The Safety and Feasibility of Oral Aspirin and Ketamine for Acute Pain Management After Total Knee Arthroplasty: A Pilot Study.

Abstract

Managing pain after total knee arthroplasty (TKA) without opioids remains a priority. Aspirin is often used after joint surgery for venous thromboembolism prophylaxis and is unique among non-steroidal anti-inflammatory drugs (NSAIDs) in providing this protection through irreversible cyclooxygenase inhibition. Oral ketamine has demonstrated analgesic benefit, but its combination with aspirin for postoperative pain control is not well established. We sought to investigate the following: (1) Is combined administration of oral ketamine and aspirin safe in patients undergoing TKA? (2) What are the observed pain control outcomes and opioid requirements associated with this regimen? We conducted a single-institution pilot study of patients undergoing primary TKA to test the safety of a proprietary oral aspirin/ketamine combination; the study was funded by the manufacturer, Vitalis Pharmaceuticals. Eligible patients were prospectively identified from the operative schedules of 7 participating arthroplasty surgeons and approached at their preoperative office visits between February 2023 and March 2023. Patients were excluded from the study if they were age <18 or >80 years, if they had a primary diagnosis other than primary osteoarthritis, an allergy to aspirin or another NSAID, any contraindications to NSAID use, use of anti-coagulant or anti-thrombotic medication, recent active bleeding requiring a transfusion or hospitalization, or scheduled for same-day discharge. Twenty patients were included. Patients received oral ketamine (40 mg) and aspirin (162 mg) every 6 hours postoperatively until discharge. The primary outcome was safety, assessed using the Side Effect Rating Scale for Dissociative Anesthetics and the Richmond Agitation Sedation Scale (RASS). Secondary outcomes included a numeric rating scale for pain and morphine milligram equivalents (MME). Descriptive statistics were used. Of the 20 patients in the final cohort, 14 patients completed the full 4-dose regimen during their 24-hour postoperative inpatient stays; 18 of the 20 patients reported no adverse effects. Two patients experienced mild dizziness after later doses, with no reported agitation or sedation on the RASS scale. Most patients (19/20) required rescue opioid doses; pain scores were similar, regardless. Mean 24-hour opioid consumption was 30.2 ± 20.4 MME. This single-institution pilot study observed that an oral aspirin/ketamine combination appeared to be safe after TKA, with minimal adverse effects. A future randomized controlled trial is needed to evaluate efficacy and opioid-sparing benefits. Level IV, pilot study.