Temporal evolution of vasospasm and clinical outcome after intra-arterial vasodilator therapy in patients with aneurysmal subarachnoid hemorrhage.

Laleh Daftari Besheli,Donnie L Bell,Joshua A Hirsch,Can Ozan Tan,Rajiv Gupta,Gustavo Pradilla

doi:10.1371/journal.pone.0174676

Laleh Daftari Besheli, Donnie L Bell + Show 4 more

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https://doi.org/10.1371/journal.pone.0174676

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Abstract

Intra-arterial (IA) vasodilator therapy is one of the recommended treatments to minimize the impact of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm refractory to standard management. However, its usefulness and efficacy is not well established. We evaluated the effect IA vasodilator therapy on middle cerebral artery blood flow and on discharge outcome. We reviewed records for 115 adults admitted to Neurointensive Care Unit to test whether there was a difference in clinical outcome (discharge mRS) in those who received IA infusions. In a subset of 19 patients (33 vessels) treated using IA therapy, we tested whether therapy was effective in reversing the trends in blood flow. All measures of MCA blood flow increased from day -2 to -1 before infusion (maximum Peak Systolic Velocity (PSV) 232.2±9.4 to 262.4±12.5 cm/s [p = 0.02]; average PSV 202.1±8.5 to 229.9±10.9 [p = 0.02]; highest Mean Flow Velocity (MFV) 154.3±8.3 to 172.9±10.5 [p = 0.10]; average MFV 125.5±6.3 to 147.8±9.5 cm/s, [p = 0.02]) but not post-infusion (maximum PSV 261.2±14.6 cm/s [p = .89]; average PSV 223.4±11.4 [p = 0.56]; highest MFV 182.9±12.4 cm/s [p = 0.38]; average MFV 153.0±10.2 cm/s [p = 0.54]). After IA therapy, flow velocities were consistently reduced (day X infusion interaction p<0.01 for all measures). However, discharge mRS was higher in IA infusion group, even after adjusting for sex, age, and admission grades. Thus, while IA vasodilator therapy was effective in reversing the vasospasm-mediated deterioration in blood flow, clinical outcomes in the treated group were worse than the untreated group. There is need for a prospective randomized controlled trial to avoid potential confounding effect of selection bias.

Highlights

Aneurysmal subarachnoid hemorrhage affects 21,000 to 33,000 individuals each year in the U.S, and accounts for approximately 5% of new stroke cases
We retrospectively obtained medical records for all patients aged 18 years or older who were admitted to our neurologic intensive care unit (NICU) from 2005 to 2013 with a diagnosis of aSAH ascertained by admission CT, MRI, or digital subtraction angiography
In 3 of those, the infarct was present at admission, in 2 (9%), the infarcts were unlikely to be related to vasospasm, and in the remaining 2 (9%) the infarct could reliably be attributed to the vasospasm but not to the IA infusions (IA therapy was performed after the diagnosis of the infarct)

Summary

Introduction

Aneurysmal subarachnoid hemorrhage (aSAH) affects 21,000 to 33,000 individuals each year in the U.S, and accounts for approximately 5% of new stroke cases. It occurs at a young age, over 40% of the patients die within 28 days, and survivors often experience long-term cognitive and physical disabilities [1,2,3,4]. Symptomatic vasospasm and cerebral ischemic injury (i.e., DCI) together account for nearly 50% of the early deaths in those who survive the initial hemorrhage and aneurysm treatment [3,8]. It is clear that any intervention to minimize the incidence and impact of cerebral vasospasm and DCI may improve clinical outcome

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