Clinical trial NCT04932083: Intrathecal Midazolam, Fentanyl and Nalbuphine as Adjuvants to Bupivacaine in Spinal Anesthesia for Cesarean Section
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain, Acute
Lead sponsor: Benha University
Sponsor class: OTHER
First posted: 2021-06-18
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Duration of effective analgesia
timeFrame: 24 hours postoperative
Secondary outcomes:
measure: The onset of sensory block:
timeFrame: 2 minutes for ten minutes, every 5 minutes for the next 20 minutes after intrathecal injection
measure: Duration of complete sensory block:
timeFrame: 12 hours postoperative
measure: Onset of complete motor blockade
timeFrame: every 2 minutes for 10 minutes after intrathecal injection
measure: Duration of motor block:
timeFrame: 6 hours postoperative
measure: Total dose of analgesic consumption
timeFrame: 24 hours postoperative
measure: Maternal adverse effects
timeFrame: 24 hours postoperative
Other outcomes:
Locations:
city: Banhā
country: Egypt
facility: Samar Rafik Amin
state: Qalubia
Study officials:
References: