Controlled-Release Oxycodone For Postoperative Analgesia After Video-Assisted Thoracic Surgery

Study Overview
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Brief Summary
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The main hypothesis of this study is that preoperative administration of controlled-release (CR) oxycodone may reduce acute postoperative pain and improve time to discharge from the post-anesthesia care unit in patients undergoing video-assisted thoracoscopy for spontaneous pneumothorax. The study drug will be compared with intravenous morphine administered 30 minutes before the end of anesthesia.

Detailed Description
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Although spontaneous pneumothorax may be treated conservatively by simple observation or chest tube insertion, up to 50% of patients treated conservatively may experience recurrence in subsequent months or years. Video-assisted thoracic surgery (VATS) is a minimally-invasive surgical approach to treat spontaneous pneumothorax and reduce the risk of recurrence. Compared to open thoracotomy, VATS may facilitate a faster recovery and lead to earlier home discharge. Totally-intravenous anesthesia (TIVA) with propofol and remifentanil is a useful anesthetic technique for VATS, as the drugs are rapidly eliminated after the end of the procedure, leading to fast recovery from anesthesia. One drawback of ultra-short-acting opioid remifentanil is residual hyperalgesia after the end of the infusion, particularly after VATS, which is associated with relatively short but intense pain after surgery. Intravenous morphine, administered just before the end of anesthesia, is the typical choice for pain relief after TIVA. However, this drug may require repeated titration and may be associated with postoperative nausea and vomiting, itchiness or drowsiness in the early postoperative period. Oxycodone, another opioid, is available in an oral controlled-release (CR) formulation which grants relatively constant plasma levels of the drug after 1 h of administration. The investigators hypothesize that administration of CR oxycodone 20 mg 1 hour before surgery may lead to better recovery parameters in the post-anesthesia care unit, thus granting earlier discharge to the surgical ward.

Official Title
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Preoperative Controlled-Release Oxycodone or Intraoperative Morphine As Transition Opioid After Intravenous Anesthesia For Video-Assisted Thoracic Surgery: a Randomized, Double-blind, Controlled Trial.

Conditions
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Anesthesia Recovery Period, Pain, Postoperative

Intervention / Treatment
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* Drug: Morphine
* Drug: oxycodone
* Procedure: Paravertebral block
* Drug: Propofol
* Drug: Remifentanil
* Drug: Paracetamol
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for video-assisted thoracic surgery for clinical diagnosis of spontaneous pneumothorax Must be able to swallow tablets 1 h before surgery American Society of Anesthesiologists (ASA) physical status class I or II Exclusion Criteria: Known allergy or other contraindications to study drugs Acute myocardial infarction ≤6 months before enrollment Serum creatinine > 2 mg/dL Body mass index (BMI) > 30 Diagnosis of psychiatric disorders Known or possible pregnancy Epilepsy Chronic opioid therapy or abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: Control<br>Control intervention will be intraoperative i.v. morphine administration 30 minutes before the end of anesthesia. | Drug: Morphine<br>* 0.15 mg/kg i.v. bolus, 30 minutes before the expected end of anesthesia<br>Procedure: Paravertebral block<br>* Three injections of 0.5% ropivacaine, 5 ml each Injections at the T5, T6 and T7 levels A 22G spinal needle will be used to contact the ipsilateral transverse process; the needle will be walked off the process and the injection will be made 1 cm deeper.<br>* Other names: Naropin®;Drug: Propofol<br>* Plasma concentration target-controlled infusion based on bispectral index values Acceptable range of concentrations: 2-4 µg/mL Target bispectral index values: 40-60 Infusion starts at 4 µg/ml target, after pre-oxygenation (i.e., start of anesthesia)<br>* Other names: Diprivan®;Drug: Remifentanil<br>* 50 µg/mL i.v. solution infused at 0.05-0.2 µg/kg/min Infusion starts 7 min before propofol infusion (i.e., start of anesthesia) Infusion rate adjusted to maintain mean arterial blood pressure within ±20% of baseline values. Infusion stopped after end of surgery and after patients are brought back to the supine position (i.e., end of anesthesia)<br>* Other names: Ultiva®;Drug: Paracetamol<br>* 1 g i.v. bolus 30 min before the end of anesthesia; 1 g i.v. bolus q8h thereafter.<br>* Other names: Perfalgan®;Drug: Morphine<br>* Patient-controlled intravenous infusion pump (IV-PCA). 50 mg morphine in 50 ml saline solution (1 mg/ml) Incremental dose: 1 mg Lock-out time: 8 min Limit: 40 mg in 4 h Background infusion: none<br>* Other names: Patient-controlled analgesia;|
| Experimental: CROxy<br>The intervention group will receive controlled-release oxycodone 1 h pre-operatively | Drug: oxycodone<br>* 20 mg p.o. 1 h before the start of anesthesia<br>* Other names: OxyContin®;Procedure: Paravertebral block<br>* Three injections of 0.5% ropivacaine, 5 ml each Injections at the T5, T6 and T7 levels A 22G spinal needle will be used to contact the ipsilateral transverse process; the needle will be walked off the process and the injection will be made 1 cm deeper.<br>* Other names: Naropin®;Drug: Propofol<br>* Plasma concentration target-controlled infusion based on bispectral index values Acceptable range of concentrations: 2-4 µg/mL Target bispectral index values: 40-60 Infusion starts at 4 µg/ml target, after pre-oxygenation (i.e., start of anesthesia)<br>* Other names: Diprivan®;Drug: Remifentanil<br>* 50 µg/mL i.v. solution infused at 0.05-0.2 µg/kg/min Infusion starts 7 min before propofol infusion (i.e., start of anesthesia) Infusion rate adjusted to maintain mean arterial blood pressure within ±20% of baseline values. Infusion stopped after end of surgery and after patients are brought back to the supine position (i.e., end of anesthesia)<br>* Other names: Ultiva®;Drug: Paracetamol<br>* 1 g i.v. bolus 30 min before the end of anesthesia; 1 g i.v. bolus q8h thereafter.<br>* Other names: Perfalgan®;Drug: Morphine<br>* Patient-controlled intravenous infusion pump (IV-PCA). 50 mg morphine in 50 ml saline solution (1 mg/ml) Incremental dose: 1 mg Lock-out time: 8 min Limit: 40 mg in 4 h Background infusion: none<br>* Other names: Patient-controlled analgesia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine consumption (intravenous titration in PACU + i.v. patient-controlled pump usage) |  | 48 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity as measured on a visual analog scale |  | 1 h after end of anesthesia | 
| Time to discharge from post-anesthesia care unit (Aldrete score >9) |  | 0-12 h after end of anesthesia | 
| Nausea or vomiting |  | 48 h | 
| Respiratory depression (SpO2 < 92% or respiratory rate <8) |  | 48 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Care, Postoperative, Analgesia, Analgesics, Opioid, Morphine, Remifentanil, Oxycodone, Anesthesia, Regional, Anesthesia, Intravenous, Preanesthetic Medication, Analgesia, Patient-Controlled