Clinical trial NCT06675500
Conditions: Atrial Fibrillation (AF) Magnesium Sulfate Post Cardiac Surgery Patients
Keywords: magnesium sulphate post cardiac surgery arrhythmia atrial fibrillation
Sponsor: Ain Shams University
Start date: 2024-11-01; Completion date: 2025-04-30
Enrollment: 130 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Atrial fibrillation (AF) is a common complication after cardiac surgery. Most studies suggest that the frequency ranges between 25-40%.

Some studies have shown that serum hypomagnesaemia is common after coronary artery bypass grafts (CABG) and other types of cardiac surgery and is associated with postoperative morbidity such as atrial tachyarrhythmia.

The aim of the present study is to investigate the anti-arrhythmic effect of Magnesium Sulfate in prevention of atrial fibrillation post cardiac surgery.

Detailed description:
Atrial fibrillation (AF) is a common complication after cardiac surgery. Most studies suggest that the frequency ranges between 25-40%.

Several reports have indicated that postoperative AF is associated with an increased length of in-hospital stay (LOS) and consequently a greater utilization of health care resources.

Postoperative AF is also associated with higher rates of postoperative stroke, compromised cardiac function, and adverse effects from drugs used to prevent AF.

Despite many years of clinical experience and a large amount of investigation, prevention, and treatment of postoperative AF remain controversial. Many questions about the mechanisms and pathophysiology of AF remain unanswered, further contributing to the ambiguity in reaching consensus about appropriate treatment. Increasing patient age, valvular lesion and dilated atrial diameter is generally considered the greatest risk factor for postoperative AF and an aging population suggest that postoperative AF will continue to be a considerable problem in the future.

Magnesium (Mg) is an important intracellular ion with electrophysiological properties. It is essential for optimal metabolic cell function. Mg has proven effective for treating eclampsia, preeclampsia, and torsade's de pointes. Other therapeutic applications such as adjunctive therapy in acute asthma exacerbations, acute coronary syndromes, acute cerebral ischemia, and postoperative pain control are under discussion.

Some studies have shown that serum hypomagnesaemia is common after coronary artery bypass grafts (CABG) and other types of cardiac surgery. and is associated with postoperative morbidity such as atrial tachyarrhythmia.

Some clinical trials have assessed the efficacy of magnesium as a method of intervention to reduce the incidence of postoperative AF. Though this study is a negative one, other studies showed that magnesium sulfate has a body of evidence supporting its anti-arrhythmic effects and safety profile in AF prevention post-surgery.

A Phase III trial is necessary to further validate the efficacy and safety of magnesium sulfate because the previous studies, while promising, have shown varying results and may have methodological limitations such as small sample sizes, lack of rigorous randomization, or not accounting for long-term outcomes. This study aims to provide definitive evidence through a well-powered randomized controlled trial, using more rigorous study designs, thereby filling an important gap in clinical evidence.

The currently considered standard preventive care for AF after cardiac surgery includes the use of beta-blockers, amiodarone, or other antiarrhythmic drugs. These measures can then be contrasted with the magnesium sulfate intervention, highlighting its potential advantages and rationale for testing in this study.

A placebo group is used in this study since magnesium sulfate has shown some benefit in previous studies, the evidence is not definitive. Therefore, a placebo group is necessary to ensure that any observed effects of magnesium sulfate are due to the treatment and not other confounding factors.

Arms: arm 1: After completion of surgical procedure and successful weaning off Cardiopulmonary bypass the patients will be divided into two groups group A will receive 2 gm of Mg Sulfate diluted in 30 cc normal 0.9 % saline via intravenous infusion over 1 hour (1 Mg sulfate ampoule = 10 cc) .

On ICU arrival group A will continue receiving 1 gm of Mg sulfate per hour for five hours via continuous IV infusion.

After 5 hours, group A will receive 200 mg of Mg sulfate per hour for 19 hours via continuous IV infusion, then oral replacement of mag added 1 gm/8 hours tablet.

Total time of Mg/placebo infusion is 24 hours, and oral tablets for 1 week just before hospital discharge.

Total serum Magnesium level will be measured immediately post weaning of cardiopulmonary bypass, on ICU arrival, after 24 and 48 hours. arm 2: After completion of surgical procedure and successful weaning off Cardiopulmonary bypass the patients will be divided into two groups group B will receive 50 cc normal 0.9 % saline via intravenous infusion over same period.

On ICU arrival group B will same volume and rate of normal saline. After 5 hours, group B will receive same fluid volume and rate of normal saline followed by oral inert starch tablets.

Total time of Mg/placebo infusion is 24 hours, and oral tablets for 1 week just before hospital discharge.

Total serum Magnesium level will be measured immediately post weaning of cardiopulmonary bypass, on ICU arrival, after 24 and 48 hours.
Interventions: intervention 1: Magnesium sulphate intervention 2: Placebo
Intervention descriptions: intervention 1: Intravenous Magnesium sulphate followed by oral tablets of Magnesium sulphate intervention 2: Intravenous infusion of Normal saline 0.9 followed by starch oral tablets

Protocol documents:
Prot_SAP_000.pdf: 
Official Title: Evaluation of the role of Magnesium in prevention of AF post cardiac 
surgery 
NCT Number: NCT06675500 
Document Date: November 1, 2024  


 
 
 
Protocol Of A Paper For Partial Fulfilment Of Research In 
Anesthesia, ICU and pain management 
  
 The title: Evaluation of the role of Magnesium in prevention of 
AF post cardiac surgery  
 
NAME OF RESEARCHER:  Sarah Hamdy Mohamed El 
Ghareeb 
Academic Position: lecturer of Anaesthesia, Intensive Care and Pain management 
Department: Faculty of Medicine-Ain Shams University 
 
NAME OF RESEARCHER: Islam Abd Al Aal Taher 
 
Academic Position: Lecturer of Anaesthesia, Intensive Care and Pain management 
Department: Faculty of Medicine-Ain Shams University 
 
NAME OF RESEARCHER:  Ahmed Abd Al Ghany 
 
Academic Position: Lecturer of Anaesthesia, Intensive Care and Pain management 
Department: Faculty of Medicine-Ain Shams University 
 
NAME OF RESEARCHER:  Noha Mohamed El Tobgy 
 
Academic Position: Lecturer of Anaesthesia, Intensive Care and Pain management 
Department: Faculty of Medicine-Ain Shams University 
 
 
 
 
 
 
Faculty of Medicine 
Ain Shams University 
2024 
 
 
 


 
 
 
 
 
  
  
  
1. INTRODUCTION/ REVIEW (Maximum 1000 words) “References are needed”  
 
Atrial fibrillation (AF) is a common complication after cardiac surgery. 
Most studies suggest that the frequency ranges between 25–40%. (1)  
 
Several reports have indicated that postoperative AF is associated with an 
increased length of in-hospital stay (LOS) and consequently a greater 
utilization of health care resources. (2) 
 
Postoperative AF is also associated with higher rates of postoperative 
stroke, compromised cardiac function, and adverse effects from drugs 
used to prevent AF. (3) 
 
Despite many years of clinical experience and a large amount of 
investigation, prevention, and treatment of postoperative AF remain 
controversial. Many questions about the mechanisms and 
pathophysiology of AF remain unanswered, further contributing to the 
ambiguity in reaching consensus about appropriate treatment. Increasing 
patient age, valvular lesion and dilated atrial diameter is generally 
considered the greatest risk factor for postoperative AF and an aging 
population suggest that postoperative AF will continue to be a 
considerable problem in the future. (4) 
 
Magnesium (Mg) is an important intracellular ion with electrophysiological 
properties. It is essential for optimal metabolic cell function. Mg has proven 
effective for treating eclampsia, preeclampsia, and torsade’s de pointes. 
Other therapeutic applications such as adjunctive therapy in acute asthma 
exacerbations, acute coronary syndromes, acute cerebral ischemia, and 
postoperative pain control are under discussion. (5) 
 


 
Some studies have shown that serum hypomagnesaemia is common after 
coronary artery bypass grafts (CABG) and other types of cardiac surgery. 
(6) and is associated with postoperative morbidity such as atrial 
tachyarrhythmia.(7) 
Some clinical trials have assessed the efficacy of magnesium as a method 
of intervention to reduce the incidence of postoperative AF.(8)  
 
 
  
2. AIM/ OBJECTIVES (Maximum 300 words)  
The primary aim of this study is to investigate the anti-arrhythmic effect of 
Magnesium Sulfate in prevention of atrial fibrillation post cardiac surgery. 
 
  
  
 
  
3. METHODOLOGY:   
Patients and Methods/ Subjects and Methods/ Material and Methods (Maximum 
1000 words) “References may be needed”  


 
This study is a prospective, randomized controlled trial that will study the postoperative     
anti-arrhythmic effect of Magnesium Sulfate and clinical outcomes of administration of 
intravenous Mg Sulfate in patients undergoing open heart surgery. 
Randomization will be performed using a computer-generated randomization sequence 
and allocation concealment to be maintained all through the time of procedure, by using 
opaque, numbered, and sealed envelopes. 
The study protocol will receive ethical approval from the Research Ethical Committee/ 
Institutional Review Boards, Faculty of Medicine Ain Shams University. 
Informed consent will be obtained from each patient before patients' allocation. 
 
Type of the study: prospective randomized clinical trial study protocol.  
 
Study Setting: The operating theaters and ICU of Cardiothoracic institute of Ain 
Shams University Hospitals.  
 
 
Study period: one year.  
 
 
Sample Size:  
 
Using PASS 15 program for sample size calculation, setting power at 80% and alpha 
error at 0.05, it is estimated that sample size of 65 patients per group (Total 130 
patients) can detect an expected medium effect size (h= 0.50) for the difference 
between two groups regarding incidence of post-operative AF using a two-sided z test. 
 
Study population:  
 
Inclusion criteria: 
• Age group: Adult patients from age of 18 years to 70 years  
• Sex: Both sexes  
• Elective open heart surgeries for coronary bypass grafting 
CABG,valvular lesion single or multiple replacement, combined CABG 
and valvular; with EF in preoperative echo is more than or equal 40%  
 
Exclusion criteria: 
• Patients refuse to give informed consent. 
• Emergency open heart surgeries     
• Redo cases. 
• Patients with preoperative serum creatinine level ≥ 1.8 mg/dL 


 
• Patients with reduced intra/post operative urine output ≤ 1 ml/kg/hour. 
• Patients with Chronic Kidney disease, Renal failure on dialysis 
• Patients with rhythm defects as proved by ECG before administration of 
Mg/Placebo. 
 
Sampling method:  
 
Patients will be randomly allocated by computer generated randomization into two 
groups A and B: 
 
• Group A (Study group): patients receiving Intravenous Mg Sulfate.  
 
• Group B (Control): patients receiving Placebo drug.  
 
 
Anesthetic management: 
Full standard preoperative assessment for cardiac surgery will be done for all patients 
included in the study before planned procedures.  
Premedication will be given according to standard protocol in cardiac anesthesia. 
Routine monitoring included a five-lead electrocardiogram, pulse oximeter and invasive 
blood pressure. Anesthesia will be induced with midazolam 0.02mg/kg and fentanyl 2-
5 microgram /kg and muscle relaxation were achieved cisatracurium 0.15 mg/kg 
intravenous. After tracheal intubation, central venous line and TEE inserted, then 
anesthesia will be maintained throughout the procedure with morphin20 microgram/kg 
/min, cisatracurium 2mg/kg/min and sevoflurane 2%. Ventilation will be adjusted to 
maintain end-tidal carbon dioxide in the range of 30-40 mmHg. 
Then after completion of surgical procedure and successful weaning off 
Cardiopulmonary bypass the patients will be divided into two groups group A will 
receive 2 gm of Mg Sulfate diluted in 30 cc normal 0.9 % saline via intravenous infusion 
over 1 hour (1 Mg sulfate ampoule = 10 cc) and group B will receive 50 cc normal 0.9 
% saline via intravenous infusion over same period.  
On ICU arrival group A will continue receiving 1 gm of Mg sulfate per hour for five 
hours via continuous IV infusion, while group B will receive same volume and rate of 
normal saline. 
After 5 hours, group A will receive 200 mg of Mg sulfate per hour for 19 hours via 
continuous IV infusion, then oral replacement of mag added 1 gm/8 hours tablet, while 
group B will receive same fluid volume and rate of normal saline followed by oral inert 
starch tablets. 
Total time of Mg/placebo infusion is 24 hours, and oral tablets for 1 week just before 
hospital discharge. 


 
Total serum Magnesium level will be measured immediately post weaning of 
cardiopulmonary bypass, on ICU arrival, after 24 and 48 hours.  
Both groups will receive standardized antiarrhythmic medications as per institutional 
protocols. 
 
Endpoints of the study: 
Primary end point: 
1. Evaluation of   incidence of atrial fibrillation during hospital stay. 
Secondary end points: 
1. Total ICU stay. 
2. Incidence of new postoperative renal impairment 
3. Total ventilation time  
4. Incidence of readmission with AF during same hospital stay 
 
 
 
Ethical considerations:  
 
The study protocol will receive ethical approval from the Research Ethical 
Committee, Faculty of Medicine Ain Shams University.  
Informed consent will be obtained from each patient before patients' allocation.  
 
 
Statistical Analysis 
Based on published meta-analyses reporting AF incidence of 30–40% in controls 
following cardiac surgery (Cook et al., 2013(11); Klinger et al., 2015(12)) and 
anticipating a 50% relative risk reduction (RRR) with our optimized Mg protocol 
(higher bolus dose, post-CPB initiation), we estimated a medium effect size (h=0.50). 
This RRR assumption was derived from: 
• Pharmacokinetic data confirming serum Mg levels >2.5 mg/dL reduce AF risk 
by 45–60% (Fairley et al., 2015(6); Shiga et al., 2004(13)) 
• Prior positive RCTs using similar high-bolus regimens (2–3g) showing 54–60% 
RRR (Miller et al., 2005 (14); Kaplan et al., 2003(15)) 
Using PASS 15, with power=80% and α=0.05, a sample size of 65 patients per group 
(total N=130) provides 85% power to detect an absolute risk reduction of 20% 
(control:40% , Mg:20%). This aligns with RCTs detecting similar effects in cardiac 
surgery cohorts (Gu et al., 2012; N=60–100/group (9)). Continuous variables were 
analyzed using independent t-tests or ANCOVA (adjusted for covariates); non-
parametric data employed Mann-Whitney U tests. Categorical outcomes used chi-
square or Fisher’s exact tests. Multivariable logistic regression adjusted for age, body 
mass index (BMI), chronic obstructive pulmonary disease (COPD), diabetes status, 


 
ejection fraction (EF), surgery type, and left atrial size (where available).Sensitivity 
analyses included propensity score matching (PSM) and Bayesian posterior 
probability estimation. 
 
 
 
 
 
 
4. REFERENCES (Maximum 20 references)   
1.Fuller JA, Adams GG, Buxton B. Atrial fibrillation after coronary artery bypass 
grafting: is it a disorder of the elderly? J Thorac Cardiovasc Surg 
1989;97:821–5. 
 
2. Hogue CW Jr, Hyder ML. Atrial fibrillation after cardiac operation: risks, 
mechanisms, and treatment. Ann Thorac Surg 2000;69:300–6. 
 
3. Almassi GH, Schowalter T, Nicolosi AC, et al. Atrial fibrillation after cardiac 
surgery: a major morbid event? Ann Surg 1997;226:501–11; discussion 
511–3. 
 
4. Leitch JW, Thomson D, Baird DK, et al. The importance of age as a predictor 
of atrial fibrillation and flutter after coronary artery bypass grafting. J Thorac 
Cardiovasc Surg 1990;100:338–42. 
 
5. Carrio ML, Lopez-Delgado JC, Javierre C, et al. Magnesium and cardiac surgery in 
the Critical Care Setting. Diet and Nutrition in Critical Care. Published online 
2015:459-472. doi:10.1007/978-1-4614-7836-2_138 
 
6. Satur CM. Magnesium and cardiac surgery. Ann R Coll Surg Engl 
1997;79:349–54. 
 
7. Aglio LS, Stanford GG, Maddi R, et al. Hypomagnesemia is common 
following cardiac surgery. J Cardiothorac Vasc Anesth 1991;5:201–8. 
 
8. Vyvyan HA, Mayne PN, Cutfield GR. Magnesium flux and cardiac surgery: a 
study of the relationship between magnesium exchange, serum magnesium 
levels and postoperative arrhythmias. Anaesthesia 1994;49:245–9. 
 
 
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