3Mg: Magnesium for Atrial Fibrillation after Cardiac Surgery (2013)

“A 3-hour intraoperative magnesium infusion did not reduce the incidence of postoperative atrial fibrillation.”

  • The 3Mg Trial Investigators

1. Publication Details

  • Trial Title: A Multicenter Randomized Controlled Trial of a 3-Hour Intraoperative Magnesium Infusion to Prevent Atrial Fibrillation After Cardiac Surgery
  • Citation: van Paassen KG, Koudstaal T, Dunning J, et al. A Multicenter Randomized Controlled Trial of a 3-Hour Intraoperative Magnesium Infusion to Prevent Atrial Fibrillation After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2013;27(3):446-451. DOI: 10.1053/j.jvca.2012.11.006
  • Published: June 2013, in The Journal of Cardiothoracic and Vascular Anesthesia
  • Author: K. K. G. van Paassen
  • Funding: Departmental research funds.

2. Keywords

  • Postoperative Atrial Fibrillation (POAF), Cardiac Surgery, Magnesium, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients undergoing cardiac surgery (Population), does a 3-hour intraoperative magnesium infusion (Intervention) compared to a saline placebo (Comparison) reduce the incidence of postoperative atrial fibrillation (POAF) (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, associated with increased morbidity, mortality, and length of stay. Magnesium has anti-arrhythmic properties, and previous, smaller studies and meta-analyses had suggested that intravenous magnesium could reduce the incidence of POAF, but the evidence was inconsistent and the optimal dosing and timing were unknown.
  • Knowledge Gap: There was a need for a well-designed, multicenter, randomized controlled trial to definitively determine if a simple, intraoperative magnesium infusion was an effective prophylactic strategy.
  • Proposed Hypothesis: The authors hypothesized that a 3-hour intraoperative magnesium infusion would reduce the incidence of POAF after cardiac surgery.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, double-blind, placebo-controlled trial (used to test the effectiveness of interventions).
  • Setting: 3 large teaching hospitals in the Netherlands.
  • Trial Period: Enrollment ran from March 2008 to September 2011.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) scheduled for on-pump cardiac surgery (e.g., CABG, valve surgery, or combined procedures).
    • Exclusion Criteria: Included pre-existing atrial fibrillation, renal failure (creatinine >200 µmol/L), or known contraindications to magnesium.
  • Intervention: Patients received an intravenous infusion of magnesium sulfate (6 mmol bolus over 15 minutes, followed by 6 mmol/hour for 2 hours and 45 minutes, for a total of 22.5 mmol over 3 hours).
  • Control: Patients received a matching intravenous infusion of 0.9% saline.
  • Management Common to Both Groups: All other aspects of anesthetic and surgical management were performed according to the standard practice of the participating centers.
  • Power and Sample Size: The authors calculated that a sample size of 600 patients would be required to have 80% power to detect a 10% absolute risk reduction in the incidence of POAF (from an expected 30% to 20%). (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: The incidence of postoperative atrial fibrillation requiring treatment during the ICU and hospital stay.
    • Secondary Outcomes: Included time to onset of AF, length of ICU and hospital stay, and in-hospital mortality.

6. Key Results

  • Enrollment and Baseline: 601 patients were randomized (300 to the magnesium group and 301 to the placebo group). The baseline characteristics were well-matched between the groups.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the incidence of postoperative atrial fibrillation. POAF occurred in 60 of 300 patients (20%) in the magnesium group and 64 of 301 patients (21%) in the placebo group (p=0.71).
  • Secondary Outcomes: There were no significant differences between the groups in any of the secondary outcomes, including time to onset of AF, length of stay, or mortality.
  • Adverse Events: The study monitored for major postoperative complications. There were no significant differences in the rates of adverse events such as re-exploration for bleeding, stroke, myocardial infarction, or renal failure between the magnesium and placebo groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who developed POAF between the two groups.
  • Key Statistic(s) Reported: The key statistics were the absolute incidence rates and the associated P-value.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.71 is much higher than the 0.05 threshold, indicating that the small difference in the incidence of POAF between the groups was not statistically significant and was very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral (showed no difference), ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, double-blind, placebo-controlled design is the gold standard for minimizing selection and performance bias, leading to a high degree of internal validity.
  • Generalizability: The inclusion of patients undergoing a range of common cardiac surgeries from three different centers increases the external validity, making the results more applicable to a broad range of clinical settings.
  • Statistical Power: The study was adequately powered to detect a clinically meaningful difference in the primary outcome.
  • Patient-Centered Outcomes: The primary outcome of POAF requiring treatment is a clinically relevant endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was well-conducted with a low risk of bias.
  • External Validity (Generalizability): The specific 3-hour intraoperative timing of the infusion may not be generalizable to other magnesium administration protocols (e.g., longer postoperative infusions).
  • Other: The overall incidence of POAF in the study (around 20%) was lower than the 30% anticipated in the power calculation. This lower event rate makes it more difficult to detect a true difference between groups if one exists.

10. Conclusion of the Authors

  • A 3-hour intraoperative magnesium infusion did not reduce the incidence of postoperative atrial fibrillation after cardiac surgery.

11. To Summarize

  • Impact on Current Practice: This high-quality trial provided strong evidence that a simple, short-duration intraoperative magnesium infusion is not an effective strategy for preventing POAF.
  • Specific Recommendations:
    • Patient Selection: For adult patients undergoing routine on-pump cardiac surgery.
    • Actionable Intervention: The results do not support the use of a short, 3-hour intraoperative magnesium infusion for the sole purpose of preventing POAF.
  • What This Trial Does NOT Mean: This trial does NOT rule out a potential benefit from other magnesium dosing regimens (e.g., longer infusions or those continued into the postoperative period).
  • Implementation Caveats: The findings of this trial should discourage the use of this specific short-duration protocol for POAF prophylaxis.

12. Context and Related Studies

  • Building on Previous Evidence: The 3Mg trial (2013) was designed to provide a definitive answer to a question that had been explored in many smaller, less conclusive studies and meta-analyses.
  • Influence on Subsequent Research: The neutral finding of this trial, along with others, has led to a shift in research towards other prophylactic strategies for POAF, such as beta-blockers, amiodarone, and different pacing strategies.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial did not address whether a longer duration of magnesium infusion, particularly one extending into the postoperative period, would be effective.
  • Future Directions: Future research in this area continues to explore the optimal multimodal strategy for preventing POAF, which may include a combination of pharmacological and non-pharmacological interventions.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question addressed a very common and clinically important postoperative complication.
  • Methods: The study design was robust (multicenter, double-blind RCT), which is a key strength. The patient population was representative of a general cardiac surgery population.
  • Results: The study reported a clear neutral finding, with no statistically significant difference in the primary outcome. The confidence interval for the difference between the groups would have crossed the line of no effect.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity means these findings are broadly applicable to similar cardiac surgery centers. The trial provides strong evidence to discourage the use of this specific, short-duration magnesium protocol.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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