IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty

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.

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