Magnesium sulfate in combination with nimodipine for the treatment of subarachnoid hemorrhage: a randomized controlled clinical study

Abstract

Objective

Cerebral vasospasm(CVS) after Subarachnoid hemorrhage (SAH) can cause delayed cerebral ischemia,secondary cerebral infarction, and rehemorrhage, which are the leading causes of mutilation and death. Nimodipine has been shown to prevent CVS. Magnesium ion (Mg²⁺) can competitively inhibit the influx of calcium (Ca²⁺) and prevent vasospasm. There is evidence that magnesium sulfate can prevent CVS and reduce infarct volume after SAH. In this study, we evaluated the efficacy and safety of intravenous magnesium sulfate combined with oral nimodipine on CVS, delayed cerebral ischemia, secondary cerebral infarction, and rehemorrhage after SAH.

Methods

This is a prospective randomized, double-blind trial of 120 patients with SAH who were recruited between January 2003 and January 2009. These patients were assigned to two groups and received the same basic treatment and symptomatic treatment. In group A, patients received 14 days of intravenous administration of 1400 mL 0.9% normal saline + 40 mL 25% magnesium sulfate, 1 mL/min, once per day, followed 7 days of intravenous administration of 500 mL 0.9% normal saline + 15 mL 25% magnesium sulfate, 1 mL/min, once per day and oral nimodipine, 20 mg once, four times a day, for 21 days. Patients in group B received identical treatment to that in group A, except that 25% magnesium sulfate was replaced by placebo. On day 22 of treatment, incidences of intracranial CVS, delayed cerebral ischemia, secondary cerebral infarction, rehemorrhage, neurologic deficits, and death were assessed and adverse events were monitored.

Results

CVS occurred in 4, 12 patients, lasting for 11.09 ± 5.38, 13.73 ± 6.24 hours, mean velocity (Vm) of 143.2 ± 12.7, 149.6 ± 18.9 cm/s in group A, B; Delayed cerebral ischemia occurred in 3, 10 patients, lasting for 13.16 ± 4.82, 15.57 ± 5.35 hours in group A, B; Secondary cerebral infarction occurred in 2 and 8 patients in groups A and B; Neurologic deficits occurred in3 and 11 patients in groups A and B, All P < 0.05; Rehemorrhage occurred in 4 and 5 patients; Death occurred in 5 and 8 patients in groups A and B, respectively, P >0.05. No obvious adverse events were found in both groups.

Conclusion

Intravenous magnesium sulfate in combination with oral nimodipine for the treatment of SAH can help reduce the incidences of CVS, delayed cerebral ischemia, secondary cerebral infarction, and neurologic deficits with good safety, but it does not reduce the incidences of rehemorrhage and death.

Keywords:

• Magnesium sulfate
• nimodipine
• subarachnoid hemorrhage
• cerebral vasospasm
• cerebral infarction
• rehemorrhage