6	Asleep and not responsive to any stimulus

Apart from these, the patients were also monitored for any respiratory depression (respiratory rate <10 breaths/min), nausea, vomiting, or any neurological complication for 24 h in the PACU.

Statistical analysis

The recorded data were compiled and entered into a spreadsheet (Micro Excel) and then exported to the data editor of SPSS Version 20.0 (SPAA Inc., Chicago, Illinois, USA). Continuous variables were expressed as mean ± standard deviation and categorical variables were summarized as frequencies and percentages. Student's independent t-test was employed for comparing continuous variables. Chi-square test was applied for comparing categorical variables. Kruskal–Wallis test was used for postoperative pain and sedation score as data were expressed as median and range. P < 0.05 was considered statistically significant. All P values were two tailed.

RESULTS

A total of 90 patients who were scheduled for elective lower abdominal surgeries were included in this study. Patients in all the groups were comparable with respect to demographic characteristics such as age, sex, weight, ASA groups, and duration of surgery [Table 3].

Table 3

Comparison of baseline demographic variables between group ropivacaine, ropivacaine+tramadol, and ropivacaine+dexamethasone (n=30)

	Group R	Group T	Group D	P
Age	45.30±6.87	46.30±6.07	42.50±7.20	0.706
Weight	74.80±7.80	75.81±7.68	72.60±6.85	0.562
Sex (female/male)	17/13	14/16	18/12	0.465
Duration of surgery (min)	45.68±5.65	46.75±6.02	45.89±5.93	0.354
ASA status, n (%)
ASA 1	16 (53)	18 (60)	17 (56)	0.321
ASA II	14 (46)	12 (40)	13 (43)

The data are expressed as mean±SD and analyzed using unpaired t-test or as n (%) and analyzed using Chi-square test. ASA=American Society of Anesthesiologist; Group R=Ropivacaine; Group T=Ropivacaine+tramadol; Group D=Ropivacine+dexamethasone; SD=Standard deviation

The postoperative sedation scores showed that patients who received caudal tramadol were awake but drowsy (RSS-3) at extubation and the state of drowsiness lasted for 1 h postextubation approximately. On the other hand, Group D and Group R did not show any significant postoperative sedation. After 1 h of extubation, there was no significant sedation seen with any drug [Table 4].

Table 4

Comparison of Ramsay sedation score scores between the three groups expressed as median (interquartile range)

	Group R	Group T	Group D	P
RSS at extubation	2.0 (2-2)	3.0 (3-3)	2.0 (2-2)	<0.001*
RSS at 1 h	2.0 (2-2)	3.0 (3-3)	2.0 (2-2)	<0.001*
RSS at 2 h	2.0 (2-2)	2.0 (2-2)	2.0 (2-2)	0.763
RSS at 3 h	2.0 (2-2)	2.0 (2-2)	2.0 (2-2)	0.763
RSS at 6 h	1.5 (1-2)	1.3 (1-2)	1.5 (1-2)	0.573
RSS at 12 h	1.0 (1-1)	1.0 (1-1)	1.0 (1-1)	0.465

Data expressed as median and interquartile range. Kruskal-Wallis test used. *Statistically significant. RSS=Ramsay sedation score, Group R=Ropivacaine; Group T=Ropivacaine+tramadol; Group D=Ropivacine+dexamethasone

The duration of analgesia with ropivacaine alone was 250 ± 52.78 min, which was the shortest among the three groups. The duration of analgesia with dexamethasone was 480 ± 45.49 min, which was significantly longer than tramadol – 360 ± 45.79 min. The duration of analgesia with both adjuvants – tramadol and dexamethasone – was significantly longer than with ropivacaine alone [Table 5].

Table 5

Comparison of duration of sensory block in group ropivacaine, group ropivacaine+dexamethasone, and group ropivacaine+tramadol (n=30)

	Group R	Group D	Group T	P
Duration of analgesia (min)	250±52.78	480±45.49	360±45.79	<0.001*

The data are expressed as mean±SD and analyzed using unpaired t-test. *Statistically significant. SD=Standard deviation, Group R=Ropivacaine; Group T=Ropivacaine+tramadol; Group D=Ropivacine+dexamethasone

MOPS comparison showed the scores to be comparable for the first 3 h. Then, there is a statistically significant difference in MOPS score at 6 and 12 h with dexamethasone and tramadol showing significantly lower scores than ropivacaine group. Again between dexamethasone and tramadol, the difference was statistically significant at 6 and 12 h with dexamethasone group showing significantly lower score than the tramadol group [Table 6].

Table 6

Comparison of modified objective pain score between group ropivacaine, group ropivacaine+dexamethasone, and group ropivacaine+tramadol (n=30)

	Group R	Group D	Group T	P
1 h	2 (2-2)	1 (1-1)	1 (1-1)	0.326
2 h	2 (2-2)	1 (1-1)	1 (1-1)	0.562
3 h	1 (1-1)	1 (1-1)	1 (1-1)	0.682
6 h	4 (3-4)	2 (2-2)	2 (2-2)	<0.001*
12 h	4 (4-4)	2 (2-2)	3 (3-3)	<0.001*

Data expressed as median and interquartile range. Analyzed by Kruskal-Wallis test. *Statistically significant. Group R=Ropivacaine; Group T=Ropivacaine+tramadol; Group D=Ropivacine+dexamethasone

Hemodynamic comparison showed that HR, SBP, DBP, and MBP show no statistically significant difference in any of the three groups. There was no incidence of bradycardia, hypotension, nausea and vomiting, respiratory depression, and neurological complication in any patient.

DISCUSSION

This study evaluates the efficacy of dexamethasone and tramadol as caudal adjuvants in the pediatric population. Apart from analgesic potential, we also investigated any significant postoperative side effects like sedation and neurological complications which may limit their utility as safe and effective adjuvants. The duration of analgesia was the primary outcome, whereas the secondary outcomes included postoperative sedation and any other postoperative complications.

The demographic data including age, weight, sex, and ASA grading were comparable in all the three groups.

The duration of analgesia produced by both tramadol and dexamethasone was significantly long as compared to ropivacaine alone. Hence, this study clearly highlights the potentiation of sensory block of ropivacaine by the addition of adjuvants, which, in our study, were dexamethasone and tramadol. Another interesting observation made during the course of this study was that this excellent analgesia was produced with minimal doses of 0.1 mg.kg−1 dexamethasone and 2 mg.kg−1 tramadol, whereas much higher doses of the same drugs are needed to produce systemic analgesia when given iv. This highlights the dose-sparing effect of the caudal approach, which can be an interesting attribute for further research.

In our study, dexamethasone showed the longest postoperative analgesic period of 480 ± 45.49 min. Dexamethasone is a drug commonly used for its antiemetic and anti-inflammatory effects. The mechanism of its analgesic effect is not clearly understood. Dexamethasone is believed to have a membrane stabilizing effect and a local anesthetic effect.[6] Another possible mechanism could be regulation of nuclear factor kappa B, thereby inhibiting central sensitization after surgery and potentiation of analgesia of the caudal block[78] without any significant adverse effect.[910]

Our results were similar to those seen by Sridhar et al.[5] who compared the efficacy of dexmedetomidine, dexamethasone, and magnesium in pediatric caudal analgesia for infraumbilical surgeries. Similar results were reported by Choudhary et al.[11] who compared the analgesic effects of ropivacaine and ropivacaine with dexamethasone in two groups of pediatric patients posted for inguinal herniotomy. Girgis[9] studied the effect of addition of dexamethasone to bupivacaine in caudal anesthesia in patients aged 1–6 years posted for inguinal herniotomy. They also found dexamethasone to prolong the postoperative analgesia. El-Feky et al.[12] who studied the effect of addition of dexmedetomidine versus fentanyl versus dexamethasone to pediatric caudal anesthesia reported dexamethasone as a drug with significant analgesic properties.

The duration of sensory block with tramadol in our study was 360 ± 45.79 min. Tramadol is a centrally acting analgesic whose analgesic effect is explained by the inhibition of monoamine reuptake. It also has a weak agonistic action on opioid receptors. Tramadol has been shown to potentiate the effect of local anesthetic in a caudal block without causing any untoward side effects.[13] Doda and Mukherjee[13] and Solanki et al.[14] demonstrated tramadol as a safe caudal adjuvant without any significant side effects. Krishnadas et al.,[15] Güneş et al.,[16] and Kamal et al.[17] showed tramadol to prolong the duration of effect of ropivacaine in caudal epidural anesthesia. Solanki et al.[14] compared tramadol and fentanyl in pediatric caudal analgesia and concluded that caudal tramadol along with 0.25% bupivacaine provided longer postoperative analgesia with lesser postoperative sedation than fentanyl.

The next important parameter we compared in our study was the degree of postoperative sedation patients experienced with either of the drugs given caudally. Postoperative sedation remains a very important concern, especially in pediatric patients. The pediatric cardiopulmonary system has a limited ability to cope with postoperative residual sedation and the ensuing respiratory depression and hypoxia. Hence, choosing a drug which causes minimal sedation is of paramount importance in the pediatric age group. In our study, RSS scores were higher for the tramadol group on immediate extubation and up to 1 h postoperatively. However, these scores did not translate into bradycardia or respiratory depression in any patient. After 1 h, the RSS scores were low and comparable for all the three groups. Similar results were seen by Sridhar et al.[5] and Solanki et al.[14] who studied the efficacy of dexamethasone and tramadol, respectively, in pediatric caudal epidural anesthesia and found them to produce no significant postoperative sedation.

There were no significant hemodynamic alterations in any patient. This can be partly attributed to the caudal approach used in our study which entails deposition of drugs in the caudal epidural space. The slow and gradual onset of sympathectomy that occurs in caudal anesthesia could be one of the reasons for hemodynamic stability. The other important factor that plays a major role is the drug introduced into the caudal space, which, in our study, were dexamethasone and tramadol along with ropivacaine. This study found these drugs to be completely hemodynamically stable.

Our results were similar to those seen by Gupta and Sharma[18] who compared tramadol to dexmedetomidine for caudal anesthesia in pediatric infraumbilical surgeries and found it to be a hemodynamically stable caudal adjuvant. Similar to our study, dexamethasone was also not found to cause any significant hemodynamic alterations in caudal anesthesia by Sridhar et al.,[5] who compared it to agents such as magnesium and dexmedetomidine.

None of the patients reported nausea, vomiting, respiratory depression, or any neurological complication in the postoperative period.

Limitations

Our study has a few limitations.

First, there is the possibility of dexamethasone and tramadol exerting anti-analgesic effects through systemic absorption from the caudal space. However, studies have shown that dexamethasone dose >0.1 mg.kg−1 iv and tramadol dose >2 mg.kg−1 i.v. are needed to produce systemic analgesia.[19] However still, the possibility of systemic analgesia cannot be completely ruled out, as we did not have a control group with i.v. dexamethasone and i.v. tramadol.

Second, in our study, we did not evaluate other important adverse effects of dexamethasone like adrenal suppression and hyperglycemia. However, earlier studies have shown that a single bolus of low-dose dexamethasone is devoid of significant side effects.[20] Therefore, even though the possibility of these side effects cannot be completely ruled out, previous data suggest that the probability of occurrence is quite low with such a low dose of 0.1 mg.kg−1 of dexamethasone.

Third, ultrasound guidance for caudal block administration should be considered in cases where the detection of sacral anatomy is difficult, especially by palpation.

Finally, this study did not include a cost analysis, but as already discussed, dexamethasone and tramadol are both cheap and easily available. Hence, the choice of the drugs was such that the patients did not have to bear any additional cost for the purpose of this study.

CONCLUSION

Dexamethasone and tramadol both provide adequate caudal anesthesia with minimal hemodynamic alterations and no significant postoperative sedation. However, dexamethasone provides a significantly longer postoperative analgesia than tramadol, making it as a superior caudal adjuvant for pediatric caudal anesthesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.