Ketamine Administration for Postoperative Pain Management in Patients Undergoing Knee Arthroplasty

This is a prospective, randomized controlled study evaluating the use of ketamine infusion as part of postoperative pain management for adult patients undergoing knee arthroplasty. The study will enroll patients aged 18 to 90 years who have undergone knee replacement surgery at the N.I. Pirogov National Medical and Surgical Center.

Participants will be randomly assigned to either the study group or the control group. Both groups will receive standardized pain management with ketoprofen and paracetamol in keeping with current guidelines. The study group will receive an additional continuous infusion of ketamine using PCA at a rate of 0.15 mg/kg/h, with 1 mg boluses available in 5-minute lockout intervals and a maximum daily dose of 500 mg. In both groups, opioid analgesics (morphine 10 mg intramuscularly as needed) will be administered if pain control is inadequate. Regional nerve blocks may be repeated under ultrasound guidance if necessary; patients requiring repeated femoral nerve block will be analyzed separately.

Pain intensity will be assessed using the NRS at 0, 2, 4, 6, 10, 14, 18, and 24 hours postoperatively. Data will be collected on the total dose of opioids used, additional analgesic requirements, the number and severity of neuropsychiatric adverse events (graded according to CTCAE), the frequency of postoperative nausea and vomiting, and the total dose and number of ketamine boluses administered.

The primary outcome is the total dose of opioid analgesics (morphine equivalents, mg) administered the first 24 hours after surgery. Secondary outcomes include pain scores at each time point, incidence and severity of neuropsychiatric side effects, frequency of postoperative nausea and vomiting, and total ketamine dose received.

The study is designed to compare the efficacy and safety of ketamine infusion in reducing opioid consumption and improving pain control after knee arthroplasty, while closely monitoring adverse events. The results aim to provide evidence for optimizing multimodal analgesia in orthopedic surgery.This clinical trial was preceded by a pilot study involving patients undergoing knee arthroplasty. The pilot phase aimed to evaluate the variability of key parameters such as pain intensity, opioid requirements, and the incidence of neuropsychiatric side effects. Based on the analysis of the investigators' published data, modifications were made in the main study protocol, including adjustments to the ketamine bolus dose within the PCA regimen to optimize efficacy and safety.

The changes were introduced to enhance pain control and minimize adverse effects in the main study population. The current trial involves these protocol refinements, and the investigators anticipate that the optimized ketamine dosing schedule will lead to improved outcomes compared to the initial regimen.

Inclusion criteria

• Age greater than 18 years and less than 90 years.
• Patients who have undergone knee arthroplasty.
• The patient has read the information sheet and signed the informed consent form.

Exclusion criteria

• Spinal anesthesia performed intraoperatively.
• Epidural analgesia administered postoperatively.
• Perioperative blockade of the sciatic nerve, genicular nerve, or lumbar plexus.
• Allergy to ketamine or non-steroidal anti-inflammatory drugs.
• Contraindications to ketamine as specified in the product instructions.
• Time from the end of surgery to study enrollment exceeds 24 hours.
• Ineffectiveness of analgesia as provided by the study protocol.