Dexmetomidine Intrathecally and Intravenously Additionally to Spinal Anaesthesia, in Total Knee Arthroplasty

Study Overview
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Brief Summary
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The present study is designed to evaluate and compare the efficacy of intrathecal dexmedetomidine (DEX) as an adjuvant to Levobupivacaine in spinal anaesthesia and DEX's intravenous administration, without loading dose, additionally to spinal anaesthesia, in patients undergoing total knee arthroplasty.

Detailed Description
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Introduction Various adjuvants like morphine, fentanyl, clonidine, ketamine are being used since long for improvement of intraoperative anaesthesia and postoperative analgesia following spinal anaesthesia. On the other hand, such adjuvants have their associated adverse effects. As a result, search for an effective adjuvant is still going on. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, has analgesic and sedative effects and nowadays, is being studied for its adjuvant action in subarachnoid anaesthesia. As far as DEX is concerned, it has been reported that it can be administered intravenously in additional to spinal anaesthesia, in order to promote sensory and motor blockade duration and postoperative analgesia, because of its synergistic action with local anaesthetics. DEX is a highly selective alpha 2 adrenergic receptor agonist with a higher α2/α1 selectivity ratio of 1620:1 than clonidine (200:1). It was first introduced to clinical as a sedative in intensive care unit. Alpha-2 adrenergic receptor agonists have been tried by many clinicians due to their sedative, anxiolytic, hypnotic, analgesic, perioperative sympatholytic and stable haemodynamic properties. DEX, specifically, has all these properties, without causing respiratory depression. Currently its adjuvant action in spinal anaesthesia and its intravenous administration, additionally to subarachnoid anaesthesia, is being explored. Aim The present study is designed to evaluate and compare the efficacy of intrathecal DEX as an adjuvant to Levobupivacaine in spinal anaesthesia and DEX's intravenous administration, without loading dose, additionally to spinal anaesthesia, in patients undergoing total knee arthroplasty. Material and Methods It will be a prospective, double blind study among 90 adult patients, undergoing total knee arthroplasty under spinal anaesthesia. This study has been approved by the Institutional Medical Ethics Committee of KAT Hospital of Athens City. Informed consent will be obtained from all subjects. The patients will be randomly allocated to 3 groups (Group I, Group II, and Group III) of 30 each. Group I will receive 3 ml Levobupivacaine 0,5 % ( 15 mg ) and normal saline intrathecally. Group II will receive Levobupivacaine 0,5% and DEX (5 μg) made up to 0,5 ml with normal saline intrathecally. Group III will receive Levobupivacaine 0,5% and normal saline and DEX in Ringer Solution intravenous at a rate of 0.25 μg/kg/h. Intravenous infusion will start 10 minutes before spinal anesthesia and will last until the end of the operation. The onset and duration of sensory and motor block, the duration of postoperative analgesia, hemodynamic parameters intraoperatively and postoperatively and adverse effects will be recorded. Hemodynamic parameters such as arterial pressure and blood pulse will be recorded every 5 minutes for the first 30 minutes, thereafter every 10 minutes till the end of surgery. Sedation scores will be assessed every 15 minutes intraoperatively using the Ramsay Sedation Scale, which is : If Awake Ramsey 1 Anxious, agitated, restless Ramsey 2 Cooperative, oriented, tranquil Ramsey 3 Responsive to commands only If Asleep Ramsey 4 Brisk response to light glabellar tap or loud auditory stimulus Ramsey 5 Sluggish response to light glabellar tap or loud auditory stimulus Ramsey 6 No response to light glabellar tap or loud auditory stimulus Side effects like sedation, nausea, vomiting, shivering will be recorded intraoperatively and postoperatively.

Official Title
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Comparison of Dexmetomidine's Efficacy as an Adjuvant to Intrathecal Levobupivacaine and Intravenous Administration Additionally to Spinal Anaesthesia, In Total Knee Arthroplasty

Conditions
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Neuromuscular Block

Intervention / Treatment
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* Drug: Levobupivacaine
* Drug: Dexmetomidine intravenously
* Drug: Normal Saline added intrathecally
* Drug: Normal Saline intrathecally
* Drug: Ringer's Lactate solution intravenously
* Drug: Dexmetomidine intrathecally


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients selected for total knee arthroplasty of approximately one and half hour (90 min) duration under spinal anaesthesia. Patients who belong to American Society of Anaesthesiologists (ASA) physical status grade I and II Exclusion Criteria:• Patients with coagulation and neurological disorders Patients allergic to DEX Patients showing unwillingness for spinal anaesthesia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Levobupivacaine intrathecally<br>3 ml Levobupivacaine 0,5% (15mg) given intrathecally once for anesthesia in total knee arthroplasty | Drug: Levobupivacaine<br>* 3 ml Levobupivacaine 0.5% (15mg) given intrathecally<br>* Other names: LB;Drug: Normal Saline intrathecally<br>* 0,5 ml Normal Saline given intrathecally given once for spinal anesthesia in total knee arthroplasty<br>* Other names: N/S;|
| Active Comparator: Dexmetomidine intrathecally<br>5 μgr Dexmetomidine given intrathecally once for anesthesia in total knee arthroplasty | Drug: Levobupivacaine<br>* 3 ml Levobupivacaine 0.5% (15mg) given intrathecally<br>* Other names: LB;Drug: Normal Saline added intrathecally<br>* Normal Saline added to 5μgr dexmetomidine up to 0,5 ml given intrathecally for spinal anesthesia in total knee arthroplasty<br>* Other names: N/S;Drug: Dexmetomidine intrathecally<br>* 5 μgr dexmetomidine given intrathecally once for anesthesia in total knee replacement<br>* Other names: DEX;|
| Active Comparator: Dexmetomidine intravenously<br>Continuous infusion of dexdemetomidine at a rate of 0.25 μg/kg/h given intravenously starting 10 min before spinal anesthesia in total knee arthroplasty | Drug: Levobupivacaine<br>* 3 ml Levobupivacaine 0.5% (15mg) given intrathecally<br>* Other names: LB;Drug: Dexmetomidine intravenously<br>* Continuous infusion of dexdemetomidine at a rate of 0.25 μg/kg/h given intravenously 10 min before spinal anesthesia in total knee arthroplasty<br>* Other names: DEX;Drug: Ringer's Lactate solution intravenously<br>* Continuous infusion of Ringer's Lactate solution given intravenously, starting 10 minutes before spinal anesthesia up to the end of the operation<br>* Other names: R/L;|
| Placebo Comparator: Normal Saline intrathecally<br>0,5 ml Normal Saline given intrathecally given once for spinal anesthesia in total knee arthroplasty | Drug: Levobupivacaine<br>* 3 ml Levobupivacaine 0.5% (15mg) given intrathecally<br>* Other names: LB;Drug: Normal Saline added intrathecally<br>* Normal Saline added to 5μgr dexmetomidine up to 0,5 ml given intrathecally for spinal anesthesia in total knee arthroplasty<br>* Other names: N/S;Drug: Dexmetomidine intrathecally<br>* 5 μgr dexmetomidine given intrathecally once for anesthesia in total knee replacement<br>* Other names: DEX;|
| Other: Normal Saline added intrathecally<br>Normal Saline added intrathecally up to 0,5 ml given intrathecally for spinal anesthesia in total knee arthroplasty | Drug: Levobupivacaine<br>* 3 ml Levobupivacaine 0.5% (15mg) given intrathecally<br>* Other names: LB;Drug: Normal Saline intrathecally<br>* 0,5 ml Normal Saline given intrathecally given once for spinal anesthesia in total knee arthroplasty<br>* Other names: N/S;Drug: Dexmetomidine intrathecally<br>* 5 μgr dexmetomidine given intrathecally once for anesthesia in total knee replacement<br>* Other names: DEX;|
| Other: Ringer's Lactate solution intravenously<br>Continuous infusion of Ringer's Lactate solution given intravenously for total knee arthroplasty will start 10 minutes before spinal anesthesia to the end of the operation | Drug: Levobupivacaine<br>* 3 ml Levobupivacaine 0.5% (15mg) given intrathecally<br>* Other names: LB;Drug: Dexmetomidine intravenously<br>* Continuous infusion of dexdemetomidine at a rate of 0.25 μg/kg/h given intravenously 10 min before spinal anesthesia in total knee arthroplasty<br>* Other names: DEX;Drug: Ringer's Lactate solution intravenously<br>* Continuous infusion of Ringer's Lactate solution given intravenously, starting 10 minutes before spinal anesthesia up to the end of the operation<br>* Other names: R/L;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset and duration of sensory block using the ' pin-prick ' method,in total knee athroplasty, using DEX as an adjuvant to intrathecal Levobuvicaine and iv administration additionally to spinal anesthesia with Levobuvicaine | By using a hypodermic needle at 2 min interval, we will assess the 'pin-prick' sensation from T12 to S1 The onset of sensory block will be tested by 'pin-prick method' using a hypodermic needle at 2 minutes interval. The time of onset will be taken from the time of injection of drug into subarachnoid space to loss of pinprick sensation to T12 level. We study 90 patients(ASAI-II) devided in 3 groups and we measure the highest level of sensory block, time for two dermatomal segments regression of sensory level, duration of sensory blockade taken as time from onset to time of return of pinprick sensation to S1 (heel) dermatomal area will be noted. | The time of onset will be taken from the time of injection of drug intrathecally to loss of pinprick sensation to T12 within 30 min. Duration of sensory blockade will be measured as time from onset to time of return of piniprick sensation to S1 level. | 
| Onset and duration of motor block using the Modified Bromage Scale, in total knee athroplasty, using DEX as an adjuvant to intrathecal Levobuvicaine and iv administration additionally to spinal anesthesia with Levobuvicaine | By using the Modified Bromage Scale we will assess the onset and duration of motor block. Grade 0 : Full flexion of knees and feet. Grade 1: Just able to flex knees, full flexion of feet. Grade 2: Unable to flex knees, but some flexion of feet possible. Grade 3; Unable to move legs or feet. | Onset time will be taken from the time of injection of drug intrathecally to the patient's inability to lift the extended leg within 30 min. The duration will be taken from time of injection of drug to the patient's ability to lift the extended leg. | 
| Duration of post-operative analgesia using the Visual Analogue Scale (VAS), in total knee arthroplasty, using DEX as an adjuvant to intrathecal Levobuvicaine and iv administration additionally to spinal anesthesia with Levobuvicaine | VAS is a scale from 0 to 10, with 0 indicating 'no pain' and 10 indicating the most severe pain, that somebody has experienced. Rescue analgesics will be given to the patients when VAS>3, which will be the cut-off point of our study. | We will record the post-operative analgesia using the Visual Analogue Scale (VAS) at the end of the surgery and 3, 6, 12,24 hours after the end of the surgeryn and at the end of the surgery. an interval of 3, 6 ,and 12 h after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic stability of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia, in total knee arthroplasy | We will record SAP intra-operatively | SAP will be recorded at the time of the spinal injection, 10, 20, 30,45, 60 min after spinal injection and at the end of the surgery. | 
| Hemodynamic stability of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia, in total knee arthroplasy | We will record DAP intra-operatively | DAP will be recorded will be recorded at the time of the spinal injection, 10, 20, 30,45, 60 min after spinal injection and at the end of the surgery. | 
| Hemodynamic stability of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia, in total knee arthroplasy | We will record HR intra-operatively | HR will be recorded will be recorded at the time of the spinal injection, 10, 20, 30,45, 60 min after spinal injection and at the end of the surgery. | 
| Adverse effects of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anaesthesia with Levobupivacaine, in total knee arthroplasy | We will record adverse effects like nausea, vomitting and shivering. | Adverse effects will be recorded will be recorded at the time of the spinal injection, 15, 30, 60 min after spinal injection, at the end of the surgery and 3, 6, 12, 24 hours after the end of the surgery | 
| Sedation will be assessed with the Ramsay Sedation Scale, in total knee arthroplasty, by using DEX as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia with Levobuvicaine | The Ramay Sedation Scale is : If awake : Ramsay 1 Anxious, agitated, restless Ramsay 2 Co-operative, oriented,tranquil, Ramsay 3 Responsive to commands only. If asleep: Ramsey 4 Brisk response to light glabellar tap or loud auditory stimulus Ramsey 5 Sluggish response to light glabellar tap or loud auditory stimulus Ramsey 6 No response to light glabellar tap or loud auditory stimulus | Sedation scores will be assessed will be recorded at the time of the spinal injection, 10, 20, 30,45, 60 min after spinal injection, at the end of the surgery and 30 minutes after the end of the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexmetomidine, intrathecally, intavenously,anesthesia