The use of therapeutic magnesium for neuroprotection during global cerebral ischemia associated with cardiac arrest and cardiac surgery in adults: A systematic review

Background: Global cerebral ischemia occurs due to reduced blood supply to the brain. This is commonly caused by a cessation of myocardial activity associated with cardiac arrest and cardiac surgery. Survival is not the only important outcome because neurological dysfunction impacts on quality of life, reducing independent living. Magnesium has been identified as a potential neuroprotective agent; however, its role in this context is not yet clear. Objectives: The objective of this review was to present the best currently available evidence related to the neuroprotective effects of magnesium during a period of global cerebral ischemia in adults with cardiac arrest or cardiac surgery. Inclusion criteria Types of participants: The current review considered adults aged over 18 years who were at risk of global cerebral ischemia associated with cardiac arrest or cardiac surgery. Studies of patients with existing neurological deficits or under the age of 18 years were excluded from the review. Types of intervention(s)/phenomena of interest: The intervention of interest was magnesium administered in doses of at least of 2 g compared to placebo to adult patients within 24 hours of cardiac arrest or cardiac surgery. Types of studies: The current review considered experimental designs including randomized controlled trials, non-randomized controlled trials and quasi-experimental designs. Outcomes: The outcome of interest were neurological recovery post-cardiac arrest or cardiac surgery, as measured by objective scales, such as but not limited to, cerebral performance category, brain stem reflexes, Glasgow Coma Score and independent living or dependent living status. To enable assessment of the available data, neuroprotection was examined by breaking down neurological outcomes into three domains - functional neurological outcomes, neurophysiological outcomes and neuropsychological outcomes. Search strategy: The search strategy aimed to find both published and unpublished studies between January 1980 and August 2014, utilizing the Joanna Briggs Institute (JBI) three-step search strategy. Databases searched included PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Australian Clinical Trials Register, Australian and New Zealand Clinical Trials Register, Clinical Trials, European Clinical Trials Register and ISRCTN Registry. Methodological quality: The studies included in this review were of moderate-to-good-quality randomized controlled trials. Studies included measured neurological outcome using functional neurological assessment, neuropsychiatric assessment or neurophysiological assessment. Data extraction: Data were extracted using standardized templates provided by the JBI Meta-analysis of Statistics Assessment and Review Instrument software. Data synthesis: Quantitative data were, where possible, pooled in statistical meta-analysis using Review Manager 5.3 (The Nordic Cochrane Centre, Cochrane; Copenhagen, Denmark). Where statistical pooling was not possible, the findings were presented in narrative form, including tables and figures, to aid in data presentation, where appropriate. Results: Seven studies with a total of 1164 participants were included in this review. Neurological outcome was categorized into three domains: functional neurological, neurophysiological and neuropsychological outcomes. Meta-analysis of three studies assessing the neuroprotective properties of magnesium administration post cardiac arrest found improved functional neurological outcome (odds ratio 0.44; 95% confidence interval 0.24-0.81). Conclusion: Magnesium may improve functional neurological outcome in patients who suffer global cerebral ischemia associated with cardiac surgery and cardiac arrest. Magnesium does not decrease neuropsychological decline. Further testing of neurological outcomes in the domains of functional outcomes, neurophysiological markers and neuropsychological tests are required to further understanding of the neuroprotective effects of magnesium. Suitable dosing regimens should be investigated prior to introduction into clinical practice. Further research is required to investigate the optimal magnesium dose.