Opioids have an important role in the treatment of postoperative pain, making them essential drugs in the field of anesthesiology. However, opioids have common side effects such as nausea, vomiting, constipation and respiratory depression. Recently there has also been focus on a less known side effect, opioid-induced hyperalgesia, when paradoxical lowering of the pain threshold increases pain after opioid use.
In her thesis, «Opioids in postoperative pain treatment. Studies on analgesic efficacy and reduction of opioid-induced side effects» Marlin Comelon has conducted three randomized controlled trials on the analgesic effect and side effects of opioids with relevance in the postoperative setting. In the first study, no effect on constipation was found from adding peripherally acting naloxone to the opioid oxycodone after hysterectomy. Naloxone did, however, not antagonize the analgesic effect of oxycodone. The second study focused on tapentadol which combines effects from µ-opioid receptors and noradrenaline reuptake inhibition for analgesia. Similar analgesic effects from tapentadol and oxycodone after hysterectomy were found, but the patients receiving tapentadol had less nausea and need for antiemetics. The third study was an experimental crossover study on healthy volunteers. It demonstrated that gradual withdrawal of remifentanil infusion, as opposed to abrupt withdrawal, could prevent opioid-induced hyperalgesia.
The two clinical studies in the thesis contribute to the evidence on which patients may have benefits from these drugs over standard treatment. Oxycodone-naloxone is not likely to have effect in patients with normal risk of postoperative constipation but can be an alternative for long-term use in patients with a high risk of constipation. Tapentadol is an option for patients with previous postoperative nausea and vomiting. The study on opioid-induced hyperalgesia helps increase awareness of adverse postoperative effects from perioperative opioids.