Controlled Study of Nimodipine in Aneurysm Patients Treated Early after Subarachnoid Hemorrhage

Mee, Edward; Dorrance, D. E.; Lowe, Derek; Neil‐Dwyer, G.

doi:10.1227/00006123-198803000-00006

Cited by 102 publications

(10 citation statements)

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“…Though nimodipine improves ischemic neurological deficits by clinical criteria and CT-documented infarction (with a pooled relative risks of 0.66 (95% CI 0.59–0.75) and 0.78 (95% CI 0.70–0.87), resp.) [111], it has little effect on angiographic vasospasm or cerebral blood flow [4, 5]. The corollary to this observation is that interventions that improve angiographic vasospasm, such as clazosentan, do not necessarily improve cerebral infarction or outcome.…”

Section: Discussionmentioning

confidence: 99%

Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Frontera

2013

Stroke Research and Treatment

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Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH). Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included. Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically. Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.

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Section: Discussionmentioning

confidence: 99%

Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Frontera

2013

Stroke Research and Treatment

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“…Nimodipine is safe, cost-effective, and reduces the risk of poor outcome and secondary ischemia (Neil-Dwyer et al, 1987;Welty, 1987;Kostron et al, 1988;Mee et al, 1988), but has very modest effects. It is used prophylactically in all patients with SAH.…”

Section: Cerebral Vasospasm After Sahmentioning

confidence: 99%

Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid hemorrhage

Kokkoris¹,

Andrews²,

Webb³

2012

Front. Endocrin.

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Calcitonin gene-related peptide (CGRP) is one of the most potent microvascular vasodilators identified to date. Vascular relaxation and vasodilation is mediated via activation of the CGRP receptor. This atypical receptor is made up of a G protein-coupled receptor called calcitonin receptor-like receptor (CLR), a single transmembrane protein called receptor activity-modifying protein (RAMP), and an additional protein that is required for Gas coupling, known as receptor component protein (RCP). Several mechanisms involved in CGRP-mediated relaxation have been identified. These include nitric oxide (NO)-dependent endothelium-dependent mechanisms or cAMP-mediated endothelium-independent pathways; the latter being more common. Subarachnoid hemorrhage (SAH) is associated with cerebral vasoconstriction that occurs several days after the hemorrhage and is often fatal. The vasospasm occurs in 30–40% of patients and is the major cause of death from this condition. The vasoconstriction is associated with a decrease in CGRP levels in nerves and an increase in CGRP levels in draining blood, suggesting that CGRP is released from nerves to oppose the vasoconstriction. This evidence has led to the concept that exogenous CGRP may be beneficial in a condition that has proven hard to treat. The present article reviews: (a) the pathophysiology of delayed ischemic neurologic deficit after SAH (b) the basics of the CGRP receptor structure, signal transduction, and vasodilatation mechanisms and (c) the studies that have been conducted so far using CGRP in both animals and humans with SAH.

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“…53,54 The combined results of the studies demonstrate that calcium channel antagonists reduce the risk of poor outcome (death or dependence), with those benefi cial results being driven mostly by nimodipine. 51,[55][56][57][58][59][60][61][62][63] The largest randomized multicenter doubleblind placebo controlled study of nimodipine evaluated 554 patients with SAH. Within 96 hours of ictus, patients received nimodipine 60 mg orally every 4 hours for 21 days or placebo.…”

Section: Calcium Channel Blockersmentioning

confidence: 99%

Cerebral Vasospasm in Critically III Patients with Aneurysmal Subarachnoid Hemorrhage: Does the Evidence Support the Ever-Growing List of Potential Pharmacotherapy Interventions?

Kiser

2014

Hosp Pharm

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The occurrence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a significant event resulting in decreased cerebral blood flow and oxygen delivery. Prevention and treatment of cerebral vasospasm is vital to avert neurological damage and reduced functional outcomes. A variety of pharmacotherapy interventions for the prevention and treatment of cerebral vasospasm have been evaluated. Unfortunately, very few large randomized trials exist to date, making it difficult to make clear recommendations regarding the efficacy and safety of most pharmacologic interventions. Considerable debate exists regarding the efficacy and safety of hypervolemia, hemodilution, and hypertension (triple-H therapy), and the implementation of each component varies substantially amongst institutions. There is a new focus on euvolemic-induced hypertension as a potentially preferred mechanism of hemodynamic augmentation. Nimodipine is the one pharmacologic intervention that has demonstrated favorable effects on patient outcomes and should be routinely administered unless contraindications are present. Intravenous nicardipine may offer an alternative to oral nimodipine. The addition of high-dose magnesium or statin therapy has shown promise, but results of ongoing large prospective studies are needed before they can be routinely recommended. Tirilazad and clazosentan offer new pharmacologic mechanisms, but clinical outcome results from prospective randomized studies have largely been unfavorable. Locally administered pharmacotherapy provides a targeted approach to the treatment of cerebral vasospasm. However, the paucity of data makes it challenging to determine the most appropriate therapy and implementation strategy. Further studies are needed for most pharmacologic therapies to determine whether meaningful efficacy exists.

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Controlled Study of Nimodipine in Aneurysm Patients Treated Early after Subarachnoid Hemorrhage

Cited by 102 publications

References 0 publications

Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid hemorrhage

Cerebral Vasospasm in Critically III Patients with Aneurysmal Subarachnoid Hemorrhage: Does the Evidence Support the Ever-Growing List of Potential Pharmacotherapy Interventions?

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