Abstract
Background and Purpose: The relationship between stroke outcome and initial presentation in a volume contracted state (VCS) has not been well established, and may intersect with concomitant diuretic use and serum potassium (K) levels. We hypothesized that stroke outcome is a function of multiple volume related factors. Methods: We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset, enrolled in acute treatment trials within the Virtual International Stroke Trials Archive. VCS was defined as a BUN-to-creatinine ratio>20 and hypokalemia as <3.5 mEq/L. The primary endpoint was modified Rankin Scale (mRS) at 90 days. Primary analysis employed generalized ordinal logistic regression over the full mRS range, with adjustment for THRIVE score, onset-to-enrollment time, and intravenous rtPA usage. Secondary analyses dichotomized the mRS. Results: Of 5971 eligible patients, 44% were in a VCS and 56% were euvolemic. Patients with VCS were older, had more vascular risk factors, more severe strokes, and were more likely taking diuretics. VCS was not significantly associated with mRS scores after adjustment (Table). Post hoc sensitivity analysis using BUN-to-creatinine ratio>30 yielded similar results. Diuretic use was associated with worse outcomes (Table), mainly driven by non-K sparing diuretics, while K-sparing diuretics tended to have the opposite effect. Hypokalemia had discordant associations with mRS, depending on the analytic approach (Table). There was no evidence of effect modification among the three exposures of VCS, diuretic use, or hypokalemia in relation to outcome (all p>0.30). Conclusions: A VCS at the time of hospitalization was associated with more severe stroke but not associated with worse functional outcome when accounting for key measurable baseline characteristics. However, diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.
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