Table 1: Experimental and clinical agents to prevent post-SAH vasospasm.

AgentMechanismReferencesSummary

Sodium nitroprusside (SN)NO donor[5662, 100104](i) Potential to improve local hemodynamics in some animal model and human studies.
(ii) Systemic hypotension, headache, nausea, vomiting, and potentially serious side effects of cyanide poisoning with both IV and intrathecal administration prevent routine use of SNP.
(iii) Intraventricular administration of SNP may be warranted in medically refractory, mechanically ventilated, and deeply sedated patients.

Nitroglycerin (GTN)NO donor[6366, 6870](i) IV administration prevents CV in animal models including primate models.
(ii) Transdermal approaches improve TCD values in clinical trials.
(iii) Serious side effects of drug tolerance, systemic hypotension, and hypertensive rebound prevent routine use of systemic nitroglycerin in clinical setting.
(iv) Intrathecal approaches effective in rabbit model, not approved in humans.
(v) Intra-arterial approaches have been documented in 2 patients who suffered vasospasm of external carotid-internal carotid bypass grafts.

NONOates, S-nitrosothiolsNO donor[52, 105](i) Cerebral vasodilator in SAH.
(ii) Some adverse neurologic events in animal models.
(iii) No clinical data available.

Sodium nitriteNO donor[17, 18, 20](i) Hemoglobin serves as nitrite reductase.
(ii) Effective cerebral vasodilator in animal models.
(iii) Prevents and reverses vasospasm in rodent and primate models without development of tolerance.
(iv) Phase 1 trials demonstrate safety in humans.

StatinsRecoupling of NOS[53, 8186, 106](i) Efficacy at prevention of vasospasm in animal models.
(ii) Discrepant clinical data regarding efficacy for vasospasm prevention.
(iii) Clinical and animal data is promising, but not regarded as standard of care.

Erythropoietin (EPO)Stimulates NOS signaling[8791](i) Efficacy at prevention of vasospasm in animal models.
(ii) High doses needed for efficacy create clinical risk for thrombosis.
(iii) Promising data from two clinical trials, but underpowered.