Sequential and Mixture Injection of Opioids and Hyperbaric Bupivacaine

Comparison of Sequential and Mixture Injection of Opioids and Hyperbaric Bupivacaine for Subarachnoid Block for Elective Caesarean Section; a Randomised Controlled Study

Neuraxial anesthesia, especially the subarachnoid block, is the preferred method for LSCS. The intrathecal spread of local anesthetic drugs is unpredictable. However, Baricity, which is the relative density of local anesthetics to that of CSF, is a key determinant of the local anesthetic spread within the subarachnoid space. Alterations in the baricity of a solution to the extent of 0.0006 g/ml-1 can alter the spread of local anesthetic solution in CSF. Patients features such as position, weight, height, and age, and local anaesthetic characteristics such as density, PH, and temperature may play a role as well.

Bupivacaine is the main local anaesthetic used frequently for the subarachnoid block. Hyperbaric bupivacaine has dextrose added at a concentration of 80 g/ml to increase its density to 1.0262 which is higher than that of cerebrospinal fluid (CSF), leading to a more predictable spread after intrathecal injection.

Opioids such as morphine and fentanyl are commonly injected as adjuvants to hyperbaric bupivacaine. Their synergistic role leads to satisfactory block at smaller subtherapeutic doses of bupivacaine which minimizes the associated side effects. The combination of fentanyl which is lipophilic opioid and morphine which is hydrophilic opioid results in rapid onset and prolonged course of perioperative analgesia. In an in vitro study, the mean densities of fentanyl and morphine were found to be 0.9957 and 1.0013 respectively while the mean density of CSF in term pregnant woman is 1.000306. Thus, opioids spread freely within the CSF interacting on the spinal and supraspinal opioid receptors. They have a synergistic effect to bupivacaine leading to adequate sensory blockade with lesser hemodynamic adverse effects.

Nevertheless, opioids are commonly mixed with hyperbaric bupivacaine in a single syringe before intrathecal injection. This practice alters the density and PH of the mixture which may impact the pharmacokinetics of each individual drug. Therefore, we hypothesize in this study that separate injection of opioids and hyperbaric bupivacaine may improve their intrathecal spread. This will not only improve the quality of anesthesia, but it will also decrease the associated hemodynamic adverse events and the incidence of undesired high sensory block levels, which all will increase the perioperative patient satisfaction.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications; Regional Anesthesia Morbidity; Bupivacaine Adverse Reaction
• Intervention / Treatment: Drug: Bupivacaine-fentanyl-Morphine.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 11111
    • Assiut University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• LSCS
• ASA I or II
• Single baby pregnancy of more than 32 weeks
• Elective or semi-elective surgery (category 3 and 4 Caesarean sections)

Exclusion Criteria:

• Abnormal Placentation
• PET
• Disordered coagulation
• Allergy to opioids or local anesthetic.
• BMI > 35
• Spine surgery
• Cardiac disease
• Extremes of height; height more than 180 or less than 140
• Multiple pregnancy or polyhydramnios

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: premixed injection; will receive an intrathecal injection of 2.4 ml hyperbaric bupivacaine 0.5%, 20 µg fentanyl, and 100 µg preservative-free morphine mixed together.	Drug: Bupivacaine-fentanyl-Morphine.; 2.4 ml Bupivacaine 0.5%, 20 µg Fentanyl and, 100 µg preservative free morphine
Active Comparator: sequential injections; will receive an intrathecal injection of 2,4 ml hyperbaric bupivacaine 0.5% followed immediately by the opioid mixture by two separate syringes.	Drug: Bupivacaine-fentanyl-Morphine.; 2.4 ml Bupivacaine 0.5%, 20 µg Fentanyl and, 100 µg preservative free morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
duration to the maximal sensory block to light touch	intraoperative

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2020
• Primary Completion (Actual): March 17, 2021
• Study Completion (Actual): March 17, 2021

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• 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; Anesthetics, Local; Fentanyl; Bupivacaine; Morphine
• Other Study ID Numbers: 17300377 (sequential)

Drug and device information, study documents

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