Intravenous Versus Oral Acetaminophen in Primary Total Hip Arthroplasty

This is a single center, prospective, randomized controlled study. 60 subjects will be
recruited (see #6 Recruitment and Compensation below). On the day of surgery, subjects will
be randomized to receive either the study intervention (intravenous acetaminophen and placebo
tablets) or the control intervention (intravenous saline and active acetaminophen tablets).
The Investigational Drug Service will prepare each intervention package, which will include
one intravenous and one oral medication dose. Only one of these routes will be active
(determined by randomization). Subjects will receive doses of both an intravenous and oral
study drug every 6 hours in order to maintain blinding, and will receive a total of 4 doses
of each (at 0, 6, 12 and 18 hours). The dose of acetaminophen in all cases will be 1000 mg.
The volume of intravenous acetaminophen (and saline) will be 100 mL. The oral dose will
consist of two (2) tablets of 500 mg each (or two matching placebo tablets).

All subjects will receive a standardized anesthetic regimen for total hip arthroplasty, as
follows:

A) Preoperative phase

Subjects will receive the following preoperative multimodal drugs:

- Pregabalin 75 mg PO

- Celecoxib 200 mg PO

- The interventional drugs, both IV and PO . The time that these drugs are administered
will be recorded as time zero. Patients will then receive a spinal anesthetic with 12.5
mg of isobaric bupivacaine. No peripheral nerve blocks will be performed.

B) Intraoperative phase All subjects will be receive propofol infusion beginning at 50
mg/kg/min and titrated to a Richmond Agitation-Sedation Scale score of -1 to -3 (drowsy to
moderate sedation). Dexamethasone 10 mg IV and ketamine 0.25 mg/kg IV up to 40 mg total will
be administered as part of the standard multimodal regimen. If required, subjects may receive
fentanyl 25 mcg IV as needed to treat discomfort. No joint infiltration will be performed by
the surgeon.

C) Postoperative phase In the Post-Anesthesia Care Unit (PACU), subjects will have an
intravenous patient-controlled analgesia (IVPCA) device connected and loading doses of
hydromorphone administered by the PACU nurse as necessary (0.2 mg q 8 min prn).

On the floor, subjects will receive:

- Pregabalin 75 mg PO BID until discharge

- Celecoxib 200 mg PO BID until discharge

- Dexamethasone 10 mg IV x 1 on postoperative day 1 (24 hours after the first dose)

- Intravenous patient-controlled analgesia (IVPCA) with hydromorphone (0.2 mg q 8 min).

The remaining 3 intervention packages (IV and PO) will be administered at 6, 12 and 18 hours
following the first dose. At time point 24 hours (i.e. the fifth dose of acetaminophen), all
subjects will begin to receive 975 mg of oral acetaminophen, continuing every six hours until
discharge.

Inclusion Criteria:

- Patients scheduled for elective, primary total hip replacement for osteoarthritis

- American Society of Anesthesiologists (ASA) Physical Classification I-III

- Weight 50 kg or greater

- Body mass index 18-40 kg/m2

Exclusion Criteria:

- Inability to consent to study

- Inability to speak English

- Pregnancy

- Weight <50 kg

- Revision hip replacement or emergency surgery

- Contraindications to spinal anesthesia: coagulopathy or bleeding diathesis, local
infection, allergy to local anesthetics

- Allergies/intolerances/contraindications to any of the multimodal agents:
acetaminophen, pregabalin, celecoxib, ketamine, or dexamethasone

- Chronic pain from a separate source other than operative hip

- Daily opioid equivalent use of 30 mg of morphine or greater at time of consent

- History of heart failure

- History of drug or alcohol abuse

- Rheumatoid arthritis

- Uncontrolled anxiety, schizophrenia or other psychiatric disorder that, in the opinion
of the investigator, may interfere with the study assessments

- Chronic malnutrition, renal or liver impairment

- Hypersensitivity to acetaminophen or any of its excipients