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Clinical Trials/NCT04932083
NCT04932083
Completed
Not Applicable

Intrathecal Midazolam is a Comparable Alternative to Fentanyl and Nalbuphine as Adjuvant to Bupivacaine in Spinal Anesthesia for Elective Cesarean Section; a Randomized Controlled Double-blind Trial

Benha University1 site in 1 country100 target enrollmentJune 20, 2021

Overview

Phase
Not Applicable
Intervention
Bupivacaine
Conditions
Pain, Acute
Sponsor
Benha University
Enrollment
100
Locations
1
Primary Endpoint
Duration of effective analgesia
Status
Completed
Last Updated
4 years ago

Overview

Brief Summary

The main limitations of spinal anesthesia are its short duration of action and do not provide prolonged postoperative analgesia when it is performed only with local anesthetics. Adding adjuvants drugs to intrathecal local anesthetics improves quality and duration of spinal blockade, and prolongs postoperative analgesia. It is also possible to reduce dose of local anesthetics, as well as total amount of systemic postoperative analgesics.

Detailed Description

Several spinal adjuvants have been used to improve spinal anesthesia quality and to prolong postsurgical analgesia; Intrathecal opioids are the most commonly utilized. Intrathecal opioids cause analgesia by binding to opioid receptors in the dorsal horn of the spinal cord. They prolong the duration of analgesia and allow early ambulation of patients. Fentanyl, a short-acting lipophilic opioid, is known to augment the quality of subarachnoid block in many studies. However, worrisome adverse effects such as pruritus, urinary retention, post-operative vomiting, and respiratory depression limit the use of opioids. Nalbuphine is a synthetic opioid with mixed agonist antagonist effect. It binds to both mu- and kappa receptors; binding of nalbuphine to mu receptors competitively displaces other mu-agonists from these receptors without any agonist activity, therefore decreasing the side effects on mu agonist (nausea, vomiting, respiratory depression, urinary retention, pruritis, and prolonged sedation). While when binding to kappa receptors, nalbuphine has agonist effect (analgesic effect) through the kappa receptors distributed in the brain and spinal cord. There have been no documented studies of nalbuphine neurotoxicity. Midazolam is a short acting benzodiazepine with anxiolytic, sedative, anticonvulsant and muscle relaxant effects, influencing GABA receptor and influence on neurons by entering chloride into them. It is water soluble in its acid formulation but is highly lipid soluble in vivo. It has been reported to have a spinally mediated anti-nociceptive effect. Previous studies have shown that intrathecal administration of midazolam added to bupivacaine improves the duration and quality of spinal anesthesia. This study is carried out to evaluate and compare the effects of intrathecal midazolam (2 mg), fentanyl (25 micrograms) and nalbuphine (800 micrograms) as additives to intrathecal hyperbaric bupivacaine (0.5 %) with regards to: onset and duration of sensory block, onset and duration of motor block, duration of effective analgesia postoperative, side effects associated with the drug.

Registry
clinicaltrials.gov
Start Date
June 20, 2021
End Date
February 24, 2022
Last Updated
4 years ago
Study Type
Interventional
Study Design
Parallel
Sex
Female

Investigators

Responsible Party
Principal Investigator
Principal Investigator

Samar Rafik Mohamed Amin

lecturer of anesthesia and surgical ICU

Benha University

Eligibility Criteria

Inclusion Criteria

  • ASA physical status I and ASA II
  • Age from 18-40 years
  • Scheduled to undergo elective cesarean section under spinal anesthesia.

Exclusion Criteria

  • ASA physical status III or IV patients.
  • Patients refuse spinal anesthesia.
  • Patients physically dependent on narcotics or benzodiazepine.
  • Patients with history of drug allergy to one of used adjuvants.
  • Patients with gross spinal abnormality, localized skin sepsis, hemorrhagic diathesis or neurological involvement/ diseases and any contraindication for spine.
  • Patients who are unable to communicate.
  • Morbid obesity.
  • Failure of spinal blockade.
  • Complicated pregnancy.

Arms & Interventions

Bupivacaine

patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.5 ml sterile water.

Intervention: Bupivacaine

Fentanyl

patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.5 ml fentanyl (25µg).

Intervention: Fentanyl

Nalbuphine

patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.8 mg nalbuphine hydrochloride in 0.5 ml sterile water.

Intervention: Nalbuphine

Midazolam

patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 2mg of midazolam in 0.5 ml sterile water.

Intervention: Midazolam

Outcomes

Primary Outcomes

Duration of effective analgesia

Time Frame: 24 hours postoperative

it is the time interval from the subarachnoid block to the first analgesic intervention (VAS \>3)

Secondary Outcomes

  • The onset of sensory block:(2 minutes for ten minutes, every 5 minutes for the next 20 minutes after intrathecal injection)
  • Onset of complete motor blockade(every 2 minutes for 10 minutes after intrathecal injection)
  • Duration of motor block:(6 hours postoperative)
  • Duration of complete sensory block:(12 hours postoperative)
  • Total dose of analgesic consumption(24 hours postoperative)
  • Maternal adverse effects(24 hours postoperative)

Study Sites (1)

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