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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain, Postoperative; Anesthesia Recovery Period
• Intervention / Treatment: Drug: Morphine; Procedure: Paravertebral block; Drug: Propofol; Drug: Remifentanil; Drug: Paracetamol; Drug: Morphine; Drug: oxycodone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • PR
    • Parma, PR, Italy, 43100
      • University Hospital / Azienda Ospedaliero-Universitaria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Control intervention will be intraoperative i.v. morphine administration 30 minutes before the end of anesthesia.	Drug: Morphine; 0.15 mg/kg i.v. bolus, 30 minutes before the expected end of anesthesia; Procedure: Paravertebral block; 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.; Other Names: Naropin®; Paravertebral nerve block; Drug: Propofol; 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); Other Names: TIVA; Diprivan®; TIVA-TCI; Propofol TCI; target-controlled infusion; TCI-TIVA; Drug: Remifentanil; 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); Other Names: TIVA; Ultiva®; Drug: Paracetamol; 1 g i.v. bolus 30 min before the end of anesthesia; 1 g i.v. bolus q8h thereafter.; Other Names: Acetaminophen; Perfalgan®; Drug: Morphine; 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; Other Names: IV-PCA; PCA; IVPCA; PCA-IV; Patient-controlled analgesia
Experimental: CROxy; The intervention group will receive controlled-release oxycodone 1 h pre-operatively	Drug: Morphine; 0.15 mg/kg i.v. bolus, 30 minutes before the expected end of anesthesia; Procedure: Paravertebral block; 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.; Other Names: Naropin®; Paravertebral nerve block; Drug: Propofol; 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); Other Names: TIVA; Diprivan®; TIVA-TCI; Propofol TCI; target-controlled infusion; TCI-TIVA; Drug: Remifentanil; 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); Other Names: TIVA; Ultiva®; Drug: Paracetamol; 1 g i.v. bolus 30 min before the end of anesthesia; 1 g i.v. bolus q8h thereafter.; Other Names: Acetaminophen; Perfalgan®; Drug: Morphine; 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; Other Names: IV-PCA; PCA; IVPCA; PCA-IV; Patient-controlled analgesia; Drug: oxycodone; 20 mg p.o. 1 h before the start of anesthesia; Other Names: OxyContin®; controlled-release oxycodone; CR oxycodone

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Parma
• Investigators: Study Chair: Guido Fanelli, MD, Section of Anesthesiology and Critical Care, Dept. of Anesthesiology, University of Parma, Italy; Study Director: Marco Berti, MD, II Unit of Anesthesia, Critical Care and Pain Medicine, University Hospital of Parma, Italy; Principal Investigator: Franca Bridelli, MD, II Unit of Anesthesia, Critical Care and Pain Medicine, University Hospital of Parma, Italy

Publications and helpful links

General Publications

• Hansen EG, Duedahl TH, Romsing J, Hilsted KL, Dahl JB. Intra-operative remifentanil might influence pain levels in the immediate post-operative period after major abdominal surgery. Acta Anaesthesiol Scand. 2005 Nov;49(10):1464-70. doi: 10.1111/j.1399-6576.2005.00861.x.
• Kaya FN, Turker G, Basagan-Mogol E, Goren S, Bayram S, Gebitekin C. Preoperative multiple-injection thoracic paravertebral blocks reduce postoperative pain and analgesic requirements after video-assisted thoracic surgery. J Cardiothorac Vasc Anesth. 2006 Oct;20(5):639-43. doi: 10.1053/j.jvca.2006.03.022. Epub 2006 Aug 8.
• Noppen M, Baumann MH. Pathogenesis and treatment of primary spontaneous pneumothorax: an overview. Respiration. 2003 Jul-Aug;70(4):431-8. doi: 10.1159/000072911.
• Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, Reder RF, Goldenheim PD. Analgesic efficacy of controlled-release oxycodone in postoperative pain. J Clin Pharmacol. 1996 Jul;36(7):595-603. doi: 10.1002/j.1552-4604.1996.tb04223.x.
• Vogt A, Stieger DS, Theurillat C, Curatolo M. Single-injection thoracic paravertebral block for postoperative pain treatment after thoracoscopic surgery. Br J Anaesth. 2005 Dec;95(6):816-21. doi: 10.1093/bja/aei250. Epub 2005 Sep 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: May 19, 2008
• First Submitted That Met QC Criteria: May 19, 2008
• First Posted (Estimate): May 21, 2008

Study Record Updates

• Last Update Posted (Estimate): January 6, 2012
• Last Update Submitted That Met QC Criteria: January 5, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Remifentanil; Analgesia; Morphine; Anesthesia, Regional; Analgesia, Patient-Controlled; Analgesics, Opioid; Oxycodone; Anesthesia, Intravenous; Preanesthetic Medication; Care, Postoperative
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Remifentanil; Propofol; Acetaminophen; Morphine; Oxycodone
• Other Study ID Numbers: ANEST-TOR-01