Clinical trial NCT03918187: Intrathecal Nalbuphine Versus Midazolam in Cesarean Section
Official title: Nalbuphine Versus Midazolam as an Adjuvant to Intrathecal Bupivacaine for Postoperative Analgesia in Patients Undergoing Cesarean Section
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cesarean Section Pain
Keywords: nalbuphine
midazolam
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2019-04-17
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Controlled comparative Double blind randomized study
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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.

Eligibility criteria: 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 .

Primary outcomes:
measure: Effective analgesic time
timeFrame: up to six hours postoperative
measure: Total postoperative analgesic dose .
timeFrame: 24 hours
measure: Onset of sensory and motor block
timeFrame: up tp five minutes after intrathecal injection
measure: duration of sensory and motor block
timeFrame: up to five hours postoperative
Secondary outcomes:
measure: Sedation score
timeFrame: one hour during surgery
measure: Apgar score
timeFrame: 1-5 minutes after delivery
measure: number of participants with hypotension , bradycardia ,vomiting , nausea , shivering number of participants with hypotension , bradycardia ,vomiting , nausea , shivering
timeFrame: up to 24 hours postoperative
Other outcomes:
Locations:
city: Zagazig
country: Egypt
facility: Olfat Abd Elmoniem Ibrahem Amin
state: Eygpt/zagazig
Study officials:
affiliation: Zagazig University
name: Olfat A I Amin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.