A Case of Hyperacute Onset of Vasospasm After Aneurysmal Subarachnoid Hemorrhage and Refractory Vasospasm Treated with Intravenous and Intraventricular Nitric Oxide: A Mini Review

Ehlert, Angelika; Manthei, Gerd; Heßelmann, Volker; Mathias, K.; Bein, Berthold; Pluta, Ryszard

doi:10.1016/j.wneu.2016.04.047

Cited by 8 publications

(7 citation statements)

References 46 publications

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“…Because Molsidomine does not seem to have a clear influence on the spasms of the large vessels but instead appears to exert its effects on the microcirculation, a synergism may have developed from the combination of Molsidomine and SNP, which exerts its effect both on the macro-and in the microcirculation. This notion is supported by earlier reports, both experimental [14,35] and clinical [17,18], of the pathophysiological importance and clinical usefulness of NO-based therapy after aSAH.…”

Section: Discussionsupporting

confidence: 77%

“…The patient rapidly developed severe vasospasm-associated brain infarctions after Molsidomine was stopped. Notably, despite the reinitiation of low-dose Molsidomine therapy, this patient did not respond with an expected MAP elevation to any SNP bolus (given every 4 h, n = 36) until the Molsidomine dose was > 6 mg/h, suggesting that a "saturation" dose of Molsidomine was necessary to exert a vasodilatory effect of SNP [18]. Afterward, no further infarctions occurred, and interestingly, each SNP bolus was accompanied by hypertension requiring an adequate response.…”

Section: Adverse Effectsmentioning

confidence: 86%

“…If despite the general treatment, including the induction of hypertension, a TCD-confirmed severe macrospasm occurred, a bedside SNP bolus was applied via an external ventricular drain (EVD). Each bolus contained 2-10 mg of SNP (mean 5.6 mg, SD 2.5 mg) [18]. The volume of the SNP bolus was adjusted for the dead space of the catheter (3 ml).…”

Section: Methodsmentioning

confidence: 99%

“…Previously, an intravenous infusion of NO-donor Molsidomine [17,18] (see "Appendix") demonstrated a significant improvement in outcomes with lower rates of DCI [17] in all-grade aSAH patients but had no impact on macrovasospasm; its effect is thought to be on microcirculation. Additionally, in an awake female patient and guided by her clinical status, multiple clinical DCIs and radiologically confirmed vasospasms were rapidly reversed by combining intravenous Molsidomine with intraventricular sodium nitroprusside (SNP) boluses, which achieved excellent outcomes [18].…”

Section: Introductionmentioning

confidence: 99%

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Nitric Oxide-Based Treatment of Poor-Grade Patients After Severe Aneurysmal Subarachnoid Hemorrhage

et al. 2019

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Background: Patients with aneurysmal subarachnoid hemorrhage (aSAH) require close treatment in neuro intensive care units (NICUs). The treatments available to counteract secondary deterioration and delayed ischemic events remain restricted; moreover, available neuro-monitoring of comatose patients is undependable. In comatose patients, clinical signs are hidden, and timing interventions to prevent the evolution of a perfusion disorder in response to fixed ischemic brain damage remain a challenge for NICU teams. Consequently, comatose patients often suffer secondary brain infarctions. The outcomes for long-term intubated patients w/wo pupil dilatation are the worst, with only 10% surviving. We previously added two nitroxide (NO) donors to the standard treatment: continuous intravenous administration of Molsidomine in patients with mild-to-moderate aSAH and, if required as a supplement, intraventricular boluses of sodium nitroprusside (SNP) in high-risk patients to overcome the so-called NO-sink effect, which leads to vasospasm and perfusion disorders. NO boluses were guided by clinical status and promptly reversed recurrent episodes of delayed ischemic neurological deficit. In this study, we tried to translate this concept, the initiation of intraventricular NO application on top of continuous Molsidomine infusion, from awake to comatose patients who lack neurological-clinical monitoring but are primarily monitored using frequently applied transcranial Doppler (TCD). Methods: In this observational, retrospective, nonrandomized feasibility study, 18 consecutive aSAH comatose/intubated patients (Hunt and Hess IV/V with/without pupil dilatation) whose poor clinical status precluded clinical monitoring received standard neuro-intensive care, frequent TCD monitoring, continuous intravenous Molsidomine plus intraventricular SNP boluses after TCD-confirmed macrospasm during the daytime and on a fixed nighttime schedule. Results: Very likely associated with the application of SNP, which is a matter of further investigation, vasospasmrelated TCD findings promptly and reliably reversed or substantially weakened (p < 0.0001) afterward. Delayed cerebral ischemia (DCI) occurred only during loose, low-dose or interrupted treatment (17% vs. an estimated 65% with secondary infarctions) in 17 responders. However, despite their worse initial condition, 29.4% of the responders survived (expected 10%) and four achieved Glasgow Outcome Scale Extended (GOSE) 8-6, modified Rankin Scale (mRS) 0-1 or National Institutes of Health Stroke Scale (NIHSS) 0-2.

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Section: Discussionsupporting

confidence: 77%

Section: Adverse Effectsmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nitric Oxide-Based Treatment of Poor-Grade Patients After Severe Aneurysmal Subarachnoid Hemorrhage

et al. 2019

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“…Case reports support the future use of peripheral intravenous infusion of the NO donor molsidomine, and intrathecal application of nitroprusside sodium in patients with IVH because they appear to reduce cerebral vasospasm ( 46 ).…”

Section: Implications Of a Confirmation Of The Hypothesismentioning

confidence: 98%

In Premature Newborns Intraventricular Hemorrhage Causes Cerebral Vasospasm and Associated Neurodisability via Heme-Induced Inflammasome-Mediated Interleukin-1 Production and Nitric Oxide Depletion

Eisenhut

Choudhury

2017

Front. Neurol.

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BackgroundIntraventricular hemorrhage (IVH) occurs in 60–70% of neonates weighing 500–750 g and 10–20% of those weighing 1,000–1,500 g. All forms of IVH have been associated with neurocognitive deficits. Both subarachnoid and IVHs have been associated with delayed vasospasm leading to neurological deficits. Pathways linking hemoglobin release from blood clots to vasospasm include heme-induced activation of inflammasomes releasing interleukin-1 (IL-1) that can cause calcium dependent and independent vasospasm. Free hemoglobin is a potent scavenger of nitric oxide (NO). Depletion of NO, a potent endogenous vasodilator, has been associated with features of vasospasm.HypothesisIn premature newborns, IVH causes cerebral vasospasm and associated neurodisability via heme-induced increased inflammasome-mediated IL-1 production and NO depletion.Confirmation of hypothesis and implicationsThis hypothesis could be confirmed in the IVH animal model with visualization of any associated vasospasm by angiography and in newborns with IVH by transcranial Doppler ultrasonography and correlation with cerebrospinal fluid IL-1 and NO metabolite levels. Confirmation of the role of heme in activation of inflammasomes causing IL-1 production and NO binding could be achieved by measuring the effect of heme scavenging interventions on IL-1 levels and levels of NO metabolites. In addition to removal of the accumulated blood of an IVH by drainage, irrigation, and fibrinolytic therapy intrathecal application of vasodilators and heme scavenging agents like haptoglobin and haemopexin and systemic treatment with inhibitors of inflammasomes like telmisartan could be used to prevent and treat cerebral vasospasm, and thus reduce the risk of associated brain injury in premature neonates.

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Cardiovascular Pharmacology in Adult Patients Undergoing Cardiac Surgery

Dabbagh

Tajbakhsh

Talebi

et al. 2018

Postoperative Critical Care for Adult Cardiac Surgical Patients

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A Case of Hyperacute Onset of Vasospasm After Aneurysmal Subarachnoid Hemorrhage and Refractory Vasospasm Treated with Intravenous and Intraventricular Nitric Oxide: A Mini Review

Cited by 8 publications

References 46 publications

Nitric Oxide-Based Treatment of Poor-Grade Patients After Severe Aneurysmal Subarachnoid Hemorrhage

Nitric Oxide-Based Treatment of Poor-Grade Patients After Severe Aneurysmal Subarachnoid Hemorrhage

In Premature Newborns Intraventricular Hemorrhage Causes Cerebral Vasospasm and Associated Neurodisability via Heme-Induced Inflammasome-Mediated Interleukin-1 Production and Nitric Oxide Depletion

Cardiovascular Pharmacology in Adult Patients Undergoing Cardiac Surgery

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