Intraoperative Magnesium Sulfate Administration During Orthotopic Liver Transplantation

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

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.

Study Overview

• Status: Unknown
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: isotonic saline; Drug: Magnesium Sulfate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ahmed A Lotfy, M.Sc.; Phone Number: +20 1068061357; Email: lotfy_23@yahoo.com
• Study Contact Backup: Name: Hany M Yassin, MD; Phone Number: +20 1023912463; Email: hmy00@fayoum.edu.eg

Study Locations

• Egypt
  • Giza, Egypt, 12573
    • Recruiting
    • Sheikh Zayed Hospital
    • Contact: Hany M Yassin, MD; Phone Number: +20 1111363602; Email: hmy00@fayoum.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: S group; Isotonic saline as placebo will be given.	Drug: isotonic saline; 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.; Other Names: Saline group
ACTIVE_COMPARATOR: M group; Magnesium sulfate will be given	Drug: Magnesium Sulfate; 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.; Other Names: Magnesium group

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	in years	1 hour before operation once patient is recruited
Height	in meters	1 hour before operation once patient is recruited
Weight	in kilogram	1 hour before operation once patient is recruited
body mass index	kilogram/meter square	1 hour before operation once patient is recruited
Surgery duration	in hours	1 minute after operation
Anesthesia duration	in hours from time of induction to withdrawal of all anesthetics	1 minute after withdrawal of all anesthetics

Collaborators and Investigators

• Sponsor: Fayoum University Hospital
• Investigators: Study Chair: Mostafa S Elhamamsy, MD, Faculty of medicine, Fayoum university; Study Director: Ahmed M Yassin, MD, Faculty of Medicine, Beni-suef University; Study Director: Abeer S Goda, MD, Faculty of medicine, Fayoum university

Publications and helpful links

General Publications

• Gucyetmez B, Atalan HK, Aslan S, Yazar S, Polat KY. Effects of Intraoperative Magnesium Sulfate Administration on Postoperative Tramadol Requirement in Liver Transplantation: A Prospective, Double-Blind Study. Transplant Proc. 2016 Oct;48(8):2742-2746. doi: 10.1016/j.transproceed.2016.08.033.
• Demiroglu M, Un C, Ornek DH, Kici O, Yildirim AE, Horasanli E, Baskan S, Fikir E, Gamli M, Dikmen B. The Effect of Systemic and Regional Use of Magnesium Sulfate on Postoperative Tramadol Consumption in Lumbar Disc Surgery. Biomed Res Int. 2016;2016:3216246. doi: 10.1155/2016/3216246. Epub 2016 Jan 28.
• Sousa AM, Rosado GM, Neto Jde S, Guimaraes GM, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: a double-blind randomized controlled trial. J Clin Anesth. 2016 Nov;34:379-84. doi: 10.1016/j.jclinane.2016.05.006. Epub 2016 Jun 5.
• Yassin HM, Abd Elmoneim AT, El Moutaz H. The Analgesic Efficiency of Ultrasound-Guided Rectus Sheath Analgesia Compared with Low Thoracic Epidural Analgesia After Elective Abdominal Surgery with a Midline Incision: A Prospective Randomized Controlled Trial. Anesth Pain Med. 2017 Jun 10;7(3):e14244. doi: 10.5812/aapm.14244. eCollection 2017 Jun.
• Karbasy SH, Derakhshan P. Effects of opium addiction on level of sensory block in spinal anesthesia with bupivacaine for lower abdomen and limb surgery: a case-control study. Anesth Pain Med. 2014 Nov 26;4(5):e21571. doi: 10.5812/aapm.21571. eCollection 2014 Dec.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2019
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): July 1, 2021

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (ACTUAL): October 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Orthotopic liver transplantation; Magnesium sulfate; Morphine requirement; Hepatotomy
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: D129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No