The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy

Sponsor

Cedars-Sinai Medical Center (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT02252432

Collaborator

(none)

114

Enrollment

Location

Arms

129.9

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research is to determine the pain-reducing effects of ketamine (Ketalar, an FDA-approved drug for anesthesia) and methadone (Dolophine, a long-acting narcotic) after lumbar laminectomy. The investigators would like to evaluate whether intraoperative use of both drugs may be able to provide better control of pain after lumbar surgery.

Condition or Disease	Intervention/Treatment	Phase
Laminectomy	Drug: Ketamine Drug: Methadone Drug: Ketamine + methadone	Phase 4

Detailed Description

During and after the surgery, patients undergoing surgery most likely need narcotics (opioids) that can cause side effects such as drowsiness and constipation. This can delay your recovery. The investigator would like to determine if the intraoperative use of ketamine and methadone will provide better pain control and reduce the use of narcotic painkiller medications (analgesics) after lumbar surgery as compared to either drug (ketamine or methadone) alone.

Ketamine is used to help to reduce the amount of the commonly used intravenous anesthetic drugs, minimize heart rate and blood pressure instability during surgery, and to improve outcomes after surgery (e.g. less pain, less constipation, less nausea and vomiting after surgery, faster return of bowel function and shortened length of hospital stay).

Ketamine is approved by the U.S. Food and Drug Administration (FDA) to be used: as an anesthetic and analgesic (painkiller). Ketamine is an "adjuvant," which is a drug that may increase the effectiveness or strength of other drugs when given at the same time. Ketamine is administered as an adjuvant during anesthesia to produce anesthetic and analgesic-sparing effects (reduce the amount of anesthetics and narcotics-painkiller drugs), hemodynamic stability (to maintain the blood pressure and heart rate within normal rank) and side effect reduction (e.g., constipation, nausea and vomiting, itching, and urinary retention). Ketamine will be used as approved in this study. Ketamine is frequently used intraoperatively for pain control in patients undergoing spine surgery at our institution and is within the standard of care. The standard of care indicates that this is one possible method which has been demonstrated to be safe and effective for patient care. This may vary at different institutions.

Methadone is approved by the U.S. Food and Drug Administration (FDA) to be used: as an opioid pain reliever, similar to morphine, and for narcotic detoxification to reduce withdrawal symptoms. The dose of methadone that will be used in this study may be slightly higher than the approved dose depending on the subject's weight. However, this dose of methadone is frequently used intraoperatively for pain control in patients undergoing spine surgery at our institution and is within the standard of care. This may vary at different institutions.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Intraoperative Ketamine and Methadone for Laminectomy: Effect on Recovery, Postoperative Pain, and Opioid Requirements

Actual Study Start Date :

Feb 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ketamine A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min))	Drug: Methadone A single dose of IV methadone (0.2 mg/kg) preinduction. Drug: Ketamine + methadone Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)
Active Comparator: Methadone Will receive a single dose of IV methadone (0.2 mg/kg) preinduction	Drug: Ketamine A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min) Drug: Ketamine + methadone Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)
Experimental: Ketamine + methadone Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)	Drug: Ketamine A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min) Drug: Methadone A single dose of IV methadone (0.2 mg/kg) preinduction.

Arm

Intervention/Treatment

Active Comparator: Ketamine

A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min))

Drug: Methadone

A single dose of IV methadone (0.2 mg/kg) preinduction.

Drug: Ketamine + methadone

Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)

Active Comparator: Methadone

Will receive a single dose of IV methadone (0.2 mg/kg) preinduction

Drug: Ketamine

A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)

Drug: Ketamine + methadone

Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)

Experimental: Ketamine + methadone

Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)

Drug: Ketamine

A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)

Drug: Methadone

A single dose of IV methadone (0.2 mg/kg) preinduction.

Outcome Measures

Primary Outcome Measures

Opioid consumption obtained from the recorded data [6 weeks]
Perioperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts) Post discharge use of opioid consumption (data obtained from the follow up questionnaires approximately day 1-3 and 6 weeks after surgery).
Postoperative pain using a Verbal Rating Scale [6 weeks]
Postoperative measured at PACU, Day 1-3 and 6 weeks after surgery

Secondary Outcome Measures

Nausea and vomiting will be measured with follow up [6 weeks]
Postoperative nausea and vomiting using a Verbal Rating Scale (0-10) at PACU, Day 1-3 and 6 weeks after surgery
Constipation (Ileus) will be measured with follow up [6 weeks]
Day 1-3 and 6 weeks after surgery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

• 18 - 80 years old of either gender, scheduled for elective lumbar laminectomy

Exclusion Criteria:

American Society of Anesthesiologists (ASA) IV and above
Intolerance, allergy, or contraindication to use of any medications used in this study
Significant coronary artery disease (abnormal stress test, myocardial infarction
within the last 3 months)
Increased intraocular pressure (e.g., untreated glaucoma)
Uncontrolled hypertension (BP > 140/90)
Sleep apnea and currently on continuous positive airway pressure (CPAP)
Increased intracranial pressure or clinical signs thereof
History of intracranial surgery, stroke, or brain aneurysm
Cardiac arrhythmias particularly prolonged QT syndrome
Drugs known to cause prolonged qT: class (IA) antiarrhythmics (quinidine, procainamide, disopyramide), class III antiarrhythmics (sotalol, dofetilide, ibutilide, amiodarone), haloperidol, thioridazine, arsenic trioxide, HIV protease inhibitors, tricyclic antidepressants
Individuals with significant psychological disorders including: schizophrenia, mania, bipolar disorder or psychosis
Pregnant or lactating women
Emergent laminectomy
Those already receiving ketamine or methadone prior to surgery
Morbid obesity (BMI > 40 kg/m2) AND/OR weight > 150 kg
Chronic renal failure ( creatinine > 2.0 mg/dL)
Liver failure e.g., active cirrhosis
Alcohol or substance abuse within in the past 3 months
Uncorrected hypokalemia, hypomagnesemia, hypocalcemia (can be due to diuretics, mineralocorticoid use, laxatives)
Chronic obstructive pulmonary disease (COPD)/Hypercarbia
Restrictive lung disease (pulmonary fibrosis, myasthenia gravis)
Congestive heart failure
Thyroid disease
Organ transplant patients
Drugs/substances known to inhibit methadone metabolism: macrolide antibiotics e.g., erythromycin, cimetidine, astemizole, voriconazole, grapefruit juice