Intraoperative Magnesium Sulfate Administration During Orthotopic Liver Transplantation

Postoperative Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03717467
• Other study ID #: D129
• Status: Recruiting
• Phase: N/A
• Start date: May 8, 2019
• Est. completion date: July 1, 2021

Study information

• Verified date: November 2020
• Source: Fayoum University Hospital
• Contact: Ahmed A Lotfy, M.Sc.
• Phone: 1068061357
• Email: lotfy_23[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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).

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

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.
• 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.

Locations

Country	Name	City	State
Egypt	Sheikh Zayed hospital	Giza

Sponsors (1)

Lead Sponsor	Collaborator
Fayoum University Hospital

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

Demiroglu M, Ün 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. — View Citation

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. — View Citation

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. — View Citation

Sousa AM, Rosado GM, Neto Jde S, Guimarães 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Age	in years	1 hour before operation once patient is recruited
Other	Height	in meters	1 hour before operation once patient is recruited
Other	Weight	in kilogram	1 hour before operation once patient is recruited
Other	body mass index	kilogram/meter square	1 hour before operation once patient is recruited
Other	Surgery duration	in hours	1 minute after operation
Other	Anesthesia duration	in hours from time of induction to withdrawal of all anesthetics	1 minute after withdrawal of all anesthetics
Primary	Postoperative Morphine consumption	in mg	24 hours after operation
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	1 minute before induction
Secondary	Heart rate	in beat per minute by electrocardiogram	1 minute before induction
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	30 seconds before intubation
Secondary	Heart rate	in beat per minute by electrocardiogram	30 seconds before intubation
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	5 minutes after beginning of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	5 minutes after beginning of surgery
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	15 minutes after beginning of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	15 minutes after beginning of surgery
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	30 minutes after beginning of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	30 minutes after beginning of surgery
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	60 minutes after beginning of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	60 minutes after beginning of surgery
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	120 minutes after beginning of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	120 minutes after beginning of surgery
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	30 minutes after end of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	30 minutes after end of surgery
Secondary	Morphine consumption	in milligram	30 minutes after end of surgery
Secondary	Visual Analog Scale	Pain score which starting from 0:no pain to 10:Worst pain	30 minutes after end of surgery
Secondary	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
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	4 hours after end of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	4 hours after end of surgery
Secondary	Morphine consumption	in milligram	4 hours after end of surgery
Secondary	Visual Analog Scale	Pain score which starting from 0:no pain to 10:Worst pain	4 hours after end of surgery
Secondary	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
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	24 hours after end of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	24 hours after end of surgery
Secondary	Morphine consumption	in milligram	24 hours after end of surgery
Secondary	Visual Analog Scale	Pain score which starting from 0:no pain to 10:Worst pain	24 hours after end of surgery
Secondary	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
Secondary	Mean arterial pressure	in mm mercury by invasive blood pressure	48 hours after end of surgery
Secondary	Heart rate	in beat per minute by electrocardiogram	48 hours after end of surgery
Secondary	Morphine consumption	in milligram	48 hours after end of surgery
Secondary	Visual Analog Scale	Pain score which starting from 0:no pain to 10:Worst pain	48 hours after end of surgery
Secondary	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
Secondary	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
Secondary	Blood serum magnesium concentration	from venous blood sample in mg/dl	12 hours before operation
Secondary	Blood serum magnesium concentration	from venous blood sample in mg/dl	15 minutes after operation
Secondary	Interleukin 6 level in blood	inflammatory mediator measured from venous blood sample	24 hours after operation
Secondary	Interleukin 8 level in blood	inflammatory mediator measured from venous blood sample	24 hours after operation
Secondary	Tumor necrosis factor alpha level in blood	inflammatory mediator measured from venous blood sample	24 hours after operation
Secondary	Incidence of shivering	as opioid related side effect	48 hours after operation
Secondary	Incidence of nausea	as opioid related side effect	48 hours after operation
Secondary	Incidence of vomiting	as opioid related side effect	48 hours after operation
Secondary	Incidence of respiratory depression	as opioid related side effect	48 hours after operation
Secondary	Incidence of somnolence	as opioid related side effect	48 hours after operation
Secondary	Incidence of oversedation	as opioid related side effect	48 hours after operation
Secondary	Incidence of itching	as opioid related side effect	48 hours after operation
Secondary	Incidence of constipation	as opioid related side effect	48 hours after operation
Secondary	Incidence of paralytic ileus	as opioid related side effect	48 hours after operation