What are the recommended medications for managing vasospasm, including cerebral vasospasm after subarachnoid hemorrhage and coronary or peripheral vasospasm?

Drugs for Vasospasm

Oral nimodipine 60 mg every 4 hours for 21 consecutive days is the only FDA-approved medication proven to improve neurological outcomes after aneurysmal subarachnoid hemorrhage and should be started within 96 hours of bleeding in all patients. 1, 2, 3

Cerebral Vasospasm After Subarachnoid Hemorrhage

First-Line Prevention: Nimodipine

Nimodipine is the cornerstone of vasospasm management and works through neuroprotective mechanisms beyond simple reversal of arterial narrowing. 1, 2 The American Heart Association gives this a Class I, Level A recommendation—the highest grade of evidence. 4, 1

Key administration details:

• Dose: 60 mg orally every 4 hours for exactly 21 days 1, 3
• Timing: Must begin within 96 hours of initial hemorrhage 1, 2
• Route: Enteral administration only—never give IV nimodipine as it can cause fatal hypotension 3
• Consistency: Interruption of therapy correlates with increased delayed cerebral ischemia (ρ=0.431, P<0.001), so maintain full dosing without gaps 1

Clinical efficacy: Nimodipine reduces cerebral infarction by 34%, adverse outcomes by 40%, and poor outcomes at 3 months by 23%. 4, 1 Critically, this benefit occurs despite no demonstrated reduction in angiographic vasospasm, indicating the drug's primary mechanism is neuroprotection rather than vasodilation. 4, 2

Managing hypotension: If nimodipine causes blood pressure drops, first attempt standard medical interventions to support blood pressure before reducing the dose. 1 Only if hypotension remains refractory should you temporarily reduce or interrupt dosing. 1

Rescue Therapy for Symptomatic Vasospasm

When delayed cerebral ischemia develops despite nimodipine (manifesting as new focal deficits not explained by hydrocephalus or rebleeding, typically days 5-14 post-bleed), escalate to: 5, 2

1. Induced hypertension with euvolemia

• First-line rescue intervention when delayed cerebral ischemia is diagnosed 5, 2
• Maintain normal circulating blood volume—avoid prophylactic hypervolemia or "triple-H" therapy 2

2. Endovascular interventions (when medical management fails)

Balloon angioplasty:

• Effective for reversing vasospasm in large proximal conducting vessels (first- and second-order segments) with thick muscular walls 4, 2
• Not safe or effective in distal perforating branches beyond second-order segments 4
• Risks include vessel occlusion, rupture, thrombus formation, and aneurysm clip displacement 4
• Early therapy (<2 hours from symptom onset) may provide better sustained clinical improvement 4
• Institutions with angioplasty capability show 16% reduction in in-hospital death compared to those without 4

Intra-arterial vasodilators:

• Used for third- and fourth-order vessels that cannot be treated with balloon angioplasty 4, 2
• Papaverine is FDA-approved for intra-arterial use in cerebral vasospasm 6
• Intra-arterial nimodipine (0.1 mg/min via diagnostic catheter) shows 76% clinical improvement in case series, though this is off-label use 7
• Papaverine has shorter durability than balloon angioplasty 4

Critical caveat: While endovascular interventions can reverse angiographic vasospasm, high-quality evidence that these procedures improve neurological outcomes is lacking. 5 Randomized trials achieving vasospasm reduction did not translate into better overall patient outcomes, underscoring that delayed cerebral ischemia involves mechanisms beyond simple arterial narrowing. 5

Drugs That Do NOT Work

The following have been tested and should NOT be used for vasospasm prevention or neuroprotection: 4, 2

• Aspirin 4
• Enoxaparin 4
• Tirilazad 4
• Endothelin-1 antagonists 4
• Intravenous nicardipine (showed 30% reduction in spasm but no outcome improvement) 4
• Prophylactic IV magnesium 2
• Statins for acute prevention 2

Coronary and Peripheral Vasospasm

Papaverine is FDA-approved for vascular spasm associated with acute myocardial infarction, angina pectoris, peripheral and pulmonary embolism, and peripheral vascular disease with a vasospastic element. 6 This represents the primary pharmacologic option for non-cerebral vasospasm.

Calcium channel blockers (particularly dihydropyridines like nifedipine) have anti-atherosclerotic properties useful for large artery disease, though short-acting formulations should be avoided in acute settings due to potential harm from rapid blood pressure reduction. 8

Monitoring for Vasospasm

To detect vasospasm early and guide therapy escalation: 5

• Clinical examination: New focal deficit (motor weakness, aphasia, neglect) not explained by hydrocephalus or rebleeding, typically appearing days 3-5, peaking days 5-14 5
• Transcranial Doppler: Lindegaard ratio of 5-6 indicates severe vasospasm warranting treatment (Class IIa, Level B-NR) 5
• CT angiography: 91% sensitivity for central vasospasm, 90% diagnostic accuracy versus conventional angiography (Class IIa, Level B-NR) 5
• Continuous EEG: In high-grade SAH, EEG alarms occur in 96.2% of patients who develop delayed cerebral ischemia, with median 1.9-day warning before clinical symptoms (Class IIa, Level B-NR) 5

Despite maximal therapy, 15-20% of patients suffer stroke or die from vasospasm, accounting for nearly 50% of deaths among those who survive to receive treatment. 5