Ketamine Administration for Postoperative Pain Management in Patients Undergoing Knee Arthroplasty

Not Applicable

Not yet recruiting

• Conditions: Knee Arthroplasty; Postoperative Pain; Pain Management; Opioid Use; Analgesia; Ketamine
• Interventions: Drug: Ketamine; Drug: Standard Analgesia

• Registration Number: NCT07059429
• Lead Sponsor: State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia

Brief Summary

This study is conducted to evaluate the effectiveness and safety of ketamine infusion for pain relief after knee replacement surgery. Adult patients who have undergone knee arthroplasty will be randomly assigned to one of two groups. The study group will receive standard pain management plus a continuous infusion of ketamine using patient-controlled analgesia (PCA), while the control group will only receive standard pain management. All patients will be monitored for pain intensity using the Numeric Rating Scale (NRS) at several time points the first 24 hours after surgery. The study will compare the total amount of opioid pain medication required, the level of pain experienced, and the frequency and severity of side effects such as nausea, vomiting, and neuropsychiatric reactions. The goal is to determine whether adding ketamine to standard pain management reduces opioid use and improves pain control without increasing side effects. The results improve pain management strategies after knee replacement surgery.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-07
• Study Start: 2025-07-01
• Study First Submitted: 2025-07-07
• Study First Submitted QC: 2025-07-09
• Last Update Submitted: 2025-07-09
• Study First Posted: 2025-07-10
• Last Update Posted: 2025-07-10
• Primary Completion: 2025-10
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ketamine Plus Standard Analgesia	Ketamine	Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
Standard Analgesia Alone	Standard Analgesia	Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.

Primary Outcome Measures

Name	Time	Method
Total Opioid Consumption in Morphine Equivalents Within 24 Hours After Surgery	24 hours postoperatively	The total dose of opioid analgesics (calculated in milligrams of morphine equivalents) administered to each patient during the first 24 hours after knee arthroplasty.

Secondary Outcome Measures

Name	Time	Method
Pain Intensity Assessed by Numeric Rating Scale (NRS)	At 0, 2, 4, 6, 10, 14, 18, and 24 hours postoperatively	Pain intensity scores measured using the NRS at specified time points (0, 2, 4, 6, 10, 14, 18, 24 hours after surgery). The NRS is an 11-point scale ranging from 0 to 10, where: 0 corresponds to "no pain," 10 corresponds to "the worst pain imaginable."
Incidence of Postoperative Nausea and Vomiting	24 hours postoperatively	The number of patients experiencing any episode of postoperative nausea or vomiting during the first 24 hours after surgery.
Incidence of Neuropsychiatric Adverse Events	24 hours postoperatively	The number of patients experiencing one or more neuropsychiatric adverse events (such as hallucinations, agitation, or dysphoria) during the first 24 hours postoperatively.
Severity of Neuropsychiatric Adverse Events	24 hours postoperatively	The maximum severity of any neuropsychiatric adverse event experienced by a patient, graded according to the Common Terminology Criteria for Adverse Events (CTCAE). The scale ranges from Grade 1 (Mild) to Grade 5 (Death). Specific conditions and symptoms may have values or descriptive comment for each level, but the general guideline is: 1. - Mild; 2. - Moderate; 3. - Severe; 4. - Life-threatening; 5. - Death
Total Number of Ketamine Boluses Administered	24 hours postoperatively	The total count of patient-initiated ketamine boluses administered via Patient-Controlled Analgesia (PCA) during the first 24 hours after surgery.
Cumulative Ketamine Dose Administered	24 hours postoperatively	The total cumulative dose of ketamine (in milligrams) administered during the first 24 hours after surgery, including both the continuous infusion and patient-initiated boluses.

Trial Locations

Locations (1)

Pirogov National Medical and Surgical Center; 🇷🇺 Moscow, Russian Federation