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Departments of
*Anesthesiology and
Pediatric Surgery, Bnai Zion Medical Center; and
Department of Clinical Biochemistry, Rambam Medical Center; and B. Rappaport, Faculty of Medicine, Technion, Haifa, Israel
Address correspondence and reprint requests to L. Gaitini, MD, Director, Department of Anesthesiology, Bnai Zion Medical Center, P.O. Box 4940, 31048, Haifa, Israel. Address e-mail to gaitini{at}netvision.net.il
| Abstract |
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Implications: This study demonstrates that adding fentanyl to bupivacaine for caudal epidural blocks has no beneficial effect on the stress response in pediatric patients undergoing inguinal herniorrhaphy, as evaluated by plasma epinephrine and norepinephrine values, compared with bupivacaine alone.
| Introduction |
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The present prospective, randomized study was designed to determine if adding fentanyl to bupivacaine, compared with bupivacaine alone in the caudal epidural block, has any effect on plasma E and NE levels as a measure of surgical stress response. In addition, we investigated the analgesic effect of the different compositions of the caudal epidural block, in a pediatric population undergoing inguinal herniorrhaphy.
| Methods |
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Patients were excluded from the study if they had: a failed block, hemoglobin of less than 11 g%, a history of asthma or allergies, episodes of intraoperative hypothermia (less than 35°C), hypoxia (SaO2 of less than 95%), hypercarbia (CO2 more than 50 mm Hg) or hypoxia, or hypothermia (with or without shivering) in the recovery room.
Failed block was defined when it was necessary to add IV fentanyl, or to increase the concentration of the inhaled anesthetics, in response to a 20% increase for more than 5 min of the systolic blood pressure and/or heart rate from the baseline values.
Group A (n = 30) patients were to have inhaled anesthesia combined with a caudal epidural block in which bupivacaine plain 0.25%, 1.0 mL/kg, was injected. Group B (n = 30) patients received an identical inhaled anesthetic combined with a caudal epidural block in which fentanyl 1.0 µg/kg was added to the bupivacaine 0.25% 1.0 mL/kg with a maximum dose of 25 mL.
Anesthesia was induced with N2O/O2 (50%/50%) and halothane, increasing the concentration by 0.5%, each 34 breaths up to 4% by mask. A laryngeal mask airway was inserted after disappearance of the eyelash reflex. End-tidal halothane was maintained in both groups at 1.5% minimal alveolar anesthetic concentration. All children were spontaneously breathing a fresh gas flow of three times the minute volume through a Bain circuit. Manual-assisted ventilation was performed to keep end-tidal CO2 between 3048 mm Hg. After the child was asleep, and before surgery, he was placed in the lateral position and a 23- or 21-gauge needle inserted into the caudal space through the sacrococcygeal membrane, by using an aseptic and nontouch technique. When the aspiration test was negative, either 1 mL/kg of bupivacaine 0.25% (Group A) or bupivacaine 0.25% 1 mL/kg with fentanyl 1 µg/kg (Group B) was injected. All blocks were performed by the same consultant anesthesiologist. The time elapsed from the caudal epidural injection to the start of surgery was 1520 min.
No patient was premedicated, and all children were anesthetized in the presence of their parents in a special induction room. No opioids or sedative drugs were given preoperatively.
Heart rate (HR), heart sounds, noninvasive systolic and diastolic blood pressure, SaO2, ETCO2, and temperature were monitored in all patients by using an TMAS/3 monitor (Datex, Engestrom, Finland).
An IV catheter was inserted in an antecubital vein, after application of EMLA® cream (ASTRA, Sodertalge, Sweden), containing lidocaine 25 mg/g and prilocaine 25 mg/g, 1 h before the induction of anesthesia. Patients were fasted for a minimum of 6 h from solid food and milk and 2 h from clear fluid. All children were adequately hydrated by using normal saline solution or lactate Ringers solution at a rate of 46 mL · kg-1 · h-1 using an infusion pump.
Blood samples of 3 mL for cathecolamine plasma levels were drawn through the venous catheter three times: at the induction time (H0), at the end of surgery (H1), and when an Aldrete recovery score (11) of 10 points was obtained in the postanesthesia care unit (PACU) (H2). All samples were centrifuged immediately for 10 min to separate the plasma and stored at -50°C; the assay was performed by reversed-phase high-performance liquid chromatography with electrochemical detection.
The normal ranges for children up to 15 yr are: E = 20500 pg/mL and NE = 701500 pg/mL (12,13).
After surgery, each patient was transferred to the PACU and observed for 11/22 h, followed by 10 h in the surgical ward before discharge.
In the PACU, respiratory rate, SaO2, HR, noninvasive blood pressure, and pain score were reported each 15 min, and the time to first IV injection of fentanyl was recorded by the nursing staff. In the surgical ward, the time to the first supplemental analgesia administeredas well as complications such as respiratory depression (respiratory breathing rate < 12/min), nausea, and vomiting or prurituswere recorded each half hour.
Postoperative pain was assessed every 15 min in the PACU by using a modified Childrens Hospital of Eastern Ontario Pain Score (mCHEOPS) (14). Patients with a pain score greater than 5 were treated with 1 µg/kg IV fentanyl, in fragmental doses in the PACU or 15 mg/kg of paracetamol on the surgical ward. Postoperative follow up was performed by an anesthesiologist unaware of the patients group.
Patients were discharged from the hospital when a score of
9, according to the modified postanesthesia discharge scoring system, was achieved (15).
Statistical analysis for a comparison between the three phases (H0, H1, and H2) of the study in each group was performed by using the analysis of variance test for repeated measurement, followed by the Bonferroni post hoc test. The unpaired Students t-test was used when each phase (H0, H1, and H2) was compared between the two groups. The equality of variances was performed by using the Levenes test. When no significant differences were obtained, a statistical power analysis was performed. The power was computed based on the results of comparisons between the phases (H0, H1, and H2), as reported in our previous study (4). Statistical significance is assumed when the two-tailed P values were
0.05.
| Results |
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There were no significant differences in the baseline (H0) of E and NE plasma levels between the two groups (P = 0.5, P = 0.9). Also, there were no significant differences in the E plasma levels between the two groups at H1 (P = 0.12) and at H2 (P = 0.5) or in the NE plasma levels between the two groups at H1 (P = 0.9) and H2 (P = 0.9) (Fig. 1). The power of the statistical tests in all the above comparisons was greater than 80%. No statistically significant differences were found in the blood pressure or the HR between the two groups at the three phases of the study (SBP: P = 0.79, P = 0.56, P = 0.77) and (DBP: P = 0.045, P = 0.18, P = 0.72). The P values of the HR at the three phases were (0.25, 0.38, and 0.73) (Table 1).
Pain score using (mCHEOPS) was similar in both groups. No statistically significant differences between the two groups were found regarding either the time of the first IV fentanyl administration or the number of patients who required fentanyl. There were also no significant differences between the two groups regarding the time of the first dose and the number of patients who received paracetamol in the ward (Table 2).
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| Discussion |
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Reduction of the stress response is highly dependent on the surgical site and the analgesic technique used. Caudal epidural analgesia/anesthesia inhibits the stress response, particularly during surgery in the lower part of the body in a pediatric population (16). It has been demonstrated that the addition of caudal block to general anesthesia significantly reduces the neurohormonal response in children undergoing ilioinguinal herniorrhaphy (5).
In contrast, the use of epidural anesthesia for upper abdominal and thoracic surgery failed to prevent the surgical stress response, despite excellent analgesia (17). Epidural morphine did not augment the effectiveness of epidural bupivacaine in suppressing postoperative elevation of cortisol, despite providing good analgesia in thoracic surgery (18). The surgical site may influence the residual afferent nociceptive activity, without conscious perception of pain, although still evoking the surgical stress response.
Our results revealed the same analgesic intensity of the caudal block whether using the mixture of fentanyl and bupivacaine or bupivacaine alone. Campbell et al. (19) had similar results when evaluating the analgesic efficacy and safety of a single caudal injection of bupivacaine 0.125%-epinephrine 1:200,000 with fentanyl 1 µg/kg, compared with bupivacaine 0.125%-epinephrine 1:200,000 in children undergoing elective urological surgery. They found no advantages to the mixture of bupivacaine-epinephrine 1:200,000 with fentanyl over the bupivacaine-epinephrine 1:200,000 without fentanyl, based on the number of patients receiving morphine within eight hours after surgery and the time of the first morphine administration.
Our results also agreed with those of Jones et al. (20), who found in a controlled study that the addition of fentanyl 1 µg/kg to lidocaine 2% placed in the caudal epidural seems to convey no benefit to postoperative analgesia in children who underwent circumcision.
Pain is the main determinant of the early catecholamine response to surgery in the lower extremity (8); however, pain measurement in children is difficult and unreliable. Each of the methods of rating pain has its limitations, particularly in the nonverbal children (20). The mCHEOPS is a valid and reliable method of assessing immediate postoperative pain for the ages of children participating in our study (14). Stress response hormone levels can therefore be used as an objective method to assess the analgesic efficacy of local anesthetics injected into the extradural space before infraumbilical or lower extremity surgery in both adult and pediatric populations.
Rucci et al. (22) reported that a mixture of bupivacaine with fentanyl prolonged the block only when a large dose (3 µg/kg) of fentanyl was used, but not with 1 or 1.5 µg/kg, in extradural block in an adult population. Welchew (23) found that both the intensity and duration of pain relief were increased as larger doses of fentanyl were added to lidocaine 1%, up to a maximum of 10 µg/kg given epidurally. Neither Rucci et al. (22) nor Welchew (23) measured catecholamine plasma levels. Their findings, however, could explain the lack of benefit we observed by adding fentanyl 1 µg/kg to bupivacaine over bupivacaine alone in the caudal block. The small dose of fentanyl, which is the common and accepted dose, is probably the reason why this mixture had an inconsequential effect on the pain scores and catecholamine plasma level and, therefore, should be increased in the routine use of caudal epidural analgesia in children.
Complete postoperative pain relief cannot be achieved by a single drug or method without significant side effects; therefore, efforts have been focused on improving pain relief by a combination of bupivacaine 0.5% and opioids such as morphine (24,25). These combinations provide effective pain relief even after upper abdominal surgery, but at the cost of motor block of the lower extremity or respiratory depression. A smaller concentration of local anesthetic or morphine leads to less pain relief. We chose the mixture of bupivacaine 0.25% and fentanyl because of the latters high lipid solubility, which offers a rapid onset of action while being less likely than morphine to migrate rostrally to the brainstem (4).
The present study demonstrates that there is no beneficial effect to the mixture of small-dose fentanyl (1 µg/kg) and bupivacaine 0.25%, compared with bupivacaine 0.25% alone when used for caudal epidural, based on pain score and catecholamine levels. The reduction of the stress response reflected by plasma catecholamines concentration could influence the clinical outcome in high-risk children. Future studies should examine the influence of larger doses of fentanyl added to local anesthetics on postoperative pain scores and catecholamine blood levels.
| References |
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