Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: a retrospective evaluation of a 12-year single-center experience.

Delayed cerebral infarction (DCI) is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). The benefits of magnesium sulfate as an alternative treatment are controversial, and most previous studies examined its benefits only as adjunctive treatment to traditional nimodipine. We retrospectively analyzed aSAH patients records with magnesium sulfate between 2010 and 2021. We aimed for a serum magnesium concentration of 2-2.5 mmol/l between post-hemorrhage days 3 and 12. The patients were separated in three groups based on average serum magnesium concentration (magnesium >2 mmol/l, reduced magnesium 1.1-1.9 mmol/l, and no magnesium). Additionally, we assessed delayed cerebral infarction (DCI) and clinical outcome at follow-up, using the modified Rankin Scale (mRS), categorized in favorable (0-3) and unfavorable outcome (4-5). In this analysis, 548 patients were included. Hereof, radiological evidence of DCI could be found in 23.0% (n = 126) of patients. DCI rates were lower if patients' average serum magnesium was higher than 2 mmol/l (magnesium 18.8%, n = 85; reduced magnesium 38.3%, n = 23; no magnesium 51.4%, n = 18; p < 0.001). Also, at the last follow-up, patients in the group with a higher serum magnesium concentration had better outcome (favorable outcome: magnesium 64.7%, n = 293; reduced magnesium 50.0%, n = 30; no magnesium 34.3%, n = 12; p < 0.001). This 12-year study reveals the value of serum concentration-guided magnesium administration in aSAH patients. Our findings demonstrate the safety and efficacy when titrated to a serum concentration of 2-2.5 mmol/l. We observed higher rates of delayed cerebral infarction and unfavorable outcomes in patients with serum concentrations below 2 mmol/l.

Effects of venovenous extracorporeal membrane oxygenation on cerebral oxygenation in hypercapnic ARDS.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in ARDS patients with hypoxemia and/or severe hypercapnia refractory to conventional treatment strategies. However, it is associated with severe intracranial complications, e.g. ischemic or hemorrhagic stroke. The arterial carbon dioxide partial pressure (PaCO2) is one of the main determinants influencing cerebral blood flow and oxygenation. Since CO2 removal is highly effective during ECMO, reduction of CO2 may lead to alterations in cerebral perfusion. We report on the variations of cerebral oxygenation during the initiation period of ECMO treatment in a patient with hypercapnic ARDS, which may partly explain the findings of ischemic and/or hemorrhagic complications in conjunction with ECMO.

Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats.

BACKGROUND: During many neurovascular procedures temporary occlusion of cerebral arteries is inevitable. Neuroprotective drugs may reduce the risk of cerebral infarction in this situation. Increasing evidence indicates neuroprotective properties of magnesium in cerebral ischemia. Previous experimental studies on the neuroprotective efficacy of magnesium-treatment in transient focal ischemia provide widely differing results using different magnesium doses and treatment-regimens. The present study was conducted to find the maximum protective dose of intravenous magnesium sulphate in a rat model of transient focal ischemia. METHODS: 45 male Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion (MCAO) by an intraluminal thread. Animals were randomly assigned to one of 4 treatment arms: (1) vehicle (2) MgSO(4) 1x0.75 mmol/kg (3) MgSO(4) 2x1 mmol/kg (4) MgSO(4) 1 mmol/kg+0.5 mmol/kg/h. Local cortical blood flow (LCBF) was continuously measured by laser-Doppler flowmetry. Functional deficits were quantified daily, infarct volumes were assessed histologically after 7 days. RESULTS: Magnesium serum levels below 3 mmol/l were well tolerated by the animals. Above 3 mmol/l cardiodepressive effects limited neuroprotection. Total infarct volumes in groups 3 and 4 were significantly reduced by 32% and 42%, respectively, compared to controls. Postoperative neurological recovery was significantly improved in magnesium-treated groups. CONCLUSION: Continuous magnesium-administration with stable serum concentrations between 2 and 3 mmol/l offered the best protection and was well tolerated. Serum concentrations above 3 mmol/l should not be exceeded. An elevation of magnesium serum levels could be useful for brain tissue protection during procedures which are prone to the risk of temporary vessel occlusion.

No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia.

OBJECT: Mild-to-moderate hypothermia is increasingly used for neuroprotection in humans. However, it is unknown whether administration of barbiturate medications in burst-suppressive doses-the gold standard of neuroprotection during neurovascular procedures-provides an additional protective effect under hypothermic conditions. The authors conducted the present study to answer this question. METHODS: Thirty-two Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion and randomly assigned to one of four treatment groups: 1) normothermic controls; 2) methohexital treatment (burst suppression); 3) induction of mild hypothermia (33 degrees C); and 4) induction of mild hypothermia plus methohexital treatment (burst suppression). Local cerebral blood flow was continuously monitored using bilateral laser Doppler flowmetry and electroencephalography. Functional deficits were quantified and recorded during daily neurological examinations. Infarct volumes were assessed histologically after 7 days. Methohexital treatment, mild hypothermia, and mild hypothermia plus methohexital treatment reduced infarct volumes by 32%, 71%, and 66%, respectively, compared with normothermic controls. Furthermore, mild hypothermia therapy provided the best functional outcome, which was not improved by additional barbiturate therapy. CONCLUSIONS: The results of this study indicate that barbiturate-induced burst suppression is not required to achieve maximum neuroprotection under mild hypothermic conditions. The magnitude of protection afforded by barbiturates alone appears to be modest compared with that provided by mild hypothermia.