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

KAT General Hospital

Status and phase: Unknown; Phase 4

Conditions: Neuromuscular Block

Treatments: Drug: Levobupivacaine; Drug: Ringer's Lactate solution intravenously; Drug: Dexmetomidine intravenously; Drug: Normal Saline intrathecally; Drug: Dexmetomidine intrathecally; Drug: Normal Saline added intrathecally

Study type: Interventional

Funder types: Other

Identifiers

NCT02966249

9092

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

---

90 participants in 6 patient groups, including a placebo group

Levobupivacaine intrathecally

Other group

Description:

3 ml Levobupivacaine 0,5% (15mg) given intrathecally once for anesthesia in total knee arthroplasty

Treatment:

Drug: Normal Saline intrathecally

Drug: Levobupivacaine

Dexmetomidine intrathecally

Active Comparator group

Description:

5 μgr Dexmetomidine given intrathecally once for anesthesia in total knee arthroplasty

Treatment:

Drug: Normal Saline added intrathecally

Drug: Dexmetomidine intrathecally

Drug: Levobupivacaine

Dexmetomidine intravenously

Active Comparator group

Description:

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

Treatment:

Drug: Dexmetomidine intravenously

Drug: Ringer's Lactate solution intravenously

Drug: Levobupivacaine

Normal Saline intrathecally

Placebo Comparator group

Description:

0,5 ml Normal Saline given intrathecally given once for spinal anesthesia in total knee arthroplasty

Treatment:

Drug: Normal Saline added intrathecally

Drug: Dexmetomidine intrathecally

Drug: Levobupivacaine

Normal Saline added intrathecally

Other group

Description:

Normal Saline added intrathecally up to 0,5 ml given intrathecally for spinal anesthesia in total knee arthroplasty

Treatment:

Drug: Dexmetomidine intrathecally

Drug: Normal Saline intrathecally

Drug: Levobupivacaine

Ringer's Lactate solution intravenously

Other group

Description:

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

Treatment:

Drug: Dexmetomidine intravenously

Drug: Ringer's Lactate solution intravenously

Drug: Levobupivacaine