Intraoperative Magnesium Administration Does Not Improve Neurocognitive Function After Cardiac Surgery
Authors: Mathew Joseph P. , White William D. , Schinderle David B. , Podgoreanu Mihai V. , Berger Miles , Milano Carmelo A. , Laskowitz Daniel T. , Stafford-Smith Mark , Blumenthal James A. , Newman Mark F. ,   Neurologic Outcome Research Group of the Duke Heart Center,   Director, Mathew Joseph P. ,   Codirector, Blumenthal James A. ,   Anesthesiology, Fontes Manuel A. , Kertai Miklos D. , Lombard Frederick W. , Mathew Joseph P. , McDonagh David L. , Monk Terri G. , Newman Mark F. , Podgoreanu Mihai V. , Stafford-Smith Mark , Swaminathan Madhav , Warner David S. , Funk Bonita L. , Balajonda Narai , Hall Roger L. , Bisanar Tiffany , Clemmons Karen L. , Li Yi-Ju , Pecora Greg , Phillips-Bute Barbara , Toulgoat-Dubois Yanne , Waweru Peter , White William D. ,   Behavioral Medicine, Babyak Michael A. , Blumenthal James A. , Browndyke Jeffrey N. , Welsh-Bohmer Kathleen A. ,   Cardiology, Mark Daniel B. , Sketch Michael H. ,   Neurology, Bennett Ellen R. , Graffagnino Carmelo , Laskowitz Daniel T. , Strittmatter Warren J. ,   Perfusion Services, Alexander Stanlin , Collins Kevin , Smigla Greg , Shearer Ian ,   Surgery, Berry Mark F. , D’Amico Thomas A. , Daneshmand Mani A. , Davis R. Duane , Gaca Jeffrey G. , Glower Donald D. , Harpole R. David , Hughes G. Chad , Jaquiss Robert D.B. , Lin Shu S. , Lodge Andrew J. , Milano Carmelo A. , Onaitis Mark W. , Schroeder Jacob N. , Smith Peter K. , Tong Betty C. 
Published: October 2013

Background and Purpose—
Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection by preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment.

Methods—
After approval by the Duke University Health System Institutional Review Board, 389 patients undergoing cardiac surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive magnesium as a 50 mg/kg bolus followed by another 50 mg/kg infusion for 3 hours or placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks postoperatively using a standardized test battery. Mean CD11b fluorescence and percentage of platelets expressing CD62P, which are markers of leukocyte and platelet activation, respectively, were assessed by flow cytometry as a secondary outcome. The effect of magnesium on postoperative cognition was tested using multivariable regression modeling, adjusting for age, years of education, baseline cognition, sex, race, and weight.

Results—

Among the 389 allocated subjects (magnesium: n=198; placebo: n=191), the incidence of cognitive deficit in the magnesium group was 44.4% compared with 44.9% in the placebo group (
P
=0.93). The cognitive change score and platelet and leukocyte activation were also not different between the groups. Multivariable analysis revealed a marginal interaction between treatment group and weight such that heavier subjects receiving magnesium were less likely to have cognitive deficit (
P
=0.06).

Conclusions—
Magnesium administered intravenously during cardiac surgery does not reduce postoperative cognitive dysfunction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00041392.