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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 12  |  Issue : 1  |  Page : 27-33
Caudal epidural sufentanil and bupivacaine decreases stress response in paediatric cardiac surgery

1 Department of Cardiac Anaesthesia, Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India
2 Department of Cardiothoracic Surgery, Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India
3 Department of Cardiac Biochemistry, Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India

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Date of Submission01-Oct-2008
Date of Acceptance12-Dec-2008


Surgery and anaesthesia are known to cause stress response. Attenuation of stress response can decrease morbidity, postoperative hospital length of stay and, thus, cost. Intrathecal and epidural techniques produce reliable analgesia in patients undergoing surgery along with stress response attenuation. The present study was undertaken to evaluate the efficacy of caudal sufentanil and bupivacaine combination on perioperative stress response in paediatric patients undergoing open heart surgery. Thirty patients (ASA grade II-III) undergoing elective corrective cardiac surgery for acyanotic congenital heart disease, were randomly allocated to two groups. In group GA ( n = 15), patients received balanced general anaesthesia. In group GC ( n = 15), in addition to general anaesthesia, caudal block with bupivacaine and sufentanil combination was given after endotracheal intubation. Monitoring included electrocardiography, invasive arterial pressure, end-tidal carbon dioxide, pulse oximetry, arterial blood gases including serum electrolytes, blood glucose, serum cortisol, urine output, central venous pressure and temperature. Haemodynamic responses in both groups were statistically similar. Serum cortisol levels were significantly lower in GC group than GA group ( P < 0.05) after sternotomy (9.87.5 vs. 34.7427.35), on cardiopulmonary bypass (CPB) (12.17 6.2 vs. 35.36 24.15), after sternal closure (14.03 5.1 vs. 37.62 20.69), 4 hours (26.64 14.61 vs. 37.62 9.13) and 24 hours (14.30 8.11 vs. 28.12 16.31) after intubation. Blood glucose levels were significantly higher in GA group as compared to GC group at sternal closure (277.46 77.25 vs.197.73 42.17) and 4 hours (255.26 73.73 vs. 185.26 57.41) after intubation ( P < 0.05).
To conclude, supplementation of caudal epidural bupivacaine and sufentanil could effectively attenuate the stress response in paediatric patients undergoing cardiac surgery under CPB in acyanotic congenital heart anomaly.

Keywords: Caudal, CPB, paediatric, stress response

How to cite this article:
Sendasgupta C, Makhija N, Kiran U, Choudhary SK, Lakshmy R, Das SN. Caudal epidural sufentanil and bupivacaine decreases stress response in paediatric cardiac surgery. Ann Card Anaesth 2009;12:27-33

How to cite this URL:
Sendasgupta C, Makhija N, Kiran U, Choudhary SK, Lakshmy R, Das SN. Caudal epidural sufentanil and bupivacaine decreases stress response in paediatric cardiac surgery. Ann Card Anaesth [serial online] 2009 [cited 2022 Nov 29];12:27-33. Available from:

   Introduction Top

Stress response to surgery comprises a number of hormonal changes initiated by neuronal activation of the hypothalamic pituitary adrenal axis. In general, the magnitude and duration of responses are proportional to the surgical injury. If stress response is not attenuated, it may result in higher postoperative morbidity and longer intensive care unit (ICU) stay. Regional anaesthesia with local anaesthetics has been shown to inhibit the stress response to surgery and can also influence postoperative outcome by its beneficial effects on organ function. [1]

Attenuation of stress response during cardiac surgery is often more difficult. Central neuraxial blockade in cardiac surgery with cardiopulmonary bypass (CPB) has been studied for a long time. A meta-analysis of 15 trials in coronary artery bypass graft surgery (CABG), enrolling 1178 patients in which patients were randomized to either general anaesthesia (GA) or general anaesthesia and thoracic epidural analgesia, showed earlier tracheal extubation, decreased pulmonary complications and cardiac dysrrythmias and decreased pain scores in the GA plus thoracic epidural group. [2] However in paediatric cardiac surgery, very few reports are available regarding influence of caudal analgesia in reducing pain and stress response with variable success. [3],[4] Bupivacaine and various narcotic combinations have been tried in adult cardiac surgeries. Although intravenous sufentanil is known to obtund the stress response, no advantage was observed by adding 0.5 g/kg sufentanil to bupivacaine over bupivacaine alone in the caudal block, in children undergoing non-cardiac surgery. [5] Literature review has not revealed any study where combination of bupivacaine and sufentanil via caudal route has been used for alleviating stress response in paediatric cardiac surgical patients. The present study was undertaken to evaluate the effectiveness of epidural sufentanil and bupivacaine in addition to general anaesthesia for attenuation of stress response in children undergoing open heart surgery for acynotic congenital heart disease.

   Materials and Methods Top

After obtaining ethical committee clearance, 30 children, weighing 5-20 Kg (ASA status II-III), having congenital acyanotic heart disease and undergoing elective open heart surgery were included in the study. Exclusion criteria included emergency cardiac surgery, parental refusal, raised intra-cranial pressure, coagulopathy, skin or soft tissue infection, severe hypovolaemia and pre-existing neurological disease. Informed written consent was obtained from the parents. Fifteen patients were allotted to each group in the current study based on a pilot study that considered a sample size of 15 patients, with 5% level of significance and 80% power, adequate. They were randomized by sealed envelope method to receive either GA in group GA ( n = 15) or caudal epidural anaesthesia along with GA in group GC ( n = 15).

All patients were premedicated with morphine 0.1 mg/kg and phenargan 0.5 mg/kg intramuscularly 1 hour before induction of anaesthesia. In the operation theatre, anaesthesia was induced with 0.5-2% halothane in 100% oxygen. After securing the intravenous access, midazolam 0.05 mg/kg, fentanyl 2 g/kg and ketamine 2 mg/kg were given intravenously. Invasive arterial pressure monitoring was started by radial artery cannulation. Intubation of trachea was facilitated with rocuronium 0.9 mg/kg. Anaesthesia was maintained in both the groups with midazolam, fentanyl, pancuronium bromide and isoflurane 0.6-1.2% in air-oxygen mixture, and patient ventilated to maintain normocapnoea (Ohmeda 210 Excel Anaesthesia Machine, BOC Health Care Company, Madison,USA). Intermittent boluses of intravenous fentanyl 2 g/kg and midazolam 0.05 mg/kg were repeated before incision, before sternotomy, at onset of CPB, on re-warming and at sternal closure in all patients. Additional boluses of fentanyl 1-2 g/kg and midazolam 0.05-0.1 mg/kg were administered intravenously, if the blood pressure and heart rate (HR) increased >15% above baseline. Electrocardiogram, HR, pulse oximetry, capnography, invasive arterial pressure, central venous pressure, urine output, temperature, arterial blood gases and blood glucose were monitored. All patients received 5% dextrose as intravenous maintenance fluid.

After intubation, the children in the GC group were positioned for caudal epidural anaesthesia. A combination of sufentanil 0.75 mg/kg and bupivacaine 2 mg/kg (0.2%) as total volume of 1 ml/kg in normal saline was injected in the epidural space under all aseptic precautions. The patients were then positioned in 15 Trendelenberg position for 15 minutes. Central venous cannulation was performed through the right internal jugular vein after intubation in GA group and after the caudal anaesthesia in the GC group.

Heparin 4 mg/kg was administered before CPB and a time interval of 60 minutes was maintained between caudal epidural anaesthesia and heparinisation in group GC patients. CPB circuit was primed with Ringer's lactate solution, mannitol, sodium bicarbonate, heparin and packed red cells to obtain a hematocrit above 20%. Once activated clotting time (ACT) reached above 450 seconds, CPB was initiated. . The aorta was clamped and cold blood cardioplegia (20 ml/kg, St Thomas Hospital solution) was administered into the aortic root and the patient cooled to 31-33C. The cardioplegia solution was repeated every 20 minutes. Perioperative steroid was not used in any patient. The alpha-stat method of acid-base management was used. A mean arterial pressure (MAP) was maintained between 30-65 mm Hg during CPB.

At the end of the intracardiac procedure, re-warming was started, aortic cross clamp removed, and if spontaneous normal sinus rhythm was not present, pacing or defibrillation was performed depending on heart rate and rhythm. Ventilation was started, haemodynamics and arterial blood gases were stabilized and patients were weaned from CPB at 35 C. Protamine was administered to reverse heparin. The patients were then shifted to ICU where resident doctors were blinded to the anaesthetic technique used. Bolus of intravenous fentanyl 1 mg/kg every hour was used for postoperative analgesia till extubation and thereafter enteral paracetamol syrup 15 mg/kg six hourly. Intermittent boluses of intravenous fentanyl 1-2 g/kg were repeated, if the HR or MAP increased >15% of baseline till extubation. The criteria for extubation were adequate level of consciousness, adequate airway reflexes, normothermia, haemodynamic stablilty, absence of arrhythmias, mediastinal drainage <1 ml/kg over 30 minutes and acceptable blood gas analysis (pH > 7.30, arterial oxygen tension > 60 mm Hg and arterial carbon dioxide tension < 50 mm Hg) at an inspired oxygen fraction of 0.4.

The HR and MAP were recorded at baseline soon after intra-arterial line placement (T1), 5 minutes after intubation (T2), 5 minutes after sternotomy (T3), on CPB at the time of maximum cooling (T4), sternal closure (T5), 4 hours after intubation (T6) and 24 hours after intubation (T7). Arterial blood was sampled at T1-T7 for determination of serum cortisol and blood glucose levels. Time of extubation and duration of stay in ICU and hospital along with any complications of caudal block or surgery were noted.

Analytical methods

Arterial blood was collected for serum cortisol measurement. Cortisol was assessed by CORTISOL Quantitative SH-101, a solid phase enzyme linked immunosorbent assay. The sensitivity of the test was 0.36 g/dl. The intra-assay coefficient of variation was 9.5% and interassay coefficient of variation was 10.1%. No adjustment was done for haemodilution. Blood glucose was measured by blood gas machine (Nova Stat Profile M, Nova Biomedical Corporation, Waltham, MA, USA) along with arterial blood gas analyses.

Complications of caudal block including hypotension, arrhythmias, neurological deficit, need for re-exploration, permanent pacemaker, renal dysfunction and mortality were noted. The postoperative morbidity was defined as marked deterioration of clinical condition leading to increased length of stay in ICU or re-intubation. Early postoperative mortality was defined as death occurring before discharge from the hospital.

Statistical analysis

Statistical package SPSS 15.0 for Windows (SPSS Inc, Chicago, IL) was used for statistical analysis. The statistical technique applied for comparison between two groups in case of continuous variables like age, body weight, height and body surface area (BSA) was Mann Whitney's test or t test. The comparison over period of time was carried out by using repeated measure analysis (Two-way ANOVA) followed by multiple comparison or post-hoc test. The P value of ≤0.05 was considered significant.

   Results Top

All enrolled patients completed the study. There was no difference between the groups concerning demographic profile [Table 1]. The CPB and aortic clamp times as well as the surgical and anaesthesia times were comparable. Minimal core temperature during CPB was similar in both groups. Requirement of midazolam, fentanyl and pancuronium were statistically similar [Table 2].

There was no difference in the HR at any stage compared with baseline in both groups [Figure 1]. The increase in MAP from baseline till sternotomy in GA group and decrease from baseline up to sternotomy in GC group was statistically insignificant [Figure 2]. There was no significant difference between the groups regarding HR and MAP at any point of time [Figure 1],[Figure 2].

Stress response

Baseline level of cortisol (in μg/dL) were similar in both the groups (11.81 11.90 in GA group vs. 8.3 8.7 in GC group; P = 0.137). The serum cortisol levels were significantly higher in GA group than GC group after sternotomy at T3 (34.74 27.35 vs. 9.8 7.5; P = 0.045), on CPB at T4 (35.36 24.15 vs. 12.17 6.2; P = 0.003), after sternal closure at T5 (37.62 20.69 vs. 14.03 5.1; P = 0.001), 4 hours after intubation at T6 (37.62 9.13 vs. 26.64 14.61; P = 0.019) and 24 hours after intubation at T7 (28.12 16.31 vs. 14.30 8.11; P = 0.002). There was no significant difference between the groups at T2, that is, 5 minutes after intubation (23.52 23.12 in GA group vs. 10.32 7.3 in GC group; P = 0.2) [Figure 3] and [Table 3].

The within group comparison revealed that there was a highly significant increase in serum cortisol levels in GA group from baseline to 5 minutes after sternotomy at T3 ( P = 0.02), on CPB at time of maximum cooling at T4 ( P = 0.009), after sternal closure at T5 ( P = 0.003), 4 hours after intubation at T6 ( P = 0.003) and 24 hours after intubation at T7 ( P = 0.008). In the GC group, significant increase in serum cortisol level was seen after sternal closure at T5 ( P = 0.04) and 4 hours ( P = 0 .01) and 24 hours after intubation ( P = 0.04) as compared with baseline level, but the increase was much less than GA group [Figure 3].

Metabolic response

Baseline blood glucose levels (in mg/dl) were comparable between the groups (144.33 43.20 in GA group vs. 133.73 33.40 in GC group; P = 0.62). Significant increase in blood glucose levels compared with baseline levels was found in both groups after sternotomy onwards, reaching highest level after CPB at sternal closure and persisted till 4 hours after intubation. The glucose levels gradually decreased to baseline at T7, that is, 24 hours after intubation (178.46 100.60 in GA group vs. 136.80 38.08 in GC group). The blood glucose levels were significantly higher in GA group as compared with GC group at sternal closure at T5, (277.46 77.25 vs. 197.73 42.17; P = 0.002) and at 4 hours after intubation at T6 (255.26 73.73 vs. 185.26 57.41; P = 0.007) [Table 3].

Postoperative course

Morbidity was similar in both groups. No neurological deficit was found in any patient secondary to caudal block or CPB. There were junctional rhythms, heart block in both groups during weaning from CPB. However, postoperatively, two patients with ventricular septal defect - one in each group - required atrio-ventricular pacing for 1-2 hours. Two patients with atrial septal defect in the GC group had sinus tachycardia in the first postoperative hour. Mechanical ventilation time, ICU and hospital stay were comparable in both the groups (P > 0.05) and there were no deaths [Table 4].

   Discussion Top

In the present study, supplementation of caudal epidural bupivacaine and sufentanil could attenuate the rise of serum cortisol and blood glucose levels in paediatric patients undergoing cardiac surgery for acynotic congenital heart anomaly.

Regional anaesthetic techniques are useful adjuncts to GA in children with congenital heart disease. The spinal and epidural anaesthesia are tolerated with limited changes in HR and arterial pressure in children below five years of age in the absence of coagulopathy. [6] In addition to reliable analgesia, the intrathecal and epidural anaesthesia produce thoracic cardiac sympathectomy and may attenuate stress response in patients undergoing cardiac surgery. [7]

Analgesia following opioids given epidurally is due to diffusion of the drug across the dura to mu-opioid receptors in substantia gelatinosa of the spinal cord as well as systemic absorption. [8],[9] The dural penetration of epidural opioid depends on lipid solubility, molecular weight and dissociation constant (pKa). [10],[11] Sufentanil was chosen by authors on the basis of its high lipid solubility, high concentration of freely diffusible unionized molecules and its potent opiate receptor binding capacity causing rapid onset of action; and possibly attenuation of the stress response to incision and sternotomy.

Caudal analgesia was chosen by the authors because complications of caudal epidural analgesia are unusual and minor. [12],[13],[14],[15] Caudal epidural analgesia for cardiac surgery may seem to be inappropriate because the site of incision is far away from the regional technique. But, if appropriate volume of anaesthetic is used by caudal route, effective analgesia can be achieved with minimal side effects. The rationale of combining epidural opioids and local anaesthetics was to use lower doses of each agent to preserve effective analgesia, and to reduce the side effects and problems associated with the use of the individual drugs. Whereas the opioid in the mixture acts by inhibiting the release of substance P in the dorsal horn of the spinal cord, the local anaesthetic blocks transmission of impulses at the level of nerve axonal membrane. These two distinctive actions contribute to the synergy of analgesic effect.

In this study, the authors used a combination of sufentanil 0.75 mg/kg and bupivacaine 2 mg/kg (0.2%) in normal saline as 1 ml/kg dose. The dose of sufentanil was as per the dose used by Benlabed et al . [16] Peterson et al . [17] used bupivacaine 0.25% at a dose of 0.5-1 ml/kg in paediatric cardiac surgery. They did not report any adverse effects related to this dosage. Bichel et al . compared caudal sufentanil, in the volume of 1.5 ml/kg, in GA-plus with GA-alone in paediatric cardiac surgery patients. [3] The 1 ml/kg volume of sufentanil and bupivacaine combination used in this study did not result in any atrioventricular block or hypotension. The epidural catheter was not used because the level of the tip of the catheter cannot be well predicted and there is the risk of curling up in the epidural space or haematoma formation. [18],[19]

In the present study, serum cortisol levels were significantly higher in the GA group than GC group after sternotomy, at the time of maximum cooling on CPB, after sternal closure, 4 hours after intubation and 24 hours after intubation. In GC group, cortisol level maintained a steady range from baseline, that is, before induction to sternal closure. It increased sharply 4 hours after intubation, probably because the effect of caudal injection started weaning off at that time. In the GA group, highly significant difference in cortisol levels from baseline persisted even 24 hours after intubation.

The blood glucose levels increased in both groups, at the time of maximum cooling on CPB and 4 hours after intubation. Part of the increase in blood glucose during CPB could be due to the administration of packed red blood cells preserved in citrate-phosphate-dextrose-adenine solution added to the prime. However, blood glucose values during CPB were found significantly higher in the GA group than the GC group. The difference persisted during 24 hours postoperatively. There was thus better glycaemic control in GC group than GA group although the glycaemic response could not be abolished completely. Bichel et al reported no significant difference in metabolic response while comparing caudal sufentanil 1.5 ml/kg plus GA with GA alone in paediatric cardiac surgery patients. [3] In the present study, probably the addition of bupivacaine to sufentanil made the difference in attenuation of the glycaemic response.

The haemodynamics remained stable in both the groups, probably due to additional fentanyl and midazolam that was administered, if there was a 15% increase in these parameters. The duration of mechanical ventilation was not significantly reduced in GC group as compared to GA group, as against an established fact in adult cardiac surgery with thoracic epidural. [20],[21],[22] It could be due to 'wearing off' of the effect of single bolus caudal epidural anaesthesia by the end of the surgery because of shorter duration of action of sufentanil. The length of ICU and hospital stay was also not statistically decreased in GC group as compared to GA group. This observation was similar to the retrospective study carried out in paediatric patients undergoing congenital heart disease repair requiring CPB, in which postinduction placement of caudal epidural injection of preservative-free morphine 70-110 g/kg, and 0.25% bupivacaine, 1 ml/kg had no effect on the length of ICU or hospital stay. [23] Our results were inconsistent with a study of 27 paediatric cardiac surgical patients receiving continuous lumber epidural morphine with reduced intravenous analgesic requirement, earlier extubation and reduced ICU stay. [24] In a recent retrospective study on children undergoing congenital heart surgery who were administered caudal analgesia with preservative-free morphine 50-100 g/kg and limited doses of intravenous fentanyl 3-5 g/kg, extubation in the recovery room was successful in the majority of patients. [25]

Limitations of the present study were wide age range of children (6 months to 7 years) due to which uniform pain score could not be formulated. Secondly, the anaesthesiologist managing the case was not blinded to the study protocol. In conclusion, combined caudal epidural anesthesia (sufentanil and bupivacaine) and GA could attenuate stress response to open heart surgery in children undergoing cardiac surgery.

   Acknowledgements Top

We are highly grateful to Mr. R K Ahuja and Dr. Guresh Kumar, department of Biostatistics, All India Institute of Medical Sciences, New Delhi, for the statistical analysis. Also, words are not enough to express gratitude to Dr. Anita Saxena, Professor, Department of Paediatric Cardiology, All India Institute of Medical Sciences, New Delhi for the co-operation to carry out this study.

   References Top

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2.Liu SS, Block BM, Wu CL. Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: a meta analysis. Anesthesiology 2004;101:153-61.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Bichel T, Rouge JC, Schlegel S, Spahr-Schopfer I, Kalangos A. Epidural sufentanil during paedaitric cardiac surgery: effects on metabolic response and postoperative outcome. Paediatr Anaesth 2000;10:609-17.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
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6.Dohi S, Naito H, Takahishi R. Age-related changes in blood pressure and duration of motor block in spinal anesthesia. Anesthesiology 1979;50:319-23.  Back to cited text no. 6    
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8.Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984;61:276-310.  Back to cited text no. 8  [PUBMED] Leon-Casasola OA, Lema MJ. Postoperative epidural opioid analgesia: what are the choices? Anesth Analg 1996;83:867-75.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
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Correspondence Address:
Neeti Makhija
Department of Cardiac Anesthesia, 7th Floor, Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9784.45010

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11 Comparison of the effect of the different consantrations of bupivacaine on stress response and postoperative analgesia in caudal analgesia [Kaudal analjezi̇de i̇ki̇ farkli konsantrasyonda bupi̇vakai̇ni̇n stres yanit ve postoperati̇f analjezi̇ üzeri̇ne etki̇leri̇ni̇n karşilaştirilmasi]
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