Factors affecting pain intensity and postoperative oxycodone requirement: Clinical and genetic perspectives

Breast cancer is one of the most common cancers in the world. The advancement in diagnostic tools and treatment options have majorly improved the prognosis of the disease. Nevertheless, every year thousands of women receive this diagnosis and undergo breast cancer surgery in hope of survival. Modern day surgery requires efficient analgesia to protect the body from the stress caused by severe pain. Therefore, analgesics are used both intra- and post-operatively. Opioids are the gold standard analgesic for moderate or severe post-operative pain and oxycodone has been the opioid most used for post-operative pain in Finland for decades. Due to the serious adverse effects, all opioids must be titrated to analgesic doses gradually, which prolongs the time it takes to reach satisfactory analgesia and predisposes patient to suffering and to the harmful physical effects of pain. The purpose of this thesis was to identify whether oxycodone has an analgesic plasma concentration, as well as which factors affect the post-operative pain intensity and oxycodone requirements after breast cancer surgery. The identification of these factors helps clinicians recognize patients at risk of severe post-operative pain and in need of higher doses of oxycodone to reach satisfactory analgesia. The study cohort consisted of 1,000 women about to undergo breast cancer surgery due to unilateral non-metastasised breast cancer. Before the surgery, each patient`s demographic data, medical history, pain, depressive symptoms and anxiety state were recorded along with heat (48°C) and cold (4°C) pain sensitivity. Anaesthesia protocol was standardized. After the surgery, all patients were titrated to satisfactory analgesia with intravenous oxycodone. The post-operative pain intensities and oxycodone requirements were recorded from the first 20 post-operative hours. Post-operative pain intensity, requirement of oxycodone and analgesic oxycodone concentrations varied significantly between patients. Factors associated with higher post-operative motion pain were young age, axillary clearance (vs. sentinel node biopsy), higher preoperative cold pain intensity and cold pain tolerance. Together these factors explained 8.5% of the variation in the motion pain intensities. Post-operative motion pain intensity was the major predictor of post-operative oxycodone requirement, together with BMI, age, axillary clearance, OPRM1 rs1799971 genotype and preoperative breast pain. Together these factors explained 28% of the total variation in oxycodone requirement. Only post-operative motion pain intensity and axillary clearance were associated with analgesic oxycodone plasma concentrations, which together explained almost 17% of the total variation. CYP2D6 genotype did not associate with the analgesic oxycodone requirement or concentration but did affect the oxymorphone and noroxymorphone plasma concentrations. The results presented in this study could help identify patients at risk of higher pain intensities and oxycodone requirements after breast cancer surgery.