Introduction. Papaverine (P) and nimodipine (N) are the most widely used vasodilators when angiographic and symptomatic vasospasm is present after subarachnoid aneurysmatic hemorrhage (SAH). Their effect is only short-lived and no direct comparisons have been undertaken to evaluate the action of both substances directly. We retrospectively assessed the effect of either P or N on angiographic diameter reduction and capillary blood flow. Methods. Fifteen SAH patients with secured aneurysms and cerebral vasospasm received intraarterial P, fifteen similar patients received N. As the primary endpoint, pre- and post-infusion arterial diameters and capillary blood flow were rated retrospectively on angiographies and compared by RM-ANOVA. Secondary endpoints were the difference in the modified Rankin Scale between the two groups on admission and at discharge, the occurrence of delayed cerebral ischemia, the separate effects on angiographic diameter and capillary blood flow and the overall response rate to the vasodilator infusion. Results. Angiographic resolution of diameter reduction and angiographically assessed capillary blood flow together differed not significantly between both groups. P infusion dilated all angiographic demonstrable vessels while N infusion was ineffective in 16% of the patients. Capillary flow on pre- and post-infusion angiographies was not different between the two groups. Conclusion. P and N seem to differ in the effect on cerebral diameter reduction in patients with vasospasm after SAH. The clinical implications remain to be established. A multimodal approach, perhaps combining different agents for intraarterial infusion in such patients, needs to be evaluated.

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient’s outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume > 30 cc) patients and 29 control patients were included. From day one until seven, blood and CSF samples were obtained, and ICH volume was calculated. OS markers, like malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-sulfhydryl (GSH), and the total antioxidant status (TAS) were measured. Clinical data on treatment and outcome were determined. Patients with mRS ≤ 4 showed significantly elevated SOD and GSH-Px levels in plasma compared to patients with poor CO (p = 0.004; p = 0.002). Initial increased TAS in plasma and increased MDA in CSF were linked to an unfavorable outcome after six months (p = 0.06, r = 0.45; p = 0.05, r = 0.44). A higher ICH volume was associated with a worse outcome at week six (p = 0.04, r = 0.47). OS plays a significant role in SBI. Larger ICHs, elevated MDA in CSF, and TAS in plasma were associated with a detrimental outcome, whereas higher plasma-SOD and -GSH-Px were associated with a favorable outcome.

To analyse the effect of the implementation of statin and magnesium treatment on delayed cerebral ischemia (DCI) and 14 day mortality in patients with subarachnoid hemorrhage (SAH). Retrospective, single-center, observational case control study. One hundred SAH patients received either simvastatin and magnesium, solely statin or no treatment. Eighteen percent (n=5) of patients receiving statin and magnesium treatment developed a DCI whereas 24% (n=5) in the statin group and 16% (n=8) in the control group had DCI. Dead by day 14 was registered in 18% (n=5) of patients in the statin and magnesium group, in 10% (n=2) in the statin group and in 27% (n=14) in the control group. None of the results reached a statistical significance level of 0.05. A trend towards a lower mortality within 14 days in patients receiving solely simvastatin and those receiving statin and magnesium as compared with the control group was found. A higher incidence for DCI was found in the statin group, whereas patients without statin and magnesium tended to have less often DCI. None of the results was statistically significant.

Introduction: Balloon angioplasty and/or selective intra-arterial vasodilator therapies are treatment options in patients with vasospasm after subarachnoid hemorrhage (SAH). We analyzed the effect of balloon angioplasty and/or selective intra-arterial vasodilator therapy in our patients. Methods: Twenty-six patients (vasodilation group, VDT) were treated with intra-arterial nimodipine. The balloon angioplasty with nimodiopine-group (BAP-N group) comprised 21 patients. The primary endpoint of this study was successful angiographic vessel dilation in vasospastic vessels after balloon angioplasty, together with nimodipine (BAP-N group), compared to intra-arterial vasodilator therapy (VDT group) with nimodipine alone. Results: A significant effect of angioplasty plus nimodipine was found in the central arteries (composite endpoint) with an OR of 2.4 (95% CI: 1.4–4.2], p = 0.002), indicating a chance of improvement of the BAP-N group of more than twice compared to nimodipine infusions alone. Significant advantages for BAP-N-therapy were also encountered in the internal carotid artery (OR 5.4, p < 0.001) and basilar artery (OR 29.7, p = 0.003). A joint analysis of all arteries combined failed to show significant benefit of BAP-N therapy (OR 1.5, p = 0.079), which was also true for cerebral peripheral arteries (OR 0.77, p = 0.367). There was no difference in clinical outcome between both groups. Conclusions: In SAH patients with vasospasm, a combination therapy of balloon angioplasty and intra-arterial nimodipine resulted in a more than doubled vasodilative effect in the central cerebral arteries compared to the sole infusion of nimodipine. Regarding the ICA and BA arteries, this beneficial effect was even more pronounced. Although there was a tendency of better effects of the BAP-N group, regarding the overall effect in all territories combined, this failed to reach statistical evidence. In cerebral peripheral arteries, no differences were observed, and there was no difference in clinical outcome, too.

Standard dosing of meropenem (2 g t.i.d.) produces CSF concentrations of only 1–2 mg/L which is inferior to the clinical breakpoint for most Gram-negative bacteria. There is therefore concern that dosing must be increased in order to achieve therapeutic CSF concentrations for bacteria with susceptibility close to clinical breakpoints. Yet, the effects of high-dose meropenem on CSF concentrations are not well described in literature. We therefore determined meropenem CSF-levels in a patient who was treated with 15 g/day of meropenem. Our patient suffered from a brain trauma and an external ventricular drainage was implanted. Later, a carbapenemase-producing Acinetobacter baumannii (OXA-23, NDM-1) was isolated from blood cultures and CSF. The MIC for meropenem was > 32 mg/L (R), and we opted for a combination therapy of meropenem, colistin and fosfomycin. Meropenem was given at an unusual high-dose (15 g/day) with the aim of achieving high CSF concentrations. CSF concentrations peaked at 64 mg/L. Yet, the patient succumbed to an intracranial bleed into a preexisting cerebral contusion. High-dose meropenem can achieve CSF levels largely superior to those achieved with commonly recommended dosing regimens. Though our patient succumbed to an intracranial bleed which could be regarded as a severe adverse event, we suggest that meropenem dosing can be increased when pathogens with increased MICs are found in the CSF. More in vivo data are however needed to determine the safety of high-dose meropenem.