Date of Award

4-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Nursing Science

Research Advisor

Anne W. Alexandrov, PhD

Keywords

hyperglycemia; ischemic stroke; reperfusion therapy; stroke outcomes

Abstract

Stroke is a major contributor to disability in the United States, with ischemic stroke accounting for approximately 87% of all cases. The use of approved reperfusion therapies, including intravenous thrombolysis with tissue plasminogen activator (tPA) and mechanical thrombectomy, has significantly improved functional outcomes for ischemic stroke patients. However, hyperglycemia at the time of hospital arrival is associated with worse outcomes, including increased infarct growth, higher rates of disability, and elevated mortality. Despite this, current stroke guidelines neither exclude hyperglycemic patients from receiving reperfusion therapy nor recommend glucose management during the hyperacute phase of care. While recent studies suggest that mild to moderate hyperglycemia can be safely treated with intravenous insulin, there is insufficient evidence to support that glucose management improves stroke outcomes. The impact of hyperglycemia treatment immediately before or after reperfusion therapy remains largely unexplored, presenting a critical gap in acute stroke care.

This dissertation examines the role of hyperglycemia in reperfusion-eligible stroke patients through three interconnected studies aimed at improving glucose management strategies. First a scoping review of existing clinical trials investigating glucose control in stroke patients, providing a comprehensive analysis of interventions aimed at managing hyperglycemia during the acute and hyperacute phases of stroke care. This review synthesizes evidence on the effectiveness, safety, and feasibility of various glucose-lowering strategies, including intravenous insulin administration and other pharmacological and non-pharmacological approaches. Furthermore, it highlights gaps in knowledge regarding the optimal timing of intervention, the impact of glucose variability, and the clinical thresholds at which treatment should be initiated to maximize patient outcomes.

Summary of findings from the scoping review was used to develop a qualitative study. Interviews with emergency department nurses’ and stroke coordinators were conducted to explore perceptions of barriers to timely glucose management in acute stroke patients. The results were published in Stroke Clinician journal in November 2024.

A retrospective study assessing the relationship between admission hyperglycemia, hemoglobin A1c levels, home diabetic medication use, and post-reperfusion outcomes, including functional recovery and complications such as symptomatic intracerebral hemorrhage. Patients were grouped into ≥180 mg/dL and < 180 mg/dL admission glucose for comparison between groups. Additionally, patients were grouped into diabetic groups to compare against dichotomous good outcome (mRS 0-2) and bad outcome (mRs 3-6). Those in the hyperglycemia group demonstrated significantly worse discharge NIHSS(p=0.034) and 3-month mRS (p=0.035) scores compared to the lowest glucose value patients. There were no significant differences in brain hemorrhage rates. Untreated diabetes patients had higher proportion of bad outcomes compared to non-diabetes patients (p=0.006) and to controlled diabetes patients (p=0.019). The median time from any reperfusion intervention to first hyperglycemic time was 14 hours and 5 minutes (IQR 4:32-32:36) for all patients, however in the lower glucose value group median was 18:36 (IQR 4:49-41:31) versus 7:49 (IQR 2:19-22:16; Z= -2.414, p=0.016) in the hyperglycemic group.

The findings from these studies aim to bridge the existing gap in hyperglycemia management in ischemic stroke care. By identifying barriers to treatment, assessing current clinical practices, and evaluating patient outcomes, this dissertation contributes to the ongoing effort to optimize glucose control strategies in the hyperacute phase of stroke management. Addressing hyperglycemia as a modifiable factor in reperfusion therapy has the potential to improve functional recovery and reduce morbidity in ischemic stroke patients.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

https://orcid.org/0000-0003-2542-7353

DOI

10.21007/etd.cghs.2025.0685

Additional Files
2025-002-Schumacher-DOA.pdf (198 kB)
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