Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 7  |  Issue : 1  |  Page : 12-18

Caudal levobupivacaine-fentanyl achieves stress response attenuation and early extubation in pediatric cardiac surgery


Department of Anesthesia and Intensive Care, Ain Shams University, Cairo, Egypt

Date of Submission13-Jun-2013
Date of Acceptance06-Jul-2013
Date of Web Publication31-May-2014

Correspondence Address:
Rasha S Bondok
MD, Department of Anesthesia and Intensive Care, Ain Shams University, 33 Hassan Maamoun st Nasr City, Cairo 11391
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.128391

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  Abstract 

Background
Adequate postoperative analgesia coupled with stress response attenuation in children are vital parts of perioperative care. The present study was carried out to evaluate the efficacy of caudal levobupivacaine and fentanyl combination on stress response, postoperative analgesia, and extubation in pediatric cardiac surgery.
Patients and methods
Fifty patients, ASA II-III, 2-8 years old, undergoing elective cardiac surgical repair were allocated randomly to two groups: group L received 0.125% levobupivacaine at a volume of 1.8 ml/kg; whereas group LF received 0.125% levobupivacaine plus fentanyl 1 μg/kg up to a volume of 1.8 ml/kg.
Results
Intraoperative fentanyl consumption was significantly low in group LF compared with group L [1.56 ± 0.64 vs. 2.76 ± 0.52 μg/kg in group LF and group L, respectively, 95% confident interval (CI) 0.862-1.538; P < 0.001]. Extubation time was significantly shorter in group LF 2.24 ± 0.87 h compared with group L (5.84 ± 1.07 h, 95% CI 2.94 − 4.25; P < 0.001). The duration of postoperative analgesia following extubation was significantly longer in group LF 4.56 ± 0.96 h compared with group L (2.21 ± 0.73 h, 95% CI 2.99 − 1.89; P < 0.001). The serum cortisol levels were significantly higher in group L than group LF at T2, after sternotomy (21.92 ± 8.39 vs. 13.40 ± 5.48 μg/dl; P < 0.001); T3, after termination of cardiopulmonary bypass (32.32 ± 6.82 vs. 20.82 ± 5.85 μg/dl; P < 0.001); and T5, at extubation (36.64 ± 9.97 vs. 25.84 ± 9.16 μg/dl; P < 0.01). Blood glucose levels increased significantly relative to baseline in both groups, but the increase was significantly lower in group LF compared with group L.
Conclusion
Caudal levobupivacaine-fentanyl is effective in pediatric cardiac surgery; it attenuates the stress response with concomitant stabilization of hemodynamics. In addition, it provides adequate postoperative analgesia and early extubation.

Keywords: Cardiac, caudal, levobupivacaine, pediatric


How to cite this article:
Al-Taher WA, Bondok RS. Caudal levobupivacaine-fentanyl achieves stress response attenuation and early extubation in pediatric cardiac surgery. Ain-Shams J Anaesthesiol 2014;7:12-8

How to cite this URL:
Al-Taher WA, Bondok RS. Caudal levobupivacaine-fentanyl achieves stress response attenuation and early extubation in pediatric cardiac surgery. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Oct 25];7:12-8. Available from: http://www.asja.eg.net/text.asp?2014/7/1/12/128391


  Introduction Top


Pain following cardiac surgery may be intense, originating from various sources including the incision, intraoperative tissue retraction and dissection, vascular cannulation sites, chest tubes, and stainless-steel wire sutures [1]. Inadequate analgesia during the postoperative period leads to uninhibited stress response, which leads to many adverse hemodynamic (tachycardia, hypertension), metabolic (increased catabolism), immunologic (impaired immune response), and hemostatic alteration (platelet activation) [1]. Adequate postoperative analgesia coupled with stress response attenuation in children are vital parts of perioperative care and can potentially decrease morbidity and enhance health-related quality of life [2]. Caudal epidural block is a reliable, safe, and effective technique for intraoperative as well as postoperative analgesia in pediatric cardiac patients [3], allowing early tracheal extubation, thereby minimizing pulmonary complications, reducing pediatric ICU length of stay, and possibly decreasing hospital length of stay [1]. Levobupivacaine, a new long-acting amide local anesthetic, is the S (−)-isomer of the racemic buivacaine. Unlike bupivacaine, it is less toxic to the central nervous system and less likely to cause myocardial depression and fatal arrhythmias [4]. As the main disadvantage of the single-shot caudal technique is its short duration of action, prolongation of caudal analgesia has been achieved by the addition of various additives [1],[5],[6],[7]. Neuroaxial administration of opioids results in excellent long-lasting analgesia when combined with local anesthetics, leading to a synergistic effect with an increase in the duration and quality of the regional anesthetic [3],[8]. Fentanyl is one of the common opioid additives with the least likelihood to cause respiratory depression when administered caudally [5].

The aim of this study was to investigate the effect of caudally administered levobupivacaine-fentanyl on perioperative stress response, postoperative analgesia, and extubation in pediatric cardiac surgery.


  Patients and methods Top


This study was a prospective, blinded, randomized, comparative study carried out in the Pediatric Cardiac Surgery Unit of Ain Shams University hospitals from July 2009 to January 2013. After obtaining Research Ethics Committee approval at the Faculty of Medicine, Ain Shams University, Egypt (FMASU REC), and written informed parental/guardian consent, 50 pediatric patients, aged 2-8 years, ASA II-III, scheduled for elective surgical repair of ventricular septal defect or atrial septal defect, were included in the study. Exclusion criteria included emergency cardiac surgery, parental refusal, previous cardiac surgery, hemodynamic instability, intraoperative deep hypothermia, skin or soft tissue infection, anticoagulant therapy, platelet counts less than 100 × 10 3 /μl, bleeding diathesis, abnormalities of the sacrum or vertebral column, and neuromuscular or convulsive disorders. Children on steroid therapy or diabetic children were also excluded. The study drugs were prepared by the coordinator of the study and the anesthetist who was in charge of the patients during the operation was blinded to group allocation. The anesthetist in charge performed the general anesthesia, caudal block, clinical care, and data collection. The children were assigned randomly to two groups using a computer-generated random number assignment: the levobupivacaine group (group L) and the levobupivacaine-fentanyl group (group LF) for caudal block. All children were fasted for at least 6 h before the procedure. Intake of clear fluids was allowed up to 2 h before induction of anesthesia. All patients received oral premedication with 0.25 mg/kg midazolam 30 min before separation from parents. All patients were anesthetized with the same technique. On arrival to the operating room, the child was transferred to the operating theater and placed on a warming blanket. Noninvasive ECG, peripheral oxygen saturation, systolic, diastolic and mean arterial pressure (MAP), and core temperature monitoring were recorded by a Drager Primus Infinity Delta Monitor (Drδger Medical, Lübeck, Germany) and baseline values were noted for each patient. Anesthesia was induced using 6 l/min of O 2 100% with sevoflurane 8 vol% (Primus; Drδger Medical). After achieving adequate depth of anesthesia, a 22 or 24 G cannula as appropriate was inserted into a peripheral vein and 10 μg/kg fentanyl was administered intravenously, sevoflurane was titrated to 2 vol% as appropriate. Appropriate size for age endotracheal intubation was facilitated with 0.15 mg/kg intravenous pancuronium using an appropriately sized uncuffed tracheal tube. Anesthesia was maintained with 1.5-2 vol% sevoflurane, titrated to the child's anesthetic requirement, in an oxygen-air mixture. Additional boluses of intravenous fentanyl 1 μg/kg were administered if MAP and heart rate (HR) increased more than 15% above baseline. Patients were mechanically ventilated with oxygen-air, FiO 2 of 0.6, to maintain normocapnea. A 20 G femoral arterial cannula was inserted and connected to a transducer for invasive arterial blood pressure monitoring and arterial blood sampling for blood gas analysis. The patients were then positioned in 15° Trendelenberg position; central venous cannulation was performed through the right internal jugular vein for continuous central venous pressure monitoring and infusion of medications. A urinary catheter was inserted by the surgeon using the appropriate size according to the patient's age and weight. After securing the endotracheal tube and vascular catheters, patients were placed in the left lateral decubitus position. The caudal block was performed under aseptic conditions. A 22-G short-bevel needle was inserted through the sacrococcygeal membrane until loss of resistance was detected, followed by gentle aspiration to detect absence of either cerebrospinal fluid or blood. One of two study treatments was then administered on the basis of the patient's weight into the caudal space. The total volume was administered over not less than one minute. Group L received 0.125% levobupivacaine [Chirocaine 0.25% (2.5 mg/ml); Abbott, Nycomed, Pharma, Elverum, Norway] at a volume of 1.8 ml/kg, whereas group LF received 0.125% levobupivacaine plus fentanyl (Fentanyl-Janssen, 2 ml, 50 μg/ml, Janssen-Cilag NV, Beerse, Belgium) 1 μg/kg to a volume of 1.8 ml/kg.

All patients received 5-6 ml/kg of lactated Ringer's solution before initiating the cardiopulmonary bypass (CPB). Median sternotomy was performed in all patients. After at least 10 min of caudal block, heparin 3 mg/kg was administered. The CPB circuit was primed with lactated Ringer's solution supplemented with heparin and fresh whole blood to obtain a hematocrit between 25 and −30%. Once activated clotting time reached at least 480 s, CPB was initiated. The aorta was clamped and cold blood cardioplegia 20 ml/kg was administered into the aortic root and the patient was cooled to 32-33°C. MAP was maintained between 30 and 65 mmHg during CPB. Aortic cross-clamp time and total bypass time were recorded.

At the end of the cardiac procedure, rewarming was started and the aortic cross-clamp was removed. After return of spontaneous normal sinus rhythm, ventilation was started, hemodynamics and arterial blood gases were stabilized, and patients were weaned from CPB at 36.5-37°C. Protamine was administered to reverse heparin. The patient was transferred to the ICU. The ICU staff were blind to the study treatment group. Before extubation, intravenous supplement fentanyl 1 μg/kg was administered every hour if MAP or HR increased above 15% of baseline. The criteria for extubation were adequate level of consciousness, adequate airway reflexes, hemodynamic stability, normothermia, absence of arrhythmias, mediastinal drainage greater than 1 ml/kg over 30 min, and acceptable blood gas analysis (pH>7.30, arterial oxygen tension >60 mmHg, and arterial carbon dioxide tension ≤45 mm Hg) at an inspired oxygen fraction of 0.4. Extubation time was recorded for all patients; this was defined as time from the end of surgery till removal of the endotracheal tube.

A Modified Objective Pain Score (MOPS) to evaluate postoperative pain in children was used [9]. Pain scores were assessed by the intensivist experienced with the use of MOPS. The scale uses five criteria: crying, movement, agitation, posture, and verbal. Each criterion was assigned a score of 0-2, with 2 being the worst, to yield a total score of 0-10. Postoperative pain was assessed every 30 min for the first 2 h following extubation: T1; every 2 h for 6 h: T2, T3 T4; then at 12 h: T5; 18 h: T6; and 24 h: T7 postoperatively. Intravenous supplement fentanyl 1 μg/kg was administered if a MOPS score was at least 4 and was recorded. Duration of analgesia was defined as the time from caudal injection to the first complaint of pain (Pain Score ≥4) necessitating the need for rescue analgesia. Duration of postoperative analgesia was defined as the time from extubation to the first complaint of pain (Pain Score ≥4) necessitating the need for rescue analgesia. Total fentanyl consumption during the first 24 postoperative hours after extubation was also recorded.

The HR and MAP were recorded at baseline soon after induction of anesthesia (T0), 10 min after caudal injection (T1), 10 min after sternotomy (T2), after termination of CPB (T3), after sternal closure (T4), and at extubation (T5). Arterial blood was sampled at T0-T2-T3 and T5 for serum cortisol and blood glucose measurement. Cortisol was assessed using a Stat Fax 2100-Microplate Reader, (Awareness Technology, Inc, Palm City, USA), a microtiter enzyme-linked immunosorbent assay. Blood glucose was measured using a Blood Glucometer (Advantage Health Service Inc., Horsham, Pennsylvania, USA). Any adverse effects such as hypotension, arrhythmias, respiratory depression (PCO 2 >50 mmHg, respiratory rate <10/min), nausea and vomiting, pruritis, neurological deficit, or need for re-exploration were recorded.

Aortic cross-clamping time, duration of cardiopulmonary bypass, total duration of surgery, and length of stay in ICU were also recorded.

Statistical analysis

A sample size of 21 patients in each study group was calculated to detect a difference in serum cortisol level of 2 SD with a power of 80% and an α error of 5%. It was assumed that the study dropout rate would be ∼20% and, therefore, a sample of 25 patients in each group was recruited. Data were collected, coded, tabulated, and then analyzed using the Statistical Package for Social Sciences, version 20 (SPSS Inc., Chicago, Illinois, USA). Normality of quantitative data distribution was tested using the Shapiro-Wilk test. Normally distributed numerical data were presented as mean ± SD, whereas categorical variables were presented as percentages and numbers.

Between-groups comparisons of numerical variables were performed by one-way analysis of variance. Tukey's honestly significant difference test and the Mann-Whitney U-test were used as a post-hoc test if indicated. Comparisons of categorical variables were performed using the χ2 -test (with Yates correction if needed). All reported P values are two tailed. A P value of less than 0.05 was considered significant.


  Results Top


All enrolled patients (25 in each group) completed the study. There were no differences between the groups in demographic data [Table 1]. The CPB and aortic cross-clamp times as well as duration of surgery and anesthesia were comparable [Table 1].
Table 1: Demographic data and operative details

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Hemodynamic parameters, HR, and MAP were comparable between both groups after induction of General anesthesia (GA) [Table 2] and [Figure 1] and [Figure 2]. After caudal block, HR and MAP decreased significantly in both groups compared with baseline values; HR and MAP were significantly low in group LF compared with group L at time intervals T2-T5 [Table 2] and [Figure 1] and [Figure 2].
Figure 1:

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Figure 2:

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Table 2: Hemodynamic changes

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Intraoperative fentanyl consumption was significantly low in group LF compared with group L [1.56 ± 0.64 vs. 2.76 ± 0.52 μg/kg in group LF and group L, respectively, 95% confident interval (CI) 0.862-1.538; P < 0.001].

Extubation time was significantly shorter in group LF 2.24 ± 0.87 h compared with group L 5.84 ± 1.07 h, 95% CI 2.94 − 4.25; P < 0.001; [Table 3]. Postoperative fentanyl consumption until time to extubation was significantly low in group LF 0.47 ± 0.56 μg/kg compared with group L 1.20 ± 0.65 μg/kg, 95% CI 0.397-1.051; P < 0.001.
Table 3: Postoperative data

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During the first 4 h T1 and T2 following extubation, patients in group LF had lower pain scores compared with group L (P < 0.001; [Figure 3]). The duration of analgesia was significantly longer in group LF compared with group L (13.56 ± 1.52 h vs. 7.67 ± 1.19 h, respectively, 95% CI 4.94-6.87; P < 0.001). The duration of postoperative analgesia following extubation was significantly longer in group LF 4.56 ± 0.96 h compared with group L 2.21 ± 0.73 h, 95% CI 2.99-1.89; P < 0.001; [Table 3].
Figure 3:

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The number of patients requiring rescue analgesia was significantly low in group LF (9 patients, 36%) compared with group L (16 patients, 64%) (P < 0.001).

Baseline levels of cortisol were similar in both groups (10.48 ± 5.85 μg/dl in group L vs. 9.28 ± 4.16 μg/dl in group LF; P = 0.424). The serum cortisol levels were significantly higher in group L than group LF at T2, after sternotomy (21.92 ± 8.39 vs. 13.40 ± 5.48 μg/dl; P < 0.001); T3, after termination of CPB (32.32 ± 6.82 vs. 20.82 ± 5.85 μg/dl; P < 0.001); and T5, at extubation (36.64 ± 9.97 vs. 25.84 ± 9.16 μg/dl; P < 0.01) [Figure 4]
Figure 4:

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In group L, a significant increase in cortisol levels was observed after sternotomy, after termination of CPB, and at extubation compared with both baseline values (P < 0.001).

Blood glucose levels were comparable between the two groups at baseline (P = 0.677). These values increased significantly relative to baseline in both groups, but the increase was significantly lower in group LF compared with group L [Table 4].
Table 4: Blood glucose levels (mg/dl)

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No neurological deficit was found in any patient; there were no events of respiratory depression, nausea, or vomiting. However, four patients in group LF had pruritis 16% (P = 0.043). ICU stay was comparable in both groups 77.64 ± 5.31 and 74.80 ± 7.09 in group L and group LF, respectively (P = 0.192).


  Discussion Top


The present study demonstrated the administration of a single-shot caudal levobupivacaine-fentanyl in attenuating the stress response reflected through maintaining lower serum cortisol and blood glucose levels with concomitant stabilization of MAP and HR in pediatric cardiac surgery. In addition, it yielded better postoperative analgesia and early endotracheal extubation.

Surgery induces a series of neuroendocrine hormonal and metabolic changes referred to as 'the stress response' [2]. The potential clinical benefits of attenuating the perioperative surgical stress response simply through attaining adequate analgesia have received considerable attention [1]. The magnitude and duration of responses are proportional to the surgical injury, which, if not attenuated, may result in postoperative morbidity and longer ICU stay [10]. Regional anesthetic techniques are useful adjuncts to GA in children undergoing cardiac surgery [3]. In addition to reliable analgesia, the epidural anesthesia produces thoracic cardiac sympathectomy, thereby improving the myocardial oxygen supply-demand balance and attenuating stress response in patients undergoing cardiac surgery [1]. Caudal epidural analgesia using a mixture of local anesthesia with opioid has been used increasingly [5-8]. Analgesia following opioid instillation in the epidural space is because of diffusion of opioids across the dura to the μ-opioid receptors in substantia gelatinosa of the spinal cord as well as systemic absorption [11]. The dural penetration of epidural opioids depends on their lipid solubility, molecular weight, and dissociation constant [12]. Fentanyl has a high lipid solubility, which makes it less likely to migrate to the brain stem, and is thereby considered safe, with the least incidence of respiratory depression [11]. There were no events of respiratory depression in either of our treatment groups. In this study, the combination of 0.125% levobupivacaine and 1 μg/kg fentanyl in a 1.8 ml/kg volume provided much longer postoperative analgesia compared with administration of 1.8 ml/kg 0.125% levobupivacaine alone. The number of patients requiring rescue analgesia was greater with levobupivacaine, 64% compared with 36% in the levobupivacaine-fentanyl group. Single-shot caudal anesthesia was administered to avoid the possibility of hematoma formation, which may probably occur with epidural catheter placement in this category of patients [13].

Our rationale of combining epidural opioids and local anesthetics was to lower doses of each agent with simultaneous administration of effective analgesia, thereby reducing the side effects associated with the use of each drug alone. Epidural opioids act by inhibiting the release of substance P in the dorsal horn of the spinal cord, whereas local anesthetics block the transmission impulses at the level of the nerve axonal membrane. These two distinctive actions contribute toward a synergistic effect in producing analgesia [6].

The rationale for choosing levobupivacaine at a concentration of 0.125% and a volume of 1.8 ml/kg in this present study was based on the following: first, as racemic bupivacaine and levobupivacaine are considered equipotent [4], we decided to use the concentration of 0.125% that has been investigated previously [14]. Second, reports on the effect of caudal epidural analgesia reducing pain and stress response in pediatric cardiac surgery are controversial [1]. The site of surgical incision is far from the regional technique; however, it was shown that if an appropriate volume of the least effective concentration of local anesthetic combined with an effective adjunct is used, effective analgesia can be achieved with minimal side effects [15]. Rojas-Perez et al. [16] concluded that a single-shot caudal bupivacaine at a volume of 1.6 ml/kg yields a preoperative analgesic level to a thoracic 3 and or 4 segment, which is insufficient for cardiac surgical procedures, whereas a volume of 1.8 ml/kg was found to produce an analgesic level reaching the thoracic 1 segment.

The use of single-shot caudal opioids with or without local anesthetics has been reported in an attempt to minimize the use of intravenous opioid administration during pediatric cardiac surgery [3] and thereby facilitate early extubation [17]. Intravenous opioids offer hemodynamic stability in these high-risk patients; however, the administration of high intravenous opioid doses requires prolonged mechanical ventilation in the postoperative ICU setting following cardiac surgery [18]. The present study showed significant low intraoperative and postoperative intravenous fentanyl requirement that thereby facilitated early endotracheal extubation in the levobupivacaine-fentanyl group. These observations were similar to other studies in which postinduction placement of caudal opioids with local anesthetics in pediatric patients undergoing congenital heart disease repair requiring CPB showed a reduced intravenous analgesic requirement and earlier extubation time [6]. In a retrospective study on pediatric patients undergoing congenital heart surgery who were administered caudal analgesia with morphine with limited doses of intravenous fentanyl, the majority successful early extubation in the recovery room [18].

Apart from providing superior analgesia, epidural opioids have been shown to blunt the stress response to surgery and CPB [19]. In the present study, serum cortisol levels were significantly higher with caudal levobupivacaine alone, which was seen after sternotomy, after termination of CPB, and at extubation. The blood glucose levels increased in both groups after termination of CPB; this increase could partly be because of the administration of packed red blood cells preserved in citrate-phosphate-dextrose-adenine solution that was added to the prime. Nevertheless, blood glucose values were significantly higher in the levobupivacaine compared with caudal levobupivacaine-fentanyl, which persisted till extubation. In this study, the addition of fentanyl to levobupivacaine contributed toward attenuating the glycemic response. Studies have reported significant differences in the metabolic response with the addition of caudal/intrathecal opioids [6],[20]. Despite increased intraoperative intravenous fentanyl consumption in the levobupivacaine group, the hemodynamic parameters were more stable with caudal levobupivacaine-fentanyl. In cardiac surgery, intravenous fentanyl, even at large doses, was found to cause minimal hemodynamic changes [21]. This was attributed to the unpredictable pharmacokinetic properties of fentanyl during CPB as fentanyl has been found to have a strong tendency to bind to the surfaces of the CPB circuit, in addition to hemodilution and drug sequestration, which further decreases its plasma concentration [22].

In conclusion, single-shot caudal levobupivacaine-fentanyl is effective in pediatric cardiac surgery; it attenuates the stress response, with concomitant stabilization of hemodynamics. In addition, it provides adequate postoperative analgesia and early extubation.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

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4.Mc leod GA, Burk D. Levobupivacaine. Anaesthesia 2001; 56:331-341.  Back to cited text no. 4
    
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14.Tarkase AS, Sirsat VS, Chauhan SD, Nikam GK, Kulkarni AG, Pachore PJ, et al. Caudal epidural anaesthesia in children: a comparative study of three different concentrations of levobupivacaine. Int J Basic Appl Med Sci 2012; 2:237-242.  Back to cited text no. 14
    
15.Gaitini LA, Somri M, Vaida SJ, Yanovski B, Mogilner G, Sabo E, et al. Does the addition of fentanyl to bupivacaine in caudal epidural block have an effect on the plasma level of catecholaminen in children? Anesth Analg 2000; 90:1029-1033.  Back to cited text no. 15
    
16.Rojas-Perez E, Castillo-Zamora C, Nava-Ocampo AA. A randomized trial of caudal block with bupivacaine 4 mg.kg−1 (1.8 ml.kg−1 ) plus morphine (150 μg.kg−1 ) vs general anaesthesia with fentanyl for cardiac surgery. Paediatr Anaesth 2003; 13:311-317.  Back to cited text no. 16
    
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20.Nasr DA, Abdelhamid HM. The efficacy of caudal dexmedetomidine on stress reponse and postoperative pain in pediatric cardiac surgery. Ann Card Anaesth 2013; 16:109-114.  Back to cited text no. 20
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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