Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage.

BACKGROUND: The effect of serum magnesium concentration on the incidence of cerebral arterial vasospasm following aneurysmal subarachnoid haemorrhage (SAH) is unclear. OBJECTIVE: To test whether induced hypermagnesaemia reduces the incidence of cerebral arterial vasospasm following aneurysmal SAH. METHODS: The study was conducted at two tertiary hospitals in Australia and patients were recruited between 1 April 2005 and 31 December 2009. Within 72 hours of aneurysmal SAH, patients were randomly assigned to a high or normal target for serum magnesium concentration (1.60-2.50 mmol/L or 0.65-1.05 mmol/L, respectively). The primary end point was cerebral arterial vasospasm diagnosed by blinded assessment of digital subtraction angiography. Secondary outcomes included severity of vasospasm and functional recovery at 90 days. Analysis was by intention to treat. RESULTS: Of 162 patients, 81 were assigned to the normal range group and 81 were assigned to the high-range group; the primary outcome was available for 78 and 79 patients, respectively. The groups had similar baseline characteristics. Vasospasm occurred in 40 patients (50.6%) and 50 patients (64.1%) assigned to high-range and normal-range groups, respectively (adjusted OR, 0.51; 95% CI, 0.26-1.02; P = 0.06). At 90 days, neurological recovery between the groups was not significantly different (adjusted OR for worse outcome, 0.71; 95% CI, 0.39-1.32; P = 0.28). Patients in the high-range group were treated with more noradrenaline to support arterial blood pressure (79 [16- 218] mg) v 59 [14-129] mg; P = 0.03) and had lower mean (SD) serum calcium concentration (1.9 [0.2] mmol/L v 2.1 [0.2] mmol/L, P < 0.001). CONCLUSION: Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups. A firm recommendation for induced hypermagnesaemia cannot be made from this study. TRIAL REGISTRATION NUMBER: ACTRN12605000058673.