Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage

Kieninger, Martin; Flessa, Julia; Lindenberg, Nicole; Bele, Sylvia; Redel, Andreas; Schneiker, André; Schuierer, Gerhard; Wendl, Christina; Graf, Bernhard M.; Silbereisen, Vera

doi:10.1007/s12028-017-0428-1

Cited by 43 publications

(41 citation statements)

References 33 publications

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“…Although generally well-tolerated, minor adverse events were condoned in favor of brain tissue salvation. Systemic adverse events in context of excessive demand, although rare, are serious complications and must be monitored closely when implementing ERT (13), sometimes necessitating rapid reduction of intraarterial nimodipine dose to curb noradrenaline demand. In a previous study, we found nimodipine serum concentrations during intraarterial application to be dose-independent (14), but the minimum effective dose is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Endovascular Rescue Treatment for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Is Safe and Effective

et al. 2019

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Background: The implementation of rescue efforts for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains largely empirical for a lack of supporting evidence, while the associated risk profile is also unclear. Objective: The present study evaluates the safety and efficacy of endovascular rescue treatment (ERT, continuous intraarterial nimodipine; IAN, transcutaneous balloon angioplasty, TBA). Methods: In this prospective observational study, we assessed periprocedural complications and side effects in context of ERT. We evaluated neurological status, multimodal neuromonitoring (p ti O 2 , lactate/pyruvate ratio, transcranial doppler), and cranial imaging (CTP, DSA). All parameters were included into multivariate analysis to determine predictors for the need of retreatment. Results: We included 33 consecutive patients with 54 ERT (IAN n = 35; TBA n = 13; TBA + IAN n = 6). We recorded no serious complications and initial improvement in all parameters (neurostatus 72.3% of patients; p ti O 2 15.0 ± 11.7 to 25.8 ± 15.5 mmHg, p < 0.0001; lactate/pyruvate ratio 46.3 ± 27.5 to 31.0 ± 9.7, p <0.05; transcranial doppler 139.0 ± 46.3 to 98.9 ± 29.6 cm/s, p < 0.05; CTP 81.6% of patients; DSA 93.1% of patients). Retreatment ( n = 16, 48.5%) was independently associated with preinterventional p ti O 2 < 5 mmHg ( p <0.01) and early (<72 h) discontinuation of IAN treatment ( p = 0.08). DCI related cerebral infarction was noted in n = 8 patients (24.2%). At 3 months after discharge, favorable outcome was noted for n = 11 (35.5%) patients. Conclusion: Provided a detailed decision tree, timely ERT can provide a relatively safe and effective treatment option in those highly-selected patients undergoing multimodality monitoring where conservative treatment options are exhausted. Continuous treatment in particular may be suitable to surpass sustained DCI and was associated with a low rate of DCI related infarction and comparably high percentage of good outcome.

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Section: Discussionmentioning

confidence: 99%

Endovascular Rescue Treatment for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Is Safe and Effective

et al. 2019

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“…Nimodipine has proven to be particularly relevant for the treatment of cerebrovascular disorders, because it achieves vasorelaxation by inhibiting calcium influx to vascular smooth muscle cells through L-type voltage gated calcium channels, and, in addition, it also exerts neuroprotection by preventing neuronal calcium overload (Scriabine, Schuurman, & Traber, 1989). Although nimodipine was proposed to increase cerebral blood flow (CBF) by its selective affinity to cerebral arteries without altering systemic blood pressure (Freedman & Waters, 1987), the approved dose can still initiate undesired side effects (Kieninger et al, 2017) including hypotension in some patients (Diringer & Zazulia, 2017;Porchet, Chioléro, & de Tribolet, 1995).…”

Section: Introductionmentioning

confidence: 99%

The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization

Szabó

Tóth

Török

et al. 2019

British J Pharmacology

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Background and Purpose: A new class of dihydropyridine derivatives, which act as co-inducers of heat shock protein but are devoid of calcium channel antagonist and vasodilator effects, has recently been developed with the purpose of selectively targeting neurodegeneration. Here, we evaluated the action of one of these novel compounds LA1011 on neurovascular coupling in the ischaemic rat cerebral cortex.As a reference, we applied nimodipine, a vasodilator dihydropyridine and wellknown calcium channel antagonist.Experimental Approach: Rats were treated with LA1011 or nimodipine, either by chronic, systemic (LA1011), or acute, local administration (LA1011 and nimodipine).In the latter treatment group, global forebrain ischaemia was induced in half of the animals by bilateral common carotid artery occlusion under isoflurane anaesthesia.Functional hyperaemia in the somatosensory cortex was created by mechanical stimulation of the contralateral whisker pad under α-chloralose anaesthesia. Spreading depolarization (SD) events were elicited subsequently by 1 M KCl. Local field potential and cerebral blood flow (CBF) in the parietal somatosensory cortex were monitored by electrophysiology and laser Doppler flowmetry.Key Results: LA1011 did not alter CBF, but intensified SD, presumably indicating the co-induction of heat shock proteins, and, perhaps an anti-inflammatory effect.Nimodipine attenuated evoked potentials and SD. In addition to the elevation of baseline CBF, nimodipine augmented hyperaemia in response to both somatosensory stimulation and SD, particularly under ischaemia. Conclusions and implications:In contrast to the CBF improvement achieved with nimodipine, LA1011 seems not to have discernible cerebrovascular effects but may up-regulate the stress response.Abbreviations: 2VO, permanent, bilateral occlusion of the common carotid arteries ("two-vessel occlusion"); CBF, cerebral blood flow; DC, direct current; EFP, evoked field potential; eNOS, endothelial NOS; Hsp, heat shock protein; LDF, laser Doppler flowmetry; LFP, local field potential; MABP, mean arterial BP; rSD, recurrent spreading depolarization; SD, spreading depolarization; SD1, the first spreading depolarization in a train of events

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“…Chemical angioplasty consisting of intraarterial administration of vasodilators is also an option that is generally used for diffuse vasospasm involving smaller arterial branches. Intraarterial nicardipine, papaverine, milrinone, nimodipine, and verapamil have been utilized in treatment of symptomatic vasospasm …”

Section: Resultsmentioning

confidence: 99%

“…Intraarterial nicardipine, papaverine, milrinone, nimodipine, and verapamil have been utilized in treatment of symptomatic vasospasm. [152][153][154][155][156] Intraarterial papaverine causes vasodilatation, likely related to alteration in cAMP. It can result in transient reversal of cerebral hypoperfusion with improvement in blood flow velocities and CBF.…”

Section: Intraarterial Treatment and Angioplastymentioning

confidence: 99%

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

et al. 2019

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Aneurysmal subarachnoid hemorrhage (aSAH) continues to be associated with significant morbidity and mortality despite advances in care and aneurysm treatment strategies. Cerebral vasospasm continues to be a major source of clinical worsening in patients. We intended to review the clinical and experimental aspects of aSAH and identify strategies that are being evaluated for the treatment of vasospasm. A literature review on aSAH and cerebral vasospasm was performed. Available treatments for aSAH continue to expand as research continues to identify new therapeutic targets. Oral nimodipine is the primary medication used in practice given its neuroprotective properties. Transluminal balloon angioplasty is widely utilized in patients with symptomatic vasospasm and ischemia. Prophylactic “triple‐H” therapy, clazosentan, and intraarterial papaverine have fallen out of practice. Trials have not shown strong evidence supporting magnesium or statins. Other calcium channel blockers, milrinone, tirilazad, fasudil, cilostazol, albumin, eicosapentaenoic acid, erythropoietin, corticosteroids, minocycline, deferoxamine, intrathecal thrombolytics, need to be further investigated. Many of the current experimental drugs may have significant roles in the treatment algorithm, and further clinical trials are needed. There is growing evidence supporting that early brain injury in aSAH may lead to significant morbidity and mortality, and this needs to be explored further.

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Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage

Cited by 43 publications

References 33 publications

Endovascular Rescue Treatment for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Is Safe and Effective

Endovascular Rescue Treatment for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Is Safe and Effective

The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

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