Introduction
Postoperative pain is often underestimated in children although it is known that pain pathways are developed by 30th week of gestation.1 Cleft lip is one of the condition which requires early surgical treatment.2 Bilateral infra-orbital nerve block is proved to produce good postoperative analgesia in patients undergoing cleft lip repair surgery.3 The advantage of infra- orbital nerve block is that it reduces the use of opioid analgesics which may lead to respiratory depression.4 Since single dose of local anaesthetic may have limited duration of action, numerous additives have been used to prolong the duration of postoperative analgesia. Dexmedetomidine, an alpha-2 agonist has been proved effective in producing prolonged postoperative analgesia when added in peripheral nerve blocks.6, 5 Hence we conducted t his prospective, randomized, double-blind study to compare the efficacy of dexmeditomidine as an adjuvant for bupivacaine in infra-orbital block in pediatric patients for cleft lip repair. The primary objective of this study was to compare the mean postoperative duration of analgesia defined as the time from the end of successful block to the time of first rescue analgesic. The number of patients requiring the rescue analgesic was also recorded. The secondary outcomes were to evaluate intra-operative and post-operative hemodynamic parameters and postoperative sedation score.
Materials and Methods
After obtaining the institutional ethical committe clearance, 80 patients belonging to American society of Anaesthesiologist Physical status(ASA) grade 1 & 2 of either sex, aged 3 months to 1 year scheduled for cleft lip rep air were considered in the study. The exclusion criteria included ASA grade 3 &4, failure to obtain consent from parents, local infection at the site of injection, associated congenital anomalies, history of upper or lower airway problems and known coagulation disorders.
Pre-anesthetic evaluation was done a day prior to the surgery involving a complete assessment of the patient with required investigations. Preoperative fasting was followed according to the standard guidelines. After obtaining written informed consent from parents, patients were randomly allocated to two groups (n=40) using computer-generated randomization numbers with a closed-seal envelope. In both the group, infra-orbital nerve block was performed bilaterally by landmark technique using 1ml of solution on each side. The B group received bupivacaine 0.25%, whereas the D group received bupivacaine 0.25% with 0.5µg/kg of Dexmedetomidine (Dextomed, neon).
General anaesthesia was induced by the inhalation of 8% sevoflurane in 100% oxygen via a face mask with spontaneous ventilation. Monitors were connected to monitor heart rate (HR), pulse oximeter (SpO2), non invasive blood pressure (NIBP), Electrocardiogram(ECG), End tidal carbon dioxide (ETCO2), body temperature and anaesthetic gas monitor (AGM). An appropriate size peripheral intravenous (IV) cannula was secured in all the patients. The patients received premedication as per the institutional protocol. No additional sedatives and analgesics were administered. Injection propofol 2mg/ kg was given IV to facilitate Oral endotracheal intubation. After successful intubation the endotracheal tube was secured centrally over the lower lip. As per the randomisation infra- orbital block was performed bilaterally by landmark technique by the anaesthesiologist blinded to the nature of the drug injected. Anaesthesia was maintained with 1 minimum alveolar concentration of sevoflurane in a 50% oxygen – nitrous oxide mixture with spontaneous ventilation. Isolyte -P solution was infused at a calculated rate according to the patients weight. The block was considered successful when the HR remained stable (not > 20% increase in heart rate (HR) or mean arterial blood pressure) compared to basal HR before the incision. If the block failed, IV fentanyl 1μg/kg was administered. At the end of the surgery and before extubation, paracetamol suppository at a dose of 10mg/kg was administered to all the patients. Patients were extubated in the operating room after pharyngeal aspiration and recovery of airway-protective reflexes.
The FLACC scale was used for assessment of postoperative pain.7 The score was interpreted as: 0: Relaxed, comfortable 1-3: Mild discomfort 4-6: Moderate pain 7-10: Severe pain or discomfort or both. The pain score was assessed every 10 minutes for one hour in post anaesthesia care unit and then every 3 h for 24 h postoperatively in surgical ward. When the pain score exceeded 4, infusion of paracetamol at a dose of 10mg/ kg was given over ten minutes. The time from the administration of block to the first analgesic request and the number of patients who received pain medication during the first 24-h were recorded. Postoperative sedation was evaluated hourly by Richmond scale for the first 3 h.8
Using the results obtained from previous studies and assuming an alpha error of 0.05 and beta error of 0.2 (power of the study 80%), a sample size of 40 patients per group was calculated. Data were presented as mean and standard deviation, median and range or numbers, and percentages. For normally distributed data, unpaired t-test was used to compare between mean values of both groups. For pain and sedation scores, Mann–Whitney U-test was used. Fisher’s exact test was used for comparison of categorical data. P ≤ 0.05 was considered as the level of statistical significance.
Results
The demographic data was comparable in both groups [Table 1]. The mean duration of postoperative analgesia was 496± 28.26 minutes and 733±49.15 minutes in Group B and Group D respectively [Table 2]. The dexmedetomidine group showed significantly prolonged duration of analgesia when compared to bupivacaine alone group(p=0.001). In Group B, 36 patients required rescue analgesics whereas in Group D 8 patients required rescue analgesics which was statistically significant. The number of times of rescue analgesics in bupivacaine group (Group B) and in and dexmedetomidine group (Group D) was 3 and 1 respectively, which was statistically significant (Figure 1). The intraoperative and postoperative HR was similar in both groups (Figure 2). The sedation score in the postoperative period was comparable in both groups.
Table 1
Patient demographic data
Table 2
| Parameter | Group B | Group D | P value |
| Number of patients requiring rescue analgesia | 36 | 8 | 0.025* |
| Duration of analgesia (mean ± SD) (minutes) | 496±28.26 | 733±49.15 | 0.001* |
Comparison of analgesic requirements
Discussion
Peripheral nerve blocks are considered as a good intraoperative and postoperative analgesic technique with limited adverse effects. The drawback of regional block is its lesser duration of action when plain local anaesthetic is used. In order to prolong the duration of nerve blocks, many additives have been evaluated. Dexmedetomidine, an α2-receptor agonist has also been evaluated for its effectiveness in prolonging the duration of postoperative analgesia.13, 12, 11, 10, 9
Various studies in adults suggested that dexmedetomidine when added to brachial plexus block significantly prolonged the duration of analgesia by at least 63% or from 7.5h to 11.9h. 14 However, studies evaluating the effectiveness of dexmedetomidine in peripheral nerve block in children are not many. Therefore we conducted this study to evaluate the effect of 0.5 µg/kg dexmedetomidine in infra - orbital nerve block in children undergoing cleft lip repair surgery. The mechanism of action of dexmedetomidine include central analgesia, vasoconstriction, and anti-inflammatory effects.15 However, none of these mechanisms can explain fully the synergistic effect of α2-adrenoceptor agonists when added to a local anaesthetic in peripheral nerve blocks. Possible mechanisms explained by few studies were that dexmedetomidine induces vasoconstriction through an action on α2 adrenoceptors or it produces analgesia peripherally by reducing nor - epinephrine release and increasing the potassium conduction in C and A‑delta neurons responsible for passage of pain stimulus, whereas it produces analgesia and sedation centrally by inhibition of substance P release in the nociceptive pathway at the level of the dorsal root ganglia and locus coeruleus.18, 17, 16
Our study results showed that 0.5µg/kg dexmedetoidine added to bupivacaine increased the duration of analgesia by 3.95 hours when compared to plain bupivacaine (Group B: 496±28.26;Group D:733±49.15). The number of patients who requested for rescue analgesics were less in Group D (20 %) as compared to Group B (90%). This was in consistent with the results reported by Karan et al.,.19 The authors used dexmedetomidine at a dose of 1 μg /kg added to ropivacaine in ultrasound-guided ilioinguinal nerve block. They reported that the duration of analgesia in group receiving dexmedetomidine–ropivacaine mixture was 16.17 ± 0.77 h, and in group receiving plain ropivacaine was 6.9 ± 1.01 h which was statistically significant. They also reported that in dexmedetomidine group only 16.67% of patients required rescue analgesic when compared to plain ropivacaine group. Similarly El‑Sayed and El Motlb 20 conducted a study wherein the authors compared dexmedetomidine and dexamethasone as adjuvants to local anaesthetic. They reported that the time of first request of analgesic was 20% longer (P=0.0001) in dexmedetomidine group (689 ± 58.2) compared to dexamethasone group (546 ± 41.6). Obayah et al.,21 also in their study reported that when dexmedetomidine is used at a dose of 1µg/kg with bupivacaine increased the duration of analgesia up to 21±24 h. In a study by Mangal et al., 1µg/kg of dexmedetomdine with ropivaciane in ultrasound guided supraclavicular block showed significant prolongation of analgesia (704.77 ± 178.414 min).22 In consistent with these studies various other studies also concluded that use of 1µg/kg dexmedetomidine produced effective and significantly prolonged analgesia. 24, 23
In our study, we also recorded the heart rate intraoperatively and postoperatively. There was no significant difference between the groups. The heart rate remained on lower side in dexmedetomidine group but none of the patients required intervention. The sedation scores were equal in both groups. In dexmedetomidine group patients were comfortable and easily arousable but was statistically not significant.