Search

Statins were shown to have neuroprotective effects, with reduced vasospasm and delayed ischemic deficits in statin-treated patients after aneurysmal subarachnoid hemorrhage in two small, randomized, controlled clinical trials published in 2005. This review consolidated data from available published studies evaluating statin treatment for subarachnoid hemorrhage. A literature search was conducted to identify original research studies published through October 2010 testing immediate treatment with a statin in statin-naïve patients following aneurysmal SAH. Six randomized controlled clinical trials and four observational studies were identified. Despite inconsistent results among studies, a meta-analysis of randomized controlled data showed a significant reduction in delayed ischemic deficits with statins. Effect on vasospasm was more difficult to determine, due to differences in definitions used among studies. Interpretations from observational studies were limited by the use of relatively small sample sizes, historical controls, and treatment variability.

Object: Delayed ischemic deficits (DIDs), a major source of disability following aneurysmal subarachnoid hemorrhage (aSAH), are usually associated with severe cerebral vasospasm and impaired autoregulation. Systemic erythropoietin (EPO) therapy has been demonstrated to have neuroprotective properties acting via EPO receptors on cerebrovascular endothelia and ischemic neurons. In this trial, the authors explored the potential neuroprotective effects of acute EPO therapy following aSAH., Methods: Within 72 hours of aSAH, 80 patients (age range 24-82 years) were randomized to receive intravenous EPO (30,000 U) or placebo every 48 hours for a total of 90,000 U. Primary end points were the incidence, duration, and severity of vasospasm and impaired autoregulation on transcranial Doppler ultrasonography. Secondary end points were incidence of DIDs and outcome at discharge and at 6 months., Results: Randomization characteristics were balanced except for age, with the EPO group being older (mean age 59.6 vs 53.3 years, p=0.034). No differences were demonstrated in the incidence of vasospasm and adverse events; however, patients receiving EPO had a decreased incidence of severe vasospasm from 27.5 to 7.5% (p=0.037), reduced DIDs with new cerebral infarcts from 40.0 to 7.5% (p=0.001), a shortened duration of impaired autoregulation (ipsilateral side, p<0.001), and more favorable outcome at discharge (favorable Glasgow Outcome Scale score, p=0.039). Among the 71 survivors, the EPO group had fewer deficits measured with National Institutes of Health Stroke Scale (median Score 2 vs 6, p=0.008)., Conclusions: This preliminary study showed that EPO seemed to reduce delayed cerebral ischemia following aSAH via decreasing severity of vasospasm and shortening impaired autoregulation.

Blood transfusions and intravenous fluids are commonly employed as rescue therapy for delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage (aSAH). We sought to determine effects of various fluid supplements on clinical outcome in patients following aSAH. Clinical events and laboratory data of 160 aSAH patients were prospectively collected as part of 2 randomised controlled trials. Outcomes at discharge and at 6 months were measured with Glasgow Outcome Scale (GOS). Favourable outcome was defined as good recovery or moderate disability on GOS. All of the 160 patients received intravenous fluid supplements with crystalloids; 122 (76.3%) also received synthetic colloids (4% succinylated gelatine or 6% pentastarch). A higher daily dose of synthetic colloids for initial resuscitation seemed to be associated with more requirements for blood transfusions (p = 0.003) and occurrence of vasospasm in poor-grade patients (p = 0.081), but blood transfusions themselves were not associated with occurrence of vasospasm. Compared with patients not receiving synthetic colloids, those receiving synthetic colloids had increased haemodilution, elevated inflammatory profiles, and decreased duration and strength of intact cerebral autoregulation. Multivariate analyses identified that blood transfusions (odds ratio, OR 3.38, p = 0.035) were associated with unfavourable outcome at discharge. Colloid fluids (OR 2.53/L/day, p = 0.025) promoted unfavourable outcome at 6 months (OR 4.45, p = 0.035), while crystalloids decreased unfavourable outcome (OR 0.27/L/day, p = 0.005). Associations between synthetic colloids and crystalloids with GOS at 6 months were dose-related. Intravenous fluid therapy using synthetic colloids or blood transfusions may be associated with increased unfavourable outcome following aSAH.

Following aneurysmal subarachnoid haemorrhage (SAH), cerebral blood flow (CBF) may be reduced, resulting in poor outcome due to cerebral ischaemia and subsequent stroke. Hypertonic saline (HS) is known to be effective in reducing intracranial pressure (ICP). We have previously shown a 20-50% increase in CBF in ischaemic regions after intravenous infusion of HS. This study aims to determine the effect of HS on CBF augmentation, substrate delivery and metabolism. Continuous monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion pressure (CPP), brain tissue oxygen (PbO2), middle cerebral artery flow velocity (FV), and microdialysis was performed in 14 poor grade SAH patients. Patients were given an infusion of 23.5% HS, and quantified xenon computerised tomography scanning (XeCT) was carried out before and after the infusion in 9 patients. The results showed a significant increase in ABP, CPP, FV and PbO2, and a significant decrease in ICP (p < 0.05). Nine patients showed a decrease in lactate-pyruvate ratio at 60 minutes following HS infusion. These results show that HS safely and effectively augments CBF in patients with poor grade SAH and significantly improves cerebral oxygenation. An improvement in cerebral metabolic status in terms of lactate-pyruvate ratio is also associated with HS infusion.