IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty
Condition: Pain, Postoperative; Opioid Use
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Acetaminophen; Acetaminophen
Intervention type(s): Drug; Drug
Intervention description(s): Oral acetaminophen, intravenous placebo; Intravenous acetaminophen, oral placebo
Intervention MeSH terms: Acetaminophen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment