Intrathecal Nalbuphine is a Comparable Safer Alternative to Fentanyl for Intraoperative Pain Management During Uterine Exteriorization

Intrathecal Nalbuphine is a Comparable Safer Alternative to Fentanyl for Intraoperative Pain Management During Uterine Exteriorization in Cesarean Section. A Randomized Controlled Trial.

In case of cesarean section (CS) delivery, spinal anesthesia is the best anesthetic choice. It is simple to perform with rapid onset of anesthesia and lower incidence of failed block. Spinal anesthesia avoids the risk of aspiration, the neonatal depressant effect that may occur with general anesthesia (GA), and provides postoperative analgesia, however, spinal anesthesia has a lesser control on the level of blockade, may give insufficient visceral pain block and may be associated with nausea and vomiting especially during peritoneal traction, closure and uterine manipulation, exteriorization and rotation. A previous study reported nausea and vomiting in up to 70.5% patients in the spinal group while the incidence of moderate to severe pain was more frequent in exteriorized uterus patients.

Increasing the dosage of intrathecal local anesthetic may contribute to a decrease in the occurrence of intraoperative visceral pain, but at the cost of the risk and adverse effects of greater blockade.A variety of adjuvants have been used to prevent these disadvantages. The commonly used adjuvants include opioids; α2 stimulants such as clonidine and dexmedetomidine; NMDA receptor antagonist such as ketamine; GABA receptor agonists such as midazolam.

The added intrathecal opioids as fentanyl and nalbuphine to local anesthetics give a sufficient intraoperative visceral analgesia when they were used in C.S., with less sympathetic block and hemodynamic effect, and reduces the need for intraoperative analgesics with prolongation of postoperative analgesia.

Nalbuphine, a mixed agonist-antagonist opioid, has a potential to attenuate the mu-opioid effects and to enhance the kappa-opioid effects. It was synthesized attempting to produce analgesia without the undesirable side effects of mu agonist. Also, its combination with mu agonist opioids was tried by many researchers to decrease the incidence and severity of the common mu agonist side effects (respiratory depression, undesirable sedation, pruritus, bradycardia, nausea, vomiting and urinary retention), plus it can antagonize spinal induced shivering. Meanwhile, the benefits of both kappa and mu analgesia can be obtained.

Few studies compared the effects of intrathecal nalbuphine (opioid agonist-antagonist) and fentanyl (opioid agonist) as adjuvants to bupivacaine in spinal blocked for CS with variable results. However, they didn't compare their ability to control the visceral pain aggravated by uterine exteriorization in cesarean section under spinal anesthesia. This study will try to answer the question is nalbuphine effective enough in such scenario to be used routinely as a safer alternative to fentanyl, which is the opioid in common practice added to bupivacaine?

Aim of the study:

To compare the ability of the used doses in the study of intrathecal nalbuphine and intrathecal fentanyl to control the visceral pain aggravated by uterine exteriorization in cesarean section under spinal anesthesia

Objectives:

• To evaluate the visual analog scale (VAS) for visceral abdominal and shoulder pain every 5 minutes and the maximum score will be recorded for 30 minutes from the time of baby delivery.
• To calculate the total fentanyl used for VAS ⩾ 4

Study Overview

• Status: Completed
• Conditions: Pain, Acute
• Intervention / Treatment: Drug: intrathecal drug injection

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Manial
    • Cairo, Manial, Egypt, 12511
      • Cairo University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• forty-two female patients
• ASA physical status I or II,
• age between 20 and 45 years,
• weight between 60 and 100 kg
• height between 160 and 180 cm

Exclusion Criteria:

• ASA III or IV,
• patient refusal,
• hypotensive patients,
• infection at the site of injection,
• coagulopathy
• weight <60 and > 100 kg,
• anticoagulant medications,
• pre-existing neurological disease.
• uncooperative patients,
• cardiac disorder
• respiratory disorder
• allergy to local anesthetics.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group F; will receive intrathecal injection of 0.5% hyperbaric bupivacaine plus 0.5 ml fentanyl (25 μg)	Drug: intrathecal drug injection; All 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. The patients will be divided equally into 3 groups according to the additive (fentanyl, nalbuphine or placebo), and all patients will receive the local anesthetic dose of 0.5% heavy bupivacaine according to weight and height; Other Names: spinal opioid injection
Experimental: Group N; will receive intrathecal injection of 0.5% hyperbaric bupivacaine plus 0.8 mg nalbuphine hydrochloride	Drug: intrathecal drug injection; All 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. The patients will be divided equally into 3 groups according to the additive (fentanyl, nalbuphine or placebo), and all patients will receive the local anesthetic dose of 0.5% heavy bupivacaine according to weight and height; Other Names: spinal opioid injection
Placebo Comparator: Group C; will receive intrathecal injection of 0.5% hyperbaric bupivacaine plus 0.5 ml normal saline	Drug: intrathecal drug injection; All 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. The patients will be divided equally into 3 groups according to the additive (fentanyl, nalbuphine or placebo), and all patients will receive the local anesthetic dose of 0.5% heavy bupivacaine according to weight and height; Other Names: spinal opioid injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intraoperative pain control	- The visual analog scale (VAS) for visceral abdominal pain in all groups after uterine exteriorization.VAS from 0 to 10 with 0 equal no pain and 10 equal the severist pain ever	30 minutes after baby delivery

Collaborators and Investigators

• Sponsor: Cairo University

Publications and helpful links

General Publications

• Bogra J, Arora N, Srivastava P. Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section. BMC Anesthesiol. 2005 May 17;5(1):5. doi: 10.1186/1471-2253-5-5.
• Gauchan S, Thapa C, Prasai A, Pyakurel K, Joshi I, Tulachan J. Effects of intrathecal fentanyl as an adjunct to hyperbaric bupivacaine in spinal anesthesia for elective caesarean section. Nepal Med Coll J. 2014 Sep;16(1):5-8.
• Pedersen H, Santos AC, Steinberg ES, Schapiro HM, Harmon TW, Finster M. Incidence of visceral pain during cesarean section: the effect of varying doses of spinal bupivacaine. Anesth Analg. 1989 Jul;69(1):46-9.
• Alahuhta S, Kangas-Saarela T, Hollmen AI, Edstrom HH. Visceral pain during caesarean section under spinal and epidural anaesthesia with bupivacaine. Acta Anaesthesiol Scand. 1990 Feb;34(2):95-8. doi: 10.1111/j.1399-6576.1990.tb03050.x.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): April 25, 2021
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: December 26, 2020
• First Submitted That Met QC Criteria: December 26, 2020
• First Posted (Actual): December 30, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: cesarean section; intrathecal nalbuphine; intrathecal fentanyl; exteriorization of the uterus
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: N- 26 / 2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: not to share

Drug and device information, study documents

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