Opioid Use, Total Knee Arthroplasty
Conditions
Keywords
Knee Arthroplasty, Dronabinol, Opioid
Brief summary
The goal of this double-blinded randomized controlled trial is to compare whether the addition of Dronabinol compared to a placebo will affect opioid intake in patients undergoing a total knee arthroplasty. The main question it aims to answer are: 1. Does perioperative dronabinol use (starting in the immediate preoperative period (enrollment before 1 PM), with BID dosing concluding the evening of POD2) affect postoperative opioid consumption 24-48 hours following total knee arthroplasty? 2. Is there an effect of perioperative dronabinol use in the total knee arthroplasty patient on POD2 pain scores with ambulation? 3. Will hospital length of stay following total knee arthroplasty be affected in patients who use perioperative dronabinol as compared to control? 4. Does the use of perioperative dronabinol affect time to reach physical therapy discharge goals in postoperative total knee arthroplasty patients? 5. Is there a change in number of postoperative oxygen desaturation events in patients following total knee arthroplasty based on perioperative dronabinol use? Participants will: * Be randomized to take the dronabinol or placebo medication in 5 dosage * Answer survey questions in regard to pain, postop nausea/vomiting, cognitive/adverse event, and outcome quality and support of decision making. * Be connected to a Masimo to record oxygen saturation and an Actigraph to record sleep quality. Researchers will compare two groups: 1) intervention group and 2) control group to see if dronabinol affects postoperative opioid consumption 24-48 hours following their total knee arthroplasty surgery.
Detailed description
The objective of this study is to examine the possible therapeutic advantages of administering perioperative dronabinol to individuals who are undergoing unilateral total knee arthroplasty (TKA). With the utilization of contemporary regional anesthetic procedures and peripheral nerve blocks, pain management is typically effective in the immediate aftermath of total knee arthroplasty (TKA) within the first day after surgery. Rebound pain is shown to occur on the second day following postoperative discharge (POD2), once the analgesic blocks administered during the procedure have ceased to be effective. Previous studies have suggested that dronabinol, a synthetic form of THC, may have potential analgesic properties. Our goal is to find out if giving dronabinol before surgery could lower the number of opioids that people need on postoperative day 2 (POD2) in people who are having total knee arthroplasty (TKA). This research could provide valuable insights into alternative pain management strategies for TKA patients, potentially minimizing opioid-related side effects and improving overall patient outcomes.
Interventions
Dronabinol is a synthetic tetrahydrocannabinol (THC) agent approved for nausea and vomiting with chemotherapy and as an appetite stimulant in AIDS patients.
OTHERPlacebo oral tablet
Non-active placebo
Sponsors
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Throughout cannabinoid research, there has been concern about potential unblinding due to the side effect profile of this class of medication. Prior meta-analyses have advocated for the use of active placebo, with concern that unblinding may misrepresent the effects of clinical trials. However, due to evidence of histamine receptor involvement in pain transmission, as well as overlap in antihistamine antiemetic use and common cannabinoid side effect profiles, we have chosen to use non-active placebo. Our hope is to elicit maximum benefit of cannabinoid dosing perioperatively without confounding variables. With use of non-active placebo, we will perform a comprehensive blinding analysis following the study period to ensure adequate blinding.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged between 18-70 years old with osteoarthrosis scheduled for primary unilateral knee arthroplasty with a participating surgeon * Planned use of regional anesthetic technique during surgery involving infiltration between the popliteal artery and the capsule of the posterior knee (IPACK), adductor canal block (ACB) and periarticular injection (PAI) * Ability to follow study protocol
Exclusion criteria
* Patients less than 18 years of age or older than 70 years of age * Contraindication to regional or neuraxial anesthetic * Intended use of general anesthesia * Revision surgery * Chronic opioid use (for \>3 months prior to surgery) * Cannabis/cannabinoid use within the last 3 months * ASA class of IV or greater * Active or history of major mental history (as defined by the Diagnostic and Statistical Manual of Mental Disorders-5 \[DSM-5\]; i.e. major depressive disorder, anxiety, bipolar disorder, schizophrenia) * History of seizures * Use of antidepressants * Use of anticonvulsants * Use of Coumadin * Use of Disulfuram * Use of Metronidazole * Non-English speakers * BMI ≥40 * Sleep Apnea
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Opioid Consumption 24-48 Hours Post-operatively | 24-48 hours post-operatively | The primary outcome of the study will be cumulative patient opioid consumption 24-48 hours post operatively, defined by total morphine equivalents (MEs). This outcome will be measured starting at recovery room entry and conclude at 48 hours after anesthesia stop time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Discharge From Physical Therapy | Post operative day 0 (beginning in the PACU)-Discharge | Time to reach discharge physical therapy goals, as defined by the number of hours required to meet the following criteria: stable vital signs during Physical therapy (PT), safe independent transfer from bed to standing as well as transfer in and out of seated position, ability to walk 40 feet only with aid of crutch or walker. This outcome will be measured prior to patient discharge. |
| Average Pain Score With Ambulation Reported on a Numeric Rating Scale (NRS) | Post operative day 1, 2, 7, 90 and 180 | Patient pain with ambulation on postoperative day (POD) 1, 2, 7, 90 and 180, defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable). |
| Average Pain Score at Rest Reported on a Numeric Rating Scale (NRS) | Post operative day 0 (beginning in the PACU), POD 1, 2, 7, 90 and 180 | Patient pain at rest upon PACU entry and in the morning of postoperative day (POD)1, POD2, POD7, POD90 and POD180 defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable). |
| Pain With Physical Therapy | Postoperative Day 1 and Postoperative Day 2 | Patient pain during morning physical therapy on postoperative day (POD)1 and 2, defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable). |
| Length of Hospital Stay (Hours) | Post operative day 0 (beginning in the PACU)-Discharge | Hospital length of stay from procedure start time to time of discharge |
| the Number of Desaturation Events | Post operative day 0 (beginning in the PACU)-48 hours post operative discharge | Postoperative desaturation events are defined as the number of times oxygen saturation dropped below 88% for at least 20 seconds or more. The number of such events will be counted per subject during the monitoring period, beginning in the immediate postoperative period on postoperative day (POD)0 (in the PACU) and will continue until the end post operative day 2/patient discharge, whichever occurs first. Oxygen desaturation is defined when measured SpO2 is less than 88%. Measurements will only be recorded if the desaturation event happens for 20 seconds or longer. |
| PainOUT Scale Questions | 24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge, 90 days post operative discharge, 180 days post operative discharge | PainOut assesses post-surgical pain by collecting data on pain intensity, interference with daily activities, and other related factors. Questionnaire uses multiple scales from 0 (none/not at all/did not interfere/extremely dissatisfied) to 10 (extreme/severe/worst pain imaginable/completely interfered/extremely satisfied). Pain severity/Interference/Symptom questions are scored from 0-10, with higher scores indicating worse outcomes. With a scale of 0-10, higher scores indicate better outcomes for the following questions: decision participation question and satisfaction question. The following questions used a scale of 1-11, where 1=0% and 11=100%: Pain relief (a higher percentage indicates better outcome) Time with severe pain (a higher percentage indicates worse outcome) |
| PainOut Count Questions | 24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge, 90 days post operative discharge, 180 days post operative discharge | The following questions used a scale of Yes/No, reporting number of patients with Yes * Been out of bed since surgery * Would have liked more pain treatment * Received information about pain treatment * Used non-medicine methods to relieve pain * Persistent painful condition for 3 months or more |
| DN4 Score | 24 hours post operative discharge, 48 hours post operative discharge, 7days post operative discharge, 3 months post operative discharge, 6 months post operative discharge | DN4 questionnaire to assess neuropathic pain on postoperative day (POD)1, 2, 7, 90 and 180. The DN4 questionnaire is a series of Yes or No questions that revolves around the characteristics that may suggest the presence or development of neuropathic conditions/pain (burning, painful cold, electric shocks, tingling, pins and needles, numbness, itching, hypoesthesia to touch, hypoesthesia to pinprick, pain increased by brushing). Total score is calculated by summing the total of the individual question scores, for a total score range of 0-10, with a score of greater than or equal to 4 indicating the patient may be suffering from neuropathic pain. |
| Opioid-Related Symptom Distress (ORSDS) Scale | 24 hours post operative discharge, 48 hours post operative discharge | The Opioid-Related Symptom Distress Scale (ORSDS) is a scale that assesses three dimensions of symptom distress (frequency, severity, and bothersomeness) for 12 symptoms. The symptom-specific ORSDS is calculated by taking the average of the three symptom distress dimensions. The composite score will be reported for postoperative day (POD)1 and POD2. If a patient denies experiencing a particular symptom, their response will be coded as 0. If they do: Frequency will be assessed using a 4 point scale: 1. rarely 2. occasionally 3. frequently 4. almost constantly with 1 being the lowest and 4 being the highest. Severity is assessed using a 4 point scale: 1. slight 2. moderate 3. severe 4. very severe with 1 being the lowest and 4 being the highest. Bothersomeness is assessed using a 5 point scale: 1. not at all 2. a little bit 3. somewhat 4. quite a bit 5. very much with 1 being the lowest and 5 being the highest. |
| Non-opioid Analgesic Consumption | PACU, POD1, POD2, POD7 | Patient consumption of non-opioid analgesics in the post-anesthesia care unit (PACU) and on postoperative day (POD)1, POD2, POD7. This was measured for acetaminophen, ibuprofen, ketorolac, meloxicam, naproxen, and gabapentin as yes/no. Number of participants who report "yes" for each non-opioid analgesic is reported. |
| Sleep Disturbance: Total Sleep Time | Post operative day 0 (beginning in the PACU)- 24 hours post operative | Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Measured during the first 24 hours postoperatively. |
| Sleep Disturbance: Wake After Sleep Onset | Post operative day 0 (beginning in the PACU)- 24 hours post operative | Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Wake After Sleep Onset is the duration of time a patient was awake after falling asleep and before getting out of bed. Measured during the first 24 hours postoperatively. |
| Sleep Disturbance: Sleep Efficiency | Post operative day 0 (beginning in the PACU)- 24 hours post operative | Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Sleep Efficiency is the ratio between total sleep time and the total time in bed. Measured during the first 24 hours postoperatively. Sleep Efficiency ratio is expressed as a percentage, where higher values represent better outcomes. |
| Sleep Disturbance: Number of Awakenings | Post operative day 0 (beginning in the PACU)- 24 hours post operative | Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Measured as number of awakenings during the first 24 hours postoperatively. |
| Cognitive Assessment | PACU, Post-Op, POD1, POD2 | Measured as yes/no for a series of 13 questions asking patients if they have experienced any: change of mood, difficulty with memory, slurring of speech, blurred vision, hallucinations, increased awareness of surroundings, palpitations, headache, dizziness, drowsiness, dry mouth, involuntary muscle twitching, or tremors. Number of participants who report "yes" for each symptom is reported. Measured in the post-anesthesia care unit (PACU), between PACU exist and midnight (Post-op), postoperative day (POD)1, POD2 |
| Opioid Consumption in the Post-anesthesia Care Unit and Postoperative Day 1 | post-anesthesia care unit and postoperative day 1 | Opioid consumption measured in morphine milligram equivalents in the post-anesthesia care unit and postoperative day 1 (analyzed as 0-24 hours after surgery) |
| Opioid Consumption at Postoperative Day 90 | Postoperative Day 90 | Number of participants reporting opioid use at postoperative day 90. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKethy Jules-Elysee, M.D.
Hospital for Special Surgery, New York
Participant flow
Recruitment details
Subject enrollment began on 03/09/2021 and ended on 10/04/2023. The last subject follow-up was completed on 04/01/2024.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63 years |
| American Society of Anesthesiologists (ASA) Class 1 | 1 participants |
| American Society of Anesthesiologists (ASA) Class 2 | 53 participants |
| American Society of Anesthesiologists (ASA) Class 3 | 2 participants |
| Body Mass Index | 29.8 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 98 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 56 |
| other Total, other adverse events | 0 / 55 | 0 / 56 |
| serious Total, serious adverse events | 0 / 55 | 0 / 56 |
Outcome results
None listed