Clinical trial NCT03717467: Intraoperative Magnesium Sulfate Administration During Orthotopic Liver Transplantation
Official title: The Influence of Intraoperative Magnesium Sulfate Administration on Postoperative Morphine Requirement in Living Donor During Orthotopic Liver Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postoperative Pain
Keywords: Magnesium sulfate
Morphine requirement
Hepatotomy
Orthotopic liver transplantation
Lead sponsor: Fayoum University Hospital
Sponsor class: OTHER
First posted: 2018-10-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Postoperative Morphine consumption
timeFrame: 24 hours after operation
Secondary outcomes:
measure: Mean arterial pressure
timeFrame: 1 minute before induction
measure: Heart rate
timeFrame: 1 minute before induction
measure: Mean arterial pressure
timeFrame: 30 seconds before intubation
measure: Heart rate
timeFrame: 30 seconds before intubation
measure: Mean arterial pressure
timeFrame: 5 minutes after beginning of surgery
measure: Heart rate
timeFrame: 5 minutes after beginning of surgery
measure: Mean arterial pressure
timeFrame: 15 minutes after beginning of surgery
measure: Heart rate
timeFrame: 15 minutes after beginning of surgery
measure: Mean arterial pressure
timeFrame: 30 minutes after beginning of surgery
measure: Heart rate
timeFrame: 30 minutes after beginning of surgery
measure: Mean arterial pressure
timeFrame: 60 minutes after beginning of surgery
measure: Heart rate
timeFrame: 60 minutes after beginning of surgery
measure: Mean arterial pressure
timeFrame: 120 minutes after beginning of surgery
measure: Heart rate
timeFrame: 120 minutes after beginning of surgery
measure: Mean arterial pressure
timeFrame: 30 minutes after end of surgery
measure: Heart rate
timeFrame: 30 minutes after end of surgery
measure: Morphine consumption
timeFrame: 30 minutes after end of surgery
measure: Visual Analog Scale
timeFrame: 30 minutes after end of surgery
measure: Assessment of sedation
timeFrame: 30 minutes after end of surgery
measure: Mean arterial pressure
timeFrame: 4 hours after end of surgery
measure: Heart rate
timeFrame: 4 hours after end of surgery
measure: Morphine consumption
timeFrame: 4 hours after end of surgery
measure: Visual Analog Scale
timeFrame: 4 hours after end of surgery
measure: Assessment of sedation
timeFrame: 4 hours after end of surgery
measure: Mean arterial pressure
timeFrame: 24 hours after end of surgery
measure: Heart rate
timeFrame: 24 hours after end of surgery
measure: Morphine consumption
timeFrame: 24 hours after end of surgery
measure: Visual Analog Scale
timeFrame: 24 hours after end of surgery
measure: Assessment of sedation
timeFrame: 24 hours after end of surgery
measure: Mean arterial pressure
timeFrame: 48 hours after end of surgery
measure: Heart rate
timeFrame: 48 hours after end of surgery
measure: Morphine consumption
timeFrame: 48 hours after end of surgery
measure: Visual Analog Scale
timeFrame: 48 hours after end of surgery
measure: Assessment of sedation
timeFrame: 48 hours after end of surgery
measure: Patient satisfaction level
timeFrame: 48 hours after end of surgery
measure: Blood serum magnesium concentration
timeFrame: 12 hours before operation
measure: Blood serum magnesium concentration
timeFrame: 15 minutes after operation
measure: Interleukin 6 level in blood
timeFrame: 24 hours after operation
measure: Interleukin 8 level in blood
timeFrame: 24 hours after operation
measure: Tumor necrosis factor alpha level in blood
timeFrame: 24 hours after operation
measure: Incidence of shivering
timeFrame: 48 hours after operation
measure: Incidence of nausea
timeFrame: 48 hours after operation
measure: Incidence of vomiting
timeFrame: 48 hours after operation
measure: Incidence of respiratory depression
timeFrame: 48 hours after operation
measure: Incidence of somnolence
timeFrame: 48 hours after operation
measure: Incidence of oversedation
timeFrame: 48 hours after operation
measure: Incidence of itching
timeFrame: 48 hours after operation
measure: Incidence of constipation
timeFrame: 48 hours after operation
measure: Incidence of paralytic ileus
timeFrame: 48 hours after operation
Other outcomes:
measure: Age
timeFrame: 1 hour before operation once patient is recruited
measure: Height
timeFrame: 1 hour before operation once patient is recruited
measure: Weight
timeFrame: 1 hour before operation once patient is recruited
measure: body mass index
timeFrame: 1 hour before operation once patient is recruited
measure: Surgery duration
timeFrame: 1 minute after operation
measure: Anesthesia duration
timeFrame: 1 minute after withdrawal of all anesthetics
Locations:
city: Giza
country: Egypt
facility: Sheikh Zayed hospital
Study officials:
affiliation: Faculty of medicine, Fayoum University
name: Mostafa S Elhamamsy, MD
role: STUDY_CHAIR
affiliation: Faculty of medicine, Beni-suef University
name: Ahmed M Yassin, MD
role: STUDY_DIRECTOR
affiliation: Faculty of medicine, Fayoum University
name: Abeer S Goda, MD
role: STUDY_DIRECTOR
affiliation: Faculty of medicine, Fayoum University
name: Hany M Yassin, MD
role: PRINCIPAL_INVESTIGATOR
References:
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