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

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

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.

Study Overview

• Status: Unknown
• Conditions: Neuromuscular Block
• Intervention / Treatment: Drug: Levobupivacaine; Drug: Normal Saline intrathecally; Drug: Normal Saline added intrathecally; Drug: Dexmetomidine intrathecally; Drug: Dexmetomidine intravenously; Drug: Ringer's Lactate solution intravenously

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Kifissia, Greece, 14561
    • Recruiting
    • Kat General Hospital of Attca
    • Contact: Ioanna Diagoupi; Phone Number: 00306976564296; Email: diag-anna@hotmail.com
    • Contact: Efi Stavropoulou; Phone Number: 00306937103320; Email: efistavropoulou@yahoo.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: KAT General Hospital
• Investigators: Study Chair: Efi Stavropoulou, KAT General Hospital of Attica; Study Chair: Cathrin Chazapis, KAT General Hospital of Athens

Publications and helpful links

General Publications

• Zhang H, Li M, Zhang SY, Fu M, Zhang SY. Intravenous Dexmedetomidine Promotes Spinal Bupivacaine Anesthesia and Postoperative Analgesia in Lower Limb Surgery: A Double-Blind, Randomized Clinical CONSORT Study. Medicine (Baltimore). 2016 Feb;95(8):e2880. doi: 10.1097/MD.0000000000002880.
• Chan IA, Maslany JG, Gorman KJ, O'Brien JM, McKay WP. Dexmedetomidine during total knee arthroplasty performed under spinal anesthesia decreases opioid use: a randomized-controlled trial. Can J Anaesth. 2016 May;63(5):569-76. doi: 10.1007/s12630-016-0597-y. Epub 2016 Jan 29.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: August 28, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Estimate): November 17, 2016
• Last Update Submitted That Met QC Criteria: November 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: dexmetomidine, intrathecally, intavenously,anesthesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Levobupivacaine
• Other Study ID Numbers: 9092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No