Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan
* Corresponding author. E-mail: shu-dohi{at}cc.gifu-u.ac.jp
Accepted for publication March 13, 2004.
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Abstract |
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Methods. We studied prospectively in 75 women in a double-blind, randomized manner: epidural morphine 6 mg day1 (n=25), epidural oxycodone 6 mg day1 (n=25) and epidural oxycodone 12 mg day1 (n=25). All patients underwent gynaecological surgery under general (isoflurane and nitrous oxide) and epidural anaesthesia. Visual analogue scale (VAS) pain scores at rest and on coughing, verbal descriptive scale (VDS) satisfaction scores, sedation scores, pruritus scores and nausea/vomiting scores were recorded for 3 days after surgery.
Results. VAS pain scores at rest in patients who received oxycodone 6 mg day1 were higher than in patients who received morphine 6 mg day1 at 6 h and on the first postoperative day and were significantly higher than in patients who received oxycodone 12 mg day1 on the first postoperative day. Scores for nausea, vomiting and pruritus in patients who received oxycodone 6 mg day1 and 12 mg day1 were lower than those in patients who received morphine. No significant differences were seen in VAS at cough and VDS satisfaction scores between the three groups.
Conclusion. Epidural oxycodone was as effective as morphine at the doses investigated, with fewer side-effects.
Keywords: anaesthetic techniques, epidural ; analgesia, postoperative ; analgesic techniques, extradural ; analgesics, opioid, morphine ; analgesics, opioid, oxycodone
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Introduction |
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Oxycodone is a semi-synthetic opioid derivative that has been in clinical use since 1917. It resembles morphine structurally and has a similar lipid solubility.6 It is thought to induce analgesia by mechanism(s) similar to morphine (mu-opioid receptor agonist).7 Recently, it has been reported that the analgesic action of oxycodone is more rapid in onset than with morphine and is mediated by kappa-opioid receptors in the spinal cord.8 Although systemic administration of oxycodone has been reported to cause fewer side-effects than morphine,9 10 only one study has compared oxycodone with morphine by epidural injection for postoperative pain relief in humans.11 Since epidural administration of morphine has been standard practice for postoperative pain relief, we compared analgesia and side-effects of epidural oxycodone with those of epidural morphine after gynaecological surgery.
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Methods |
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General anesthesia was induced with i.v. thiopental 45 mg kg1 supplemented with fentanyl 3 µg kg1, and tracheal intubation was facilitated with i.v. vecuronium 0.10.2 mg kg1. Anaesthesia was maintained with inhalation of isoflurane, nitrous oxide (67%) and oxygen and intermittent i.v. fentanyl. The total use of fentanyl was recorded. After tracheal intubation, a nasogastric tube was inserted and the gastric contents aspirated.
On termination of surgery, each of the 75 patients received one of the following: (i) epidural morphine 2 mg bolus with bupivacaine 0.25%, 10 ml before starting the infusion of morphine at 6 mg day1 for 3 days; (ii) epidural oxycodone 2 mg bolus with bupivacaine 0.25%, 10 ml before starting the infusion of oxycodone at 6 mg day1 for 3 days; (iii) epidural oxycodone 4 mg bolus with bupivacaine 0.25%, 10 ml before starting the infusion of oxycodone at 12 mg day1 for 3 days. All patients received continuous epidural infusion (total volume 36 ml, infusion rate 0.5 ml h1). Before discharge from the OR, approximately within 2 h after the bolus administration of epidural oxycodone or morphine with bupivacaine, we measured arterial blood gases and pHa. (Supplementary oxygen was given by face mask.) Until the day after surgery, patients were given oxygen by nasal canula and oxyhemoglobin saturation () was monitored.
In order to examine the efficacy of the treatment regimens employed, the following values were recorded every 3 h after surgery for 6 h, then once a day for the first days after surgery: (i) pain score at rest and on coughing using a 10 cm visual analogue scale (VAS) (0 mm=no pain; 100 mm=worst unbearable pain); (ii) score on a verbal descriptive scale (VDS) of the fulfillment of the patient's need for analgesia (0=most satisfactory, 10=worst status); (iii) sedation score (1=awake and no sedation; 5=asleep and difficult to rouse); (iv) nausea score (1=none, 2=slight, 3=mild, 4=moderate, 5=severe); (v) vomiting score (1=none, 2=single vomit, 3=multiple vomiting); (v) pruritus score (1=none, 2=slight, 3=mild, 4=moderate, 5=severe).
Treatment for postoperative pain and side-effects was at the patient's request and was recorded. Analgesia was provided with diclofenac sodium 25 mg (first choice) or pentazocine 15 mg at intervals of 3 h, as required. Nausea and vomiting was treated with i.v. metoclopramide 10 mg at intervals of 3 h, as required. Pruritus was treated with diphenhydramine ointment on request. Arterial pressure (AP), heart rate (HR) and respiratory rate (RR) were also recorded over the same time period.
Statistical analysis
In order to have 80% power of detecting a 35% reduction in VAS pain scores with a significance level of 0.05 (two tailed), and using the method described by Motulsky,12 we required 25 subjects in each group.
All data are expressed either as the mean (SD) (parametric values) or as the median and 95th percentile (non-parametric values) unless stated otherwise. Patient characteristics were analysed using one-way ANOVA. AP and HR after surgery were analysed using repeated-measures ANOVA. Quantitative non-parametric data were compared using the KruskalWallis test. If a significant result was obtained, post hoc analysis was performed using Bonferroni test for multiple comparisons. Significance was set at P<0.05.
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Results |
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Discussion |
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The antinociceptive potency of oxycodone seems to depend on the route of administration. Systemic oxycodone has been reported to be 0.71.3 times more potent than morphine given i.v. When i.v. patient-controlled analgesia administration was used, patients requested a dose of oxycodone that was equal to that of morphine for postoperative analgesia after mastectomy;17 the total consumption of each opioid was approximately 60 mg over 24 h. However, in contrast to i.m., subcutaneous and rectal administration,1820 intrathecal or epidural oxycodone is associated with variable analgesic effects. Kalso and colleagues21 examined the spinal antinociceptive effect of oxycodone, and found that intrathecal oxycodone was more than 14 times less potent than morphine in rats. For epidural administration, Backlund and colleagues11 found that oxycodone was 10 times less potent than morphine in patients after abdominal surgery. Our results also indicated a wide individual variability for both VAS and VDS satisfaction score, with epidural oxycodone similar to epidural morphine. Since we have found that oxycodone administered into the brainstem medial pontine reticular formation in rats did not produce any antinociceptive effects,22 the reduced potency and individual variability observed in patients who received epidural oxycodone might be attributable to lack of a supraspinal action.
Undesirable side-effects such as pruritus and nausea are common with epidural morphine and are believed to be caused via mu-opioid receptor stimulation at the supraspinal level.2325 It is not clear why the need for anti-emetics was significantly less in those who received epidural oxycodone 12 mg day1 in our study. Since patient characteristics were similar between the three groups, it may be that oxycodone, when administered in the epidural space, is less emetogenic than morphine. Although oxycodone has effects at both mu- and kappa-opioid receptors, the affinity of oxycodone for the mu-opioid receptor has been reported to be one-tenth that of morphine.26 This may account for the fewer side-effects and less analgesia when compared with the same dose of epidural morphine.
In conclusion, our data indicate that epidural oxycodone is as effective as morphine when given at twice the dose, perhaps with fewer side-effects. However, a large degree of interpatient variability suggests the need for further comparative study.
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Acknowledgments |
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Footnotes |
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References |
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