Clinical trial NCT00528177: Morphine vs. Oxycodone for Postoperative Pain Management
Official title: Phase 4: A Comparison of Intravenous Administration of Morphine vs. Oxycodone for Postoperative Pain Management Following Laparoscopic Hysterectomy or Myomectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hysterectomy
Myoma
Postoperative Pain
Opioids
Keywords: kappa-opioid receptor
my-opioid receptor
oxycodone
morphine
postoperative pain
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2007-09-12
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether oxycodone provides better analgesia compared to morphine after laparoscopic hysterectomy or myomectomy.

Detailed description: Traditionally, a 1:1 ratio in analgesic potency between intravenous morphine and oxycodone has been presumed (1-2), but one study demonstrated a 3:2 ratio between those drugs (3). During the last years, several studies indicate that oxycodone has the potential of mediating pain relief through the kappa-opioid receptor (4-6), and not only on the my-opioid receptor like most other opioids used in the clinic. Kappa-opioid receptors are widely distributed in visceral organs, and this may explain why Kalso (3) found less need for oxycodone compared to morphine in patients undergoing abdominal surgery.

The aim of this study is to investigate whether patients with visceral postoperative pain need less oxycodone compared to morphine, and whether patients receiving oxycodone experience better pain relief and less adverse effects compared to patients receiving morphine.

Before start of surgery, the patients will be tested with PainMatcher, an instrument testing electrical pain threshold in the skin (7-10), to ensure that both groups have the same pain threshold before surgery.

References

1. Kalso E. Oxycodone. Journal of Pain \& Symptom Management 2005; 29: S47-S56.
2. Silvasti M, Rosenberg P, Seppala T, Svartling N, Pitkanen M. Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia. Acta Anaesthesiol Scand 1998; 42: 576-80.
3. Kalso E, Poyhia R, Onnela P, Linko K, Tigerstedt I, Tammisto T. Intravenous morphine and oxycodone for pain after abdominal surgery. Acta Anaesthesiol Scand 1991; 35: 642-6.
4. Staahl C, Christrup LL, Andersen SD, Arendt-Nielsen L, Drewes AM. A comparative study of oxycodone and morphine in a multi-modal, tissue-differentiated experimental pain model. Pain 2006; 123: 28-36.
5. Ross FB, Smith MT. The intrinsic antinociceptive effects of oxycodone appear to be kappa-opioid receptor mediated. Pain 1997; 73: 151-7.
6. Sandner-Kiesling A, Pan HL, Chen SR, James RL, Haven-Hudkins DL, Dewan DM, Eisenach JC. Effect of kappa opioid agonists on visceral nociception induced by uterine cervical distension in rats. Pain 2002; 96: 13-22.
7. Alstergren P, Forstrom J, Alstergren P, Forstrom J. Acute oral pain intensity and pain threshold assessed by intensity matching to pain induced by electrical stimuli. Journal of Orofacial Pain 2003; 17: 151-9.
8. Lundeberg T, Lund I, Dahlin L, Borg E, Gustafsson C, Sandin L, Rosen A, Kowalski J, Eriksson SV. Reliability and responsiveness of three different pain assessments. Journal of Rehabilitation Medicine 2001; 33: 279-83.
9. Nielsen PR. Prediction of post-operative pain by an electrical pain stimulus. Acta Anaesthesiol Scand 2007; 51: 582-6.
10. Stener-Victorin E, Kowalski J, Lundeberg T. A new highly reliable instrument for the assessment of pre- and postoperative gynecological pain. Anesth \& Analg 95: 151-7.

Eligibility criteria: Inclusion Criteria:

* Patients (American Society of Anaesthesiologists (ASA) I, II and III) due for elective, laparoscopic, non-malignant gynaecologic surgery: Hysterectomy or myomectomy.
* Written informed consent.
* Age: 18 to 70 years.

Exclusion Criteria:

* Patients having used non-steroidal anti-inflammatory drugs (NSAIDs) the last 24 hours.
* Sensitivity towards the study drugs.
* Cardiovascular risk conditions: Heart failure, unstable hypertension, coronary artery disease.
* Patients using opioids, steroids or anti-emetic drugs.
* Serious mental disease.

Primary outcomes:
measure: Dosage relation between oxycodone and morphine. Pain score (VAS). Adverse effects.
timeFrame: Within the first postoperative day (24 hours).
Secondary outcomes:
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Ullevaal University Hospital
Study officials:
affiliation: Ullevaal University Hospital
name: Johan Ræder, Prof.MD,Phd
role: STUDY_DIRECTOR
References:
citation: Lenz H, Sandvik L, Qvigstad E, Bjerkelund CE, Raeder J. A comparison of intravenous oxycodone and intravenous morphine in patient-controlled postoperative analgesia after laparoscopic hysterectomy. Anesth Analg. 2009 Oct;109(4):1279-83. doi: 10.1213/ane.0b013e3181b0f0bb.