Association between dehydration trajectory, delayed cerebral ischemia, and functional outcome in patients with aneurysmal subarachnoid hemorrhage: assessment of interaction and mediation.

Background: Blood urea/creatinine (U/Cr) ratio is considered to be an ideal biomarker of dehydration. We investigated the association between the U/Cr ratio trajectory and delayed cerebral ischemia (DCI) as well as functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). Additionally, we explored the role of DCI as a mediator and its interaction with dehydration.

Methods: Consecutive aSAH patients were reviewed. A latent class growth mixture model (LCGMM) was applied to classify the dehydration trajectory over 7 days. Multivariate logistic regression was conducted to examine associations between dehydration trajectories, DCI, and poor outcome. Furthermore, causal mediation analysis combined with a four-way decomposition approach was employed to quantify the extent to which DCI mediates or interacts with dehydration in influencing poor outcomes.

Results: A total of 519 aSAH patients were included. By applying the LCGMM method, we categorized participants into three dehydration trajectory groups: low group (n=353), decreasing group (n=97), and high group (n=69). Multivariate analysis demonstrated that dehydration trajectory was independently associated with both DCI and poor outcome. The effect of dehydration trajectory on poor outcome was partially mediated by DCI, involving both pure mediation and mediated interaction. Specifically, the excess relative risk of DCI was decomposed into four components: controlled direct effect (66.42%), mediation only (16.35%), interaction only (6.09%), and mediated interaction (11.16%).

Conclusion: Among aSAH patients, dehydration trajectory was significantly associated with poor functional outcome, with DCI serving as a partial mediator through both direct and interaction effects.