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Randomized Controlled Trial
. 2013 Dec;44(12):3407-13.
doi: 10.1161/STROKEAHA.113.002703. Epub 2013 Oct 8.

Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery

Joseph P Mathew  1 , William D White, David B Schinderle, Mihai V Podgoreanu, Miles Berger, Carmelo A Milano, Daniel T Laskowitz, Mark Stafford-Smith, James A Blumenthal, Mark F Newman; Neurologic Outcome Research Group (NORG) of The Duke Heart Center
Collaborators, Affiliations
Randomized Controlled Trial

Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery

Joseph P Mathew et al. Stroke. 2013 Dec.

Abstract

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.

Keywords: blood platelets; cardiopulmonary bypass; cognition.

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Figures

Figure 1
Figure 1
CONSORT diagram showing the flow of participants.
Figure 2
Figure 2
Magnesium, weight, and probability of cognitive deficit at baseline cognitive index=0, years of education=12, age=68, race=Caucasian, and gender=male (2a) or probability of cognitive decline after adjusting for preoperative cognitive score, years of education, and gender (2b). Heavier patients receiving magnesium tended toward better cognitive outcome. UCL = upper confidence limit; LCL = lower confidence limit
Figure 2
Figure 2
Magnesium, weight, and probability of cognitive deficit at baseline cognitive index=0, years of education=12, age=68, race=Caucasian, and gender=male (2a) or probability of cognitive decline after adjusting for preoperative cognitive score, years of education, and gender (2b). Heavier patients receiving magnesium tended toward better cognitive outcome. UCL = upper confidence limit; LCL = lower confidence limit
Figure 3
Figure 3
Magnesium levels (3a), platelet activation (3b) and leukocyte (3c) activation in the magnesium and placebo groups. CPB = cardiopulmonary bypass. * = p < 0.0001.
Figure 3
Figure 3
Magnesium levels (3a), platelet activation (3b) and leukocyte (3c) activation in the magnesium and placebo groups. CPB = cardiopulmonary bypass. * = p < 0.0001.
Figure 3
Figure 3
Magnesium levels (3a), platelet activation (3b) and leukocyte (3c) activation in the magnesium and placebo groups. CPB = cardiopulmonary bypass. * = p < 0.0001.
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