Oxycodone Versus Morphine for Analgesia After Laparoscopic Endometriosis Resection

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

Disclosures

BMC Anesthesiol. 2021;21(194) 

In This Article

Methods

Patients and Study Design

This prospective randomized double-blinded clinical trial, which adhered to CONSORT guidelines and included a completed CONSORT checklist as an additional file, was approved and was performed from April 2019 to August 2019, in accordance with the Helsinki Declaration of the World Medical Association. This study has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR1900021870).

After obtaining the patients' written informed consent, 50 adults (20–55 years of age), presenting with American Society of Anesthesiologists (ASA) physical status I and II, and scheduled for laparoscopic DIE resection under general anesthesia, were included in the trial. Patients were excluded in case of drug or alcohol addiction; known allergy to any drug used in the study; chronic opioid therapy in the 3 months before surgery; chronic therapy with antidepressants or clonidine; a history of abdominal surgery; bilirubin level > 3.0 mg/dL; aspartate aminotransferase and/or alanine aminotransferase > 250 IU; body mass index (BMI) > 30 kg/m2 or < 18 kg/m2; postoperative recovery in the intensive care unit; prolongation of operation time; and surgical complications during operation (such as bleeding…etc.).

The day before the operation, the patients were instructed carefully to use a visual analogue scale (VAS; score range, 0 cm [no pain] to 10 cm [worst pain]) to measure the degree of pain. If VAS > 3, patients received analgesia by pressing intravenous patient-controlled analgesia (IV-PCA) device until VAS ≤ 3. Meanwhile, the three main pain components after laparoscopic surgery were explained in detail as described below to the patients.[9] Incisional pain was defined as wound pain located in the abdominal wall, which may be superficial and clear to localize. Visceral pain was defined as pain inside the abdomen, which may be deep, dull, and difficult to localize. Shoulder pain was defined as pain in the shoulder. After patients receiving analgesia by pressing the analgesic device, we asked patients what kind of prominent pain caused them to press the analgesic device and recorded it.

Patients were randomly assigned to 2 groups, morphine (M, n = 25) group, and oxycodone (O, n = 25) group by using a computer-generated random number table. Patients received morphine or oxycodone IV-PCA (morphine or oxycodone 1 mg/ml; no background infusion; bolus 0.05 mg/kg, 2 ml; and a lock-out time of 8 min) for 24 h postoperatively. At the end of the operation, a 0.1 mg/kg dose of morphine or oxycodone was given. Allocation concealment was performed using a sealed envelope approach because randomly generated treatment allocations were placed in sealed opaque envelopes. The envelopes were opened by a nurse who was not involved in this study just before the induction of anaesthesia. The anaesthesiologists who were responsible for the anaesthesia and analgesia during the operation were blinded to the group allocation. The nurses who prepared the analgesic device were not involved in the observation, pain scoring of patients, and treatment of the patients during the operating room. The surgeons and observers were also blinded to the group allocation.[10]

Surgical Procedure

All patients received standardized general anaesthesia without premedication. General anaesthesia was induced with 2 mg/kg propofol, 3 μg/kg fentanyl, and 0.15 mg/kg cisatracurium following standard monitoring including arterial blood pressure, electrocardiogram, Narcotrend (MonitorTechnik, Bad Bramstedt, Germany), arterial oxygen saturation, and end-tidal carbon dioxide monitoring. Anaesthesia was maintained with 2–3% sevoflurane to keep the Narcotrend depth-of-anaesthesia value between 30 and 50. Remifentanil was continuously infused at the rate of 0.15–0.25 μg/kg/min. At the end of the surgery, a 0.1 mg/kg dose of tropisetron was given. Patients were transferred to the post-anaesthesia care unit (PACU) after surgery.

The pressure of carbon dioxide was maintained at 12 mmHg during the operation. All surgical interventions were performed by the same surgeons with high experience in performing laparoscopic interventions. Details of the surgical method used were reported in Setälä et al..[11]

Clinical Observations

For each patient, the age, BMI, duration of surgery and PACU, time of carbon dioxide pneumoperitoneum, ASA class, and excised site were recorded. The primary endpoint of the study was total morphine or oxycodone consumption during the 24 h after laparoscopic DIE lesion resection. Morphine or oxycodone consumption at 2 h, 4 h, 8 h, 12 h and 24 h after surgery were also recorded. Secondary outcomes included the time to first request for analgesia, the number of IV-PCV bolus, pain, sedation, the incidence of nausea, respiratory depression, vomiting, and bradycardia. The pain was evaluated at 2, 4, 8, 12 and 24 h after operation. The following parameters including the number of IV-PCV bolus, nausea, vomiting, sedation, respiratory depression, and bradycardia were recorded at the same time intervals. Nausea and vomiting were recorded as present or absent. Sedation was scored according to the Ramsay sedation scale. Respiratory depression was recorded as present or absent and was defined as a respiratory rate < 8 breaths/min or peripheral capillary oxygen saturation (SpO2) < 95% without oxygen treatment. Bradycardia was recorded as present or absent and was defined as a heart rate < 50 beats/min.[10]

Statistical Analysis

Postoperative opioid consumption in the first 24 h after surgery was considered the primary efficacy variable. Based on an unpublished pilot study with 20 patients undergoing laparoscopic DIE resection where a mean morphine and mean oxycodone consumption of 20 and 15 mg, respectively (standard deviation of 5 mg) was used. The calculated sample size was 23 individuals in each group (α = 0.05; power = 0.9). Finally, 25 patients in each group were planned for inclusion.

The normality of continuous data was tested using the Shapiro–Wilk test. Normally distributed parameters were presented as mean ± standard deviation and analysed using the Student's t-test. Non-normally distributed parameters were presented as medians [interquartile range (IQR)] and analysed using the Mann–Whitney U test. The Bonferroni correction was used for multiple measures. Categorical data were described as numbers or percentages and analysed with the chi-square or Fisher's exact tests, as appropriate. The difference in continuous variables over time was tested by the repeated-measures analysis of variance. Statistical significance was defined as p < 0.05. SPSS Statistics version 26.0 for Windows was used to perform all analyses.[10]

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