The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy

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

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.

Study Overview

• Status: Terminated
• Conditions: Laminectomy
• Intervention / Treatment: Drug: Methadone; Drug: Ketamine + methadone; Drug: Ketamine

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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 + 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)
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: Methadone; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Consumption Obtained From the Recorded Data	Perioperative use of opioid consumption inside the hospital (recorded by study staff and data obtained from patient charts)	1 day
Postoperative Pain	Postoperative pain was measured at PACU using a Verbal Rating Scale from 0 to 10. Where 0= no pain and 10= maximum pain experienced	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nausea and Vomiting	The number of participants who experienced nausea and vomiting	1 day
Number of Participants With Constipation at Follow up	Day one, day three after surgery	3 days

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Roya Yumul, M.D., PhD., Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2013
• Primary Completion (Actual): January 1, 2023
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimated): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Perioperative outcomes; Length of hospital stay; KETAMINE; METHADONE; POSTOPERATIVE PAIN; OPIOID REQUIREMENTS
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Ketamine; Methadone
• Other Study ID Numbers: Pro00030109