Management of endothelial dysfunction in septic shock - role of albumin administration

Sep 28, 2026

Sepsis is a major global health problem with high morbidity, mortality, and economic burden. Its definition has evolved, and Sepsis-3 highlights life-threatening organ dysfunction caused by a dysregulated host response. Endothelial dysfunction is central to sepsis pathogenesis, involving increased vascular permeability and inflammatory activation. Human serum albumin maintains oncotic pressure and endothelial integrity. This narrative review summarizes endothelial changes in sepsis and evaluates evidence for albumin administration to manage endothelial dysfunction across preclinical and clinical studies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

Sepsis and organ dysfunction

Endothelial dysfunction mechanisms

Albumin and endothelial integrity

Oncotic and non-oncotic albumin roles

Clinical debate and safety considerations

Narrative review scope

Endothelial dysfunction in sepsis

Role of albumin administration

Martin‑Loeches et al. Journal of Intensive Care (2026) 14:1 [https://doi.org/10.1](https://doi.org/10.1) 186/s40560‑025‑00836‑5 Journal of Intensive Care RESEARCH Open Access Management of endothelial dysfunction in septic shock: role of albumin administration Ignacio Martin-Loeches1,2,3*, Alejandro Rodríguez4, Lene Russell5,6, Michelle S. Chew7,8, Sharon Einav9,10, Andrew Conway Morris11,12 and Marc Leone13 Abstract Sepsis is a significant global health issue, with high morbidity, mortality, and economic burden. Its definition has evolved, with the latest Sepsis-3 criteria emphasizing life-threatening organ dysfunction due to a dysregulated host response. Endothelial dysfunction plays a critical role in sepsis pathogenesis, characterized by increased permeability and inflammatory responses. Human serum albumin, the most abundant protein in the bloodstream, is essential for maintaining oncotic pressure and endothelial integrity. This narrative review provides an overview of endothelial changes during sepsis and their impact on organ damage. We also explore the role of albumin administration in managing endothelial dysfunction in sepsis and discuss the available preclinical and clinical evidence. Keywords Sepsis, Endothelium, Albumin, Fluid resuscitation, Endothelial dysfunction *Correspondence: Ignacio Martin-Loeches[drmartinloeches@gmail.com](drmartinloeches@gmail.com) 1 Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James’s Hospital, D08 NHY1 Dublin, Ireland 2 School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland 3 Trinity Centre for Biomedical Engineering, Dublin, Ireland 4 Critical Care Unit, Joan XXIII University Hospital, Tarragona, Spain 5 Department of Intensive Care, Copenhagen University Hospital HerlevGentofte, Copenhagen, Denmark 6 Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark 7 Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Huddinge, Sweden 8 Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden 9 Department of Intensive Care Medicine, Maccabi Healthcare System, Jerusalem, Israel 10 Department of Anaesthesiology and Intensive Care, Hebrew University Faculty of Medicine, Jerusalem, Israel 11 Perioperative, Acute, Critical Care and Emergency Medicine Section, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK 12 JVF Intensive Care Unit, Addenbrooke’s Hospital, Cambridge, UK 13 Department of Anesthesiology and Intensive Care, North Hospital, Assistance Publique Hôpitaux Universitaires de Marseille, Aix Marseille University, Marseille, France Background Sepsis is a systemic condition that affects nearly all organs and tissues [1]. The effective management of sepsis within the initial hours of diagnosis may be crucial for preventing organ failure and improving patient outcomes [2]. The endothelium, a thin layer of cells lining the interior surface of blood vessels, responds to inflammation and infection in a manner that may significantly damage vascular function and, secondarily, organ function. These responses include a phenotypic shift (i.e., proapoptotic, proinflammatory, proadhesive, and procoagulant), and activation of a “danger signaling” cascade in response to the presence of microbial toxins. The result of this process is damage to the glycocalyx and endothelial cell apoptosis. These, in turn, lead to an increased permeability to proteins and fluids, causing interstitial leakage, tissue edema, and organ failure [1, 3]. Consequently, the ability to reduce endothelial dysfunction may be an essential component for improved treatment of sepsis. Human serum albumin, the most abundant protein in the bloodstream, is crucial not only for regulating oncotic pressure, but also for its non-oncotic roles, which include tran

FAQs

What role does endothelial dysfunction play in sepsis?

Endothelial dysfunction drives increased permeability and inflammatory responses, leading to glycocalyx damage and endothelial cell apoptosis. These changes promote interstitial leakage, tissue edema, and ultimately organ failure.

How can human serum albumin affect endothelial function in sepsis?

Albumin helps maintain oncotic pressure and endothelial integrity. It also has non-oncotic functions, including transporting substances and supporting acid–base balance.

Why is albumin administration in critically ill patients still debated?

Although albumin has an established safety record in multiple diseases, evidence of benefit in critically ill patients remains contested. Current use should be reserved for situations with demonstrated advantages.

Sep 28, 2026

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