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

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

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.

Study Overview

• Status: Completed
• Conditions: Lower Limb Surgeries
• Intervention / Treatment: Drug: normal saline; Drug: Dexmedetomidine; Drug: Nalbuphine

Detailed Description

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].

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manal S Farmawy, MD; Phone Number: 002 01006330206; Email: manalsfarmawy@gmail.com

Study Locations

• Egypt
  • Elsharqya
    • Zagazig, Elsharqya, Egypt, 44519
      • Faculty of medicine, Zagazig university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: control group; 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; 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).
Active Comparator: dexmedetomidine group; 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; 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).
Active Comparator: nalbuphine group; 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; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zagazig University
• Investigators: Study Director: Howaida A Kamal, MD, Faculty of medicine, zagazig university, Zagazig, Elsharqya, Egypt, 44519

Publications and helpful links

General Publications

• Chatrath V, Attri JP, Bala A, Khetarpal R, Ahuja D, Kaur S. Epidural nalbuphine for postoperative analgesia in orthopedic surgery. Anesth Essays Res. 2015 Sep-Dec;9(3):326-30. doi: 10.4103/0259-1162.158004.
• Shruthi AH, Sudheesh K, Nethra SS, Raghavendra Rao RS, Devika Rani D. THE EFFECT OF A SINGLE DOSE OF MAGNESIUM SULPHATE AS AN ADJUVANT TO EPIDURAL BUPIVACAINE FOR INFRAUMBILICAL SURGERIES: A PROSPECTIVE DOUBLE-BLIND, RANDOMIZED CONTROL TRIAL. Middle East J Anaesthesiol. 2016 Feb;23(4):449-55.
• Gupta K, Rastogi B, Gupta PK, Singh I, Bansal M, Tyagi V. Intrathecal nalbuphine versus intrathecal fentanyl as adjuvant to 0.5% hyperbaric bupivacaine for orthopedic surgery of lower limbs under subarachnoid block: A comparative evaluation. Indian J Pain. 2016; 30:90-5.
• Chiruvella S, Donthu B, Nallam SR, Salla DB. Postoperative Analgesia with Epidural Dexmedetomidine Compared with Clonidine following Total Abdominal Hysterectomies: A Prospective Double-blind Randomized Trial. Anesth Essays Res. 2018 Jan-Mar;12(1):103-108. doi: 10.4103/aer.AER_207_17.
• Soliman AAM, Melika ASM. Epidural bupivacaine and dexmedetomidine versus bupivacaine and opioids for lower vascular surgery. J Med Sci Res. 2018; 1:158-63.
• Paul A, Nathroy A, Paul T. A comparative study of dexmedetomidine and fentanyl as an adjuvant to epidural bupivacaine in lower limb surgeries. J Med Sci. 2017; 37:221-6.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): May 15, 2022

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: combined spinal-epidural anesthesia; lower limb surgeries; Epidural Nalbuphine; Epidural Dexmedetomidine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Dexmedetomidine; Nalbuphine
• Other Study ID Numbers: 16-8-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: planned after the completion of the study and publication
• IPD Sharing Time Frame: planned after the completion of the study and publication
• IPD Sharing Access Criteria: principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No