The pharmacological effects of oxycodone closely resemble those of morphine.1 The analgesic potency between oxycodone and morphine is presumed to have a 1:1 ratio in postoperative pain after surgery, with mixed somatic and visceral pain components.2,3 Like morphine, oxycodone seems to be a selective μ-opioid receptor agonist.4–6
Experiments in rodents suggest that oxycodone also has an effect at the κ-opioid receptor.7–9
In an experimental pain model in humans, oxycodone had a superior analgesic effect in visceral pain compared with equivalent doses of morphine.10,11
One 2-h study of patients after abdominal surgery demonstrated higher potency and less sedation when oxycodone was compared with morphine.12 This may suggest a potentially better analgesic efficacy of oxycodone in visceral pain and less side effects. The aims of our study were to compare the analgesic potency, pain scores, and side effects of oxycodone versus morphine in a clinical model of visceral pain for 24 h postoperatively (i.e., laparoscopic hysterectomy).
The protocol of this randomized, double-blind study was approved by the Regional Committee for Medical Research Ethics in Eastern Norway. (ClinicalTrails.gov ID: NCT 00528177).
Adult women (18–70 yr) scheduled for laparoscopic supracervical hysterectomy or total laparoscopic hysterectomy were included after a written informed consent had been obtained.
Exclusion criteria were regular use of acetaminophen, nonsteroidal antiinflammatory drugs, corticosteroids, antiemetics, or opioids. All patients were tested for electrical pain threshold (EPT) in the hand preoperatively with Painmatcher®-PM (Cefar Medical AB, Lund, Sweden).13–15 Painmatcher was used to compare EPT and maximum EPT to demonstrate similarity between the two groups before surgery.
The patients were instructed in the use of a visual analog scale (VAS) where 0 mm corresponded to no pain and 100 mm corresponded to the worst pain imaginable. Patient-controlled analgesia (PCA) (Gemstar®, Abbott Laboratories, Abbott Park, IL) was used for postoperative pain management.
Randomization was based on computer-generated codes stored in sequentially numbered, sealed envelopes. The patients received general anesthesia with target-controlled infusions of propofol and remifentanil. The inspired gas mixture was 40% oxygen. N2O was not used nor was neuromuscular blockade.
After induction of anesthesia, all patients received 40 mg parecoxib IV. Before skin incision, the surgeon injected bupivacaine (5.0 mg/mL) with epinephrine (5 μg/mL), into all incisional areas, for a total of 20 mL. The patients then received 1.25 mg droperidol IV for antiemetic prophylaxis and 1 g acetaminophen IV.
Pain medication after surgery was acetaminophen 1 g every sixth hour, and PCA oxycodone or morphine IV until 24 h after the end of surgery.
Both groups received 0.07 mg opioid/kg 10–15 min before the end of surgery; Group O oxycodone and Group M morphine. After emergence, both groups received PCA 0.015 mg opioid/kg, oxycodone or morphine, every time the button was pushed with a 5-min lockout interval.
The accumulated opioid consumption and pain scores (VAS at rest and when coughing) were recorded at 30 min, 1, 2, 3, 4, and 24 h after the end of the surgery. Postoperative nausea or vomiting, itching, and sedation were also recorded.
Postoperative opioid consumption during 0–24 h was considered the primary efficacy variable. Based on a previous trial,16 a sample size estimate with a mean morphine consumption of 25 mg with a standard deviation of 10 indicated that 45 patients per group would give a power of 80% at a P level of 0.05 for detecting a mean difference in opioid consumption of at least 25% between the groups. Data were analyzed using independent sample’s t-test for continuous variables with nearly normal distribution, otherwise the Mann–Whitney U-test was used. The χ2 test was used for categorical data. Repeated measures analysis of variance (ANOVA) and area under the curve (AUC) were used for VAS scores. Repeated measures ANOVA was used at the sedation scores. Data were analyzed in SPSS 16.0. The significance level was set to 0.05.
Ninety-one patients were studied per protocol for the planned preoperative and postoperative period (Fig. 1). Demographic data and anesthesia characteristics were similar in the two groups, and there were no differences in the mean preoperative EPT between the groups (Table 1). Mean VAS at rest at the first PCA request was similar between the groups, 53 mm in Group O and 54 mm in Group M (P = 0.71), but the mean time from emergence to first use of PCA was different, mean 20 min in Group O and 16 min in Group M (P = 0.038). The accumulated 24 h oxycodone consumption was significantly less compared with the accumulated morphine consumption (13.3 ± 10.4 mg vs 22.0 ± 13.1 mg, P = 0.001) (Fig. 2).
VAS scores at rest and during coughing were significantly less at 30 min and 1 h after surgery in Group O (Figs. 3 and 4), using repeated measures ANOVA. Median AUC of pain at rest was 222 mm × h in Group O and 227 mm × h in Group M, P = 0.59, and when coughing 567 mm × h in Group O and 429 mm × h in Group M, P = 0.35.
The overall sedation level postoperatively was significantly less in Group O compared with Group M, P = 0.006 (Fig. 5).
There were no significant differences in the incidence of nausea, vomiting, or itching.
The accumulated oxycodone consumption was significantly less compared with the accumulated morphine consumption. Group O had less pain during the first postoperative hour and was less sedated throughout the study.
The 2:3 potency ratio found by Kalso et al.12 in patients undergoing open abdominal surgery is approximately the same as the potency ratio in our study, but this is in contrast to other studies with mainly somatic postoperative pain, where a 1:1 potency ratio was found.2,3
We also found a significantly longer time to the first PCA oxycodone request after a standardized dose of either morphine or oxycodone before the end of surgery. This may indicate that oxycodone has a longer-acting effect or is more potent.
Our results support the findings in experimental studies in humans, demonstrating that oxycodone is more potent than morphine in the treatment of visceral pain.10,11
A possible explanation is that oxycodone has κ-opioid receptor agonist properties,7–9 although this is disputed.17
The difference in initial pain relief may also be explained by differences in the time to onset of analgesic effect; when the onset is slow, the patient will tend to request PCA more frequently and thereby receive a higher dose. Although morphine is considered to be a slower-acting drug, few clinical studies on this issue suggest a fairly similar time to onset (about 5–8 min) and peak effect (about 20–30 min) for both drugs given as IV bolus.18,19
The authors thank Tomas Draegni, Anna Söderstam, and the recovery ward staff at the gynecological department for the help they have provided.
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© 2009 International Anesthesia Research Society
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