Clinical trial NCT02966249: Dexmetomidine Intrathecally and Intravenously Additionally to Spinal Anaesthesia, in Total Knee Arthroplasty
Official title: Comparison of Dexmetomidine's Efficacy as an Adjuvant to Intrathecal Levobupivacaine and Intravenous Administration Additionally to Spinal Anaesthesia, In Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Neuromuscular Block
Keywords: dexmetomidine, intrathecally, intavenously,anesthesia
Lead sponsor: KAT General Hospital
Sponsor class: OTHER
First posted: 2016-11-17
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: 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
timeFrame: 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 outcomes:
measure: Hemodynamic stability of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia, in total knee arthroplasy
timeFrame: 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.
measure: Hemodynamic stability of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia, in total knee arthroplasy
timeFrame: 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.
measure: Hemodynamic stability of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anesthesia, in total knee arthroplasy
timeFrame: 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.
measure: Adverse effects of DEX, used as an adjuvant to intrathecal Levobupivacaine and intravenous administration additionally to spinal anaesthesia with Levobupivacaine, in total knee arthroplasy
timeFrame: 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
measure: 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
timeFrame: 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
Other outcomes:
Locations:
city: Kifissia
country: Greece
facility: Kat General Hospital of Attca
Study officials:
affiliation: KAT GENERAL HOSPITAL OF ATTICA
name: Efi Stavropoulou
role: STUDY_CHAIR
affiliation: KAT General Hospital of Athens
name: Cathrin Chazapis
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.