Osteoarthritis,Knee
Conditions
Keywords
Analgesia, postoperative pain, periarticular, arthroplasty, pain management
Brief summary
The purpose of this study is to compare different medication combinations used in a periarticular injection after total knee replacement surgery(TKR). A periarticular injection is an injection that is given into the tissues surrounding the knee joint. The injection is given while the patient is still in surgery. The study will compare the level of pain management, length of hospital stay, range of motion and side effects from subjects receiving one of four different combinations of medication in a periarticular injection. The medications used in the injections are approved medications routinely used for pain management. Approximately 160 subjects will participate in this study. The surgeon, study personnel, and patients will be blinded to the combination of medications each patient receives. The pharmacist will prepare the 4 different combinations of medications, randomize each patient to the particular combination of medications, and maintain the study drug documentation.
Detailed description
Data Collection: Data will be collected from the patient's pre-operative office visit, up to six weeks post-operatively. Variables Pre-operative Collection: * Vital signs * Hb/Hct * Age * Sex * BMI * WOMAC Score - Screen Failure at 36 or 12 * Visual Analog Scale (VAS) Intra-operative Collection: * Duration of surgery * Tourniquet time * Time of periarticular injection Post-operative Collection: * Pain Scores in the inpatient post-anesthesia care unit (PACU) using the 1- to 10- point Visual Analog Scale (VAS) an admission to unit, 1 hour, 2 hour, and on discharge. * VAS pain scores every 8 hours on the Orthopaedic floor * Use of supplementary narcotics * Use of anti-emetics * Serious Adverse Events (SAE) including deep vein thrombosis (DVT) formation, pulmonary embolism (PE), myocardial infarct or other serious cardiac event, excessive bleeding * Length of hospital stay * Requirement for inpatient rehabilitation versus discharge home * Hours/Days to straight leg raise -POD 1, 2, 3 by MD on rounds. * Days to independent ambulation * Hemoglobin and Hematocrit levels on post-operative days one and two * Presence/Absence of Bowel/Bladder Function Data to be Collected by Physical Therapist: POD 1, 2, 3, Numerical Rating Scale (NRS) Pain with Ambulation * Use of Assisted Devices * Distance walked * Range of Motion(ROM) (using Goniometer)- active and passive. Treatment Periods Screening Visit Day 0 - Day of surgery Visit Day 1, 2, 3 (Post-operative days 1, 2, and 3) 6 Week visit in Office
Interventions
DRUGRopivacaine
Ropivacaine 5mg/ml (49.25 ml)
DRUGToradol
Toradol 30mg/ml (1 ml)
DRUGClonidine
Clonidine 0.1 mg/ml (0.08mg - 0.8 ml)
DRUGEpinephrine
Epinephrine 1 mg/ml (0.5 ml)
Sponsors
Towson Orthopaedic Associates
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Men and Women aged 30 to 85 years 2. Voluntary, written informed consent given to participate in this clinical investigation
Exclusion criteria
1. Pregnant or lactating women 2. Presence of allergies or contraindication to any medications indicated in the study 3. Contraindication to or failure of spinal anesthesia 4. Known drug or alcohol abuse or psychologic disorder that could affect follow-up care or treatment outcomes 5. Patients with a diagnosis of inflammatory arthritis 6. Previous major bone surgery in the operative knee 7. Simultaneous, bilateral TKRs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | 2 days after surgery | Patient pain was assessed during hospitalization using the VAS Pain Scale, a numerical rating scale ranging from 0 (no pain) to 10 (severe pain). A lower score represents a better outcome. Pain was assessed preoperatively, 1 hour postoperatively in the post anesthesia unit, and then every 8 hours on the Orthopedic inpatient unit, for a duration of 2 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Narcotic Consumption During Hospitalization | 4 days | A variety of pain medications were used after surgery to keep patients comfortable. Narcotic use was recorded as morphine equivalents. We report the mean narcotic consumption for each group for the day of surgery as well as post operative day 1,2, and 3. |
| Knee Society Pain Scores at 6 Week Follow-up Appointment | 6 weeks after surgery | Patients were assessed for pain at their 6 week follow-up appointment using the Knee Society Rating Scale. Using this scale patients are given a pain score ranging from 0 (severe pain) to 50 (No Pain). This is determined as follows: No pain/50 points, Mild or occasional pain/45 points, pain with stairs only/40 points, pain with walking and stairs/30 points, Moderate/occasional pain/ 20 points,continual pain/10 points, severe pain/0 points. We report the mean score for each group. A higher score represents a better outcome. |
Participant flow
Recruitment details
All patients scheduled for Total Knee Replacement (TKR), by the investigator and considered suitable for participation,were recruited for the study from Jan 2010 through June 2011.
Pre-assignment details
Before assignment to groups all participants were screened for certain exclusion criteria including; pregnant/lactating women, allergies/contraindications to study medications/spinal anesthesia, drug/alcohol abuse, psychologic disorder, diagnosis of inflammatory arthritis, previous major surgery to operative knee, and simultaneous bilateral TKR's.
Participants by arm
| Arm | Count |
|---|---|
| ROP/EPI/TOR/CLO Ropivicaine 5mg/ml (49.25 ml) Epinephrine 1 mg/ml (0.5 ml) Toradol 30mg/ml (1 ml) Clonidine 0.1 mg/ml (0.08mg - 0.8 ml) | 40 |
| ROP/EPI/TOR Ropivicaine 5mg/ml (49.25 ml) Epinephrine 1 mg/ml (0.5 ml) Toradol 30mg/ml (1 ml) | 40 |
| ROP/EPI/CLO Ropivicaine 5mg/ml (49.25 ml) Epinephrine 1 mg/ml (0.5 ml) Clonidine 0.1 mg/ml (0.08mg - 0.8 ml) | 40 |
| ROP/EPI Ropivicaine 5mg/ml (49.25 ml) Epinephrine 1 mg/ml (0.5 ml) | 40 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 2 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ROP/EPI/TOR | ROP/EPI/CLO | ROP/EPI/TOR/CLO | ROP/EPI | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 24 Participants | 27 Participants | 29 Participants | 101 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 16 Participants | 13 Participants | 11 Participants | 59 Participants |
| Age Continuous | 66.29 years STANDARD_DEVIATION 8.2 | 68.26 years STANDARD_DEVIATION 7.47 | 66.74 years STANDARD_DEVIATION 8.07 | 69.25 years STANDARD_DEVIATION 8.67 | 67.64 years STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 40 participants | 40 participants | 40 participants | 40 participants | 160 participants |
| Sex: Female, Male Female | 23 Participants | 25 Participants | 23 Participants | 27 Participants | 98 Participants |
| Sex: Female, Male Male | 17 Participants | 15 Participants | 17 Participants | 13 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 |
Outcome results
Primary
Numerical Rating Scale (NRS) Pain Scores During Hospitalization.
Patient pain was assessed during hospitalization using the VAS Pain Scale, a numerical rating scale ranging from 0 (no pain) to 10 (severe pain). A lower score represents a better outcome. Pain was assessed preoperatively, 1 hour postoperatively in the post anesthesia unit, and then every 8 hours on the Orthopedic inpatient unit, for a duration of 2 days.
Time frame: 2 days after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 1 Hour Post Op | 1.06 scores on a scale 0-10 | Standard Deviation 1.74 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 8 Hour Post Op | 1.52 scores on a scale 0-10 | Standard Deviation 1.54 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 16 Hour Post Op | 1.85 scores on a scale 0-10 | Standard Deviation 1.69 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 24 Hour Post Op | 2.33 scores on a scale 0-10 | Standard Deviation 2.06 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 32 Hour Post Op | 2.18 scores on a scale 0-10 | Standard Deviation 2.13 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 40 Hour Post Op | 2.54 scores on a scale 0-10 | Standard Deviation 2.2 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 48 Hour Post Op | 2.41 scores on a scale 0-10 | Standard Deviation 2.25 |
| ROP/EPI/TOR/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale Preoperatively | 1.93 scores on a scale 0-10 | Standard Deviation 2.07 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 40 Hour Post Op | 2.35 scores on a scale 0-10 | Standard Deviation 2.31 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 32 Hour Post Op | 2.66 scores on a scale 0-10 | Standard Deviation 2.13 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 8 Hour Post Op | 1.52 scores on a scale 0-10 | Standard Deviation 1.56 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale Preoperatively | 2.47 scores on a scale 0-10 | Standard Deviation 2.25 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 48 Hour Post Op | 1.97 scores on a scale 0-10 | Standard Deviation 1.72 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 24 Hour Post Op | 2.56 scores on a scale 0-10 | Standard Deviation 1.76 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 16 Hour Post Op | 2.22 scores on a scale 0-10 | Standard Deviation 2.36 |
| ROP/EPI/TOR | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 1 Hour Post Op | 1.90 scores on a scale 0-10 | Standard Deviation 1.04 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 48 Hour Post Op | 2.56 scores on a scale 0-10 | Standard Deviation 2.2 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 16 Hour Post Op | 2.75 scores on a scale 0-10 | Standard Deviation 2.36 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 24 Hour Post Op | 3.63 scores on a scale 0-10 | Standard Deviation 2.86 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 32 Hour Post Op | 3.62 scores on a scale 0-10 | Standard Deviation 2.19 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 40 Hour Post Op | 3.28 scores on a scale 0-10 | Standard Deviation 2.49 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale Preoperatively | 2.43 scores on a scale 0-10 | Standard Deviation 2.4 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 1 Hour Post Op | 2.67 scores on a scale 0-10 | Standard Deviation 3.06 |
| ROP/EPI/CLO | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 8 Hour Post Op | 3.93 scores on a scale 0-10 | Standard Deviation 2.57 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 16 Hour Post Op | 2.41 scores on a scale 0-10 | Standard Deviation 1.65 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 24 Hour Post Op | 2.96 scores on a scale 0-10 | Standard Deviation 2.28 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 8 Hour Post Op | 2.82 scores on a scale 0-10 | Standard Deviation 1.93 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 1 Hour Post Op | 1.60 scores on a scale 0-10 | Standard Deviation 2.01 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 32 Hour Post Op | 3.13 scores on a scale 0-10 | Standard Deviation 2.07 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale Preoperatively | 2.13 scores on a scale 0-10 | Standard Deviation 2.48 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 48 Hour Post Op | 2.11 scores on a scale 0-10 | Standard Deviation 1.98 |
| ROP/EPI | Numerical Rating Scale (NRS) Pain Scores During Hospitalization. | Vas Pain Scale - 40 Hour Post Op | 2.80 scores on a scale 0-10 | Standard Deviation 2.27 |
Secondary
Knee Society Pain Scores at 6 Week Follow-up Appointment
Patients were assessed for pain at their 6 week follow-up appointment using the Knee Society Rating Scale. Using this scale patients are given a pain score ranging from 0 (severe pain) to 50 (No Pain). This is determined as follows: No pain/50 points, Mild or occasional pain/45 points, pain with stairs only/40 points, pain with walking and stairs/30 points, Moderate/occasional pain/ 20 points,continual pain/10 points, severe pain/0 points. We report the mean score for each group. A higher score represents a better outcome.
Time frame: 6 weeks after surgery
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ROP/EPI/TOR/CLO | Knee Society Pain Scores at 6 Week Follow-up Appointment | 45 Scores on a scale 0-50 |
| ROP/EPI/TOR | Knee Society Pain Scores at 6 Week Follow-up Appointment | 43 Scores on a scale 0-50 |
| ROP/EPI/CLO | Knee Society Pain Scores at 6 Week Follow-up Appointment | 45 Scores on a scale 0-50 |
| ROP/EPI | Knee Society Pain Scores at 6 Week Follow-up Appointment | 45 Scores on a scale 0-50 |
Secondary
Narcotic Consumption During Hospitalization
A variety of pain medications were used after surgery to keep patients comfortable. Narcotic use was recorded as morphine equivalents. We report the mean narcotic consumption for each group for the day of surgery as well as post operative day 1,2, and 3.
Time frame: 4 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ROP/EPI/TOR/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 2 | 40.71 mg | Standard Deviation 29.67 |
| ROP/EPI/TOR/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Day of Surgery | 46.92 mg | Standard Deviation 22.29 |
| ROP/EPI/TOR/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 1 | 46.54 mg | Standard Deviation 29.14 |
| ROP/EPI/TOR/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 3 | 20.45 mg | Standard Deviation 19.88 |
| ROP/EPI/TOR | Narcotic Consumption During Hospitalization | Morphine Equivalent Day of Surgery | 43.09 mg | Standard Deviation 25.33 |
| ROP/EPI/TOR | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 2 | 42.69 mg | Standard Deviation 37.28 |
| ROP/EPI/TOR | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 1 | 47.95 mg | Standard Deviation 35.89 |
| ROP/EPI/TOR | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 3 | 18.72 mg | Standard Deviation 20.73 |
| ROP/EPI/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Day of Surgery | 55.20 mg | Standard Deviation 28 |
| ROP/EPI/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 1 | 64.61 mg | Standard Deviation 41.71 |
| ROP/EPI/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 2 | 50.07 mg | Standard Deviation 44.11 |
| ROP/EPI/CLO | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 3 | 21.97 mg | Standard Deviation 22.38 |
| ROP/EPI | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 1 | 51.08 mg | Standard Deviation 39.98 |
| ROP/EPI | Narcotic Consumption During Hospitalization | Morphine Equivalent Day of Surgery | 52.50 mg | Standard Deviation 27.12 |
| ROP/EPI | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 3 | 15.54 mg | Standard Deviation 21.77 |
| ROP/EPI | Narcotic Consumption During Hospitalization | Morphine Equivalent Post Operative Day 2 | 36.76 mg | Standard Deviation 35.28 |