A comparison of dexamethasone and clonidine as an adjuvant for caudal blocks in pediatric urogenital surgeries.

BACKGROUND: Caudal block is a reliable regional analgesic technique for pediatric urogenital surgeries. Various adjuvants have been tried to enhance the duration of action of bupivicaine. Though clonidine is extensively used as an adjuvant in caudal anaesthesia, it can have troublesome adverse effects like bradycardia, hypotension and sedation. Lately dexamethasone has become popular as an adjuvant in paediatric caudals due to its safety profile. AIM: The aim of this study was to compare dexamethasone and clonidine coadministered with bupivicaine caudally in paediatric patients undergoing urogenital surgeries in terms of analgesia and adverse effects. SETTINGS AND
DESIGN: Prospective, double blinded randomised study. SUBJECTS AND
METHOD: Sixty American Society of Anesthesiologists physical status I and II children, aged 1-6 years undergoing urogenital surgeries were allocated in 2 groups: Group I: 0.5 mL.kg-1 of 0.25% bupivicaine with dexamethasone 0.1 mg.kg-1 in 1 ml normal saline (NS) Group II: 0.5 mL.kg-1 of 0.25% bupivicaine with clonidine 1 μg.kg-1 diluted in 1 ml normal saline. The parameters studied included duration of analgesia, intraoperative and postoperative hemodynamics, sedation scores and incidence of adverse effects like wound dehiscence, bleeding, vomiting and respiratory depression. STATISTICAL ANALYSIS USED: Statistical analysis was carried out using Stata Version 10. After checking for the normality assumption, t-test for comparing means of two independent samples was used for comparing baseline continuous variables. P values <0.05 were considered significant.
RESULTS: Patients in Group II had longer duration of analgesia postoperatively. Patients in this group also had lower heart rate and more sedation scores.
CONCLUSION: Our study shows that caudal dexamethasone is a good alternative to clonidine with more stable hemodynamics and lesser sedation scores in the immediate postoperative period. Both the drugs offer good analgesia postoperatively with the duration of analgesia more in clonidine.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Caudal block is the most commonly used regional anesthetic technique in pediatric urogenital surgeries. The major disadvantage of a single-shot caudal block is the short duration of action despite using a long-acting local anesthetic like bupivicaine. There were suggestions of double caudal technique, but there is a risk of toxicity due to the high volume of local anesthetic.[1]

Various adjuncts such as opioids, neostigmine, ketamine, and alpha two (α2) agonists have been studied to increase the duration of action of bupivacaine in caudal anesthesia.[234] Although the use of caudal clonidine (α2 agonist) has shown to have sustained analgesia, their use can have troublesome side effects such as bradycardia, hypotension, and sedation.[5] During the last few years, use of caudal dexamethasone has become increasingly popular due to lack of adverse effects seen with other adjuvants.[6]

Dexamethasone is a well-known corticosteroid used as an analgesic and antiemetic perioperatively. There are studies demonstrating the role of dexamethasone administered caudally, epidurally, and in brachial plexus block.[78] Although caudal dexamethasone may not be Food and Drug Administration approved there are enough in vitro and in vivo studies which prove the safety of the drug.[2910] No study has compared caudal clonidine with dexamethasone in pediatric urogenital surgeries. Hence, we designed this prospective, double-blinded study with the aim of comparing both these drugs in terms of analgesia and associated adverse effects.

METHODS

This prospective randomized double-blinded study was conducted over a period of 1 year from December 2014 to December 2015 in our institute, All India Institute of Medical Sciences, Patna, India. After the approval of Institutional Ethical Committee, a total of sixty American Society of Anesthesiologists (ASA) I and II children, aged 1–6 years undergoing urogenital surgeries under general anesthesia were included in this study. Written informed consent was taken from the patients parents preoperatively. Exclusion criteria included children who were ASA III or more, had a history of diabetes, known allergy to the drugs, coagulopathy, infection at puncture site, preexisting neurological disease, or spinal anomalies.

The sample size was estimated on the basis of time to first analgesic requirement in test and control group. At 80% power and 5% level of significance, the sample size was estimated to be approximately n = 30 in each group taking a difference of 2.5 h as clinically relevant. Computer-generated randomization table was used to assign the children in either of the two groups: Group I (dexamethasone) or Group II (clonidine).

Group I received 0.5 mL/kg of 0.25% bupivacaine in which dexamethasone 0.1 mg.kg diluted to 1 ml with normal saline (maximum volume 20 ml).

Group II received 0.5 mL/kg of 0.25% bupivacaine in which clonidine 1 μg/kg was diluted to 1 ml with normal saline (maximum volume 20 ml).

A pharmacist was asked to prepare all study medications according to the group assigned. An investigator (clinical professor), who was blinded to group allocations performed caudal blocks in all patients. Intraoperative measurements were made by the second investigator unaware of the group allotments.

Premedication in the form of pedicloryl 100 mg/kg was administered orally 4 h before the surgery. Intravenous access of all the patients was secured in the preoperative holding area, and maintenance fluid started. Standard monitors including electrocardiography, noninvasive arterial pressure, pulse oximetry, carbon dioxide, and gas analyzer were applied during induction and maintenance of anesthesia. Anesthesia was induced with 3 mg/kg of propofol and 1 µg/kg fentanyl. Appropriately sized I gel was inserted to secure the airway. Anesthesia was maintained with sevoflurane in air and oxygen. The depth of anesthesia was adjusted accordingly with a goal of 35–40 mmHg end-tidal carbon dioxide. Spontaneous breathing was maintained during surgery. After completion of surgery, I gel was removed, and the child was sent to a postanesthetic care unit once awake.

After induction of anesthesia, children were placed in a left lateral decubitus position, and ultrasound guided caudal block was given. A total of 20 G cannula was inserted in the caudal space and the drug given. Anterior displacement of the dura mater as observed by the ultrasound confirmed the spread of the drug. Fifteen minutes after performing the caudal block, surgery was initiated. An increase in the heart rate or mean arterial pressure (MAP) of more than 15% compared with baseline after incision indicated the failure of the block. The patient was excluded from the study and rescue analgesia in the form of 1–2 µg/kg fentanyl given.

Heart rate, MAP, peripheral oxygen saturation (SPO2) was measured every 15 min till 3 h after the start of the surgery. Postoperative care was provided by nursing staff that were blinded to the group allotment. Pain was assessed using Faces Legs Activity Cry Consolability tool ([FLACC], 0–10) [Table 1] at 30 min and hourly thereafter till 24 h after operation. Children with an FLACC score of more than 4 were administered 15 mg/kg paracetamol syrup orally. Ramsay sedation score was assessed every 15 min till 3 h postoperatively (1 = anxiety and completely awake, 2 = completely awake, 3 = awake but drowsy, 4 = asleep but responsive to verbal commands, 5 = asleep but responsive to tactile stimulus, and 6 = asleep and not responsive to any stimulus).

Table 1

Faces, leg, activity, cry, consolability scale

Adverse effects including bradycardia (heart rate [HR] <60/min), hypotension (80% of baseline MAP), respiratory depression (SPO2 < _{95%), nausea, vomiting, and emergence agitation were documented. These adverse effects were treated with atropine 0.01–0.02 mg/kg, ephedrine 5 mg/kg and oxygen supplementation using oxygen mask, respectively. One week after the surgery, any evidence of wound dehiscence was noted.}

Statistical analysis

Statistical analysis was carried out using Stata Version 10 (Stata Corp., Houston, Texas, USA). After checking for the normality assumption, t-test for comparing means of two independent samples was used for comparing baseline continuous variables. Descriptive analysis was performed for all variables. Repeated-measures analysis of variance was used to compare continuous variables. Post hoc testing was performed with Scheffé's F-test. P < 0.05 was considered significant.

RESULTS

Demography

Four patients were excluded from the study due to inadequate caudal anesthesia. These patients required rescue analgesia after incision. The thirty patients in each group had no difference in relation to demographics (age, sex, weight, ASA status) and duration of surgery [Table 2].

Table 2

Demography and other clinical parameters

Mean arterial pressure

The mean MAP decreased in both groups significantly over 3 h [Figure 1]. The mean MAP in Group I was 65.57 ± 3.23 mmHg which decreased to 63.97 ± 3.18 mmHg over the 3 h. The mean MAP in Group II decreased from 64.83 ± 2.80 mmHg to 62.63 ± 2.37 mmHg. However, there was no statistical difference between the mean MAPs of both group.

Figure 1

Trend of mean arterial pressure in both groups over 3 h. Group I = Dexamethasone, Group II = Clonidine

Heart rate

The baseline HR in Group I was 105.7 ± 13.93 beats/min which decreased to 102.7 ± 13.00 beats/min over the 3 h. In Group II, the baseline HR decreased from 105.9 ± 13.52 to 95.33 ± 12.44 beats/min. The mean HR was statistically lower in Group II when compared to Group I [P = 0.0281, Figure 2].

Figure 2

Trend of heart rate in both groups over 3 h. Group I = Dexamethasone, Group II = Clonidine

Analgesia

There was significant prolongation of duration of analgesia in Group II (15 h) when compared to Group I (8 h) P < 0.001. Furthermore, the median of total analgesic top ups required in the first 24 h was significantly lower in Group II (1.3) when compared to Group I (2.5) [P < 0.001, Table 3].

Table 3

Analgesic requirement in the postoperative period

Faces Legs Activity Cry Consolability score

The average FLACC scores were lower in Group II than in Group I throughout the 24 h and this difference was statistically significant P < 0.001 [Figure 3].

Figure 3

Trend of average Faces Legs Activity Cry Consolability score in both groups over 24 h. Group I = Dexamethasone, Group II = Clonidine

Sedation score

Ramsay sedation score was significantly higher in Group II when compared to Group I over a period of 3 h [P < 0.001, Figure 4].

Figure 4

Trend of sedation scores over 3 h. Group I = Dexamethasone, Group II = Clonidine

Adverse effects

There was no statistically significant difference in the incidence of hypotension, vomiting, and wound dehiscence in both groups. Two patients in Group II had bradycardia when compared to no patients in Group I. This difference was not statistically significant (P > 0.05).

DISCUSSION

Our study shows that caudal dexamethasone is a good alternative to caudal clonidine with more stable hemodynamics and lesser sedation scores in the immediate postoperative period. Both dexamethasone and clonidine offer good analgesia postoperatively with the duration of analgesia being statistically more in clonidine.

Dexamethasone has been used as an analgesic through various routes. It has a direct local anesthetic action and also acts by inhibiting the transcription factor nuclear factor-kB (NF-kB) which is expressed in the nervous system.[11] Hence, epidural action is more due to its action on NF-kB by preventing central sensitization. Although there are controversies surrounding the use of dexamethasone perineurally, there are enough studies to prove otherwise.[121314151617] Till date, no significant adverse-effects have been reported for epidural dexamethasone. Complications like wound infection and postoperative bleeding have been documented with high-dose corticosteroids.[1819] We used low-dose dexamethasone (0.1 mg/kg) with no incidence of adverse effects. The duration of analgesia was increased up to 8 h in patients of the dexamethasone group. This is in accordance with the study done by Kim et al. wherein dexamethasone increased the duration of analgesia when added to ropivicaine.[6] The pain scores were significantly lower at 6 and 24 h. Clonidine is α2 agonist which was used previously as an antihypertensive. Its use has gradually increased in anesthesia practice as a premedicant, sedative, and adjuvant.[51819] Coadministration of clonidine with local anesthetic has shown to improve its efficacy in caudal and peripheral nerve blocks.[1920] Analgesic effect of clonidine is due to its direct action on the nociceptive neurons at spinal level or indirectly at the α2 receptors by crossing the blood brain barrier.[15] In this study, coadministration of clonidine along with bupivacaine increased the duration of analgesia significantly ranging from 13 to 16 h. This increase is similar to other studies where the duration had increased significantly.[14]

Hypotension and bradycardia are two common side effects of neuraxial clonidine. This is attributed to the stimulation of α2 inhibitory neurones in the medullary vasomotor center of the brainstem causing a reduction in sympathetic outflow.[2122] These results are more pronounced in adults and with higher doses of clonidine. In this study, HR was lower in the clonidine group. Two patients suffered from bradycardia where atropine had to be administered. MAP was comparable in both groups.

Sedation after epidural clonidine results from activation of α2-adrenoceptors in the locus coeruleus, an important modulator of vigilance. This suppresses the spontaneous firing rate of the nucleus, thereby resulting in increased activity of inhibitory interneurones such as γ-aminobutyric acidergic pathways to produce central nervous system depression.[22] In this study, the sedation scores were higher in the clonidine group in the immediate postoperative period. Patients who were administered dexamethasone had lesser sedation score which was desirable by the parents as the child was comfortable and awake. Similar results were found in a study done by Singh et al. where they had used caudal clonidine for pediatric patients undergoing exploratory laparotomy.[23]

There have been reports of respiratory depression due to caudal clonidine. None of our patients suffered from this adverse effect.[24] These are solitary reports, and the effect is more pronounced in neonates. There are studies which show an increase in the incidence of postoperative nausea vomiting after the use of caudal clonidine (2 µg/kg).[25] We used a lower dose and did not encounter this adverse effect. There have been no reports of respiratory depression or vomiting after caudal dexamethasone nor did we encounter it in our test group.

Clonidine has been used at various doses caudally: 1–5 µg/kg. We chose a dose of 1 µg/kg as it is associated with longer duration of analgesia[2627] and less postoperative emergence agitation. The dose of dexamethasone was chosen based on a study done earlier by Kim et al.[6]

The strengths of the study include a standardized method of premedication, anesthesia, and analgesia. FLACC scale was chosen for pain assessment as it is an objective, simple, reliable, and valid scale.[28] The pain was assessed till 24 h postoperatively. This is in contrast to other studies where pain assessment was done only till 6 h.[29] In this study, pain assessment was done by health professional and did not involve the parents. This was to prevent any inconsistency or bias when medicating the kids.

There are few limitations of our study. First, it is a single-centric study with a small sample size. Second, the analgesic role of dexamethasone through systemic absorption cannot be completely excluded from our study design. In a study done by Hong et al. intravenous dexamethasone (0.5 mg/kg) prolonged the duration of analgesia of caudal ropivicaine after pediatric infraumbilical surgeries. Hence, a third group using intravenous dexamethasone could have been included in this study.[30] Despite these limitations, our study like few other studies clearly shows that caudal dexamethasone prolongs the duration of analgesia at a low dose given caudally in pediatric patients undergoing urogenital surgeries.[3132]

CONCLUSION

Caudal dexamethasone (0.1 mg/kg) is a good alternative to caudal clonidine (1 µg/kg) due to good pain control, stable hemodynamics, and less postoperative sedation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.