The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy

• ClinicalTrials.gov Identifier: NCT02252432
• Recruitment Status: Enrolling by invitation
• First Posted: September 30, 2014
• Last Update Posted: February 11, 2022
• Sponsor: Cedars-Sinai Medical Center
• Information provided by (Responsible Party): Roya Yumul, M.D.,PhD., Cedars-Sinai Medical Center

Tracking Information

• First Submitted Date: September 26, 2014
• First Posted Date: September 30, 2014
• Last Update Posted Date: February 11, 2022
• Actual Study Start Date: February 2013
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 29, 2014)

• Opioid consumption obtained from the recorded data [ Time Frame: 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 [ Time Frame: 6 weeks ]
  Postoperative measured at PACU, Day 1-3 and 6 weeks after surgery

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 29, 2014)

• Nausea and vomiting will be measured with follow up [ Time Frame: 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 [ Time Frame: 6 weeks ]
  Day 1-3 and 6 weeks after surgery

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy
• Official Title: Intraoperative Ketamine and Methadone for Laminectomy: Effect on Recovery, Postoperative Pain, and Opioid Requirements
• 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.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Laminectomy

Intervention

• 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.
• 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)

Study Arms

• 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))
  Interventions:

  • Drug: Methadone
  • Drug: Ketamine + methadone
• Active Comparator: Methadone
  Will receive a single dose of IV methadone (0.2 mg/kg) preinduction
  Interventions:

  • Drug: Ketamine
  • Drug: Ketamine + methadone
• 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)
  Interventions:

  • Drug: Ketamine
  • Drug: Methadone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: September 29, 2014): 114
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02252432
• Other Study ID Numbers: Pro00030109
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Roya Yumul, M.D.,PhD., Cedars-Sinai Medical Center
• Study Sponsor: Cedars-Sinai Medical Center
• Collaborators: Not Provided

Investigators

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

• PRS Account: Cedars-Sinai Medical Center
• Verification Date: February 2022