Analgesia, Ketamine, Knee Arthroplasty, Opioid Use, Pain Management, Postoperative Pain
Conditions
Keywords
Ketamine, Knee Replacement, Total Knee Arthroplasty, Postoperative Analgesia, Patient-Controlled Analgesia, PCA, Opioid Sparing, Multimodal Pain Management, Morphine Consumption, Neuropsychiatric Side Effects, Nausea and Vomiting
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.
Interventions
DRUGKetamine
Ketamine administered intravenously at 0.15 mg/kg/h via PCA with 1 mg boluses, 5-minute lockout, maximum 500 mg per 24 hours after knee arthroplasty.
Standard analgesia includes ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty; morphine 10 mg IM as needed for rescue therapy.
Sponsors
State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups: the intervention group (standardized postoperative analgesia plus ketamine infusion via patient-controlled analgesia), or the control group (standardized postoperative analgesia without ketamine). Randomization will be performed using permuted blocks of six patients. There will be no crossover or switching between groups; all interventions and assessments will be conducted independently and concurrently for both groups. The study is single-center and prospective.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Assessed by Numeric Rating Scale (NRS) | 2-10 hours and 10-24 hours postoperatively | Pain intensity measured using the 11-point Numeric Rating Scale (NRS), where 0 = no pain and 10 = worst pain imaginable, averaged across two time intervals: 2-10 hours (mean of time points 2, 4, 6, 10h) and 10-24 hours (mean of time points 14, 18, 24h) after surgery. |
| 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. |
| Number of Participants With Neuropsychiatric Adverse Events | 0-10 hours and 10-24 hours postoperatively | Number of participants experiencing neuropsychiatric adverse events during 0-10 hours (NPA 0-10 hours) and 10-24 hours (NPA 10-24 hours) after knee arthroplasty. |
| 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 |
| 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. |
Countries
Russia
Contacts
STUDY_DIRECTORBoris Teplykh, MD
Pirogov National Medical and Surgical Center
PRINCIPAL_INVESTIGATORIvan Shcheparev, MD, PhD
Pirogov National Medical and Surgical Center
Participant flow
Recruitment details
Patients undergoing knee arthroplasty at Pirogov National Medical and Surgical Center were sequentially recruited and randomly assigned to intervention or control group.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 8.47 |
| Body Mass Index (BMI) | 31.08 kg/m² STANDARD_DEVIATION 12.73 |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment Russia | 46 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 0 / 50 | 3 / 50 |
| serious Total, serious adverse events | 1 / 50 | 1 / 50 |
Outcome results
None listed