Continuous infusion of low-dose unfractionated heparin after aneurysmal subarachnoid hemorrhage: a preliminary study of cognitive outcomes

Robert F James; Nicolas K Khattar; Zaid S Aljuboori; Paul S Page; Elaine Y Shao; Lacey M Carter; Kimberly S Meyer; Michael W Daniels; John Craycroft; John R Gaughen; M Imran Chaudry; Shesh N Rai; D Erik Everhart; J Marc Simard

doi:10.3171/2017.11.JNS17894

Continuous infusion of low-dose unfractionated heparin after aneurysmal subarachnoid hemorrhage: a preliminary study of cognitive outcomes

J Neurosurg. 2018 May 11:1-8. doi: 10.3171/2017.11.JNS17894. Online ahead of print.

Authors

Robert F James^{1

2}, Nicolas K Khattar¹, Zaid S Aljuboori¹, Paul S Page¹, Elaine Y Shao², Lacey M Carter², Kimberly S Meyer¹, Michael W Daniels³, John Craycroft³, John R Gaughen⁴, M Imran Chaudry⁵, Shesh N Rai³, D Erik Everhart^{6

7}, J Marc Simard^{8

9}

Affiliations

¹ 1Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky.
² 2Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, North Carolina.
³ 3Department of Bioinformatics and Biostatistics, University of Louisville School of Public Health, Louisville, Kentucky.
⁴ 4Sentara Martha Jefferson Hospital, Charlottesville, Virginia.
⁵ 5Comprehensive Stroke and Cerebrovascular Center, Medical University of South Carolina, Charleston, South Carolina; Departments of.
⁶ 6Psychology and.
⁷ 7Internal Medicine, East Carolina University, Greenville, North Carolina; and Departments of.
⁸ 8Neurosurgery.
⁹ 10Physiology, University of Maryland School of Medicine, Baltimore, Maryland.

PMID: 29749915
DOI: 10.3171/2017.11.JNS17894

Abstract

OBJECTIVECognitive dysfunction occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH) survivors. Low-dose intravenous heparin (LDIVH) infusion using the Maryland protocol was recently shown to reduce clinical vasospasm and vasospasm-related infarction. In this study, the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive changes in aSAH patients treated with the Maryland LDIVH protocol compared with controls.METHODSA retrospective analysis of all patients treated for aSAH between July 2009 and April 2014 was conducted. Beginning in 2012, aSAH patients were treated with LDIVH in the postprocedural period. The MoCA was administered to all aSAH survivors prospectively during routine follow-up visits, at least 3 months after aSAH, by trained staff blinded to treatment status. Mean MoCA scores were compared between groups, and regression analyses were performed for relevant factors.RESULTSNo significant differences in baseline characteristics were observed between groups. The mean MoCA score for the LDIVH group (n = 25) was 26.4 compared with 22.7 in controls (n = 22) (p = 0.013). Serious cognitive impairment (MoCA ≤ 20) was observed in 32% of controls compared with 0% in the LDIVH group (p = 0.008). Linear regression analysis demonstrated that only LDIVH was associated with a positive influence on MoCA scores (β = 3.68, p =0.019), whereas anterior communicating artery aneurysms and fevers were negatively associated with MoCA scores. Multivariable linear regression analysis resulted in all 3 factors maintaining significance. There were no treatment complications.CONCLUSIONSThis preliminary study suggests that the Maryland LDIVH protocol may improve cognitive outcomes in aSAH patients. A randomized controlled trial is needed to determine the safety and potential benefit of unfractionated heparin in aSAH patients.

Keywords: ACoA = anterior communicating artery; DND = delayed neurological deficit; LDIVH = low-dose intravenous heparin; MMSE = Mini–Mental State Examination; MoCA = Montreal Cognitive Assessment; WFNS = World Federation of Neurological Societies; aSAH = aneurysmal subarachnoid hemorrhage; cognitive dysfunction; low-dose intravenous heparin; mRS = modified Rankin Scale; subarachnoid hemorrhage; vascular disorders.