Low Dose Ketamine Infusion for Postoperative Analgesia After Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study evaluates continous infusion of low-dose ketamine during intraoperative and postoperative periods at three different doses to provide postoperative analgesia in total knee arthroplasty cases. Patients enrolled randomly into one of 2, 4, 6 μg / kg / min perioperative ketamine groups. All groups were given spinal anesthesia and intravenous patient controlled anesthesia. Ketamine was started when sensorial block reached T10 dermatome level before the skin incision. By the end of the operation, in all groups, ketamine infusions were reduced by half doses. Intravenous patient-controlled analgesia device was set to 2 mg bolus morphine with no basal infusion for 48 hours during the postoperative period.

Detailed Description
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Multimodal analgesia, which involves the administration of two or more analgesic agents targeting different levels of pain pathways, is used to improve pain control while also to reduce opioid use and related side effects. Pain can be treated at various neurophysiological levels, including peripheral, spinal and cortical targets. One of the agents used in the multimodal analgesia technique is ketamine. Ketamine acts on the central nervous system (CNS) and has local anesthetic effect. Ketamine is an N-methyl D-Aspartate (NMDA) receptor antagonist, which appears to be the main mechanism of anesthetic and analgesic action at CNS and spinal cord receptors. Other mechanisms of action of ketamine include the interaction with opioid receptors, particularly mu and kappa receptors. Another effect is that it has local anesthetic effect in high doses. Studies have shown that ketamine is an effective agent in the treatment of postoperative pain. Continuous infusion of low-dose ketamine after total knee arthroplasty significantly reduced morphine consumption, and provided early rehabilitation without increasing side effects. However, when these studies are considered, there is no information about the optimal dose of ketamine that reduces opioid consumption at the highest level. In our study, continuous infusion of low-dose ketamine at different doses was planned to provide postoperative analgesia. Therefore, our first aim in this study was to find out the optimal dose that reduced morphine consumption for postoperative analgesia after TKA with continuous ketamine infusion at different doses. The secondary objectives are to evaluate early and late period pain, side effects, length of hospital stay, patient satisfaction, and recovery.

Official Title
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Low Dose Ketamine Infusion for Postoperative Analgesia After Total Knee Arthroplasty: Optimum Dose to Reduce Morphine Consumption

Conditions
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Postoperative Pain

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • ASA I-Ⅲ female patients scheduled for unilateral total knee arthroplasty Exclusion Criteria: Patients younger than 18 years of age ASA Ⅳ and above patients Having previous knee surgery on the same side Patients with allergies to drugs to be used in the study Contraindication for spinal anesthesia Body mass index 40 kg / m2 and above patients Opioid tolerance Patients with neurological or psychiatric disorders Patients who do not have the ability to use patient controlled analgesia device

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>All patients were revived spinal anesthesia with 3 mL marcaine 0.5% and after surgery a 2 mg bolus morphine PCA pump was connected to them. Before the skin incision, when sensorial block reached T10 dermatome level 2 μg / kg / min ketamine was started in Group 1. By the end of the operation ketamine infusion was reduced to 1 μg / kg / min. | |
| Group 2<br>All patients were revived spinal anesthesia with 3 mL marcaine 0.5% and after surgery a 2 mg bolus morphine PCA pump was connected to them. Before the skin incision, when sensorial block reached T10 dermatome level 4 μg / kg / min ketamine was started . By the end of the operation ketamine infusion was reduced to 2 μg / kg /min and continued. | |
| Group 3<br>All patients were revived spinal anesthesia with 3 mL marcaine 0.5% and after surgery a 2 mg bolus morphine PCA pump was connected to them. Before the skin incision, when sensorial block reached T10 dermatome level 6 μg / kg / min ketamine was started . By the end of the operation ketamine infusion was reduced to 3 μg / kg /min and continued. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal dose of Ketamine to reduce morphine consumption | Ketamine infusions 2μg 4μg and 6μg / kg / min will be started preoperatively in group 1, 2 and 3 respectively when sensory block level reaches T10 after spinal anesthesia, and they will be reduced by half by the end of the operation. Ketamine infusion will be continued for 48 hours postoperatively. | 48 hours from the operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early and late period pain | The pain status of the patients at rest and in motion with 100 mm visual pain scale (VAS) (0= no pain and 100 = intolerable pain) will be evaluated and recorded preoperative and postoperative at 2nd, 6th, 12th, 24th and 48th hours.and after 3 months | 3 months from the operation | 
| side effects, | Nausea, vomiting, itching, respiratory depression, hallucination and diplopia | 3 months | 
| length of hospital stay | Hospital stay (as day) required for active knee flexion to 90 degrees (measured with goniometer) will be recorded. | 3 months | 
| patient satisfaction | 5 point likert scale | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, analgesia, Postoperative, Ketamine, Morphine