Intra-Venous Acetaminophen and Muscle Relaxants After Total Knee

Study Overview
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Brief Summary
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This is a prospective, three-arm, randomized, open-label trial to determine if a new pain control protocol which includes regular dosing of intravenous acetaminophen and orphenadrine for 48 hours after total knee surgery reduces the need for opioid pain medication and reduces average pain scores.

Detailed Description
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This research will be a prospective, three-arm, randomized, open-label trial to assess opioid use and patient reported outcomes after 48 hours of regular IV acetaminophen and muscle relaxant (IVAM) orphenadrine administration following total knee replacement surgery. 180 patients (60 in each arm) will be randomized to receive the standard group treatment, the IVAM group treatment, or to the control grouptreatment. Standard Group Treatment: includes peripheral nerve single injection or catheter infusions (48 hours) as requested by the surgeon; preoperative (single dose) intravenous acetaminophen (1000 mg) and orphenadrine (60 mg); intraoperative spinal anesthesia or general anesthesia as determined by the anesthesia attending physician; postoperative oral oxycodone (5 mg) with acetaminophen (325 mg) (PRN dosing), oral orphenadrine (100 mg) every 12 hours for 3 doses, and intravenous hydromorphone (PRN dosing) for breakthrough pain. Control Group Treatment: includes peripheral nerve single injection or catheter infusions (48 hours); preoperative (single dose) intravenous acetaminophen (1000 mg) intraoperative spinal anesthesia or general anesthesia as determined by the anesthesia attending physician; and postoperative oral oxycodone and acetaminophen (PRN dosing), and intravenous hydromorphone (PRN dosing) for breakthrough pain. IVAM Group Treatment: includes peripheral nerve single injection or catheter infusions (48 hours); preoperative intravenous acetaminophen (1000 mg) and orphenadrine (60 mg); intraoperative spinal anesthesia or general anesthesia as determined by the anesthesia attending physician; postoperative intravenous acetaminophen (1000 mg) every 6 hours routine for total of 8 doses and intravenous orphenadrine (60 mg) every 12 hours for total of 4 doses; oral oxycodone (5 mg) (PRN dosing), and intravenous hydromorphone (PRN dosing) for breakthrough pain.

Official Title
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Intra-Venous Acetaminophen and Muscle Relaxants After Total Knee Arthroplasty (TKA). Prospective, Randomized, Open-label Trial to Determine if Switching From Oral to Intravenous Acetaminophen and Orphenadrine for 48 Hours After TKA Improves Outcomes.

Conditions
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Unilateral Knee Arthroplasty

Intervention / Treatment
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* Drug: Preop acetaminophen IV
* Drug: Preop orphenadrine IV
* Drug: Postop oral oxycodone & acetaminophen
* Drug: Postop hydromorphone IV
* Drug: Postop oral orphenadrine
* Drug: Postop oral oxycodone
* Drug: Postop acetaminophen IV
* Drug: Postop orphenadrine IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-85 Primary, unilateral total knee arthroplasty American Society of Anesthesiologist (ASA) physical status I, II, or III Exclusion Criteria: Chronic pain (as determined by regular opioid use in the month preceding surgery) Preoperative use of centrally acting muscle relaxants in the 24 hours preceding surgery Peripheral regional anesthesia procedures other than femoral nerve injections or catheters for postoperative pain control (such as popliteal block) Severe renal dysfunction, creatinine > 2.0 Allergy or other contraindications to use of orphenadrine and/or acetaminophen Pregnant or breast feeding Abnormal Liver Function Tests(LFT) and / or history of chronic/excessive alcohol abuse. History of Hepatitis, B or C, History of cirrhosis or hepatic insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Preop acetaminophen IV 1000 mg, Postop oral oxycodone & acetaminophen (5/325 mg) 1 to 2 tabs every 4 hours PRN, and Postop hydromorphone IV 0.5 mg every 4 hours PRN | Drug: Preop acetaminophen IV<br> <br> * Other names: Ofirmev;Drug: Postop oral oxycodone & acetaminophen<br> <br> * Other names: Percocet;Drug: Postop hydromorphone IV<br> <br> * Other names: Dilaudid;|
| Active Comparator: Standard<br>Preop acetaminophen IV 1000 mg, Preop orphenadrine IV 60 mg, Postop oral orphenadrine 100 mg every 12 hours for 3 doses, Postop oral oxycodone & acetaminophen (5/325 mg) 1 to 2 tabs every 4 hours PRN, Postop hydromorphone IV 0.5 mg every 4 hours PRN | Drug: Preop acetaminophen IV<br> <br> * Other names: Ofirmev;Drug: Preop orphenadrine IV<br> <br> * Other names: Norflex;Drug: Postop oral oxycodone & acetaminophen<br> <br> * Other names: Percocet;Drug: Postop hydromorphone IV<br> <br> * Other names: Dilaudid;Drug: Postop oral orphenadrine<br> <br> * Other names: Norflex;|
| Experimental: IVAM<br>Preop acetaminophen IV 1000 mg, Preop orphenadrine IV 60 mg, Postop acetaminophen IV 1000 mg every 6 hours for 7 doses, Postop orphenadrine IV 60 mg every 12 hours for 3 doses, Postop oral oxycodone 5 mg 1 to 2 tabs every 4 hours PRN, Postop hydromorphone IV 0.5 mg every 4 hours PRN | Drug: Preop acetaminophen IV<br> <br> * Other names: Ofirmev;Drug: Preop orphenadrine IV<br> <br> * Other names: Norflex;Drug: Postop hydromorphone IV<br> <br> * Other names: Dilaudid;Drug: Postop oral oxycodone<br> <br> * Other names: Roxicodone;Drug: Postop acetaminophen IV<br> <br> * Other names: Ofirmev;Drug: Postop orphenadrine IV<br> <br> * Other names: Norflex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Routine Pain Intensity Scores | verbal subjective assessment by patient reported to nursing at standard assessment times as an ordinal number between 0 and 10 (inclusive) where 0 is no pain and 10 is the maximum pain imaginable | 48 hours | 
| Abbreviated Pain Intensity Scores | Verbal subjective assessment by patient reported to nursing at standard assessment times as either mild, moderate, or severe. | 48 hours | 
| Opioid Consumption, | recorded by nursing with dose and time. Cumulative and total opioid consumption will be analyzed. | 48 hours | 
| Physical therapy metrics/goals | measured and recorded by physical therapist in daily chart notes quantifying ability to get out of bed, range of motion (in flexion/extension degrees) and average and maximum ambulation (in feet) during postoperative days 0 to 2. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PACU discharge | Time to discharge from the PACU will be measured from PACU arrival to time of PACU discharge criteria met in minutes. | 48 hours | 
| Hospital Discharge | Time to discharge from the hospital will be measured from time/date of surgical incision to time/date that hospital discharge criteria is met, measured in hours. | 48 hours | 
| Patient satisfaction | 19 point validated questionnaire of perioperative satisfaction with items for regional anesthesia | 48 hours | 
| Cost as measured by | study medication acquisition cost reported by pharmacy, study medication administration cost reported by pharmacy and nursing, length of stay cost reported by hospital accounting. | 48 hours |