Methadone Versus Placebo in Spine Fusion

Postoperative Pain Clinical Trial

Official title:

The Effect of Methadone on Perioperative Analgesia After Posterior Lumbar Fusion - A Randomized, Placebo-controlled, Double-blinded Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01125059
• Other study ID #: STU00027431
• Status: Withdrawn
• Phase: N/A
• First received: May 11, 2010
• Last updated: April 21, 2015
• Start date: May 2010
• Est. completion date: January 2014

Study information

• Verified date: April 2015
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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?

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Methadone
0.2 mg/kg methadone IV bolus
• Saline
3 mL saline IV bolus

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Feinberg School of Medicine, Northwestern University

Country where clinical trial is conducted

United States, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. doi: 10.1097/ALN.0b013e3181a105de. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hydromorphone postoperative opioid consumption (POC) at 48 hours	PCA opioid consumption during the initial postoperative 48 hours after arriving in the PACU	48 hrs	No
Secondary	Intraoperative remifentanil consumption	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)	the 8 hours prior to arrival in the recovery room	No
Secondary	pain at rest and with movement (numerical Rating Scale, NRS)		1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs	No
Secondary	the level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale)		1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs	Yes
Secondary	the number of occurrences of ventilatory depression during each evaluation interval		1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs	Yes
Secondary	number of occurrences of nausea (resulting in treatment)		1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs	No
Secondary	recorded emesis		1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs	No
Secondary	occurrence of pruritus		1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs	No
Secondary	Hydromorphone postoperative opioid consumption (POC)	PCA opioid consumption at postoperative 1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs after arriving in the PACU	1 hr, 6 hrs, 12 hrs, 24 hrs, 36 hrs	No