Opioid Use, Pain, Postoperative
Conditions
Brief summary
The purpose of this study is to determine how well two different methods of administrating Tylenol reduce pain and improve patient satisfaction after total hip replacement (THR) surgery. The methods of administration are orally, via a pill that is to be swallowed, and intravenously. Our aim is to determine whether oral or intravenous administration of Tylenol will reduce opioid consumption and opioid-related side effects after THR.
Detailed description
A) Opioid use after THA. Opioid use after THA can be 90 mg (+/-79) in morphine equivalents when using epidural bupivacaine / hydromorphone and multimodal analgesia. Less than 1/3 of this was via the epidural (26/90 mg). Patients reported ORSDS composite scores of 0.58 B) IV vs oral acetaminophen. The therapeutic blood concentration of acetaminophen for pain relief is 10 mcg/ml. After an oral, single dose: In 24 fasting adult subjects, the maximal blood concentration (Cmax) of 7.7 to 17.6 mcg/mL occurred within 1 hour following a single 1000-mg dose of oral acetaminophen (liquid or caplet). Acetaminophen crosses the blood-brain barrier. Central diffusion to the brain and spinal fluid occurs within 15 to 45 minutes with maximum cerebrospinal fluid concentrations occurring at 2 to 4 hours. \[Product Information: TYLENOL(R) oral, acetaminophen oral. McNeil Consumer Healthcare, Skillman, NJ, 2010\]. In a randomized, double-blind, placebo-controlled, single-dose study, acetaminophen 1,000 mg provided significantly greater efficacy in treating postsurgical dental pain compared with acetaminophen 650 mg and placebo. Oral, multiple-dose, immediate-release, elderly patients: In 12 very elderly patients (mean age, 89 years), the Cmax was 23.9 mcg/mL following the administration of acetaminophen 1000 mg orally 3 times daily for 5 days. In adult subjects, the mean Cmax was 28 +/- 21 mcg/mL at the end of a 15-minute IV infusion of acetaminophen 1000 mg. \[Product Information: OFIRMEV(TM) intravenous infusion, acetaminophen intravenous infusion. Cadence Pharmaceuticals Inc., San Diego, CA, 2010\]. The oral medication has an excellent absorption and at least 85% bioavailability, but peak concentration occurs later than the IV, and the therapeutic blood concentration for pain relief (10mcg/ml) may not be achieved after one oral dose (7-17mcg/ml).A full stomach delays the absorption. With multiple doses, in elderly patients, or with renal/ liver failure, the blood concentration is higher. Epidural bupivacaine / clonidine (Liu). Pain scores (NRS) after THA with activity on POD1 can be 3.4 mean (2.6 SD) when using epidural bupivacaine / clonidine and multimodal analgesia. Low-opioid protocol (oxycodone may be too strong for some; cannot use Vicodin due to acetaminophen) Choice of instruments (CAM, ORSDS, Pain OUT). The ORSDS is a 4-point scale that evaluates 12 symptoms (nausea, vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness or difficulty staying awake, feeling lightheaded or dizzy, feeling confused, feelings of general fatigue or weakness, itchiness, dry mouth and headache) via 3 symptom distress dimensions (frequency, severity, bothersomeness). It is validated for use after orthopaedic surgery, specifically including TKA patients receiving epidural analgesia and femoral nerve blockade. Patients can meet criteria for delirium by CAM by having acute onset of inattention as well as either disorganized thinking or altered level of consciousness.Patients without acute onset can also meet criteria for delirium if inattention, disorganized thinking and altered level of consciousness are all present, with at least one factor judged to be fluctuating. CAM has been widely applied and has been specifically used to evaluate elderly TKA patients receiving epidural analgesia and femoral nerve blockade. The Patient Outcome Questionnaire by the American Pain society is used for quality improvement, and measures 6 aspects of quality, including (1) pain severity and relief; (2) impact of pain on activity, sleep, and negative emotions; (3) side effects of treatment; (4) helpfulness of information about pain treatment; (5) ability to participate in pain treatment decisions; and (6) use of nonpharmacological strategies.
Interventions
DRUGAcetaminophen
Oral acetaminophen, intravenous placebo
Sponsors
Mallinckrodt
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Adult * Scheduled for an elective primary THA with a participating surgeon, * Planned for Combined Spinal Epidural anesthesia (CSE) and Patient Controlled Epidural Analgesia (PCEA) * English-speaking * Patients that did not receive pre-operative opioids
Exclusion criteria
* Hepatic or renal insufficiency, as defined by abnormal readings on liver and kidney functioning tests. * Hypersensitivity or contraindication to protocol medication * Contraindication for CSE and PCEA * Incapable to provide consent/answer questions in English * Revision or urgent surgery * Receiving Periarticular Injections * History of opioid use * Patients on disability or worker's compensation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain With Physical Therapy on Post-operative Day 1 | 24 hours after the operation (post-operative day 1) | Numerical rating scale of pain on a scale of 0-10, with 0 representing the minimum value of no pain and 10, representing the maximum, defined as being pain as bad as imaginable. |
| Opioid Use | Day of surgery to post-operative day 3 | Oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database. |
| Opioid Side Effects | 24 hours after surgery (Post-operative day 1) | The Opioid-Related Symptom Distress Scale (ORSDS) is a Likert scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. Frequency is rated on a 4-point scale (1= 'Rarely', 4= 'Almost constantly'). Severity is rated on a 4-point scale (1= 'Slightly', 4= 'Very'). Bothersomeness is rated on a 5-point scale (0.8= 'Not at all', 4.0= 'Very much'). The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS score is the average of 12 symptom-specific scores. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Tylenol Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo
Acetaminophen: Oral acetaminophen, intravenous placebo | 77 |
| Intravenous Tylenol Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo
Acetaminophen: Intravenous acetaminophen, oral placebo | 77 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Oral Tylenol | Intravenous Tylenol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 38 Participants | 75 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 39 Participants | 79 Participants |
| Age, Continuous | 65 years STANDARD_DEVIATION 10 | 63 years STANDARD_DEVIATION 10 | 64 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 75 Participants | 149 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 70 Participants | 69 Participants | 139 Participants |
| Region of Enrollment United States | 77 participants | 77 participants | 154 participants |
| Sex: Female, Male Female | 42 Participants | 49 Participants | 91 Participants |
| Sex: Female, Male Male | 35 Participants | 28 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 76 |
| other Total, other adverse events | 0 / 75 | 0 / 76 |
| serious Total, serious adverse events | 0 / 75 | 0 / 76 |
Outcome results
Primary
Opioid Side Effects
The Opioid-Related Symptom Distress Scale (ORSDS) is a Likert scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. Frequency is rated on a 4-point scale (1= 'Rarely', 4= 'Almost constantly'). Severity is rated on a 4-point scale (1= 'Slightly', 4= 'Very'). Bothersomeness is rated on a 5-point scale (0.8= 'Not at all', 4.0= 'Very much'). The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS score is the average of 12 symptom-specific scores.
Time frame: 24 hours after surgery (Post-operative day 1)
Population: Three patients withdrew from the protocol, but were followed using intention-to-treat principles. One patient did not wish to answer the postoperative questions, 1 could not swallow the pills, and 1 received a different anesthetic/analgesic protocol due to pre-existing expectations. In addition, ORSDS on POD 1 was not recorded for two patients who were lost to follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Tylenol | Opioid Side Effects | 0.4 score on a scale | Standard Deviation 0.3 |
| Intravenous Tylenol | Opioid Side Effects | 0.3 score on a scale | Standard Deviation 0.3 |
Primary
Opioid Use
Oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database.
Time frame: Day of surgery to post-operative day 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Tylenol | Opioid Use | 108 Oral Morphine Equivalent (mg) | Standard Deviation 63 |
| Intravenous Tylenol | Opioid Use | 121 Oral Morphine Equivalent (mg) | Standard Deviation 71 |
Primary
Pain With Physical Therapy on Post-operative Day 1
Numerical rating scale of pain on a scale of 0-10, with 0 representing the minimum value of no pain and 10, representing the maximum, defined as being pain as bad as imaginable.
Time frame: 24 hours after the operation (post-operative day 1)
Population: Three patients withdrew from the protocol, but were followed using intention-to-treat principles. One patient did not wish to answer the postoperative questions, 1 could not swallow the pills, and 1 received a different anesthetic/analgesic protocol due to pre-existing expectations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Tylenol | Pain With Physical Therapy on Post-operative Day 1 | 3.6 score on a scale | Standard Deviation 2.4 |
| Intravenous Tylenol | Pain With Physical Therapy on Post-operative Day 1 | 3.9 score on a scale | Standard Deviation 2.4 |