Methadone vs Magnesium in Spinal Fusion

• Sponsor: Nationwide Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01795495
• Collaborator: (none)
• Enrollment: 63
• Location: 1
• Arms: 3
• Duration (Months): 36
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Significant pain may occur following posterior spinal fusion despite the use of conventionally accepted techniques including patient controlled analgesia. If detected, a significant reduction in opioid requirements may lead to improved patient satisfaction and decreased opiate side effects.

The current study would use a prospective, randomized trial investigating the efficacy of one of 2 regimens as adjuncts to intraoperative anesthesia and postoperative analgesia, along with a third control group. The patients would be randomized to receive remifentanil plus a single intraoperative dose of methadone; remifentanil plus a bolus followed by an infusion of magnesium; or remifentanil alone. In addition, the two medications being studied might make it easier to determine the efficacy of neurophysiologic monitoring including somatosensory evoked potential (SSEP) (amplitude and latency) and motor evoked potential (MEP) (mA) required to elicit the response.

The purpose of this study would be to explore the effects of intraoperative methadone vs magnesium on intraoperative anesthetic requirements, postoperative opioid requirements, the efficacy of neurophysiologic monitoring including SSEP and MEP, inspired concentration of desflurane, remifentanil, and the need for intraoperative supplemental agents to control blood pressure.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Scoliosis	Drug: Methadone hydrochloride; Drug: Magnesium Sulfate; Drug: Remifentanil	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Analgesia Following Posterior Spinal Fusion: Methadone vs Magnesium
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Remifentanil This arm will receive remifentanil alone as is the current practice.	Drug: Remifentanil
Experimental: Remifentanil plus methadone This arm will receive the current analgesic remifentanil plus and adjunct dose of methadone hydrochloride.	Drug: Methadone hydrochloride; This drug will be used in conjunction with remifentanil as an adjunct analgesic. Remifentanil + methadone (0.1 mg/kg IV over 15 minutes) just after induction of anesthesia; Other Names: Methadone
Experimental: Remifentanil plus magnesium This arm will receive the current analgesic remifentanil plus an adjunct dose of magnesium sulfate.	Drug: Magnesium Sulfate; This drug will be given with remifentanil as an adjunct analgesic. Remifentanil + magnesium (50 mg/kg bolus over 30 minutes followed by 10 mg/kg/hour).; Other Names: Magnesium

Outcome Measures

Primary Outcome Measures

1. Intra- and Post-operative Pain Relief [Intra-operative and 24 hours post-operatively]

   To prospectively compare the effects of intra-operative methadone and magnesium on postoperative opioid requirements. Total amount of hydromorphone administered in OR, recovery room (PACU), and on the inpatient ward 24 hours post-operatively.

Secondary Outcome Measures

1. Post-operative Pain Scores [Post-operatively to 24 hours]

   VAS pain score - 0 being no pain and 10 being worst pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients older than 12, and younger than 19 years of age undergoing posterior spinal fusion for idiopathic scoliosis

• American Society of Anesthesiologist (ASA) physical status I or II

• Parents/Guardian willing and able to authorize informed consent

• Patients willing and able to authorize assent

Exclusion Criteria:

• Patients presenting with neuromuscular scoliosis

• Patients deemed at increased risk of adverse reactions due to the presence of pre-existing severe organ system dysfunction, including debilitating lung disease, severe obstructive sleep apnea, severe congenital or acquired heart disease, and/or severe renal impairment

• Patients who are both being currently treated for a psychological disorder and have a history of hospitalization for said disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nationwide Children's Hospital	Columbus	Ohio	United States	43205

Sponsors and Collaborators

• Nationwide Children's Hospital

Investigators

• Principal Investigator: David P. Martin, MD, Nationwide Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Elsharnouby NM, Elsharnouby MM. Magnesium sulphate as a technique of hypotensive anaesthesia. Br J Anaesth. 2006 Jun;96(6):727-31. Epub 2006 May 2.
• Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
• Levaux Ch, Bonhomme V, Dewandre PY, Brichant JF, Hans P. Effect of intra-operative magnesium sulphate on pain relief and patient comfort after major lumbar orthopaedic surgery. Anaesthesia. 2003 Feb;58(2):131-5.
• Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED. Perioperative pharmacokinetics of methadone in adolescents. Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5.
• Stemland CJ, Witte J, Colquhoun DA, Durieux ME, Langman LJ, Balireddy R, Thammishetti S, Abel MF, Anderson BJ. The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Paediatr Anaesth. 2013 Jan;23(1):51-7. doi: 10.1111/pan.12021. Epub 2012 Sep 14.

• Responsible Party: David P. Martin, Clinical Assistant Professor, Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT01795495
• Other Study ID Numbers: IRB13-0036; Active
• First Posted: Feb 20, 2013
• Last Update Posted: Feb 8, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by David P. Martin, Clinical Assistant Professor, Nationwide Children's Hospital: Spinal Fusion; Scoliosis; Methadone; Magnesium; Adolescents; Back Surgery
• Additional relevant MeSH terms: Scoliosis; Magnesium Sulfate; Remifentanil; Methadone

Study Results

Participant Flow

Arm/Group Title	Remifentanil	Remifentanil Plus Methadone	Remifentanil Plus Magnesium
Arm/Group Description	This arm will receive remifentanil alone as is the current practice. Remifentanil	This arm will receive the current analgesic remifentanil plus and adjunct dose of methadone hydrochloride. Methadone hydrochloride: This drug will be used in conjunction with remifentanil as an adjunct analgesic. Remifentanil + methadone (0.1 mg/kg IV over 15 minutes) just after induction of anesthesia	This arm will receive the current analgesic remifentanil plus an adjunct dose of magnesium sulfate. Magnesium Sulfate: This drug will be given with remifentanil as an adjunct analgesic. Remifentanil + magnesium (50 mg/kg bolus over 30 minutes followed by 10 mg/kg/hour).
Period Title: Overall Study
STARTED	20	22	21
COMPLETED	19	22	19
NOT COMPLETED	1	0	2

Baseline Characteristics

Arm/Group Title	Remifentanil	Remifentanil Plus Methadone	Remifentanil Plus Magnesium	Total
Arm/Group Description	This arm will receive remifentanil alone as is the current practice. Remifentanil	This arm will receive the current analgesic remifentanil plus and adjunct dose of methadone hydrochloride. Methadone hydrochloride: This drug will be used in conjunction with remifentanil as an adjunct analgesic. Remifentanil + methadone (0.1 mg/kg IV over 15 minutes) just after induction of anesthesia	This arm will receive the current analgesic remifentanil plus an adjunct dose of magnesium sulfate. Magnesium Sulfate: This drug will be given with remifentanil as an adjunct analgesic. Remifentanil + magnesium (50 mg/kg bolus over 30 minutes followed by 10 mg/kg/hour).	Total of all reporting groups
Overall Participants	20	22	21	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.2 (1.4)	15.4 (1.2)	15.3 (1.9)	15.0 (1.6)
Sex: Female, Male (Count of Participants)
Female	17 85%	17 77.3%	18 85.7%	52 82.5%
Male	3 15%	5 22.7%	3 14.3%	11 17.5%
BMI (kg/m2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	21.6 (4.3)	22.8 (5.7)	24.2 (5.6)	22.6 (5.3)

Outcome Measures

1. Primary Outcome

Title	Intra- and Post-operative Pain Relief
Description	To prospectively compare the effects of intra-operative methadone and magnesium on postoperative opioid requirements. Total amount of hydromorphone administered in OR, recovery room (PACU), and on the inpatient ward 24 hours post-operatively.
Time Frame	Intra-operative and 24 hours post-operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Remifentanil	Remifentanil Plus Methadone	Remifentanil Plus Magnesium
Arm/Group Description	This arm will receive remifentanil alone as is the current practice. Remifentanil	This arm will receive the current analgesic remifentanil plus and adjunct dose of methadone hydrochloride. Methadone hydrochloride: This drug will be used in conjunction with remifentanil as an adjunct analgesic. Remifentanil + methadone (0.1 mg/kg IV over 15 minutes) just after induction of anesthesia	This arm will receive the current analgesic remifentanil plus an adjunct dose of magnesium sulfate. Magnesium Sulfate: This drug will be given with remifentanil as an adjunct analgesic. Remifentanil + magnesium (50 mg/kg bolus over 30 minutes followed by 10 mg/kg/hour).
Measure Participants	19	22	19
Mean (Standard Deviation) [mg/kg]	0.34 (0.11)	0.26 (0.1)	0.38 (0.1)

2. Secondary Outcome

Title	Post-operative Pain Scores
Description	VAS pain score - 0 being no pain and 10 being worst pain.
Time Frame	Post-operatively to 24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Remifentanil	Remifentanil Plus Methadone	Remifentanil Plus Magnesium
Arm/Group Description	This arm will receive remifentanil alone as is the current practice. Remifentanil	This arm will receive the current analgesic remifentanil plus and adjunct dose of methadone hydrochloride. Methadone hydrochloride: This drug will be used in conjunction with remifentanil as an adjunct analgesic. Remifentanil + methadone (0.1 mg/kg IV over 15 minutes) just after induction of anesthesia	This arm will receive the current analgesic remifentanil plus an adjunct dose of magnesium sulfate. Magnesium Sulfate: This drug will be given with remifentanil as an adjunct analgesic. Remifentanil + magnesium (50 mg/kg bolus over 30 minutes followed by 10 mg/kg/hour).
Measure Participants	19	22	19
Mean (Standard Deviation) [units on a scale]	4.6 (2.2)	5.1 (1.8)	5.1 (1.2)

Adverse Events

Arm/Group Title	Remifentanil		Remifentanil Plus Methadone		Remifentanil Plus Magnesium
Arm/Group Description	This arm will receive remifentanil alone as is the current practice. Remifentanil		This arm will receive the current analgesic remifentanil plus and adjunct dose of methadone hydrochloride. Methadone hydrochloride: This drug will be used in conjunction with remifentanil as an adjunct analgesic. Remifentanil + methadone (0.1 mg/kg IV over 15 minutes) just after induction of anesthesia		This arm will receive the current analgesic remifentanil plus an adjunct dose of magnesium sulfate. Magnesium Sulfate: This drug will be given with remifentanil as an adjunct analgesic. Remifentanil + magnesium (50 mg/kg bolus over 30 minutes followed by 10 mg/kg/hour).
All Cause Mortality
	Remifentanil		Remifentanil Plus Methadone		Remifentanil Plus Magnesium
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Remifentanil		Remifentanil Plus Methadone		Remifentanil Plus Magnesium
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/22 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Remifentanil		Remifentanil Plus Methadone		Remifentanil Plus Magnesium
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/22 (0%)		0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.