Intrathecal Midazolam, Fentanyl and Nalbuphine as Adjuvants to Bupivacaine in Spinal Anesthesia for Cesarean Section

Pain, Acute Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04932083
• Other study ID #: RC6-5-2021
• Status: Completed
• Phase: N/A
• Start date: June 20, 2021
• Est. completion date: February 24, 2022

Study information

• Verified date: March 2022
• Source: Benha University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 24, 2022
• Est. primary completion date: January 14, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Pain
• Pain, Acute

Intervention

Drug:
• Bupivacaine
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.5 ml of sterile water will be added.
• Fentanyl
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.5 ml of fentanyl (25µg) will be added.
• Nalbuphine
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.8 mg nalbuphine hydrochloride in 0.5 ml sterile water will be added.
• Midazolam
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.4 ml of midazolam (2mg) + 0.1 ml of sterile water will be added.

Locations

Country	Name	City	State
Egypt	Samar Rafik Amin	Banha	Qalubia

Sponsors (1)

Lead Sponsor	Collaborator
Benha University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of effective analgesia	it is the time interval from the subarachnoid block to the first analgesic intervention (VAS >3)	24 hours postoperative
Secondary	The onset of sensory block:	it is the time from end of intrathecal injection to absence of pain at T5 dermatome.	2 minutes for ten minutes, every 5 minutes for the next 20 minutes after intrathecal injection
Secondary	Duration of complete sensory block:	it is the time interval from the subarachnoid block to the first sensation of pain (VAS >0).	12 hours postoperative
Secondary	Onset of complete motor blockade	it is the time per minutes from intrathecal injection until Bromage scale to be 3.	every 2 minutes for 10 minutes after intrathecal injection
Secondary	Duration of motor block:	it is the time per minutes from intrathecal injection until Bromage score 0.	6 hours postoperative
Secondary	Total dose of analgesic consumption	if VAS pain score >3, intravenous 30 mg keterolac will be administered and can be repeated after 6 h if needed. If the mother was still complaining of pain or the VAS is still greater than 3 after 20 min from ketorolac injection, she will be given intravenous pethidine in a dose of 0.5 mg/kg.	24 hours postoperative
Secondary	Maternal adverse effects	All mothers will be monitored for the associated adverse effects such as postoperative nausea and vomiting (PONV), sedation, pruritus, hypotension, bradycardia, shivering, and respiratory depression.	24 hours postoperative