Inflammation and Neurological Outcomes in Cardiac Arrest - a Narrative Review of Serum Biomarker Investigations

Abstract

Background: Hypoxic-ischemic brain injury (HIBI) is a significant cause of disability following cardiac arrest (CA). Activation of the inflammatory cascade is central to HIBI pathophysiology and drives post-cardiac arrest syndrome (PCAS), which can induce further secondary brain injury. Although numerous studies have described this mechanism in preclinical models, translating this knowledge to therapeutic targets and neurological outcomes in humans is variable and incomplete. The impact of inflammation on the neurovascular unit, comprising neurons, astroglia, and capillary endothelium, may play a significant role in outcomes but is poorly understood in humans.

Objective: This narrative review explores studies examining PCAS, inflammation, and neurological outcomes in adult CA and classifies them into interrelated pathomechanisms.

Methods: We searched multiple databases using a search string constructed from core concepts, including inflammation, CA, neurovascular unit components, and neurologic outcomes. We screened abstracts published from database conception until July 2024 and excluded animal/in-vitro studies, unrelated topics, duplicates, foreign language articles, reviews/commentaries, studies without neurological outcomes, and case studies.

Results: The biomarkers studied fit into three general domains: reperfusion-induced oxidative stress, local and systemic inflammatory response, and coagulopathy associated with endothelial injury. Numerous markers were associated with neurological outcomes after CA, but few demonstrated a strong association in multivariate analysis. Few clinical trials of therapies for CA have studied impacts on the inflammatory cascade or have targeted inflammatory components. Associations between inflammation reduction and neurological outcomes are variable. However, various limitations reduce the applicability of these trials.

Conclusions: Inflammatory mechanisms in PCAS may hold the key to secondary brain injury and warrant larger, more systematic studies to establish therapeutic targets to improve neurological outcomes.

Keywords: cardiac arrest; inflammation; neurological outcomes; prognostication.