Circulating biomarkers of vasoplegia: a systematic review.

Background: Vasoplegia is characterised by persistent hypotension and reduced systemic vascular resistance despite preserved cardiac output, commonly arising in sepsis, following major surgery, and within systemic inflammatory responses. Despite its clinical significance and association with poor outcomes, there is no universally accepted definition or standardised biomarker, impeding early diagnosis, stratification, and targeted therapy. While individual studies have examined biomarkers within specific clinical contexts such as septic shock or cardiac surgery, no comprehensive synthesis across all aetiologies of vasoplegia has previously been undertaken.

Objectives: To systematically evaluate and synthesise the current evidence regarding circulating biomarkers associated with the incidence, severity, prediction, and progression of vasoplegia across diverse critical care and perioperative populations. As well as review definitions used across literature.

Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines and registered on PROSPERO (CRD42024438786). Studies were included if they investigated adult patients in critical care or perioperative settings with vasoplegia defined by reduced vascular resistance and hypotension requiring vasopressors.

Results: A total of 43 studies met inclusion criteria. The included studies examined 39 unique biomarkers, with renin and adrenomedullin being the most frequently studied. Heterogeneity in definitions of vasoplegia, outcome measures, and comparator populations precluded meta-analysis. However, several biomarkers demonstrated potential clinical utility: elevated renin levels correlated with vasopressor requirements and haemodynamic instability, while adrenomedullin levels were predictive of vasoplegia development and duration.

Conclusions: The lack of standardisation in biomarker assay methods and vasoplegia definitions remains a significant barrier to comparative analysis. Whilst this review highlights renin and adrenomedullin as promising candidate biomarkers for vasoplegia, the heterogeneity in study design, biomarker measurement, and diagnostic criteria underscores the urgent need for a consensus definition of vasoplegia, standardised sampling protocols, and unified outcome measures. Future research should focus on biomarker-guided risk stratification and personalised therapies, with an emphasis on validating predictive and mechanistic roles across diverse vasoplegic phenotypes.