Continuous intra-arterial nimodipine infusion in refractory symptomatic vasospasm after subarachnoid hemorrhage

Despite advances in medical and endovascular therapy cerebral vasospasm still contributes substantially to the high morbidity and in patients with aneurysmal subarachnoid hemorrhage (SAH) (Diringer et al. 2011). Reduction in cerebral blood flow (CBF) and brain tissue oxygen tension (PbtO2) may result in ischemic brain damage which is commonly referred to as delayed cerebral ischemia (Dorsch 2011). Currently, established treatment strategies for cerebral vasospasm comprise prophylactic oral nimodipine treatment and induced hypertension (Kassell et al. 1982; Muench et al. 2007; Raabe et al. 2005).

Advances in endovascular therapy have offered new perspectives in the treatment of symptomatic vasospasm including transluminal balloon angioplasty (Dion et al. 1990) and pharmacological dilatation with spasmolytic drugs (Weant et al. 2010). Although efficacious, angioplasty is limited to large vessels; the effect of intra-arterial drugs is temporary and restricted to the infusion period. Continuous intra-arterial nimodipine (IAN) treatment may overcome these limitations and has been reported to be safe in symptomatic cerebral vasospasm after SAH (Wolf et al. 2010; Musahl et al. 2011; Ott et al. 2014; Doukas et al. 2011).

Here, a case with refractory symptomatic vasospasm developing delayed cerebral ischemia (DCI) successfully treated with continuous IAN and her corresponding clinical and imaging findings are presented.

Here we describe a favorable clinical course of a non-traumatic SAH-patient with refractory vasospasm successfully treated with selective continuous intra-arterial nimodipine.

Cerebral vasospasm still contributes to high mortality and morbidity after SAH (Dorsch 2011). Currently recommended treatments for vasospasm are limited to prophylactic oral or intravenous nimodipine (Dorhout Mees et al. 2007), permissive hypertension (Kassell et al. 1982), and balloon angioplasty (Diringer et al. 2011; Dion et al. 1990). We did not perform balloon angioplasty in our patient as this is not a routinely available procedure at our institution. Other pharmacological attempts to decrease large vessel vasospasm are potentially efficacious, however did not translate into improved outcome (Macdonald et al. 2011). Intra-arterial application of spasmolytic drugs resulted in transient restoration of cerebral circulation, however is limited to the infusion period (Weant et al. 2010). Endovascular continuous intra-arterial treatment may be interesting and has been shown to be safe and feasible, however should be interpreted with caution due to limited experience (Wolf et al. 2010; Musahl et al. 2011; Doukas et al. 2011). The concept of continuous application is supported by the selective treatment of the affected vessels, the possibility to treat large and small vessel vasospasm and the prolonged effect. Continuous selective IAN has been successfully administered at a dose between 0.4 and 2 mg/h (Wolf et al. 2010; Musahl et al. 2011; Ott et al. 2014; Doukas et al. 2011). No significant hypotension, which could decrease perfusion and worsen ischemia, occurred in those patients. Potentially associated risks like dislocation of the angiography catheter, catheter-thrombosis and brain damage secondary to the alcoholic solution of nimodipine did not occur, neither in our patient, nor in patients of those case series. Dilatation of spastic arteries starts within a few hours and is long-lasting. A treatment course of 44 h was safe in our patient, however may be increased to up to 5 days as shown by previous reports (Wolf et al. 2010; Musahl et al. 2011).

A concern of intra-arterial vasodilator therapy is a secondary increase in intracranial pressure (ICP) associated with a decrease in brain tissue oxygenation. Although we did not measure brain tissue oxygen tension (P_btO₂) in our patient, clinical improvement did not suggest this nor a rise in ICP. In unconscious patients multimodal neuromonitoring devices measuring P_btO₂, local cerebral blood flow and ICP may be helpful to monitor IAN treatment (Musahl et al. 2011). In a series of 30 patients with refractory vasospasm a prompt increase in cerebral blood flow was observed (Ott et al. 2014).

Our patient had developed effortful, slow and non-fluent speech associated with MRI-DWI hyperintensities in the cortical and subcortical left frontal region, an area functionally related to speech motor control (Ackermann et al. 1996). Signs and symptoms redeveloped when IAN was discontinued suggesting a direct effect of IAN on intracranial hemodynamics. So far, IAN cannot be recommended as routine treatment for refractory cerebral vasospasm after SAH, however may be added to endovascular treatment options (Ott et al. 2014). One important limiting factor is the need for systemic heparinization and the possible risk of recurrent intracranial hemorrhage, particularly in patients with presumed ruptured aneurysms that had not yet been identified or secured.

Continuous selective intra-arterial infusion of nimodipine may be considered in selected patients with symptomatic high grade vasospasm refractory to standard treatment including angioplasty. The potential benefits of IAN should be balanced with procedure-related risks in symptomatic refractory vasospasm after SAH.