Laminectomy
Conditions
Keywords
KETAMINE, METHADONE, POSTOPERATIVE PAIN, OPIOID REQUIREMENTS, Length of hospital stay, Perioperative outcomes
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.
Interventions
DRUGKetamine
A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)
DRUGMethadone
A single dose of IV methadone (0.2 mg/kg) preinduction.
DRUGKetamine + 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)
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Consumption Obtained From the Recorded Data | 1 day | Perioperative use of opioid consumption inside the hospital (recorded by study staff and data obtained from patient charts) |
| Postoperative Pain | 1 day | Postoperative pain was measured at PACU using a Verbal Rating Scale from 0 to 10. Where 0= no pain and 10= maximum pain experienced |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nausea and Vomiting | 1 day | The number of participants who experienced nausea and vomiting |
| Number of Participants With Constipation at Follow up | 3 days | Day one, day three after surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min))
Methadone: A single dose of IV methadone (0.2 mg/kg) preinduction.
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) | 5 |
| Methadone Will receive a single dose of IV methadone (0.2 mg/kg) preinduction
Ketamine: A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)
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) | 6 |
| 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)
Ketamine: A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)
Methadone: A single dose of IV methadone (0.2 mg/kg) preinduction. | 2 |
| Total | 13 |
Baseline characteristics
| Characteristic | Ketamine | Methadone | Ketamine + Methadone | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 5 Participants | 2 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 2 Participants | 12 Participants |
| Region of Enrollment United States | 5 Participants | 6 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 0 / 5 | 0 / 6 | 0 / 2 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 0 / 2 |
Outcome results
Primary
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)
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Opioid Consumption Obtained From the Recorded Data | 23 milligram morphine equivalents | Standard Deviation 20 |
| Methadone | Opioid Consumption Obtained From the Recorded Data | 30 milligram morphine equivalents | Standard Deviation 16 |
| Ketamine + Methadone | Opioid Consumption Obtained From the Recorded Data | 26 milligram morphine equivalents | Standard Deviation 40 |
Primary
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
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Postoperative Pain | 3.3 score on a scale | Standard Deviation 2 |
| Methadone | Postoperative Pain | 4.1 score on a scale | Standard Deviation 1 |
| Ketamine + Methadone | Postoperative Pain | 4.0 score on a scale | Standard Deviation 1.2 |
Secondary
Nausea and Vomiting
The number of participants who experienced nausea and vomiting
Time frame: 1 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Nausea and Vomiting | 0 Participants |
| Methadone | Nausea and Vomiting | 1 Participants |
| Ketamine + Methadone | Nausea and Vomiting | 0 Participants |
Secondary
Number of Participants With Constipation at Follow up
Day one, day three after surgery
Time frame: 3 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Number of Participants With Constipation at Follow up | 0 Participants |
| Methadone | Number of Participants With Constipation at Follow up | 1 Participants |
| Ketamine + Methadone | Number of Participants With Constipation at Follow up | 0 Participants |