Methadone Versus Placebo in Spine Fusion - Full Text View

Purpose

Research Question: What is the influence of methadone on postoperative analgesia after lumbar interbody fusion in opioid naïve patients or patients who are taking less than equivalent of 15 mg IV morphine each day? What is the incidence of opioid related postoperative side effects after the administration of methadone in the operating room?
Hypothesis: (1) We hypothesize that 0.2 mg/kg of methadone will result in decreased postoperative hydromorphone consumption compared to hydromorphone alone in opioid naïve patients or patients who are taking less than the equivalent of 15 mg IV morphine a day undergoing lumbar interbody fusion. (2) We hypothesize that the incidence of opioid related postoperative side effects will not be increased by the administration of methadone in the operating room.

Condition	Intervention
Postoperative Pain	Drug: Methadone Drug: Saline

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Effect of Methadone on Perioperative Analgesia After Posterior Lumbar Fusion - A Randomized, Placebo-controlled, Double-blinded Study

Resource links provided by NLM:

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Methadone Methadone hydrochloride

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

Hydromorphone postoperative opioid consumption (POC) at 48 hours [ Time Frame: 48 hrs ] [ Designated as safety issue: No ]
PCA opioid consumption during the initial postoperative 48 hours after arriving in the PACU

Secondary Outcome Measures:

Intraoperative remifentanil consumption [ Time Frame: the 8 hours prior to arrival in the recovery room ] [ Designated as safety issue: No ]
intraoperative consumption of remifentanil--the amount of remifentanil used in the OR (i.e., the 2-8 hours prior to arrival in the recovery room)
pain at rest and with movement (numerical Rating Scale, NRS) [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs ] [ Designated as safety issue: No ]
the level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale) [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs ] [ Designated as safety issue: Yes ]
the number of occurrences of ventilatory depression during each evaluation interval [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs ] [ Designated as safety issue: Yes ]
number of occurrences of nausea (resulting in treatment) [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs ] [ Designated as safety issue: No ]
recorded emesis [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs ] [ Designated as safety issue: No ]
occurrence of pruritus [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs ] [ Designated as safety issue: No ]
Hydromorphone postoperative opioid consumption (POC) [ Time Frame: 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs ] [ Designated as safety issue: No ]
PCA opioid consumption at postoperative 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs after arriving in the PACU

Estimated Enrollment:	80
Study Start Date:	May 2010
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Methadone Group	Drug: Methadone 0.2 mg/kg methadone IV bolus
Placebo Comparator: Placebo Group	Drug: Saline 3 mL saline IV bolus

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

ASA physical status I, II, and III, male and non-pregnant female
English-speaking patients
Ages 18-75 years
Undergoing elective one or two level posterior lumbar interbody fusion

Exclusion Criteria:

Use of more than the equivalent of 15 mg of IV morphine/24 hr in the past 2 weeks.
Use of drugs within the past 6 months that effect the pharmacokinetics or pharmacodynamics of opioids (i.e., benzodiazepines, anti-retroviral agents, rifampin, ketoconazole, erythromycin, or phenytoin).
history of substance abuse at any time in the past
known QT prolongation
Non-elective operations (i.e., cancer or trauma)
severe hepatic impairment (serum albumin < 3.0 g/dL in the presence of a history of liver disease)
pregnancy
inability to operate a patient-controlled analgesia device

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01125059

Locations

United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Feinberg School of Medicine, Northwestern University

Investigators

Principal Investigator:

Dhanesh K Gupta, M.D.

Northwestern University Feinberg School of Medicine

More Information

Publications:

Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995 Dec 20;274(23):1870-3. Review.

Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. Review.

Taylor S, Kirton OC, Staff I, Kozol RA. Postoperative day one: a high risk period for respiratory events. Am J Surg. 2005 Nov;190(5):752-6.

Taylor S, Voytovich AE, Kozol RA. Has the pendulum swung too far in postoperative pain control? Am J Surg. 2003 Nov;186(5):472-5.

Liu N, Kuhlman G, Dalibon N, Moutafis M, Levron JC, Fischler M. A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg. 2001 Jan;92(1):31-6.

Joris J, Kaba A, Lamy M. Transition between anesthesia and post-operative analgesia: relevance of intra-operative administration of analgesics. Acta Anaesthesiol Belg. 2001;52(3):271-9. Review.

Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):576-91. Review.

Yaksh TL, Hua XY, Kalcheva I, Nozaki-Taguchi N, Marsala M. The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7680-6. Review.

Parker RK, Holtmann B, White PF. Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements after abdominal hysterectomy. Anesthesiology. 1992 Mar;76(3):362-7.

Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. No abstract available.

Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51.

Egan TD, Huizinga B, Gupta SK, Jaarsma RL, Sperry RJ, Yee JB, Muir KT. Remifentanil pharmacokinetics in obese versus lean patients. Anesthesiology. 1998 Sep;89(3):562-73.

Lemmens HJ, Brodsky JB, Bernstein DP. Estimating ideal body weight--a new formula. Obes Surg. 2005 Aug;15(7):1082-3.

Bowdle TA, Even A, Shen DD, Swardstrom M. Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate. Anesth Analg. 2004 Jun;98(6):1692-7, table of contents.

Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.

Apfelbaum JL, Gan TJ, Zhao S, Hanna DB, Chen C. Reliability and validity of the perioperative opioid-related symptom distress scale. Anesth Analg. 2004 Sep;99(3):699-709, table of contents.

van Dorp EL, Kest B, Kowalczyk WJ, Morariu AM, Waxman AR, Arout CA, Dahan A, Sarton EY. Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology. 2009 Jun;110(6):1356-63.

Responsible Party:	Dhanesh Gupta, Associate Professor of Anesthesiology & Neurological Surgery, Northwestern University
ClinicalTrials.gov Identifier:	NCT01125059 History of Changes
Other Study ID Numbers:	STU00027431
Study First Received:	May 11, 2010
Last Updated:	February 14, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

hydromorphone
lumbar posterior spinal fusion
lumbosacral spondylosis
Spinal Fusion

Additional relevant MeSH terms:

Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Methadone
Analgesics, Opioid
Analgesics
Sensory System Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on May 23, 2013