Outcomes of Intra-arterial Treatment for Patients with Cerebral Vasospasm Following Subarachnoid Hemorrhage Adrian Chen1, Timothy White, Thomas Link, Athos Patsalides, Amir Dehdashti, Ina Teron, Kevin Shah, Justin Turpin, Daniel Toscano, Henry Woo 1 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell 2 Department of Neurosurgery, Northwell Health
INTRODUCTION
RESULTS
• Subarachnoid hemorrhage (SAH) accounts for 7% of all strokes worldwide and carries an exceptionally high disease burden
Table I: Presenting characteristics of milrinone and non-milrinone vasospasm treatment groups. Milrinone Verapamil and P-value (n=30) Nicardipine (n=27) Age, median [IQR] 59 [18] 53 [23] 0.09 Sex, n (%) 0.1 Male 8 (26) 13 (48) Female 22 (73) 14 (51) Race, n (%) 0.9 mFS, median [IQR] 3.5 [1] 3 [1] 0.6 Hunt Hess, median [IQR] 3 [1] 2 [1] 0.4 Medications, n (%) Antiplatelets 15 (50) 7 (25) 0.1 Anticoagulants 25 (83) 17 (62) 0.1 Antihypertensives 12 (40) 8 (29) 0.6 Comorbid conditions, n (%) Diabetes 4 (13) 2 (7) 0.7 Hypertension 18 (60) 14 (51) 0.6 Prior smoking history 5 (16) 3 (11) 0.7
• Hemorrhagic insult triggers cerebral vasospasm in 70% of all SAH patients, a main etiology for delayed cerebral ischemia • Cerebral vasospasm is characterized by narrowing of cerebral blood vessels, leading to severe cerebral hypoxia • Endovascular, intra-arterial therapy involves the directcatheter administration of vasodilators (e.g., nimodipine or milrinone) into the affected blood vessel, allowing for targeted treatment of specific regions. • No standardized guidelines for intra-arterial therapy exists for vasospasms, and influence of various vasodilators on clinical outcomes remain unknown. Objective: To evaluate the impact of patient characteristics and intra-arterial treatment on clinical outcomes in patients with cerebral vasospasm following subarachnoid hemorrhage (SAH)
METHODS • Inclusion Criteria: Patients 18-80 years old with a diagnosis of nontraumatic, aneurysmal SAH were included. • Exclusion Criteria: Traumatic or intracranial mass lesion induced SAH, death due to PE, MI, sepsis or other medical complications, and lack of follow-up visits were excluded. • Patients were separated into a milrinone- or nicardipine vasospasm treatment groups. • Patient characteristics included demographic factors, comorbidities, Hunt Hess, modified Fisher, and antithrombotic status. •
Vasospasm treatment outcomes included time to 1st
intervention, vasospasm recurrence, post-intervention assessment, neurological/CV adverse event, Lindegaard ratio, hospital LOS, and modified Rankin score at discharge • Multivariate logistic regression analyses of pre-existing conditions associated with a recurring vasospasm event after initial treatment intervention.
Figure I. Severe cerebral vasospasm visualization in distal right A1 segment of the anterior communicating artery a) pre- and b) post-milrinone administration
a
b
Figure II. Kaplan-Meier survival analysis for time to first intervention and Fig. II) recurrent vasospasm events between intra-arterial milrinone and verapamil/nicardipine
Table II: Outcome measures for post-vasospasm treatment using either milrinone or verapamil and nicardipine. Milrinone Verapamil and P-value (n=30) Nicardipine (n=27)
Vasospasm occurrences, n (%) Multiple Singular Post-int. assessment, n (%) Vasospasm improved Vasospasm stable Lindegaard ratio, median [IQR] Neurological AE, n (%) Cardiovascular AE, n (%) Hospital LOS, median days [IQR] mRS at Discharge, median [IQR]
19 (63) 11 (36)
9 (33) 18 (67)
27 (90) 3 (10) 4.5 [2.2] 15 (50) 8 (26) 25 [23] 3 [4]
19 (70) 8 (29) 4.7 [1.7] 15 (55) 6 (22) 22 [13] 1 [2]
0.03 0.06 0.8 0.8 >0.9 0.5 0.008
Table III. Unadjusted and adjusted Hazard Ratios (HRs) with 95% CIs for milrinonetreatment outcomes with non-milrinone (reference group) Unadjusted Adjusted* Vasospasm Recurrence 3.46 (1.19,9.38), p=0.034 0.13 (0.01, 0.75), p=0.037 Neuro AE 0.79 (0.27, 2.19), p=0.79 2.34 (0.48, 13.55), p=0.31 Cardio AE 1.02 (0.31, 3.38), p>0.99 12.28 (1.53, 186.0), p=0.035 *Adjusted for antithrombotic status, diabetes, hypertension, headache, nausea, Hunt Hess, modified Fischer score, and age
CONCLUSION • Milrinone as an intra-arterial therapy effectively decreases recurrent vasospasm events in the context of cerebral vasospasm. • Cardiovascular adverse effects occurred more frequently with milrinone than with verapamil/nicardipine intra-arterial vasospasm treatment.
REFERENCES Dodd WS, Laurent D, Dumont AS, et al. Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review. J Am Heart Assoc. 2021;10(15):e021845. doi:10.1161/JAHA.121.021845 Santos-Teles AG, Ramalho C, Ramos JGR, et al. Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review. Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática. Rev Bras Ter Intensiva. 2020;32(4):592-602. doi:10.5935/0103-507X.20200097 Duman E, Karakoç F, Pinar HU, Dogan R, Fırat A, Yıldırım E. Higher dose intra-arterial milrinone and intra-arterial combined milrinone-nimodipine infusion as a rescue therapy for refractory cerebral vasospasm. Interv Neuroradiol. 2017;23(6):636-643. doi:10.1177/1591019917732288
CONTACT
achen7@pride.hofstra.edu