Intrathecal Nalbuphine Versus Midazolam in Cesarean Section

Nalbuphine Versus Midazolam as an Adjuvant to Intrathecal Bupivacaine for Postoperative Analgesia in Patients Undergoing Cesarean Section

Adequate pain management is important to facilitate the functional recovery and enable the patients for rapid rehabilitation of normal activity .

Various adjuvants were being used with intrathecal bupivacain to prolong & improve postoperative pain relief in patients undergoing cesarean section .

The aim of this study was to compare intrathecal nalbuphine versus intrathecal midazolam in patient undergoing cesarean section. The investigators primary aims were to compare the characteristics of sensory and motor block, the effective analgesic time, and analgesic requirement. Secondary aims were to compare the side effects, sedation score and apgare score.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Pain
• Intervention / Treatment: Drug: Bupivacaine; Drug: Nalbuphine; Drug: Midazolam

Detailed Description

Analgesia is the main point for each patient postoperatively. It is important to provide good analgesia with less hazardous (1). Cesarean section is a painful operation in need for adequate postoperative analgesia (1). Adequate pain management is important to facilitate the functional recovery and enable the patients for rapid rehabilitation of their normal activity (2).

Cesarean section was done under general anesthesia (GA) or regional anesthesia. The subarachnoid blockade is the preferred procedure (3). It avoids the depressant effect of GA on neonate and also the risk of aspiration, with better postoperative pain relief. However the most commonly local anesthetic used, hyperbaric bupivacaine has limited effect lasts for 1.5 - 2 hours (4). Its onset was slow with short duration of postoperative analgesia (3).

Adjuvant drugs added to bupivacaine intrathecally improve the duration and quality of the blockade and prolong the postoperative analgesia (5). Various adjuvants were being used such as alpha2 agonists, neostigmine, opiates, and ketamine etc, yet no drug was identified to specifically inhibit nociception without side effects (6).

Nalbuphine is a synthetic opioid with mixed agonist antagonist effect. It provides a significantly rapid onset of pain relief probably because of its lipophilic properties. It binds to both mu-and kappa receptors, binding of nalbuphine to mu receptors competitively displace other mu-agonists from these receptors without any agonist activity. Therefore decrease the side effects of mu agonist (nausea, vomiting, respiratory depression , urinary retention, pruritis and prolonged sedation) (7). While when binds to kappa receptors nalbuphine has agonist effect (analgesic effect) through the kappa receptors distributed in the brain and spinal cord(1). There were no documented studies of nalbuphine neurotoxicity (5, 8).

Benzodiazepines are used mainly for sedation, anoxiolysis and amnesia. Discovery of their receptors in spinal cord allow the use of midazolam intrathecally for analgesia. Several studies show that the addition of intrathecal midazolam potentiates the analgesic effect of intrathecal bupivacain without significant side effects, or neurotoxicity (9, 10).

There are several studies studied the effect of intrathecal nalbuphine and intrathecal midazolam but to The investigators knowledge no study compares between them.

The aim of this study was to compare intrathecal nalbuphine versus intrathecal midazolam in patient undergoing cesarean section. The investigators primary aims were to compare the characteristics of sensory and motor block, the effective analgesic time, and analgesic requirement. Secondary aims were to compare the side effects, sedation score and apgare score.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Eygpt/zagazig
    • Zagazig, Eygpt/zagazig, Egypt, 002055
      • Olfat Abd Elmoniem Ibrahem Amin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: -

• Female gender .
• Age : 18 - 40 years old .
• Physical status : ASA II .
• Elective cesarean section

Exclusion Criteria:

• - Patient refusal .
• History of hypertension or cardiac diseases .
• Psychiatric disorders .
• Coagulopathy .
• Allergy to study drugs .
• Contraindication to spinal anesthesia .
• Failure of spinal anesthesia .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bupivacaine; 12.5 mg hyperbaric bupivacaine + 0.5 ml 0.9% normal saline .	Drug: Bupivacaine; compare between nalbuphine versus midazolam as an adjuvant to intrathecal bupivacain to evaluate postoperative analgesia .
Active Comparator: nalbuphine; 12.5 mg hyperbaric bupivacaine + 1 mg nalbuphine add in 0.5 ml 0.9% normal saline.	Drug: Nalbuphine; compare between nalbuphine versus midazolam as an adjuvant to intrathecal bupivacain to evaluate postoperative analgesia .
Active Comparator: midazolam; 12.5 mg hyperbaric bupivacaine + 2.5 mg midazolam .	Drug: Midazolam; compare between nalbuphine versus midazolam as an adjuvant to intrathecal bupivacain to evaluate postoperative analgesia .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective analgesic time	the time start from intrathecal injection to the first analgesic dose.	up to six hours postoperative
Total postoperative analgesic dose .	the analgesic dose consumed	24 hours
Onset of sensory and motor block	the time of onset of sensory and motor block	up tp five minutes after intrathecal injection
duration of sensory and motor block	the time of duration of sensory and motor block	up to five hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation score	score of sedation: 1= awake and alert 2 = sedated ,respond to verbal stimules 3= sedated respond to a mild physical status 4=sedated respond to a moderate or strong physical stimuls 5= not arousable 5 is the higher value	one hour during surgery
Apgar score	score for baby	1-5 minutes after delivery
number of participants with hypotension , bradycardia ,vomiting , nausea , shivering number of participants with hypotension , bradycardia ,vomiting , nausea , shivering	incidence of hypotension , bradycardia ,vomiting , nausea , shivering	up to 24 hours postoperative

Collaborators and Investigators

• Sponsor: Zagazig University
• Investigators: Principal Investigator: Olfat A I Amin, MD, Zagazig University

Publications and helpful links

General Publications

• Amin OAI, Ibrahem MA, Salem DAE. Nalbuphine versus Midazolam as an Adjuvant to Intrathecal Bupivacaine for Postoperative Analgesia in Patients Undergoing Cesarean Section. J Pain Res. 2020 Jun 11;13:1369-1376. doi: 10.2147/JPR.S242545. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2019
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: April 7, 2019
• First Submitted That Met QC Criteria: April 14, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 24, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: midazolam; nalbuphine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Local; Midazolam; Bupivacaine; Nalbuphine
• Other Study ID Numbers: 5305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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