Epidural Nalbuphine Versus Dexmedetomidine as Adjuvants to Bupivacaine in Lower Limb Surgeries

Study Overview
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Brief Summary
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Combined spinal epidural anesthesia (CSE) with bupivacaine alone is not sufficient to cover pain sequel during lower limb surgeries. Previous studies used addition of either Nalbuphine or dexmedetomidine to bupivacaine in epidural anesthesia giving a good result in pain control. In this study the investigators will evaluate and compare the addition of either Nalbuphine or dexmedetomidine to bupivacaine in epidural anesthesia to evaluate the analgesic efficacy of either drug.

Detailed Description
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Surgical patients need adequate and effective intraoperative anesthesia and postoperative analgesia. Neuroaxial block including lower limb spinal and epidural blocks have a long history of effective anesthesia and lower limb pain relief. Spinal anesthesia is a simple method requiring small dose of local anesthetic agent to give immediate and effective sensory and motor block. But one of its major side effects is hypotension and difficulty in controlling the level of the block [1]. Meanwhile, epidural anesthesia is a safe, well-practiced, not expensive neuroaxial block technique that provides intraoperative anesthesia and postoperative analgesia. So, the combined spinal epidural block (CSE) aims to achieve intense sensory and motor anesthesia and prolong the duration of analgesia intraoperative extending to postoperative period [2]. Neuroaxial anesthesia and analgesia provide perfect analgesic effect by inhibiting nociceptive transmission from peripheral to central neuronal system, but this advantage limited by short half-life of the current local anesthetics. Bupivacaine is a local anesthetic which belongs to amide group of anesthetic agents that has been widely used for local infiltration, peripheral nerve block, spinal and epidural anesthesia and despite relatively long duration of action, still has insufficient time for postoperative analgesia [3]. Several neuroaxial adjuvants such as (opioids, dexamethasone, magnesium sulphate, midazolam and dexmedetomidine) can be added to local anesthetics to prolong its duration of anesthesia and decrease the dose requirement of local anesthetics [4]. Nalbuphine, a derivative of 14-hydroxy morphine is a strong analgesic with mixed kappa agonist and µ antagonist properties. Its potency is equal to morphine, but exhibits a ceiling effect on respiratory depression. It has the potential to maintain and enhance µ-opioid based anesthesia while simultaneously mitigating the µ-opioid side effects [5]. Dexmedetomidine is an imidazole compound. It is a highly selective α-2 adrenergic agonist with an affinity 8 times more specific when compared to clonidine. It has sedative, sympatholytic and analgesic effects that blunt cardiovascular responses both intraoperative and in the perioperative period. Patients remain calm and sedated when undisturbed but arouse readily with stimulation [6]. Dexmedetomidine causes manageable hypotension and bradycardia, but the striking feature of this drug is the lack of opioid-related adverse effects like respiratory depression, pruritis, nausea, and vomiting [7].

Official Title
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Epidural Nalbuphine Versus Dexmedetomidine as Adjuvants to Bupivacaine in Lower Limb Surgeries Under Combined Spinal-epidural Anesthesia

Conditions
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Lower Limb Surgeries

Intervention / Treatment
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* Drug: normal saline
* Drug: Dexmedetomidine
* Drug: Nalbuphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient acceptance. BMI 25-29.9 kg/m2. ASA I and ASA II. Scheduled for elective lower limb orthopedic surgeries under (CSE) block. Exclusion Criteria: Patient with known allergy to study drugs, Patients suffering from severe chronic diseases (cardiac, renal, hepatic and neurological or diabetes), Patients with infection at the site of spinal-epidural block, Drug addict patients, Patients on long term steroid therapy, Patients with abnormalities in vertebral spine, Mentally retarded or uncooperative patients, Patients receive anti-coagulant therapy or suspected coagulopathy.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 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: Parallel Assignment
Interventional Model Description: The patients will be divided randomly by a computer-generated randomization table into three equal groups
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: control group<br>patient will be given epidural bolus dose of 12ml (10ml 0.25% bupivacaine + 2ml normal saline), top up dose of 8ml will be given postoperative (6ml 0.25% bupivacaine + 2ml normal saline). | Drug: normal saline<br>* Surgery will be started under spinal anesthesia. When sensory block regress to T12 dermatome Epidural bolus dose will be given epidural bolus dose of 12ml (10ml 0.25% bupivacaine + 2ml normal saline) The onset of sensory blockade injected epiduraly with maximal cephalic spread will be assessed by bilateral pinprick method along the midclavicular line, every 5 min for 30 min and then every 30 min. top up dose of 8ml will be given postoperative (6ml 0.25% bupivacaine + 2ml normal saline).<br>|
| Active Comparator: dexmedetomidine group<br>patient will be given epidural bolus dose of 12ml (10ml 0.25% bupivacaine + 100µg dexmedetomidine in 2ml volume), top up dose of 8ml will be given postoperative (6ml 0.25% bupivacaine + 20µg dexmedetomidine in 2ml volume) | Drug: Dexmedetomidine<br>* Surgery will be started under spinal anesthesia. When sensory block regress to T12 dermatome Epidural bolus dose will be given epidural bolus dose of 12ml (10ml 0.25% bupivacaine + 100µg dexmedetomidine in 2ml volume) The onset of sensory blockade injected epiduraly with maximal cephalic spread will be assessed by bilateral pinprick method along the midclavicular line, every 5 min for 30 min and then every 30 min. top up dose of 8ml will be given postoperative (6ml 0.25% bupivacaine + 20µg dexmedetomidine in 2ml volume).<br>|
| Active Comparator: nalbuphine group<br>patient will be given epidural bolus dose of 12ml (10ml 0.25% bupivacaine + 10mg nalbuphine in 2ml volume), top up dose of 8ml will be given postoperative (6ml 0.25% bupivacaine + 2mg nalbuphine in 2ml volume) | Drug: Nalbuphine<br>* Surgery will be started under spinal anesthesia. When sensory block regress to T12 dermatome Epidural bolus dose will be given epidural bolus dose of 12ml (10ml 0.25% bupivacaine + 10mg nalbuphine in 2ml volume) The onset of sensory blockade injected epiduraly with maximal cephalic spread will be assessed by bilateral pinprick method along the midclavicular line, every 5 min for 30 min and then every 30 min. top up dose of 8ml will be given postoperative (6ml 0.25% bupivacaine + 2mg nalbuphine in 2ml volume).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of epidural analgesia | time elapsed from epidural injection of LA until VAS score (≥3) | within 24 hour postoperative | 
| Maximum level of sensory blockade | the maximum sensory dermatome level after 30 min of administering the local anesthetic in the epidural space | after 30 min of administering the local anesthetic in the epidural space | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of top up doses required | When sensory block regress to T12 dermatome Epidural bolus dose will be given | within 24 hour postoperative | 
| assessment of changes in patient's level of sedation | assessment of patient's level of sedation using Ramsey sedation score; where 1=patient is anxious and agitated or restless, or both. 2= Patient is co-operative, oriented, and tranquil. 3= Patient responds to commands only. 4= Patient exhibits brisk response to light glabellar tap or loud auditory stimulus. 5= Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus. 6= Patient exhibits no response. | Sedation scores will be recorded just before the initiation and 2 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidural Nalbuphine, Epidural Dexmedetomidine, combined spinal-epidural anesthesia, lower limb surgeries