Ischemic Preconditioning, Postoperative Pain, Total Knee Arthroplasty
Conditions
Brief summary
The application of a tourniquet for 5 minutes and subsequent reperfusion before actual inflation of the tourniquet for total knee arthroplasty (ischemic preconditioning) decreases the level of local inflammation and therefore postoperative pain in response to reperfusion of the ischemic extremity.
Detailed description
During knee surgery your surgeon routinely uses a device called a tourniquet that allows us to temporarily cut of blood supply to the site of surgery. This helps to reduce blood loss and improves operating conditions. When allowing blood back into your leg at the end of the procedure, debris (bone, fat, tissue breakdown products and cement from the surgery) gets washed out and gains access to the rest of your body. In the vast majority of cases this event bares no major clinical consequences, but can rarely result in signs of inflammation of various body systems. Patients with evidence of impaired organ system function such as pre-existing lung and heart disease may be more vulnerable. Previous studies suggest that cutting off the blood supply for a short period of time just before a prolonged episode, could lead to a decrease in the extent of tissue breakdown products in this extremity and may thus be associated with a decrease in the inflammation of other organ systems. We propose to study this theory in knee surgery patients by looking at levels of markers of inflammation present in the blood before and after surgery.
Interventions
PROCEDUREIschemic Preconditioning
In the study group, the patients' operative limb will be preconditioned by inflating the tourniquet for 5 minutes, followed by deflation and a 5-minute reperfusion period. Subsequently, the tourniquet will be inflated for the entire length of the operation (before skin incision to after insertion of the final components). In the control group, the tourniquet will be used for the entire length of the operation without a preconditioning phase.
Sponsors
University of Massachusetts, Worcester
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* All patients undergoing primary total knee arthroplasty
Exclusion criteria
* Patients who chronically use narcotics (\<1 month). * Patients with contraindications (severe peripheral vascular disease, presence of femoral-popliteal bypass grafts, etc.) or no plan for tourniquet use as determined by the clinical care team. * Patients who are on corticosteroids prior to their surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Pain at Rest and Exercise as Assessed by Visual Analogue Scale (VAS) Scores at 48h After Surgery | 48hrs after surgery | Visual Analogue Scale (VAS) are used to measure the intensity of pain. The total scale ranged from 0 (no pain) to 10 (excruciating pain). The average value at POD 48hours was reported for each arm/group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Oxygenation Over Calf at 48h After Surgery | At 48 hrs after surgery | muscle tissue oxygenation was measured using a novel noninvasive near infrared spectroscopy device at baseline and at 48 hours postoperatively |
| Levels of Interleukin 6 (IL6) in Drainage Fluid at 24hr Postoperatively | At 24 hours postoperatively | — |
| Periarticular Circumference of the Knee at 6h, 24h, and 48h | measured at 6 hours, 24 hours, and 48 hours | Periarticular circumference of the knee as compared to contralateral side as crude marker of swelling at 6h, 24, and 48h postoperatively. The data from the specified time points (6h, 24h, and 48h) were combined and the average value was reported for each arm/group. |
| Overall Epidural Volume | At 48hrs after surgery | Postoperative pain management included an epidural infusion of 10mcg/ml bupivacaine 0.06%/hydromorphone with a basal rate of 4 mL, a demand dose of 4 mL, and a lockout of 10 minutes. Basal rates were reduced to 2 mL and 0 mL in the morning of postoperative Days 1 and 2, respectively and epidural catheters removed on postoperative Day 2. Overall epidural volume was the total volume given over 48 hours. |
| Physical Therapy Milestone | Up to discharge date | Amount of time until patients reached their physical therapy milestone (40 ft ambulation) during admission |
| Levels of Leukocytes in Drainage Fluid at 24hr Postoperatively | 24 hours postoperatively | — |
| Levels of TNF-alpha in Drainage Fluid at 24hr Postoperatively | 24 hours postoperatively | — |
| Hospital Length of Stay | Up to discharge date | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ishcemic Preconditioning In the study group, the patients' operative limb will be preconditioned by inflating the tourniquet for 5 minutes, followed by deflation and a 5-minute reperfusion period. Subsequently, the tourniquet will be inflated for the entire length of the operation (before skin incision to after insertion of the final components).
Ischemic Preconditioning: In the study group, the patients' operative limb will be preconditioned by inflating the tourniquet for 5 minutes, followed by deflation and a 5-minute reperfusion period. Subsequently, the tourniquet will be inflated for the entire length of the operation (before skin incision to after insertion of the final components). In the control group, the tourniquet will be used for the entire length of the operation without a preconditioning phase. | 30 |
| Control In the control group, the tourniquet will be used for the entire length of the operation without a preconditioning phase. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Ishcemic Preconditioning | Control | Total |
|---|---|---|---|
| Age, Customized Age | 66.5 years | 72.5 years | 70.8 years |
| Sex: Female, Male Female | 19 Participants | 14 Participants | 33 Participants |
| Sex: Female, Male Male | 11 Participants | 16 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Postoperative Pain at Rest and Exercise as Assessed by Visual Analogue Scale (VAS) Scores at 48h After Surgery
Visual Analogue Scale (VAS) are used to measure the intensity of pain. The total scale ranged from 0 (no pain) to 10 (excruciating pain). The average value at POD 48hours was reported for each arm/group.
Time frame: 48hrs after surgery
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ishcemic Preconditioning | Postoperative Pain at Rest and Exercise as Assessed by Visual Analogue Scale (VAS) Scores at 48h After Surgery | VAS score at rest | 1.75 score on a scale |
| Ishcemic Preconditioning | Postoperative Pain at Rest and Exercise as Assessed by Visual Analogue Scale (VAS) Scores at 48h After Surgery | VAS score with exercise | 3 score on a scale |
| Control | Postoperative Pain at Rest and Exercise as Assessed by Visual Analogue Scale (VAS) Scores at 48h After Surgery | VAS score at rest | .71 score on a scale |
| Control | Postoperative Pain at Rest and Exercise as Assessed by Visual Analogue Scale (VAS) Scores at 48h After Surgery | VAS score with exercise | 1.38 score on a scale |
p-value: 0.04395% CI: [-1.4, -0.02]GEE
Secondary
Hospital Length of Stay
Time frame: Up to discharge date
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ishcemic Preconditioning | Hospital Length of Stay | 100.6 hours |
| Control | Hospital Length of Stay | 99.4 hours |
p-value: 0.8656Wilcoxon (Mann-Whitney)
Secondary
Levels of Interleukin 6 (IL6) in Drainage Fluid at 24hr Postoperatively
Time frame: At 24 hours postoperatively
Population: IL-6 levels could not be measured for all patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ishcemic Preconditioning | Levels of Interleukin 6 (IL6) in Drainage Fluid at 24hr Postoperatively | 3.79 pg/ml |
| Control | Levels of Interleukin 6 (IL6) in Drainage Fluid at 24hr Postoperatively | 3.57 pg/ml |
p-value: 0.763Wilcoxon (Mann-Whitney)
Secondary
Levels of Leukocytes in Drainage Fluid at 24hr Postoperatively
Time frame: 24 hours postoperatively
Population: some patients were lost to follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ishcemic Preconditioning | Levels of Leukocytes in Drainage Fluid at 24hr Postoperatively | 2487 cells/mm^3 | Standard Deviation 2415.74 |
| Control | Levels of Leukocytes in Drainage Fluid at 24hr Postoperatively | 2038 cells/mm^3 | Standard Deviation 1778.74 |
p-value: 0.526Wilcoxon (Mann-Whitney)
Secondary
Levels of TNF-alpha in Drainage Fluid at 24hr Postoperatively
Time frame: 24 hours postoperatively
Population: some patients were lost to follow up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ishcemic Preconditioning | Levels of TNF-alpha in Drainage Fluid at 24hr Postoperatively | 3.72 pg/ml |
| Control | Levels of TNF-alpha in Drainage Fluid at 24hr Postoperatively | 3.76 pg/ml |
p-value: 0.526Wilcoxon (Mann-Whitney)
Secondary
Muscle Oxygenation Over Calf at 48h After Surgery
muscle tissue oxygenation was measured using a novel noninvasive near infrared spectroscopy device at baseline and at 48 hours postoperatively
Time frame: At 48 hrs after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ishcemic Preconditioning | Muscle Oxygenation Over Calf at 48h After Surgery | 75 percentage of muscle tissue | Standard Deviation 22.4 |
| Control | Muscle Oxygenation Over Calf at 48h After Surgery | 69 percentage of muscle tissue | Standard Deviation 18.5 |
p-value: 0.584Wilcoxon (Mann-Whitney)
Secondary
Overall Epidural Volume
Postoperative pain management included an epidural infusion of 10mcg/ml bupivacaine 0.06%/hydromorphone with a basal rate of 4 mL, a demand dose of 4 mL, and a lockout of 10 minutes. Basal rates were reduced to 2 mL and 0 mL in the morning of postoperative Days 1 and 2, respectively and epidural catheters removed on postoperative Day 2. Overall epidural volume was the total volume given over 48 hours.
Time frame: At 48hrs after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ishcemic Preconditioning | Overall Epidural Volume | 140.5 mL | Standard Deviation 68.4 |
| Control | Overall Epidural Volume | 160.8 mL | Standard Deviation 70.1 |
p-value: 0.043t-test, 2 sided
Secondary
Periarticular Circumference of the Knee at 6h, 24h, and 48h
Periarticular circumference of the knee as compared to contralateral side as crude marker of swelling at 6h, 24, and 48h postoperatively. The data from the specified time points (6h, 24h, and 48h) were combined and the average value was reported for each arm/group.
Time frame: measured at 6 hours, 24 hours, and 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ishcemic Preconditioning | Periarticular Circumference of the Knee at 6h, 24h, and 48h | 2.3 cm | Standard Deviation 3.2 |
| Control | Periarticular Circumference of the Knee at 6h, 24h, and 48h | 1.5 cm | Standard Deviation 1.1 |
p-value: 0.602GEE
Secondary
Physical Therapy Milestone
Amount of time until patients reached their physical therapy milestone (40 ft ambulation) during admission
Time frame: Up to discharge date
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ishcemic Preconditioning | Physical Therapy Milestone | 2.0 days |
| Control | Physical Therapy Milestone | 3.0 days |
p-value: 0.8422Wilcoxon (Mann-Whitney)