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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| S group | Placebo Comparator | Isotonic saline as placebo will be given. |
|
| M group | Active Comparator | Magnesium sulfate will be given |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| isotonic saline | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative Morphine consumption | in mg | 24 hours after operation |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ahmed A Lotfy, M.Sc. | Contact | 1068061357 | +20 | lotfy_23@yahoo.com |
| Hany M Yassin, MD | Contact | 1023912463 | +20 | hmy00@fayoum.edu.eg |
| Name | Affiliation | Role |
|---|---|---|
| Mostafa S Elhamamsy, MD | Faculty of medicine, Fayoum University | Study Chair |
| Ahmed M Yassin, MD | Faculty of medicine, Beni-suef University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sheikh Zayed hospital | Recruiting | Giza | 12573 | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27788811 | Background | 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. | |
| 27022607 | Background |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| D008278 | Magnesium Sulfate |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Patient will be randomly assigned to one of the two groups. An independent anesthesiologist who will not be participating in the study prepares the study medications.
|
| Magnesium Sulfate | Drug | 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. |
|
|
| 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 |
| 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 |
| Abeer S Goda, MD |
| Faculty of medicine, Fayoum University |
| Study Director |
| Hany M Yassin, MD | Faculty of medicine, Fayoum University | Principal Investigator |
| 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. |
| 27687417 | Background | 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. |
| 28856110 | Background | 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. |
| 25798378 | Background | 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. |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D017670 |
| Sodium Compounds |
| D017616 | Magnesium Compounds |
| D013431 | Sulfates |
| D013464 | Sulfuric Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |