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

Purpose

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.

Condition	Intervention	Phase
Anesthesia Recovery Period Pain, Postoperative	Drug: Morphine Drug: oxycodone Procedure: Paravertebral block Drug: Propofol Drug: Remifentanil Drug: Paracetamol	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Preoperative Controlled-Release Oxycodone or Intraoperative Morphine As Transition Opioid After Intravenous Anesthesia For Video-Assisted Thoracic Surgery: a Randomized, Double-blind, Controlled Trial.

Resource links provided by NLM:

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Morphine sulfate Oxycodone Acetaminophen Oxycodone hydrochloride Propofol Remifentanil hydrochloride

U.S. FDA Resources

Further study details as provided by University of Parma:

Primary Outcome Measures:

Morphine consumption (intravenous titration in PACU + i.v. patient-controlled pump usage) [ Time Frame: 48 h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pain intensity as measured on a visual analog scale [ Time Frame: 1 h after end of anesthesia ] [ Designated as safety issue: No ]
Time to discharge from post-anesthesia care unit (Aldrete score >9) [ Time Frame: 0-12 h after end of anesthesia ] [ Designated as safety issue: Yes ]
Nausea or vomiting [ Time Frame: 48 h ] [ Designated as safety issue: Yes ]
Respiratory depression (SpO2 < 92% or respiratory rate <8) [ Time Frame: 48 h ] [ Designated as safety issue: Yes ]

Enrollment:	22
Study Start Date:	July 2008
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Paravertebral nerve block Naropin® 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: Propofol TCI target-controlled infusion TIVA TCI-TIVA TIVA-TCI Diprivan® 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: PCA IVPCA IV-PCA PCA-IV Patient-controlled analgesia
Experimental: CROxy The intervention group will receive controlled-release oxycodone 1 h pre-operatively	Drug: oxycodone 20 mg p.o. 1 h before the start of anesthesia Other Names: controlled-release oxycodone CR oxycodone OxyContin® 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: Paravertebral nerve block Naropin® 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: Propofol TCI target-controlled infusion TIVA TCI-TIVA TIVA-TCI Diprivan® 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: PCA IVPCA IV-PCA PCA-IV Patient-controlled analgesia

Arms

Assigned Interventions

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:

Paravertebral nerve block
Naropin®

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:

Propofol TCI
target-controlled infusion
TIVA
TCI-TIVA
TIVA-TCI
Diprivan®

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:

PCA
IVPCA
IV-PCA
PCA-IV
Patient-controlled analgesia

Experimental: CROxy

The intervention group will receive controlled-release oxycodone 1 h pre-operatively

Drug: oxycodone

20 mg p.o. 1 h before the start of anesthesia

Other Names:

controlled-release oxycodone
CR oxycodone
OxyContin®

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:

Paravertebral nerve block
Naropin®

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:

Propofol TCI
target-controlled infusion
TIVA
TCI-TIVA
TIVA-TCI
Diprivan®

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:

PCA
IVPCA
IV-PCA
PCA-IV
Patient-controlled analgesia

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00681174

Locations

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

Sponsors and Collaborators

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

More Information

Publications:

Noppen M, Baumann MH. Pathogenesis and treatment of primary spontaneous pneumothorax: an overview. Respiration. 2003 Jul-Aug;70(4):431-8. Review.

Hansen EG, Duedahl TH, Rømsing 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.

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.

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. Epub 2005 Sep 30.

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. Epub 2006 Aug 8.

Responsible Party:	Guido Fanelli, Professor of Anesthesiology and Critical Care Medicine, University of Parma
ClinicalTrials.gov Identifier:	NCT00681174 History of Changes
Other Study ID Numbers:	ANEST-TOR-01
Study First Received:	May 19, 2008
Last Updated:	January 5, 2012
Health Authority:	Italy: Ethics Committee

Keywords provided by University of Parma:

Care, Postoperative
Analgesia
Analgesics, Opioid
Morphine
Remifentanil

Oxycodone
Anesthesia, Regional
Anesthesia, Intravenous
Preanesthetic Medication
Analgesia, Patient-Controlled

Additional relevant MeSH terms:

Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Acetaminophen
Morphine
Oxycodone
Remifentanil
Propofol
Anesthetics
Antipyretics
Physiological Effects of Drugs

Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Analgesics, Opioid
Narcotics
Anesthetics, Intravenous
Anesthetics, General
Hypnotics and Sedatives

ClinicalTrials.gov processed this record on June 17, 2013