Magnesium During CEA May Improve Cognitive Outcome

BY JEFF EVANS

WASHINGTON -- Magnesium infused intravenously at an appropriately low dose during elective carotid endarterectomy and in the immediate postoperative period may protect against cognitive decline after the procedure, Dr. William J. Mack reported at the annual meeting of the American Association of Neurological Surgeons.

The randomized trial of 92 patients who underwent elective carotid endarterectomy (CEA) for asymptomatic or symptomatic stenosis of more than 60% found that patients who received an infusion of magnesium were 73% less likely to have cognitive decline on a series of five neuropsychometric tests 1 day after surgery than were patients who received an infusion of saline, said Dr. Mack, a resident in the department of neurological surgery at Columbia University, New York.

MAGNESIUM INFUSION CONFERRED A 73% LOWER LIKELIHOOD OF COGNITIVE DECLINE AFTER SURGERY THAN DID SALINE INFUSION.

The risk of major morbidity after CEA is very low, but findings from standard neuropsychometric testing have shown that more than 25% of patients experience cognitive decline after undergoing the procedure, he said.

"Encouraging results from both animal and clinical studies have supported the use of IV magnesium as a potential therapy in cerebral ischemia," including decreases in infarct volume when given up to 6 hours after the onset of ischemia in animal models and decreases in mortality and disability in several small clinical studies.

The earlier randomized, controlled Intravenous Magnesium Efficacy in Stroke (IMAGES) study evaluated the benefit of magnesium when given to patients within 12 hours of the onset of acute stroke. Except in a very small subgroup of patients with noncortical strokes, magnesium did not significantly improve death or disability at 90 days (Lancet 2004;363:439-45).

Some critics thought that the 12-hour time window of the IMAGES study may have been too long. The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial, which is now enrolling nearly 1,300 patients for a phase III study, will try to address this shortcoming by having paramedics administer magnesium to stroke patients in the field. The mean time to administration of magnesium from the onset of symptoms has so far been 120 minutes.

In the current study, 49 patients were treated with magnesium. These patients received a 100-mL loading dose infused over 25 minutes, followed by a continuous infusion of 400 mL during the next 24 hours. This treatment group was split into three subgroups: one that received a 2-g loading dose and 8-g continuous infusion; a second that received a 2-g loading dose and a 16-g continuous infusion; and a third that received a 4-g loading dose and a 16-g continuous infusion.

All of the neuropsychometric tests (Boston Naming Test, Trail-Making Test Parts A and B, Controlled Oral Word Association, and Rey Complex Figure Test) were performed more than 3 hours after sedation or anesthesia. Patients also were excluded if they had a pain score greater than 5 on a 10-point scale. The researchers excluded 16 patients who were originally randomized in the study because they had high postoperative pain, refused testing, or had complications.

After combining the results of the neuropsychometric tests into a total deficit score that measured the level of global cognitive decline, Dr. Mack and his associates found that magnesium infusion overall conferred a 73% lower likelihood of having cognitive decline after the surgery than did saline infusion. Patients who had a prior CEA were more than five times more likely to have cognitive decline regardless of the study arm they were in. However, patients with symptomatic stenosis were 70% less likely to have cognitive decline than were asymptomatic patients.

Analysis of the results with logistic regression according to dosing regimens was impossible without combining the low- and medium-dose subgroups because all of the patients in the low-dose group had good outcomes, Dr. Mack said. These two subgroups had similar intraoperative blood levels of magnesium. The patients in these two combined subgroups were 91% less likely to have cognitive decline than were saline-infused patients.

Patients in the highest-dose group did not have any better outcomes than did the saline-infused patients, possibly because their magnesium blood levels were greater than 4.5 mg/dL at 15 minutes into the infusion and remained high through 24 hours. In the gynecologic and obstetrics literature, magnesium infusion during neuropsychometric testing for eclampsia caused decreased attention and memory when serum magnesium levels became substantially elevated, Dr. Mack said.

Magnesium may exert its neuroprotective effect by blocking noncompetitive N-methyl-D-aspartate receptors, enhancing regional cerebral blood flow, acting as an antagonist to voltage-gated calcium channels, or recovering cellular energy after cerebral reperfusion, he suggested.

"Improvement in cognitive function after CEA has been the subject of investigation for more than 2 decades. The authors here have found that intraoperative magnesium prevents a predictable decline in cognition," said Dr. George Andros when asked to comment on this article.

"This simple intervention appears to provide neuroprotection without any reported adverse effects. The question at this point is whether should we act with cautious optimism and add this to our treatment regimen with CEA and CAS or await corroborating investigations," added Dr. Andros, who is editor of VASCULAR SPECIALIST, a vascular surgeon and the director of vascular services and the Diabetic Foot Center at Providence-Saint Joseph Medical Center in Burbank, Calif.