Oxycodone and Sufentanil for Analgesia in Hip Surgery

Study Overview
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Brief Summary
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We design this randomized controlled trial to compare the safety and efficacy of Oxycodone and Sufentanil for postoperative patient-controlled analgesia in patients undergoing hip surgery, with a view to finding the optimal postoperative analgesic regime with fewer adverse reactions and promoting patients' rehabilitation.

Detailed Description
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Hip surgery is a common type of orthopedic surgery. The pathologies are complex, including chronic conditions such as femoral head necrosis, primary hip dysplasia, hip joint osteoarthritis and rheumatoid arthritis, as well as acute diseases such as femoral neck fractures and intertrochanteric fractures. The surgical treatment includes closed reduction and internal fixation, open reduction and internal fixation, hemiarthroplasty (femoral head replacement), and total hip arthroplasty, etc. The population of patients undergoing hip surgery has a high proportion of elderly (>65 years old), with multiple preoperative comorbidities, and significant postoperative pain. We must achieve the balance between the providing sufficient analgesia and minimizing associated adverse reactions perioperatively for such group of patients, therefore promoting patients' rehabilitation. Sufentanil, a pure μ receptor agonist with active metabolite, is a long-acting strong opioid which has high analgesic efficacy. It is commonly used in anesthesia practice, not only for intraoperative analgesia, but also postoperative pain relief, i.e. a popular drug of choice used for Patient Control Intravenous Analgesia (PCIA). However, sufentanil is associated with high incidence of postoperative nausea and vomiting (PONV), respiratory depression and other adverse reactions, which could negatively affect the patient's analgesic satisfaction, and compromise the course of postoperative recovery. It is important to establish an effective and safe postoperative analgesic regime that can achieve the comparable analgesic efficacy with reduced incidence of adverse reactions. Oxycodone is a semi-synthetic opioid which is extracted from the thebaine, it activates both μ and κ opioid receptors. It has been reported to have good analgesic effect and lower incidence of adverse reactions such as PONV in comparison with Morphine, and could be a reasonable option for PCIA. As Oxycodone can agonize κ receptors and reduce visceral pain, most of the existing studies on Oxycodone are focused on laparoscopic cholecystectomy and other abdominal surgeries, with the average age of study patients is between 40 to 55 years old, and also lack of large sample studies. Based on the abovementioned literatures, we propose the hypothesis that in hip surgery, compared with Sufentanil PCIA, the equipotency dose of Oxycodone PCIA can achieve the same postoperative analgesic efficacy and may also reduce the incidence of adverse reactions associated with opioids.

Official Title
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Comparison of Oxycodone and Sufentanil for Analgesic Efficacy After Hip Surgery: a Prospective, Multicenter Randomized Controlled Trial

Conditions
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Analgesia, Patient-Controlled

Intervention / Treatment
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* Drug: Oxycodone Hydrochloride
* Drug: Sufentanil Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing unilateral hip surgery, sign the informed consent form Age above 18 years old Exclusion Criteria: Pregnant or lactating women Patients with history of drug abuse, including but not limited to opioids, amphetamines, ketamine, etc Allergic to opioids Have history of nervous system diseases such as peripheral neuropathy, or psychiatric mental illness Other conditions that the investigators consider unsuitable for participation in the study, such as deaf, Parkinson's disease, and difficult to communication etc

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxycodone group<br>PCIA is formulated at 0.4 mg/ml of oxycodone. | Drug: Oxycodone Hydrochloride<br>* Subjects will receive patient' controlled intravenous analgesia in analgesic pump with 0.4 mg/ml of oxycodone for postoperative analgesia.<br>|
| Active Comparator: Sufentanil group<br>PCIA is formulated at 2 μg/ml of sufentanil. | Drug: Sufentanil Citrate<br>* Subjects will receive patient' controlled intravenous analgesia in analgesic pump with 2 μg/ml of sufentanil for postoperative analgesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative numerical rating scales (NRS) at rest | Resting NRS pain scores at 2 h after surgery. | Up to 72 hours after operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative NRS on movement | Postoperative NRS pain score on movement, up to 72hr. | Up to 72 hours after operation | 
| Postoperative complications | Incidence of postoperative adverse reactions and complications | Up to 30 days after operation | 
| Residual amount of drug | Residual amount of drug in the analgesic pump. | Up to 72 hours after operation | 
| Length of stay (LOS) in hospital | Time frame from the day of hospital admission to discharge from the hospital (unit: days) | Up to 30 days after operation | 
| Postoperative LOS | Time frame from the day of operation to discharge from the hospital (unit: days). | Up to 30 days after operation | 
| Re-admission rate | The incidence of re-admission within 30 days after surgery. | Up to 30 days after operation | 
| Total in-hospital cost. | Total hospitalization expenses after the destruction of costly consumables in orthopedic operation. | Up to 30 days after operation | 
| Time from the end of operation to the first onset of PONV | Time from the end of operation to the first onset of PONV | Up to 30 days after operation | 
| The severity of first PONV and the most severe PONV | The severity of PONV is scored from 0 to 10, and 0 represents no PONV at all, and 10 represents very severe PONV. | Up to 30 days after operation | 
| Motion of hip joints | Range of motion of hip joints during 3 days after operation. | Up to 72 hours after operation | 
| Straight leg raising time | Time from the end of operation to the time that patient can raise his affected lower limb by himself (Unit: hour). | Up to 72 hours after operation | 
| Ground exercise time | Time from the end of operation to the time that patient can do the ground exercise by himself (Unit: hour). | Up to 72 hours after operation | 
| Mobilization time | Time frame from the end of operation to able to walk without external assistance (Walking aids such as crutches can be used, unit: hour). | Up to 72 hours after operation | 
| Incidence of post operative nausea and vomiting (PONV) | The proportion of subjects who experienced PONV | Up to 72 hours after operation |