Hip Arthroplasty
Conditions
Keywords
Total hip arthroplasty, Total hip replacement, Pain, postoperative, Ketorolac, Patients undergoing unilateral total hip arthroplasty
Brief summary
Chronic pain in patients following total hip replacement seems to be a significant problem. Previous research has shown that more effective pain management in the early postoperative period may decrease the incidence of the development of chronic pain states. This study will evaluate whether ketorolac (a non steroidal anti-inflammatory drug) given into the spinal fluid before surgery will reduce the area of sensitivity (or pain to light touch) following surgery. Patients will be monitored during their postoperative hospital stay and then contacted by telephone at 8 weeks and 6 months after surgery and questioned about any pain they are having at their surgical site. Patients that are still experiencing pain at 6 months will be asked to return to the medical center for the study staff to assess their pain or sensitivity at the surgical site.
Detailed description
Surgery results in hypersensitivity to mechanical stimuli surrounding the wound and in a subset of patients, also results in chronic pain. The purpose of the study is to test whether intrathecal ketorolac, by selectively and effectively blocking cyclooxygenase in the spinal cord, will reduce hypersensitivity surrounding the surgical wound in patients with high risk for developing chronic pain after surgery. We have chosen to study patients having total hip arthroplasty (THA) because chronic pain seems to be a significant problem after surgery. We will sample cerebrospinal fluid (CSF) prior to injection of the study medication for subsequent prostaglandin E2 (PGE2) analysis in each patient. We will also assess each patient at 48 hours after their surgery for hypersensitivity at their surgical site.
Interventions
DRUGketorolac tromethamine opthalmic solution
ketorolac 2 mg will be added to the patient's routine spinal anesthetic for surgery
DRUGplacebo
placebo will be added to the patient's routine spinal anesthetic for surgery
Sponsors
National Institute of General Medical Sciences (NIGMS)
Wake Forest University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) physical status I, II, III * \> Age 18 * Primary unilateral total hip arthroplasty under spinal anesthesia
Exclusion criteria
* Known allergy to study medication * Weight \> 300 pounds * Obstructive sleep apnea * Patients with severe renal (kidney) or hepatic (liver) disease, allergy to ketorolac, amino amide local anesthetic, or contraindications to spinal anesthesia * Patients on dialysis for kidney failure or patients that are jaundice or have a diagnosis of liver failure * Patients routinely taking narcotic pain medications for pain other than their primary hip pain * Patients that are taking Lyrica (pregabalin) or Gabapentin (neurontin) for the treatment of seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area of Hypersensitivity to Mechanical Stimuli Surrounding the Wound 48 Hours After Surgery | 48 hours | Hyperalgesia (using a von Frey filament) and allodynia (using a cotton swab) were evaluated around the surgical site 48 hours after surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Present Pain Intensity | 6 months | Pain was assessed preoperatively, 2 days, and 2 and 6 months after surgery using a 0-10 (10 being worse) verbal Present Pain Intensity (PPI) scale |
| McGill Pain Intensity | 6 months | Pain was assessed 2 days and 2 and 6 months after surgery using a validated questionnaire wherein subjects rate the degree to which adjectives describe the intensity of their pain experience. This is termed the McGill Pain Intensity Score and is scored from 0 to 33 with 33 being the highest pain intensity. |
| McGill Affective Pain | 6 months | Pain was assessed 2 days, and 2 and 6 months after surgery using a validated questionnaire wherein subjects rate the degree to which adjectives describe the emotional component of their pain experience. This is termed the McGill Pain Affective Score and is scored from 0 to 12 with 12 being the highest pain emotional impact. |
| Neuropathic Pain Symptom Inventory | 6 months | Pain was assessed 2 days, and 2 and 6 months after surgery using a validated questionnaire to assess the degree of neuropathic characteristics of pain. This is termed the Neuropathic Pain Symptom Inventory which is scored 0-100 with 100 being the worst possible pain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketorolac ketorolac 2 mg
ketorolac tromethamine opthalmic solution: ketorolac 2 mg will be added to the patient's routine spinal anesthetic for surgery | 30 |
| Placebo placebo will be added to the patient's routine spinal anesthetic for surgery
placebo: placebo will be added to the patient's routine spinal anesthetic for surgery | 32 |
| Total | 62 |
Baseline characteristics
| Characteristic | Ketorolac | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 7 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 25 Participants | 52 Participants |
| Region of Enrollment United States | 30 participants | 32 participants | 62 participants |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 29 |
| serious Total, serious adverse events | 0 / 28 | 0 / 29 |
Outcome results
Primary
Area of Hypersensitivity to Mechanical Stimuli Surrounding the Wound 48 Hours After Surgery
Hyperalgesia (using a von Frey filament) and allodynia (using a cotton swab) were evaluated around the surgical site 48 hours after surgery.
Time frame: 48 hours
Population: These are data from the 57 subjects who remained in the study at the time of the primary outcome measure 48 hr after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketorolac | Area of Hypersensitivity to Mechanical Stimuli Surrounding the Wound 48 Hours After Surgery | 0 area in centimeters squared |
| Placebo | Area of Hypersensitivity to Mechanical Stimuli Surrounding the Wound 48 Hours After Surgery | 0 area in centimeters squared |
Comparison: Power calculation assumed that all subjects would have an area of hypersensitivity surrounding the wound at 48 hours. We found that only 1 subject in the placebo group and 3 subjects in the ketorolac group had non-zero areas of hypersensitivity.p-value: =0.94Wilcoxon (Mann-Whitney)
Secondary
McGill Affective Pain
Pain was assessed 2 days, and 2 and 6 months after surgery using a validated questionnaire wherein subjects rate the degree to which adjectives describe the emotional component of their pain experience. This is termed the McGill Pain Affective Score and is scored from 0 to 12 with 12 being the highest pain emotional impact.
Time frame: 6 months
Population: Some subjects were missed to follow up at different times
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketorolac | McGill Affective Pain | Postoperative: 2 days | 2.3 units on a scale | Standard Deviation 2.5 |
| Ketorolac | McGill Affective Pain | Postoperative: 2 months | 0.4 units on a scale | Standard Deviation 0.8 |
| Ketorolac | McGill Affective Pain | Postoperative: 6 months | 0.1 units on a scale | Standard Deviation 0.8 |
| Placebo | McGill Affective Pain | Postoperative: 2 days | 2.3 units on a scale | Standard Deviation 2.5 |
| Placebo | McGill Affective Pain | Postoperative: 2 months | 0.5 units on a scale | Standard Deviation 0.8 |
| Placebo | McGill Affective Pain | Postoperative: 6 months | 0.4 units on a scale | Standard Deviation 0.8 |
p-value: =0.66ANOVA
Secondary
McGill Pain Intensity
Pain was assessed 2 days and 2 and 6 months after surgery using a validated questionnaire wherein subjects rate the degree to which adjectives describe the intensity of their pain experience. This is termed the McGill Pain Intensity Score and is scored from 0 to 33 with 33 being the highest pain intensity.
Time frame: 6 months
Population: Some subjects were missed to follow up at different times
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketorolac | McGill Pain Intensity | Postoperative: 6 months | 1.4 units on a scale | Standard Deviation 3.8 |
| Ketorolac | McGill Pain Intensity | Postoperative: 2 days | 11 units on a scale | Standard Deviation 6.3 |
| Ketorolac | McGill Pain Intensity | Postoperative: 2 months | 2.3 units on a scale | Standard Deviation 3.3 |
| Placebo | McGill Pain Intensity | Postoperative: 6 months | 1.2 units on a scale | Standard Deviation 2.2 |
| Placebo | McGill Pain Intensity | Postoperative: 2 days | 10 units on a scale | Standard Deviation 6.6 |
| Placebo | McGill Pain Intensity | Postoperative: 2 months | 3.1 units on a scale | Standard Deviation 4.1 |
p-value: =0.87ANOVA
Secondary
Neuropathic Pain Symptom Inventory
Pain was assessed 2 days, and 2 and 6 months after surgery using a validated questionnaire to assess the degree of neuropathic characteristics of pain. This is termed the Neuropathic Pain Symptom Inventory which is scored 0-100 with 100 being the worst possible pain.
Time frame: 6 months
Population: Some subjects were missed to follow up at different times
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketorolac | Neuropathic Pain Symptom Inventory | Postoperative: 2 days | 13 units on a scale | Standard Deviation 13 |
| Ketorolac | Neuropathic Pain Symptom Inventory | Postoperative: 2 months | 2.9 units on a scale | Standard Deviation 4.6 |
| Ketorolac | Neuropathic Pain Symptom Inventory | Postoperative: 6 months | 2.4 units on a scale | Standard Deviation 6.6 |
| Placebo | Neuropathic Pain Symptom Inventory | Postoperative: 2 days | 21 units on a scale | Standard Deviation 14 |
| Placebo | Neuropathic Pain Symptom Inventory | Postoperative: 2 months | 4.5 units on a scale | Standard Deviation 7.2 |
| Placebo | Neuropathic Pain Symptom Inventory | Postoperative: 6 months | 1.4 units on a scale | Standard Deviation 3.2 |
p-value: =0.83ANOVA
Secondary
Present Pain Intensity
Pain was assessed preoperatively, 2 days, and 2 and 6 months after surgery using a 0-10 (10 being worse) verbal Present Pain Intensity (PPI) scale
Time frame: 6 months
Population: Some subjects were missed to follow up at different times
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketorolac | Present Pain Intensity | Postoperative: 2 days | 2.1 units on a scale | Standard Deviation 1.8 |
| Ketorolac | Present Pain Intensity | Postoperative: 2 months | 0.6 units on a scale | Standard Deviation 1.2 |
| Ketorolac | Present Pain Intensity | Preoperative | 1.7 units on a scale | Standard Deviation 1.5 |
| Ketorolac | Present Pain Intensity | Postoperative: 6 months | 0.4 units on a scale | Standard Deviation 0.6 |
| Placebo | Present Pain Intensity | Postoperative: 6 months | 0.1 units on a scale | Standard Deviation 0.2 |
| Placebo | Present Pain Intensity | Postoperative: 2 days | 2.5 units on a scale | Standard Deviation 2.3 |
| Placebo | Present Pain Intensity | Preoperative | 1.6 units on a scale | Standard Deviation 1.1 |
| Placebo | Present Pain Intensity | Postoperative: 2 months | 0.2 units on a scale | Standard Deviation 0.3 |
p-value: =0.78ANOVA