Valproic Acid, Magnesium Sulphate, Rocuronium Requirement, Postoperative Analgesia

Study Overview
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Brief Summary
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The investigators hypothesized that valproic acid will increase rocuronium requirement and MgSO4 infusion would reduce requirement of muscle relaxant in craniotomy patients preloaded with sodium valproate.

Detailed Description
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Magnesium sulfate (MgSO4) is known to reduce requirement of muscle relaxant.

Official Title
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Effects of Valproic Acid and Magnesium Sulphate on Rocuronium Requirement and Postoperative Analgesia in Patients Undergoing Craniotomy for Cerebrovascular Surgery

Conditions
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Cerebral Aneurysm

Intervention / Treatment
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* Drug: Magnesium Sulfate
* Drug: 0.9% saline
* Drug: 0.9% saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18- 65 years American society of anesthesiology physical status 1,2 scheduled for elective craniotomy for aneurysm clipping or for superficial temporal artery-middle cerebral artery anastomosis Exclusion Criteria: body mass index <18.5 or >24.9 kg m-2; neuromuscular, renal, cardiovascular or hepatic insufficiency; Glasgow coma scale (GCS) <15; allergy to the study drugs; medications influencing NDMRs; breast feeding; pregnancy; and preoperative epilepsy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mg_orfil<br>patients preloaded with sodium valproate receives MgSO4 during the craniotomy. | Drug: Magnesium Sulfate<br>* MgSO4 infusion: 50mg/kg bolus followed by continuous infusion<br>* Other names: MgSO4;|
| Placebo Comparator: control_orfil<br>patients preloaded with sodium valproate receives 0.9% saline as placebo. | Drug: 0.9% saline<br>* 0.9% saline as same dose as MgSO4 as placebo<br>* Other names: NaCl;Drug: 0.9% saline<br>* 0.9% saline as same dose as MgSO4 as placebo<br>* Other names: NaCl;|
| Placebo Comparator: control_no orfil<br>patients not preloaded with sodium valproate receives 0.9% saline as placebo. | Drug: 0.9% saline<br>* 0.9% saline as same dose as MgSO4 as placebo<br>* Other names: NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rocuronium | Roc 0.15mg/kg is injected when train of four (TOF) becomes 2 which is measured with TOF-watch Sx. The total amount of Roc that injected is recorded. The intervals of each Roc 0.15mg/kg injection will also be recorded. | participants will be followed for the duration of the surgery, an expected average of 5.5 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hemodynamics | mean arterial pressure and heart rate is measured for the duration of the surgery, an expected average of 5.5 hours; postoperative 24 hour; postoperative 48 hour. | participants will be followed for the duration of the surgery, an expected average of 5.5 hours; postoperative 24 hour; postoperative 48 hour | 
| total amount of anesthetics | total amount of propofol and remifentanil infused is measured. | participants will be followed at the end of the surgery, an expected average of 5.5 hours after induction of anesthesia.. | 
| Magnesium concentration | serum Magnesium concentration is measured just prior to anesthetic drug administration, 3 hour after the induction of anesthesia, and at the end of the surgery. | from the induction of anesthesia until end of the surgery | 
| side effects | complicaton associated with MgSO4 including muscle weakness, hot flush, and nausea/ vomiting. | participants will be followed for the duration of the surgery, an expected average of 5.5 hours; postoperative 24 hour; postoperative 48 hour. | 
| pain, nausea & vomiting, analgesics use, antiemetics use, nicardipine use | Pain will be assessed using numeric rating scale at 6 h, 24 h, and 48 h postoperately. Cumulative dose of analgesics and nicardipine, incidence of nicardipine and antiemtics use during 48h postoperatively will be recorded. | patients will be followed from the end of the operation until postoperativ 48 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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craniotomy, sodium valproate, rocuronium