Clinical trial NCT03558516
Conditions: Meningioma
Keywords: Meningioma Magnesium Montreal cognitive assessment blood loss controlled hypotension blood transfusion neuroprotective anesthesia
Sponsor: Mahidol University
Start date: 2018-08-01; Completion date: 2020-02-18
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Meningioma is the most common central nervous system tumor and craniotomy with tumor removal was associated with moderate blood loss and blood transfusion. Magnesium has hypotensive effect and probably reduce intraoperative blood loss. Whether or not magnesium sulphate can reduce intraoperative blood loss and improve postoperative cognitive function is still inconclusive. So the investigators conduct the randomized control trial to compare the effect of magnesium with placebo control in blood loss and cognitive function in meningioma patient undergoing craniotomy.

Detailed description:
The investigators enroll 120 patient who admitted for craniotomy for meningioma removal. Then, the patients will be divided into two groups. The first group or group Mg will receive magnesium sulphate 40 mg/kg infuse for 30 min (started at skin incision), and then infuse magnesium sulphate 10 mg/kg/hr until the dura will be closed. The another group or normal saline group will receive the same amount of 0.9% sodium chloride. The anesthesia and surgery are standardized. The recorded data include patient demographic data, intraoperative blood loss, hemodynamics and pre and postoperative Montreal cognitive assessment score.

Arms: arm 1: The patient will receive magnesium sulfate injection 40 mg/kg infuse over 30 min started at skin incision and continuous drip 10 mg/kg/hr until the dura is closed arm 2: The patient will receive 0.9% sodium chloride the same amount of magnesium sulphate infuse over 30 min started at skin incision and continuous drip until the dura is closed
Interventions: intervention 1: Magnesium group intervention 2: Normal saline group
Intervention descriptions: intervention 1: We will dilute magnesium 6 gram with 0.9% sodium chloride to 30 ml. The patient will receive magnesium sulfate 40 mg/kg infuse over 30 min started at skin incision and continuous drip 10 mg/kg/hr until the dura is closed. Anesthesia is standardized with propofol, fentanyl, cisatracurium and sevoflurane. Vasopressor or antihypertensive drug are used to control hemodynamics. intervention 2: The patient will receive 0.9% sodium chloride the same amount of magnesium sulphate infuse over 30 min started at skin incision and continuous drip until the dura is closed. Anesthesia is standardized with propofol, fentanyl, cisatracurium and sevoflurane. Vasopressor or antihypertensive drug are used to control hemodynamics.

Protocol documents:
Prot_000.pdf: 
The effects of magnesium sulphate on intraoperative 
blood loss in meningioma patient undergoing 
craniotomy with tumor removal: A prospective 
randomized study. 
 
NCT number: NCT03558516 
 
Document date: 1 August 2018 
 
 
 
 
 
 


Study protocol 
The protocol was approved by the institutional ethics committee (SI 259/2018). After 
obtaining written informed consent from all patients, a randomized double-blinded placebo-
controlled trial was conducted on 80 patients. This study was registered at Clinical Trials.gov 
(NCT03558516). The patients will be randomized into 2 groups in blocks of 4 by computer-
generated numbers. The sequence numbers and groups will be placed inside concealed 
envelopes, which will be opened by researchers. The researchers will enroll the participants 
but will not take part in patient care. 
We will enroll patients aged between 18-70 years, American Society of 
Anesthesiologist (ASA) grade I and II, diagnosed of supratentorial meningioma and underwent 
craniotomy with tumor removal at Siriraj hospital, Mahidol university. The exclusion criteria 
included all of the following conditions; preoperatively unstable hemodynamics requiring 
vasopressors or vasodilators, heart disease or heart block, liver disease Child Pugh Score C, 
Renal insufficiency or estimated glomerular filtration rate (e-GFR) < 60 mL/min, allergy 
history of magnesium or any drug use in study protocol, use calcium channel blocker before 
operation, pregnancy, receive magnesium sulfate to treatment other conditions, baseline 
serum magnesium more than 2.6 mg/dl, BMI > 30 kg/m2, and prone to brain herniation from 
increased intracranial pressure. 
  
On the day before surgery, the informed consent will be obtained and 
baseline cognitive function will be measured by Montreal Cognitive Assessment (MOCA) test. 


  
At the operating room, standard monitorings will be used. General anesthesia 
will be inducted with propofol 1.5-2.0 mg/kg, fentanyl 1-2 mcg/kg, and then cis-atracurium 
0.15 mg/kg will be given for facilitating tracheal intubation. Then, the extra-large bore 
intravenous lines will be accessed and radial artery will be cannulated for continuous 
arterial pressure monitoring. A baseline blood sampling for magnesium level will be 
obtained. 
Group Mg (Study group) patients will receive 40 mg/kg of magnesium sulphate 
loading in 30 minutes at incision and then continuous drip 10 mg/kg/hr until dura will be 
closure. Group NSS (Control group) patients will receive normal saline with the same 
amount for loading and continuous infusion. Identical infusion syringes of magnesium (Mg) 
and placebo will be prepared and labeled by the research staff that will not provide care 
for the patients. 
  
Anesthesia will be maintained with sevoflurane not exceeding 1 minimal 
alveolar concentration (MAC) with supplemental of intermittent fentanyl 0.5-1 mcg/kg, and 
continuous cis-atracurium 0.06-0.1 mg/kg/hr. If the depth of anesthesia is not adequate, 
propofol 2-6 mg/kg/hr continuous will be given. 
 
Hematocrit levels will be measured every 2-3 hours. Intraoperative 
transfusion triggered for packed red cell is a hematocrit < 27%. Magnesium level will be 
measured at beginning and 4 hours. If magnesium level is more than 4 mg/dl, study drug 
will be stopped. Intraoperative bleeding will be measured by collection in suction bottle, 
plastic bags, drapes, and soaked gauzes subtracting the amount of irrigating fluid. 


After the uneventful operation, the patients will be extubated and transferred to 
neurosurgical intensive care unit. Some patients will remain intubation and post-operative 
ventilation will be continued and reasons for remaining intubation will be noted.  
Postoperative cognitive function test (MOCA) will be done at postoperative day 3-7 
when patient has less pain and recover enough for comfortable testing. 
The measure outcomes are intraoperative blood loss, amount of pack red cell (PRC) 
transfusion requirement, anesthetic requirement and postoperative MOCA score. 


Monitoring & IV access
Special equipment preparation
1.
Equipment for arterial line insertion for continuous BP monitoring
(A-line may be not required, according to anesthesiologist in charge)
2.
Two syringe pumps for study drug and muscle relaxant administration
3.
Study drug (be prepared by investigator)
4.
Two heparin tubes (green capped tube)
5.
Equipment for hematocrit assessment
The effects of magnesium sulphate on intraoperative blood loss in meningioma patient 
undergoing craniotomy with tumor removal: A prospective randomized study.
Study Protocol
-
Standard monitoring (NIBP, Pulse oximetry, EKG, End tidal CO2)
-
Arterial line insertion (before or after induction)
Induction
-
Fentanyl 1-2 mcg/kg
-
Propofol 1.5-2 mg/kg
-
Cis-atracurium 0.15 mg/kg then wait for 4 minutes before intubation
-
Use Sevoflurane in Air:Oxygen 1:1, Sevoflurane < 1 MAC
-
Positioning as usual
-
Aspirate blood from A-line 3 ml into heparin tube for assess baseline Mg level
(Aspirate from vein if no A-line)
Maintenance
-
Prepare study drug in syringe pump
-
At skin incision Study drug 0.2 ml/kg loading drip in 30 minutes for example BW 60 kg use 
drug 0.2x60 = 12 ml drip 24 ml/hr for 30 minutes then IV continuous 0.05 ml/kg/hr for example 
BW 60 kg administer 3 ml/hr
-
Use Cis-atracurium IV continuous infusion 0.06-0.1 ml/kg/hr
-
Give intermittent Fentanyl 0.5-1 mcg/kg/hr according to anesthesiologist in charge
-
If Depth of anesthesia is not adequate or brain is tight, you can use
Propofol 2-6 mg/kg/hr according to anesthesiologist in charge
-
Assess Hematocrit before PRC transfusion, PRC is transfused when Hct.<27%
-
4 hours after skin incision Aspirate blood from A-line 3 ml into heparin tube for assess Mg level 
(Aspirate from vein if no A-line)
If you have any problem or question please contact Dr.Thanawut 0816291621 or Dr.Manee 09-5280


End of the case
Intraoperative hypotension
Intraoperative hypertension
-
Stop Study drug when dura was closure
-
Discontinue muscle relaxant at least 30 minute before operation finish
-
Record Intraoperative blood loss (Primary outcome)
SBP<90 mmHg or 
decrease <20% from baseline
1. Increase Sevoflurane to 1 MAC
wait for 5 min, if BP still high
2. Fentanyl 25 mcg
not exceed 2 times, wait for 5 minute
(total 10 mins) if BP still high
3. Propofol intermittent bolus or continuous 
drip if depth of anesthesia Is not adequate
4. If depth of anesthesia is adequate,
Nicardipine 0.2-0.4 mg in titration or
Labetalol 2.5-5 in titration or
Continuous drip according to 
anesthesiologist in charge
SBP>140 mmHg or 
increase >20% from baseline
1.
Fluid resuscitation or
2.
Vasopressor
according to anesthesiologist in charge
Reversal and Extubation
-
Use Glycopyrrolate 0.4 mg and Neostigmine 2.5 mg as reversal agents
-
If residual neuromuscular blocking effect is suspected, evaluate train of four before 
extubation
-
Extubation when patients fully awake, open eyes and follow command
-
Record time when fully awake and extubation (Secondary outcome)
-
If remain intubation, please note the reason for remaining intubation
Step for sending lab investigation
-
Send heparin tube to laboratory within 2 hours
-
8.00 am – 4.00 pm contact research officer
-
After 6.00 pm contact Dr.Thanawut
If you have any problem or question please contact Dr.Thanawut 0816291621 or Dr.Manee 09-5280

SAP_001.pdf: 
The effects of magnesium sulphate on intraoperative 
blood loss in meningioma patient undergoing 
craniotomy with tumor removal: A prospective 
randomized study. 
 
NCT number: NCT03558516 
 
Document date: 1 August 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
The collected data will be analyzed by Statistical Package for the Social Sciences 
(SPSS) software version 18.0 (SPSS Inc., Chicago, IL, USA). Data will be described in terms of 
frequencies (number and percent of cases), mean ± standard deviation, median (range) 
when appropriate. Chi-square or Fisher’s exact test will be used for comparing categorical 
data. Student’s t-test will be used for comparing continuous data with normal distribution. 
Comparison of nonparametric variables will be done using Mann-Whitney test. The p-value < 
0.05 will be considered statistical significance.