Oxycodone Versus Morphine for Analgesia After Laparoscopic Endometriosis Resection

Lijun Niu; Lihong Chen; Yanhua Luo; Wenkao Huang; Yunsheng Li


BMC Anesthesiol. 2021;21(194) 

In This Article


In this prospective double-blind randomized controlled study, the results presented some significant findings. First, visceral pain was the dominating pain in the first 24 h after laparoscopic DIE resection. Second, morphine IV-PCA and oxycodone IV-PCA could provide effective and safe analgesia. Meanwhile, oxycodone consumption was significantly less than morphine consumption. Finally, the incidence of nausea and vomiting in the oxycodone group was lower than the morphine group. These results suggested that oxycodone was more potent than morphine for analgesia after laparoscopic DIE resection.

In the present study, oxycodone consumption was significantly less than morphine consumption, which suggested that the analgesic potencyof oxycodone was higher than morphine, and was consistent with studies of Lenz et al.[8] and Li et al..[12] Furthermore, the average time to first request for opioid in the oxycodone group was significantly shorter than the morphine group, and the total number of bolus in oxycodone group was significantly less than the morphine group, which further confirmed that oxycodone was potent than morphine for analgesia. The main possible reason was that oxycodone also activated the κ receptor, which was more effective in reducing visceral pain, and visceral pain was the major component of the pain after laparoscopic DIE resection.

Oxycodone is a semisynthetic opioid that may be an agonist of the central and peripheral κ- as well as μ-opioid receptors.[5] A lot of studies demonstrate that intravenous oxycodone is an effective treatment for acute postoperative pain. Hwang et al.[13] found oxycodone significantly relieved immediate postoperative pain in patients undergoing laparoscopic cholecystectomy. Tanskanen et al.[14] found PCA with oxycodone provided satisfactory postoperative pain relief after craniotomy. In our study, the VAS score was acceptableand was not different between groups, which indicated that with PCA technology, oxycodone and morphine could effectively reduce the pain after laparoscopic DIE resection.

Moreover, some studies have shown that oxycodone can better relieve visceral pain. In a volunteer research experiment, Staahl et al.[15] found oxycodone was clearly superior to both placebo and morphine in pain modulation to thermally and mechanically induced visceral pain. In a study of laparoscopic cholecystectomy, An et al.[7] found preemptive oxycodone 0.1 mg/kg administration could effectively suppress visceral pain when compared to an equal dose of sufentanil. The main reason was that oxycodone was not only the μ-opioid receptor agonist but also the κ-opioid receptor agonist.[8,15] κ-opioid receptor has been suggested as a possible target for attenuating visceral pain. It raises the threshold for visceral pain stimulation, thereby blocking peripheral pain signals and thus attenuating input to the central nervous system, finally alleviating visceral pain.[16]

However, some studies have shown that the analgesic potency of oxycodone was not better than that of morphine. Pedersen et al.[17] found that oxycodone was not superior in the treatment of visceral pain after percutaneous kidney stone operation. The possible reasons were that the pain intensity after percutaneous kidney stone operation may be too low to yield a significant difference in opioid consumption and this study only analysed the consumption of morphine and oxycodone 4 h after surgery. In another study[18] comparing morphine and oxycodone in patients with corrective breast or lumbar spinal surgery in which patients used IV-PCA for postoperative pain relief, a similar amount of morphine and oxycodone was needed for sufficient analgesia. The main reason may be that the main type of pain after these surgeries was not visceral pain.

Postoperative pain management after laparoscopic surgery remains a great challenge. One of the important reasons is that the components of pain after laparoscopic surgery are complex. Pain after laparoscopic surgery can be divided into incision pain, shoulder pain and visceral pain.[4] The characteristics of postoperative pain vary from procedure to procedure. For example, incisional pain dominated in incidence and intensity compared with visceral pain and shoulder pain during 24 h after laparoscopic cholecystectomy.[19] Visceral pain was the dominating pain after uncomplicated laparoscopic fundoplication[20] and laparoscopic inguinal hernia repair.[21] Shoulder pain was the most intense pain in postoperative 24 h after total laparoscopic hysterectomy.[4] The reasons for the different types of pain in different surgeries are unclear, which may be related to the site of surgical separation and resection, and pressure and time of carbon dioxide pneumoperitoneum.

Since the major pain components are different, interventions targeting the major pain are necessary to obtain better pain relief. For example, local anesthesia infiltration and nerve block are more suitable for postoperative analgesia with incision pain as the main pain. NSAIDs are more appropriate for postoperative analgesia in shoulder pain as the dominating pain. Therefore, it is important to identify prominent pain and analyse the impact of analgesic interventions on prominent pain in order to get better postoperative analgesia. In this study, we explored the most important pain component within 24 h. The results showed that during 24 h after laparoscopic DIE resection, visceral pain was the prominent pain that prompted patients to request analgesia at almost all observation time points, which was different from pain characteristics of laparoscopic cholecystectomy and laparoscopic hysterectomy.

The pathophysiological mechanisms of visceral pain are extremely complex and poorly understood. One of the important mechanisms is peripheral and/or central pathway sensitization, which increases the perception of visceral stimulation and leads to visceral hypersensitivity, and may be affected by multiple conditions, including stress, mood, and some conditions induced by surgery, for example, organ injury or stretch of intense force by distension or contraction, peritoneal inflammation, local acidosis, and visceral mucosa ischemia.[22] The possible reasons for the dominating pain after laparoscopic DIE resection was visceral pain might be that laparoscopic DIE resection needed to explore and resect more tissues and organs inside the abdomen, such as rectum, ureter, vagina, and required longer carbon dioxide pneumoperitoneum time which might induce visceral mucosa ischemia.

Postoperative nausea and vomiting (PONV) are common adverse effects in PCA with opioids. It is known the use of opioids is a risk factor of PONV. Opioids cause nausea and vomiting by stimulating the chemoreceptor trigger zone in the medulla via μ-receptor.[23] Although many patients eventually develop tolerance to this side effect, nausea and vomiting during the early phase of treatment often lead patients to discontinue opioid therapy, resulting in analgesic undertreatment. Therefore, reduction the incidence of PONV is expected to improve the overall quality of analgesic efficacy. It is reported that oxycodone had lower incidence of POVN than other opioids. In a study of elective abdominal surgery,[24] oxycodone IV-PCA showed lower incidence of PONV than sufentanil IV-PCA during postoperative pain management. In our study, we found that the incidence of PONV was lower in the oxycodone group than that in the morphine group. The reasons were listed as follows. Firstly, oxycodone has a weaker u-receptor affinity than morphine,[25] which may mitigate gastrointestinal side effects caused by μ-receptor agonism. Second, in this study, patients in the oxycodone group required less oxycodone. It is known that opioid-related side effects such as nausea and vomiting are dose-dependent. As a result, patients treated with oxycodone had lower incidence of PONV. However, Kim et al.[26] found that the incidence of PONV was higher in oxycodone IV-PCA than fentanyl IV-PCA in the postoperative analgesia of laparoscopic supracervical hysterectomy. The main reason may be that the ratio of oxycodone to fentanyl (potency ratio 75:1) was too high. More studies are still needed to determine whether oxycodone has a lower incidence of PONV than other opioids.

There was no difference in the incidence of respiratory depression, or bradycardia between groups, and no clinically significant postoperative respiratory depression or bradycardia was observed. The possible reasons might be that most patients did not use the PCA device to completely eliminate their pain, or PCA technology could effectively reduce respiratory depression and bradycardia.

There were some limitations in the present study. First, we only explored the main type of pain after laparoscopic DIE resection, but did not evaluate the frequency and intensity of the three types of pain. Further research was to characterize the early pain characteristics. Second, we did not follow up the patients to evaluate whether chronic pain was reduced with the oxycodone in the study. Future research should also focus on the long-term effects. The third limitation was that the patients' pain thresholds were not tested before conducting the study.