Intraoperative Magnesium Sulfate Administration During Orthotopic Liver Transplantation

Study Overview
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Brief Summary
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The aim of study is to assess the effect of intraoperative use of magnesium sulfate in liver donating patients in reducing post-operative morphine requirements in early postoperative 24 hour in adult living liver donor.The authors hypothesize that magnesium sulfate can be used to efficiently reduce postoperative morphine consumption in the early 24 hours postoperatively as evident in other surgery types.

Detailed Description
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Introduction A lot of recent trials emphasized that perioperative magnesium sulfate (MgSO4) infusion has general anesthetic properties that could reduce anesthetic drug consumption and postoperative analgesia requirements in several types of surgery. Optimal post-operative pain control is necessary for early mobilization, improved respiratory function, and deep venous thrombosis. Administration of multimodal analgesics could limit the excessive use of systemic opioid analgesia especially (morphine), which has a high rate of postoperative side effects as sedation, respiratory depression, ileus, nausea, vomiting, constipation, urine retention, and itching. Therefore, medications and adjuvant drugs reducing the need for opioids have become widely used as parts of multimodal analgesia. Post-operative pain management begins with pre-operative planning and formulating a pain management plan that is tailored to an individual patient's liver function, respiratory and coagulation status, comorbidities and extent of resection. Anesthetic technique: Patients will be premedicated with tablet of alprazolam 0.25 mg the night before and 2 hours before surgery. Upon arrival in operating room usual monitoring will be established including heart rate, blood pressure, electrocardiogram (ECG),and temperature. After induction of anesthesia, an arterial line will be inserted for continuous monitoring of blood pressure and frequent blood gas analysis. End-tidal carbon dioxide (capnography) will be attached. General anesthesia will be administered using propofol 2 mg/kg, morphine 0.1 mg/kg and atracurium besylate 0.5 mg/kg followed by oral endotracheal intubation. Maintenance of general anesthesia with a mixture of isoflurane and 50% oxygen in air, morphine 2 mg/ h, mechanical ventilation will be adjusted to keep arterial oxygen saturation < 95 % and end-tidal carbon dioxide between 35 and 40 mmHg. Atracurium (0.15 mg/kg) will be administered every 30 min. Baseline intravenous infusion rate of lactated ringers solution will be set at (6ml/ kg/h) in both groups, additional solution will be infused if required. Magnesium sulfate infusion and anesthetic agents will be discontinued at the end of operation. The postoperative residual neuromuscular blockade will be reversed by using neostigmine 0.04 mg/kg and atropine 0.02 mg/kg. Then the patient will be extubated and transferred to the post-anesthesia care unit (PACU) for 1-hour observation. Statistical analysis: Statistical analysis will be done using Statistical Package for Social Sciences (SPSS) version 19 for Windows software. Data will be collected from all patients during and after anesthesia. Descriptive statistics (mean, standard deviation, or median and ranges) will be calculated. Comparative statistics between the two groups will be applied. Unpaired t-test will be used to compare the mean values between the two groups. The Kolmogorov-Smirnov test will be implemented to check the normality of continuous data distribution (P ≤ 0.05) Mann-Whitney-U test will be used to compare diﬀerence between the two groups for non-parametric variables (e.g.VAS). While the Chi-square test will be used to compare the categorical variables between both groups. The significant result will be considered when P value was less than (0.05). Sample size calculations of this trial will be done upon the following assumption, α = 0.05 β = 0.2, effect size will be =0.7.The effect size is calculated by using G*Power software version 3.1.9.2 (Institute of Experimental Psychology, Heinrich Heine University, Dusseldorf, German) and the authors found that 25 patients in each group have a power of 80% and plan to recruit 30 patients per group to account for possible dropout.

Official Title
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The Influence of Intraoperative Magnesium Sulfate Administration on Postoperative Morphine Requirement in Living Donor During Orthotopic Liver Transplantation

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: isotonic saline
* Drug: Magnesium Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age (18-50). American Society of Anesthesiology (ASA) physical state I or II. Normal serum electrolytes. Exclusion Criteria: Impaired hepatic or renal functions. Various degree of heart block. Hypertension Diabetes Myopathy or any neurological disorder. History of long term opioid use Patients treated with calcium channel blockers Patients with known allergy to drug used. Pregnant woman Obesity (Body Mass Index > 30).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: S group<br>Isotonic saline as placebo will be given. | Drug: isotonic saline<br>* 100 ml of isotonic saline over 15 min immediately before induction of anesthesia and then 15 mg/kg/h by continuous I.V. infusion until the end of operation.<br>* Other names: Saline group;|
| Active Comparator: M group<br>Magnesium sulfate will be given | Drug: Magnesium Sulfate<br>* 40 mg/kg of magnesium sulfate in 100 ml of isotonic saline over 15 min immediately before induction of anesthesia and then 15 mg/kg/h by continuous I.V. infusion until the end of operation.<br>* Other names: Magnesium group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Morphine consumption | in mg | 24 hours after operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean arterial pressure | in mm mercury by invasive blood pressure | 1 minute before induction | 
| Heart rate | in beat per minute by electrocardiogram | 1 minute before induction | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 30 seconds before intubation | 
| Heart rate | in beat per minute by electrocardiogram | 30 seconds before intubation | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 5 minutes after beginning of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 5 minutes after beginning of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 15 minutes after beginning of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 15 minutes after beginning of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 30 minutes after beginning of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 30 minutes after beginning of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 60 minutes after beginning of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 60 minutes after beginning of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 120 minutes after beginning of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 120 minutes after beginning of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 30 minutes after end of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 30 minutes after end of surgery | 
| Morphine consumption | in milligram | 30 minutes after end of surgery | 
| Visual Analog Scale | Pain score which starting from 0:no pain to 10:Worst pain | 30 minutes after end of surgery | 
| Assessment of sedation | By 5-point sedation Ramsay score where 5:aroused only by shaking 4:difficult response to verbal 3:mostly sleeping but easily aroused 2:drowsy 1:awake | 30 minutes after end of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 4 hours after end of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 4 hours after end of surgery | 
| Morphine consumption | in milligram | 4 hours after end of surgery | 
| Visual Analog Scale | Pain score which starting from 0:no pain to 10:Worst pain | 4 hours after end of surgery | 
| Assessment of sedation | By 5-point sedation Ramsay score where 5:aroused only by shaking 4:difficult response to verbal 3:mostly sleeping but easily aroused 2:drowsy 1:awake | 4 hours after end of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 24 hours after end of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 24 hours after end of surgery | 
| Morphine consumption | in milligram | 24 hours after end of surgery | 
| Visual Analog Scale | Pain score which starting from 0:no pain to 10:Worst pain | 24 hours after end of surgery | 
| Assessment of sedation | By 5-point sedation Ramsay score where 5:aroused only by shaking 4:difficult response to verbal 3:mostly sleeping but easily aroused 2:drowsy 1:awake | 24 hours after end of surgery | 
| Mean arterial pressure | in mm mercury by invasive blood pressure | 48 hours after end of surgery | 
| Heart rate | in beat per minute by electrocardiogram | 48 hours after end of surgery | 
| Morphine consumption | in milligram | 48 hours after end of surgery | 
| Visual Analog Scale | Pain score which starting from 0:no pain to 10:Worst pain | 48 hours after end of surgery | 
| Assessment of sedation | By 5-point sedation Ramsay score where 5:aroused only by shaking 4:difficult response to verbal 3:mostly sleeping but easily aroused 2:drowsy 1:awake | 48 hours after end of surgery | 
| Patient satisfaction level | By 5-point scale where 1: very unsatisfactory 2:unsatisfactory 3:neutral 4:satisfactory 5:Excellent | 48 hours after end of surgery | 
| Blood serum magnesium concentration | from venous blood sample in mg/dl | 12 hours before operation | 
| Blood serum magnesium concentration | from venous blood sample in mg/dl | 15 minutes after operation | 
| Interleukin 6 level in blood | inflammatory mediator measured from venous blood sample | 24 hours after operation | 
| Interleukin 8 level in blood | inflammatory mediator measured from venous blood sample | 24 hours after operation | 
| Tumor necrosis factor alpha level in blood | inflammatory mediator measured from venous blood sample | 24 hours after operation | 
| Incidence of shivering | as opioid related side effect | 48 hours after operation | 
| Incidence of nausea | as opioid related side effect | 48 hours after operation | 
| Incidence of vomiting | as opioid related side effect | 48 hours after operation | 
| Incidence of respiratory depression | as opioid related side effect | 48 hours after operation | 
| Incidence of somnolence | as opioid related side effect | 48 hours after operation | 
| Incidence of oversedation | as opioid related side effect | 48 hours after operation | 
| Incidence of itching | as opioid related side effect | 48 hours after operation | 
| Incidence of constipation | as opioid related side effect | 48 hours after operation | 
| Incidence of paralytic ileus | as opioid related side effect | 48 hours after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatotomy, Magnesium sulfate, Morphine requirement, Orthotopic liver transplantation