Intrathecal Nalbuphine Versus Midazolam in Cesarean Section

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cesarean Section Pain

Intervention / Treatment
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* Drug: Bupivacaine
* Drug: Nalbuphine
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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 .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Controlled comparative Double blind randomized study
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nalbuphine, midazolam