Feasibility of intraventricular nicardipine prolonged release implants in patients following aneurysmal subarachnoid haemorrhage
ABSTRACT Intracisternal nicardipine prolonged release implants (NPRI) have been shown to be effective in the prophylaxis of cerebral vasospasm (VS). However, they cannot be used in patients following coil occlusion of the aneurysm. As a certain dissemination of nicardipine within the cerebrospinal fluid (CSF) has been described, we examined the feasibility of intraventricular use of NPRI in patients that underwent clip and coil occlusion of their aneurysms following aneurysmal subarachnoid haemorrhage (aSAH). By comparison with an historical control group, an estimation of their effectivity in regard to angiographic vasospasm and the development of cerebral infarction has been performed.
Thirty-one patients suffering from aSAH were prospectively included in this trial. Study participants received prior to clipping (n = 17) or coiling (n = 14) 6 (n = 15) or 10 NPRI (n = 16) into the lateral ventricles. Physiological data were collected, proximal and global VS were determined using pre-operative and day 8 ± 1 angiography, and incidence of hydrocephalus and VS related infarcts were evaluated and compared to a historical control group consisting of 16 operated patients without NPRI implantation.
Intraventricular NPRI were tolerated well. There were no adverse side effects detectable, physiological variables such as heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP) and electrolytes showed no difference compared to control. There was no difference in the proportion of patients that required CSF shunting. A significant positive angiographic effect could only be observed in clipped patients (proximal vessel diameters: control, 80 ± 30%; NPRI 90 ± 24%; incidence of moderate/severe global VS: control, 73%; NPRI, 41%).
The use of intraventricular NPRI seems to be safe and tolerated well. There is preliminary evidence for effectivity on angiographic VS for clipped patients only. A further increase of the effective dose might also exert efficacy in the subset of patients following coil occlusion.
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ABSTRACT: Nicardipine prolonged release implants (NPRI) have been shown to decrease the incidence of cerebral vasospasm and infarcts significantly in patients after aneurysmal subarachnoid haemorrhage (SAH) following microsurgical clipping. Yet, the comparison with results after endovascular coiling is lacking. This study was conducted to determine the differences in the incidence of cerebral vasospasm and infarctions between those two treatment modalities The design of this investigation reflects a case-control study; 27 patients suffering from acute SAH were treated by microsurgical clipping and received an intracisternal implantation of NPRI. Twenty-seven matching consecutive patients after microsurgical treatment without implantation of NPRI or endovascular treatment, respectively, served as controls. The incidence of angiographic vasospasm and cerebral infarctions were documented. All groups were comparable concerning demographics and severity of SAH. Twenty-four of 81 patients developed angiographic vasospasm (>33% constriction). The incidence of vasospasm was 48%, 44% and 11% for patients after endovascular treatment, microsurgical clipping without NPRI and microsurgical clipping with NPRI, respectively. New cerebral infarctions occurred in 28%, 22% and 7% of the treated patients, respectively. A good clinical recovery 1 year after the initial bleeding (modified Rankin scale 0-2) was seen in 48%, 50% and 77% of the treated patients, respectively. The use of NPRI during microsurgical clipping was confirmed to be safe and effective. Patients who received intracisternally implanted NPRI during clipping after aneurysmal SAH yielded significantly lower vasospasm and infarction rates, and showed a better clinical outcome when compared with clipping without NPRI and also when compared with endovascular coiling.Acta Neurochirurgica 08/2011; 153(11):2119-25. DOI:10.1007/s00701-011-1129-8 · 1.79 Impact Factor
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ABSTRACT: Cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage remains a considerable challenge in neurocritical care medicine. This review aims to cover the recent novel aspects and results in CVS treatment. On the basis of the recent literature, treatment focusing on CVS alone is outdated. A considerable amount of evidence suggests CVS not to be the sole cause of delayed cerebral ischemia (DCI) and poor outcome. Early brain injury, cortical spreading depolarization, inflammation and microthrombosis have recently been discussed as additional factors. The results of a well designed phase III trial, using an endothelin-1 antagonist, indicated a decrease in the occurrence of CVS but did not change the clinical outcome significantly. Induced hypertension is currently recommended for treating suspected DCI, whereas hemodilution and hypervolemia are not. Endovascular intervention is only recommended in case of refractory symptomatic CVS. A couple of newer treatment strategies are under evaluation. Phase III trials are underway for magnesium sulfate and statins. Clinical trials aiming specifically at recently discussed factors other than CVS have not been reported. Reviewing the recent literature, there have been some updates on recommendations and newer treatment modalities are under evaluation. However, a novel treatment with convincing evidence has not been reported so far.Current opinion in critical care 04/2012; 18(2):119-26. DOI:10.1097/MCC.0b013e32835075ae · 3.18 Impact Factor
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ABSTRACT: Nimodipine improved outcome in patients with subarachnoid hemorrhage (SAH) although hypotension limited the dose that could be administered systemically. Subarachnoid delivery of nicardipine or nimodipine may be more efficacious. We tested the efficacy of cisternal application of sustained release nicardipine and nimodipine in SAH in monkeys and dogs, respectively. SAH was created in 13 cynomolgus macaques by placement of autologous blood clot around right middle cerebral, anterior cerebral, and internal carotid arteries. Placebo poly-D,L-lactide coglycolide (PLGA), nicardipine PLGA or mibefradil PLGA was inserted in the clots. Catheter and computed tomography angiography (CTA) were performed at baseline and 7 days later (day 7). Cerebral infarction was assessed on day 7 by magnetic resonance imaging. Six dogs underwent baseline angiography and injection of autologous blood plus PLGA or nimodipine-loaded PLGA microparticles into the cisterna magna. Blood injection was repeated 2 days later and angiography 7 and 14 days later. Animals were euthanized and brains were examined histologically. Cerebrospinal fluid and serum nimodipine concentrations were measured. Nicardipine, but not mibefradil PLGA decreased vasospasm in monkeys (paired t-tests) although there was no significant effect on infarctions see on MRI. In dogs, nimodipine-PLGA produced high local concentrations of nimodipine that were associated with reduced basilar artery vasospasm. No untoward histological effects were observed. There was no reduction in microthrombi in animals treated with nimodipine PLGA compared to placebo PLGA. Site-specific, sustained release formulations of dihydropyridines can deliver high concentrations to the cerebrospinal fluid without causing systemic side effects, and may reduce angiographic vasospasm after SAH. Since nimodipine improves outcome in patients with SAH without necessarily preventing vasospasm, further studies are warranted.Current neurovascular research 04/2012; 9(2):139-48. DOI:10.2174/156720212800410894 · 2.74 Impact Factor