IV Tylenol: IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
Detailed Description
-
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
-
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Oral Tylenol Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo |
Drug: Acetaminophen
Oral acetaminophen, intravenous placebo
|
Experimental: Intravenous Tylenol Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo |
Drug: Acetaminophen
Intravenous acetaminophen, oral placebo
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Hospital for Special Surgery | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Hospital for Special Surgery, New York
- Mallinckrodt
Investigators
- Principal Investigator: Jacques Ya Deau, MD, PhD, Hospital for Special Surgery, New York
Study Documents (Full-Text)
More Information
Publications
- Gelotte CK, Auiler JF, Lynch JM, Temple AR, Slattery JT. Disposition of acetaminophen at 4, 6, and 8 g/day for 3 days in healthy young adults. Clin Pharmacol Ther. 2007 Jun;81(6):840-8. Epub 2007 Mar 21.
- Gordon DB, Polomano RC, Pellino TA, Turk DC, McCracken LM, Sherwood G, Paice JA, Wallace MS, Strassels SA, Farrar JT. Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) for quality improvement of pain management in hospitalized adults: preliminary psychometric evaluation. J Pain. 2010 Nov;11(11):1172-86. doi: 10.1016/j.jpain.2010.02.012. Epub 2010 Apr 18.
- Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8.
- Jules-Elysee KM, Goon AK, Westrich GH, Padgett DE, Mayman DJ, Ranawat AS, Ranawat CS, Lin Y, Kahn RL, Bhagat DD, Goytizolo EA, Ma Y, Reid SC, Curren J, YaDeau JT. Patient-controlled epidural analgesia or multimodal pain regimen with periarticular injection after total hip arthroplasty: a randomized, double-blind, placebo-controlled study. J Bone Joint Surg Am. 2015 May 20;97(10):789-98. doi: 10.2106/JBJS.N.00698.
- Liu SS, Bae JJ, Bieltz M, Wukovits B, Ma Y. A prospective survey of patient-controlled epidural analgesia with bupivacaine and clonidine after total hip replacement: a pre- and postchange comparison with bupivacaine and hydromorphone in 1,000 patients. Anesth Analg. 2011 Nov;113(5):1213-7. doi: 10.1213/ANE.0b013e318228fc8b. Epub 2011 Aug 4.
- Qi DS, May LG, Zimmerman B, Peng P, Atillasoy E, Brown JD, Cooper SA. A randomized, double-blind, placebo-controlled study of acetaminophen 1000 mg versus acetaminophen 650 mg for the treatment of postsurgical dental pain. Clin Ther. 2012 Dec;34(12):2247-2258.e3. doi: 10.1016/j.clinthera.2012.11.003. Epub 2012 Nov 28.
- Rade MC, Yadeau JT, Ford C, Reid MC. Postoperative delirium in elderly patients after elective hip or knee arthroplasty performed under regional anesthesia. HSS J. 2011 Jul;7(2):151-6. doi: 10.1007/s11420-011-9195-2. Epub 2011 Feb 11.
- Singla NK, Parulan C, Samson R, Hutchinson J, Bushnell R, Beja EG, Ang R, Royal MA. Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen. Pain Pract. 2012 Sep;12(7):523-32. doi: 10.1111/j.1533-2500.2012.00556.x. Epub 2012 Apr 24.
- Yadeau JT, Liu SS, Rade MC, Marcello D, Liguori GA. Performance characteristics and validation of the Opioid-Related Symptom Distress Scale for evaluation of analgesic side effects after orthopedic surgery. Anesth Analg. 2011 Aug;113(2):369-77. doi: 10.1213/ANE.0b013e31821ae3f7. Epub 2011 Apr 27.
- 2016-209
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Oral Tylenol | Intravenous Tylenol |
---|---|---|
Arm/Group Description | Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo Acetaminophen: Oral acetaminophen, intravenous placebo | Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo Acetaminophen: Intravenous acetaminophen, oral placebo |
Period Title: Overall Study | ||
STARTED | 77 | 77 |
COMPLETED | 75 | 77 |
NOT COMPLETED | 2 | 0 |
Baseline Characteristics
Arm/Group Title | Oral Tylenol | Intravenous Tylenol | Total |
---|---|---|---|
Arm/Group Description | Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo Acetaminophen: Oral acetaminophen, intravenous placebo | Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo Acetaminophen: Intravenous acetaminophen, oral placebo | Total of all reporting groups |
Overall Participants | 77 | 77 | 154 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
40
51.9%
|
39
50.6%
|
79
51.3%
|
>=65 years |
37
48.1%
|
38
49.4%
|
75
48.7%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
65
(10)
|
63
(10)
|
64
(10)
|
Sex: Female, Male (Count of Participants) | |||
Female |
42
54.5%
|
49
63.6%
|
91
59.1%
|
Male |
35
45.5%
|
28
36.4%
|
63
40.9%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
3
3.9%
|
2
2.6%
|
5
3.2%
|
Not Hispanic or Latino |
74
96.1%
|
75
97.4%
|
149
96.8%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
3
3.9%
|
3
1.9%
|
Asian |
1
1.3%
|
0
0%
|
1
0.6%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
4
5.2%
|
4
5.2%
|
8
5.2%
|
White |
70
90.9%
|
69
89.6%
|
139
90.3%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
2
2.6%
|
1
1.3%
|
3
1.9%
|
Region of Enrollment (participants) [Number] | |||
United States |
77
100%
|
77
100%
|
154
100%
|
Outcome Measures
Title | Pain With Physical Therapy on Post-operative Day 1 |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Oral Tylenol | Intravenous Tylenol |
---|---|---|
Arm/Group Description | Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo Acetaminophen: Oral acetaminophen, intravenous placebo | Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo Acetaminophen: Intravenous acetaminophen, oral placebo |
Measure Participants | 75 | 76 |
Mean (Standard Deviation) [score on a scale] |
3.6
(2.4)
|
3.9
(2.4)
|
Title | Opioid Use |
---|---|
Description | Oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database. |
Time Frame | Day of surgery to post-operative day 3 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Oral Tylenol | Intravenous Tylenol |
---|---|---|
Arm/Group Description | Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo Acetaminophen: Oral acetaminophen, intravenous placebo | Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo Acetaminophen: Intravenous acetaminophen, oral placebo |
Measure Participants | 65 | 61 |
Mean (Standard Deviation) [Oral Morphine Equivalent (mg)] |
108
(63)
|
121
(71)
|
Title | Opioid Side Effects |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Oral Tylenol | Intravenous Tylenol |
---|---|---|
Arm/Group Description | Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo Acetaminophen: Oral acetaminophen, intravenous placebo | Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo Acetaminophen: Intravenous acetaminophen, oral placebo |
Measure Participants | 74 | 75 |
Mean (Standard Deviation) [score on a scale] |
0.4
(0.3)
|
0.3
(0.3)
|
Adverse Events
Time Frame | 3 days | |||
---|---|---|---|---|
Adverse Event Reporting Description | Patients with a high likelihood to experience serious adverse effects, have pre-existing conditions which may put the patient at risk for adverse effects, or have contradictions to the medications in this study were not enrolled. The likelihood of serious risks occurring is low since the required doses are not high enough to cause adverse liver damage. Furthermore, the dosage of acetaminophen will be closely monitored. | |||
Arm/Group Title | Oral Tylenol | Intravenous Tylenol | ||
Arm/Group Description | Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo Acetaminophen: Oral acetaminophen, intravenous placebo | Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo Acetaminophen: Intravenous acetaminophen, oral placebo | ||
All Cause Mortality |
||||
Oral Tylenol | Intravenous Tylenol | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/75 (0%) | 0/76 (0%) | ||
Serious Adverse Events |
||||
Oral Tylenol | Intravenous Tylenol | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/75 (0%) | 0/76 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Oral Tylenol | Intravenous Tylenol | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/75 (0%) | 0/76 (0%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Jacques Yadeau |
---|---|
Organization | Hospital for Special Surgery |
Phone | (212) 774-2224 |
Yadeauj@hss.edu |
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