Influence Of Low Dose Intrathecal Naloxone On Bupivacaine - Fentanyl Spinal Anaesthesia For Lower Limb Orthopedic Surgery In Elderly Patients

Fentanyl is a safer alternative than morphine in the management of postoperative pain in elderly. However, pruritus, nausea and vomiting are unwanted side effects of intrathecal fentanyl administration, that can decrease patient satisfaction with anaesthesia, delay post anaesthesia care unit ( PACU ) discharge, and increase costs.

The incidence of pruritus with neuraxial fentanyl is high. The incidence of pruritus in non-obstetric surgery patients after intrathecal fentanyl ranges from 53% to 79%.

Naloxone hydrochloride is a pure opioid competitive antagonist. Small doses of naloxone may reduce Fentanyl-associated adverse effects, such as pruritus, nausea and vomiting without affecting analgesia.

Study Overview

• Status: Completed
• Conditions: Elderly; Anesthesia, Spinal
• Intervention / Treatment: Drug: Bupivacaine-fentanyl

Detailed Description

The aim of this study is to evaluate the effect of adding low dose intathecal naloxone to bupivacaine - fentanyl spinal anesthesia in elderly patients scheduled for unilateral lower limb orthopedic surgeries on opioid induced side effects namely pruritus, postoperative analgesia and the incidence of postoperative cognitive dysfunction (POCD) in elderly.

A four category verbal rating scale VRS-4 ( 0 to 3 scale ) will be used for assessment of intrathecal fentanyl induced side effects including pruritus, nausea, vomiting and shivering.

Mini Mental State Examination ( MMSE ) test will be applied to all patients pre- and post- operative to assess the incidence and the degree of POCD.

An 11 points Verbal Numerical Rating Scale VNRS for pain assessment will be also applied to all patients postoperatively to assess the effect on postoperative analgesia.

• Cannulation: Peripheral cannulae ( size 20 gauge or 18 gauge ) will be inserted to all patients . Ringer's acetate warmed up to 37°C will be infused slowly at rate of 7ml/kg, 30 min before induction of spinal anaesthesia. A single intravenous ( I.V. ) dose of prophylactic antibiotic after a negative sensitivity test will be given to all patients 15-30 min. before operation.
• Induction: Patient will receive spinal anaesthesia with 12.5 mg hyperbaric Bupivacaine 0.5% ( 2.5 mL ) plus 25 µg Fentanyl ( 0.5 mL ) and 20 µg Naloxone ( prepared in 0.5 mL normal saline ) added in the same syringe in a total volume of 3.5 mL..
• Spinal anaesthesia will be conducted while the patients are in the sitting position and under complete aseptic conditions; a lumber puncture at L3-4 or L4-5 interspaces will be performed with a 25- gauge Quincke spinal needle after infiltrating the skin with 2 ml of lidocaine 2%. After a successful dural puncture and ensuring free flow of cerebrospinal fluid, injectates will be injected slowly over 20 seconds without barbotage or aspiration according to group of the patient. Immediately, patients will be turned into the supine position. Oxygen 2-3 L/min will be applied to all patients via nasal prongs.

Evolution and regression of sensory and motor block will be evaluated. Sensation will be assessed by pinprick in the mid-clavicular line as follows; Grade 0: Sharp pain felt, Grade I: Analgesia, dull sensation felt, Grade II: Anesthesia, no sensation felt. Motor blockade will be assessed according to Modified Bromage Scale.

Hemodynamics ( mean arterial blood pressure MAP, heart rate HR and oxygen saturation SpO2 ) will be also recorded at predetermined accurate times.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Kasralainy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 60y of either gender.
• ASA physical status III or below.
• Patients scheduled for elective unilateral lower limb orthopedic surgery.

Exclusion Criteria:

• Morbid obese patients.
• Severe or uncompensated cardiovascular, renal, hepatic or endocrinal diseases.
• Allergy to one of the agents used.
• Severely altered consciousness level.
• Coagulopathy
• Increased intracranial pressure
• Neuromuscular diseases
• Severe spinal deformity
• Patients on opioid analgesics or opioid abuse
• Multi traumatized patients
• Patients with preoperative Mini Mental State Examination ( MMSE ) scoring < 24

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bupivacaine-Fentanyl Spinal Anaesthesia	Drug: Bupivacaine-fentanyl; Bupivacaine-Fentanyl (BF) group (46 patients): will receive spinal anaesthesia with 12.5 mg hyperbaric Bupivacaine 0.5% (2.5 mL) plus 25 µg Fentanyl (0.5 mL) and (0.5 mL) normal saline added in the same syringe in a total volume of 3.5 mL. Bupivacaine-Fentanyl-Naloxone (BFN) group (46 patients): will receive spinal anaesthesia with 12.5 mg hyperbaric Bupivacaine 0.5% (2.5 mL) plus 25 µg Fentanyl (0.5 mL) and 20 µg Naloxone (prepared in 0.5 mL normal saline) added in the same syringe in a total volume of 3.5 mL.; Other Names: Naloxone hydrochloride
Active Comparator: Bupivacaine-Fentanyl-Naloxone Spinal Anaesthesia	Drug: Bupivacaine-fentanyl; Bupivacaine-Fentanyl (BF) group (46 patients): will receive spinal anaesthesia with 12.5 mg hyperbaric Bupivacaine 0.5% (2.5 mL) plus 25 µg Fentanyl (0.5 mL) and (0.5 mL) normal saline added in the same syringe in a total volume of 3.5 mL. Bupivacaine-Fentanyl-Naloxone (BFN) group (46 patients): will receive spinal anaesthesia with 12.5 mg hyperbaric Bupivacaine 0.5% (2.5 mL) plus 25 µg Fentanyl (0.5 mL) and 20 µg Naloxone (prepared in 0.5 mL normal saline) added in the same syringe in a total volume of 3.5 mL.; Other Names: Naloxone hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of fentanyl - induced pruritus	A four category verbal rating scale VRS-4 ( 0 to 3 scale ) which will be will be explained to all patients, where ( 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms ) with the basal preoperative value is being recorded.	4 hours postoperative

Secondary Outcome Measures

Outcome Measure	Time Frame
The time for first postoperative analgesic requirements	24 hours
Cognitive function using Mini Mental State Examination (MMSE) scoring	24 hours
postoperative nausea and vomiting	24 hours

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Collaborators: Mansoura University
• Investigators: Principal Investigator: Mohamed Y. Makharita, professor, Mansoura University

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 10, 2021

Study Registration Dates

• First Submitted: December 13, 2020
• First Submitted That Met QC Criteria: December 13, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 14, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: elderly; spinal anesthesia; naloxone; pruritus; post operative cognitive dysfunction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Narcotic Antagonists; Anesthetics, Local; Fentanyl; Naloxone; Bupivacaine
• Other Study ID Numbers: MS/19.09.830

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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