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

Study Overview
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Brief Summary
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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

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

Conditions
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Pain, Acute

Intervention / Treatment
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* Drug: intrathecal drug injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group F<br>will receive intrathecal injection of 0.5% hyperbaric bupivacaine plus 0.5 ml fentanyl (25 μg) | Drug: intrathecal drug injection<br>* 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<br>* Other names: spinal opioid injection;|
| Experimental: Group N<br>will receive intrathecal injection of 0.5% hyperbaric bupivacaine plus 0.8 mg nalbuphine hydrochloride | Drug: intrathecal drug injection<br>* 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<br>* Other names: spinal opioid injection;|
| Placebo Comparator: Group C<br>will receive intrathecal injection of 0.5% hyperbaric bupivacaine plus 0.5 ml normal saline | Drug: intrathecal drug injection<br>* 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<br>* Other names: spinal opioid injection;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intrathecal nalbuphine, intrathecal fentanyl, exteriorization of the uterus, cesarean section