What are the treatments for refractory intracranial vasospasm following subarachnoid hemorrhage (SAH)?

From the Guidelines

Treatments for refractory intracranial vasospasm after subarachnoid hemorrhage should prioritize endovascular interventions, including intra-arterial vasodilator infusion and balloon angioplasty, as they have shown to be effective in reducing vasospasm and improving outcomes, as supported by the most recent guidelines from the American Heart Association/American Stroke Association 1.

Medical Management

Medical management typically begins with hemodynamic augmentation therapy, which involves hypertension, hypervolemia, and hemodilution to improve cerebral perfusion. This is achieved using vasopressors like norepinephrine or phenylephrine to maintain systolic blood pressure between 160-180 mmHg, along with intravenous fluids to maintain euvolemia. Nimodipine, a calcium channel blocker, is administered at 60 mg every 4 hours orally for 21 days to reduce vasospasm risk 1.

Endovascular Interventions

For refractory cases, endovascular treatments become necessary, including:

• Intra-arterial vasodilator infusion (verapamil 5-10 mg, nicardipine 5-15 mg, or milrinone 5-15 mg per vessel) directly into affected arteries
• Balloon angioplasty, which is effective for accessible proximal vessels with mechanical dilation of the spastic segment Some centers use continuous lumbar drainage of cerebrospinal fluid to reduce irritant blood products.

Emerging Therapies

Emerging therapies include:

• Intraventricular administration of tissue plasminogen activator
• Intravenous magnesium sulfate
• Endothelin receptor antagonists
• Statins These interventions work by different mechanisms: calcium channel blockers prevent calcium influx into vascular smooth muscle cells, angioplasty mechanically stretches the vessel wall, and vasodilators directly relax vascular smooth muscle. Treatment selection depends on vasospasm severity, affected vessels, patient condition, and institutional expertise 1.

Key Considerations

Key considerations in the management of refractory intracranial vasospasm include:

• Early diagnosis and treatment
• Close monitoring of patient condition and vasospasm severity
• Institutional expertise and availability of endovascular interventions
• Individualized treatment selection based on patient-specific factors By prioritizing endovascular interventions and considering these key factors, healthcare providers can optimize outcomes for patients with refractory intracranial vasospasm after subarachnoid hemorrhage.

From the FDA Drug Label

In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood-brain barrier; concentrations of nimodipine as high as 12. 5 ng/mL have been detected in the cerebrospinal fluid of nimodipine-treated subarachnoid hemorrhage (SAH) patients. Nimodipine has been shown, in 4 randomized, double-blind, placebo-controlled trials, to reduce the severity of neurological deficits resulting from vasospasm in patients who have had a recent subarachnoid hemorrhage (SAH). The trials used doses ranging from 20 to 30 mg to 90 mg every 4 hours, with drug given for 21 days in 3 studies, and for at least 18 days in the other Among analyzed patients (72 nimodipine, 82 placebo), there were the following outcomes. * p = 0. 001, nimodipine vs placebo Delayed Ischemic Deficits (DID) Permanent Deficits Nimodipine n (%) Placebo n (%) Nimodipine n (%) Placebo n (%) DID Spasm Alone 8 (11) * 25 (31)5 (7)* 22 (27)

The treatment for refractory intracranial vasospasm following subarachnoid hemorrhage (SAH) is Nimodipine.

• The recommended dose is 60-90 mg every 4 hours.
• Nimodipine has been shown to reduce the severity of neurological deficits resulting from vasospasm in patients with SAH.
• The use of Nimodipine tends to improve good recovery of SAH patients with poor neurological status post-ictus, while decreasing the numbers with severe disability and vegetative survival 2.

From the Research

Treatments for Refractory Intracranial Vasospasm

Treatments for refractory intracranial vasospasm following subarachnoid hemorrhage (SAH) include:

• Intra-arterial nimodipine administration, which has been shown to be effective in treating cerebral vasospasm refractory to medical therapy 3, 4, 5
• Intrathecal nimodipine lavage, which has been demonstrated to be feasible and safe in patients with severe vasospasm resistant to established medical and endovascular treatment strategies 4
• Intra-arterial milrinone infusion, which has been found to be a safe and effective treatment for patients who develop refractory symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage 6
• Other therapeutic drugs, including Ca2+ channel antagonists, magnesium sulfate, clazosentan, statins, cilostazol, eicosapentaenoic acid, fasudil hydrochloride, and edaravone, which have been frequently studied in recent years 7

Administration Methods

Different administration methods have been used to deliver these treatments, including:

• Intra-arterial infusion via a diagnostic catheter in the internal carotid artery or vertebral artery 3, 5
• Intrathecal infusion via a lumbar catheter 4
• Intra-arterial infusion at a rate of 0.25 mg/min, with a total dose of 10-15 mg 6

Efficacy and Safety

The efficacy and safety of these treatments have been evaluated in various studies, with results showing:

• Significant angiographic response and improvement in neurological condition 3, 6
• Feasibility and safety of intrathecal nimodipine lavage in patients with severe vasospasm resistant to established medical and endovascular treatment strategies 4
• No serious adverse effects observed 4, 5