BJA Advance Access originally published online on June 23, 2006
British Journal of Anaesthesia 2006 97(3):385-388; doi:10.1093/bja/ael155
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Efficacy of three doses of tramadol with bupivacaine for caudal analgesia in paediatric inguinal herniotomy
1 Department of Anaesthesia and Intensive Care, Vardhman Mahavir Medical College and Safdarjang Hospital New Delhi, India
2 Department of Biostatistics, AIIMS New Delhi, India
3 Central Hospital New Delhi, India
*Corresponding author. E-mail: drsunilprakash{at}rediffmail.com
Accepted for publication May 5, 2006.
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Abstract |
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Background. This study was designed to evaluate the analgesic efficacy of three doses of tramadol, administered caudally with bupivacaine, in providing postoperative pain relief in children.
Methods. Eighty children, aged between 2 and 8 yr, undergoing inguinal herniotomy were randomly allocated to receive bupivacaine 0.25% 0.75 ml kg–1 (Group B; n=20), bupivacaine 0.25% 0.75 ml kg–1 with tramadol 1 mg kg–1 (Group BT1; n=20), bupivacaine 0.25% 0.75 ml kg–1 with tramadol 1.5 mg kg–1 (Group BT1.5; n=20), or bupivacaine 0.25% 0.75 ml kg–1 with tramadol 2 mg kg–1 (Group BT2; n=20) by the caudal route immediately after induction of general anaesthesia. Heart rate, arterial pressure and oxygen saturation were monitored. Postoperative pain was assessed at regular intervals for 24 h using All India Institute of Medical Sciences pain score. Analgesia was supplemented whenever pain score was 
4. Duration of analgesia and requirement for additional analgesics was noted.
Results. Duration of analgesia was longer in Group BT2 [(mean (SD) 12 (0.9) h] compared with Group B [4 (1) h], Group BT1 [8 (0.9) h], or Group BT1.5 [11 (1) h]; all P<0.001. Total consumption of rescue analgesic was significantly lower in group BT2 compared with other groups (P<0.001). There were no significant changes in heart rate, arterial pressure and oxygen saturation between groups. Adverse effects were not observed.
Conclusions. Caudal tramadol 2 mg kg–1, combined with bupivacaine 0.25% 0.75 ml kg–1, provided longer duration of postoperative analgesia and reduced requirement for rescue analgesic compared with tramadol 1 mg kg–1 or 1.5 mg kg–1 in children undergoing inguinal herniotomy.
Keywords: anaesthetic techniques, epidural; analgesia, postoperative; analgesics opioid, tramadol; surgery, paediatric
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Introduction |
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Caudal epidural block with bupivacaine is a common local anaesthetic technique in paediatric anaesthesia. However, a single caudal injection of bupivacaine provides analgesia for only 2–4 h. The administration of opioids into the epidural space significantly prolongs the duration of caudal analgesia but is associated with a number of unpleasant side-effects including the potentially serious risk of respiratory depression. Tramadol, a synthetic analogue of codeine, is a racemic mixture of two enantiomers: (+)-tramadol and (–)-tramadol. The (+)-enantiomer has a moderate affinity for the opioid µ-receptor and also inhibits serotonin uptake, while the (–)-enantiomer is a potent norepinephrine inhibitor.1 These complementary properties result in an opioid with an analgesic potency approximately equal to that of meperidine, but without any respiratory depressant effect.2 3
It has previously been demonstrated that the addition of tramadol to bupivacaine for caudal epidural block in children significantly prolongs the duration of postoperative analgesia.4–8 The dose of tramadol used for caudal epidural block has ranged between 1 and 2 mg kg–1 in these studies. The purpose of this prospective, randomized, double-blind study was to identify the dose of tramadol, as adjunct to bupivacaine caudal epidural block, that would produce maximum duration of caudal analgesia with minimal adverse effects in children undergoing inguinal herniotomy.
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Methods |
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After approval by the hospital ethics committee and written informed parental consent, we studied 80 children, ASA I or II, aged between 2 and 8 yr, who were undergoing unilateral inguinal herniotomy. Children in whom caudal block was contraindicated (infection at the site of block, bleeding diathesis, pre-existing neurological or spinal disease, or abnormalities of the sacrum) were excluded from the study. Patients were fasted for 6 h before the procedure. Clear fluids (10 ml kg–1 body weight) were allowed up to 3 h before the procedure. No premedication was administered.
After cannulation of a suitable vein, anaesthesia was induced with thiopental 4–6 mg kg–1 or with inhalation of halothane and nitrous oxide in oxygen. Anaesthesia was maintained via a facemask with the same volatile agents. No sedatives or opioids were administered during operation.
Patients were allocated randomly (sealed envelope, random number table) to receive one of four solutions, the volume injected into the caudal epidural space being 0.75 ml kg–1. Group B received plain bupivacaine 0.25% 0.75 ml kg–1; Group BT1 received plain bupivacaine 0.25% 0.75 ml kg–1 combined with tramadol 1 mg kg–1; Group BT1.5 received plain bupivacaine 0.25% 0.75 ml kg–1 combined with tramadol 1.5 mg kg–1; Group BT2 received plain bupivacaine 0.25% 0.75 ml kg–1 combined with tramadol 2 mg kg–1. Preservative free tramadol was used (Supridol, Neon Laboratories Limited, India). After induction of anaesthesia and before surgery, patients were placed in the lateral position, and a 23-gauge needle was inserted into the caudal epidural space. After negative aspiration for blood or cerebrospinal fluid, the study solution was administered.
Patients were monitored during operation for heart rate, ECG, ventilatory frequency, end-tidal carbon dioxide and arterial oxygen saturation continuously and non-invasive blood pressure every 5 min (Cardiocap II, Datex-Ohmeda, Finland). Adequate intraoperative analgesia was defined by haemodynamic stability, as indicated by the absence of an increase in heart rate or systolic arterial pressure greater than 15% compared with baseline values obtained just before surgical incision.
Anaesthesia was discontinued at the completion of skin closure. After the operation, time from discontinuation of anaesthesia to spontaneous eye opening and the duration of surgery were noted. Pain in the postoperative period was assessed by using All India Institute of Medical Sciences (AIIMS) pain discomfort scale.9 The scale uses five criteria: ventilatory frequency, heart rate, discomfort, cry and pain at site of operation. Each criterion scores from 0 to 2 to give a possible total score of 0–10. Assessments were made by an investigator (who was blinded to the mixture used for caudal injection) at 1, 2, 3, 4, 6, 8, 12 and 24 h after recovery from anaesthesia. AIIMS score was evaluated by the nursing staff (who were unaware of the treatment given) during the remaining period. Patients received acetaminophen 10 mg kg–1 orally as rescue analgesic when AIIMS score was 4.
Time for first analgesic (time between caudal injection and first administration of rescue analgesic) and the total consumption of analgesic in the first 24 h were recorded. Assessment of sedation was done at 1 and 4 h by using an objective score based on eye opening (eyes open spontaneously=0, eyes open in response to verbal stimulation=1, eyes open in response to physical stimulation=2).10
Duration of motor block (by determining when the child began to move his legs), time to first void and side-effects (emesis, urinary retention, facial flushing or pruritus), if any, were recorded.
To assess the difference among the groups for continuous variables, one-way ANOVA was used with post hoc analysis. For finding association among the categorical variables, two-way ANOVA was used. P< 0.05 was regarded as statistically significant. Statistical software SAS 8.0 (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis.
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Results |
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The four groups of patients were comparable with respect to age, weight, gender distribution and duration of surgery (Table 1). No statistically significant differences were observed in intraoperative and postoperative heart rate, arterial pressure, ventilatory frequency and oxygen saturation between the four groups.
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The results are given as mean (SD). The time to first administration of rescue analgesia was 4 (1) h in Group B, 8 (0.9) h in Group BT1, 11 (1) h in Group BT1.5 and 12 (0.9) h in Group BT2 (Table 2). The duration of analgesia in Group B was significantly shorter than that in the other three groups (all P<0.001). The difference in mean time to first analgesia between groups BT1, BT1.5 and BT2 was also significant (all P<0.001).
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Total consumption of analgesic was significantly higher in Group B [450.3 (93.2) mg] compared with that in Group BT1 [297.8 (90.7) mg], Group BT1.5 [294.1 (99.1) mg], and Group BT2 [189.0 (68.6) mg]; all P<0.001. Fifteen patients in Group B required between 3 and 4 doses of postoperative analgesic compared with 5, 3 and 0 patients in groups BT1, BT1.5 and BT2, respectively (Table 3).
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There was no significant difference in duration of time from discontinuation of anaesthesia to spontaneous eye opening between the four groups; P=0.91 (Table 2). Sedation scores at 1 and 4 h after surgery were comparable in the four groups (Table 4). None of the patients had motor block on emergence from anaesthesia. Time to first void was significantly longer in Group BT2 compared with that in Group B; P<0.001 (Table 2). No child required bladder catheterization.
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The incidence of emesis was not statistically different between the groups; P=0.498 (Table 2). Facial flushing or pruritus was not observed.
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Discussion |
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This study has supported the findings of previous work and confirmed the efficacy of tramadol in paediatric postoperative pain control.4 6 8 Addition of tramadol to bupivacaine administered caudally provided a dose-related increase in postoperative analgesia. Dose of 2 mg kg–1 of tramadol was significantly more effective than 1 mg kg–1 and 1.5 mg kg–1. There was no difference in postoperative sedation between the groups as evident by the time to spontaneous eye opening and sedation scores at 1 and 4 h after operation.
Senel and colleagues4 examined the analgesic efficacy of bupivacaine 0.25% 1 ml kg–1, tramadol 1.5 mg kg–1 in normal saline, or bupivacaine 0.25% 1 ml kg–1 mixed with tramadol 1.5 mg kg–1 in children undergoing herniorrhaphy. Their results showed that patients who received bupivacaine and tramadol had a significantly longer time period to administration of first analgesic [13 (2) h] than either the bupivacaine group [10 (2) h] or the tramadol alone group [5 (1) h]. This is comparable with the duration of postoperative analgesia of 11 (1) h observed in the group receiving bupivacaine 0.75 ml kg–1 combined with tramadol 1.5 mg kg–1 in our study.
Caudal tramadol (2 mg kg–1) provided reliable postoperative analgesia similar to caudal morphine (0.03 mg kg–1) in quality and duration of pain relief in children undergoing herniorrhaphy.5 Batra and colleagues6 concluded that caudal tramadol 1 mg kg–1 can be safely used for postoperative analgesia with a longer duration as compared with caudal bupivacaine.
Prosser and colleagues8 reported that the addition of tramadol (2 mg kg–1) to caudal bupivacaine (2 mg kg–1) provided a mean duration of analgesia of 10 (2) h. The addition of tramadol did not prolong significantly the action of caudal bupivacaine. This is because the mean duration of action of caudal bupivacaine in their study [9 (3) h] was much longer than that reported in other studies.11 12 Differences in the type of surgery, method of pain scoring, dosage and volume of administered medication, and calculation of analgesia time probably account for this discrepancy. Also, postoperative pain was assessed for only 12 h after caudal injection.
It is not clear whether the prolonged duration of action of caudal tramadol is caused by slow absorption across the dura or slow-uptake of tramadol from the epidural space into the systemic circulation. Our institution lacks the facilities to estimate serum tramadol concentrations, hence it was not possible to do so in our study. However, lower plasma levels after epidural administration of tramadol have been reported in most clinical studies. Chrubasik and colleagues,13 in their study of 21 patients given epidural tramadol infusion, found mean plateau serum concentrations of around 300 µg ml–1 that were far lower than those seen with i.v. tramadol treatment.14
The data from Murthy and colleagues7 study suggest that injection of tramadol in the epidural space appears to act only as a depot for immediate and delayed systemic absorption. It is of interest to note that tramadol is one of the few drugs that is administered in the same dose both epidurally and i.v. Gunes and colleagues15 concluded that caudal tramadol (2 mg kg–1) provided better and long-lasting postoperative analgesia (>24 h) than i.v. tramadol 2 mg kg–1 [2 (0.6) h]. Majority of patients (30 of 34 patients), receiving tramadol i.v., needed supplementary analgesia, whereas no boys given caudal tramadol required postoperative analgesia during the 24 h study period. Tramadol has been reported to depress the spinal nociceptive receptors in the rat, indicating that, similarly to morphine, it acts at the spinal level.16
The most frequently reported side-effect of epidural tramadol is nausea. We found a low incidence of emesis with all three doses of tramadol compared with previous reports.6 8 Similar results were reported by Senel and colleagues4 who found that the addition of tramadol 1.5 mg kg–1 to bupivacaine did not result in any significant increase in the incidence of emesis. The longer time to first void in patients receiving tramadol 2 mg kg–1, though statistically significant, appears clinically acceptable. No child required bladder catheterization.
We used the AIIMS discomfort scale for assessment of pain because it provides allowance for thirst and hunger, avoids duplication of behaviour, and includes physiological changes such as heart rate and respiration, which can be measured without causing discomfort to the patient. For this reason, it is a clinically relevant scoring system and has been validated for use in children.9
In summary, when tramadol 2 mg kg–1 is used to prolong the duration of caudal epidural analgesia with bupivacaine in children, the duration of analgesia is longer and the requirement for postoperative analgesia less than that seen with tramadol 1 or 1.5 mg kg–1, without an increase in adverse effects.
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