Current knowledge and challenges of sepsis-associated encephalopathy.
Intensive Care Med 2026 Jun 16. [Online ahead of print]

Abstract

Encephalopathy is a common complication of sepsis, occurring in up to 70% of patients admitted to the intensive care unit. It is primarily characterized by a deterioration in condition, ranging from delirium to coma, but also by electroencephalographic changes and seizures. Sepsis-associated encephalopathy (SAE) is linked to increased mortality, which rises in proportion to the severity of both clinical manifestations and electroencephalographic abnormalities, and is frequently followed by long-term cognitive impairment and functional disability. The pathophysiology of SAE is complex and includes a disturbance in neurotransmission together with a dysfunction of different brain cells and functional complexes (blood-brain barrier, neurovascular coupling, synapses). Neuroinflammation and ischemia are its main processes. Its cellular mechanisms include bioenergetic failure and oxidative stress. The frontal cortex, hippocampus, limbic system, and brainstem are particularly vulnerable to these events. Currently, management relies primarily on controlling sepsis and applying recommendations for delirium, including the avoidance of neurotoxic agents. Developing a specific treatment would depend on a better understanding of its pathophysiology, through a relevant experimental model, as well as on the identification of biomarkers with diagnostic, pathophysiological, and/or prognostic value. This contemporary review synthesizes current data on the epidemiology, mechanisms, characteristics and complications of SAE, as well as priorities for therapeutic progress.

Authors+Show Affiliations

Shankar-Hari M0000-0002-5338-2538Centre for Critical Illness Research, School of Immunology and Microbial Sciences, King's College London, London, UK.
Benghanem S0000-0003-2544-0291Medical Intensive Care Unit, Cochin Hospital, Assistance Publique-Hôpitaux de Paris-Centre (APHP-Centre), Paris, France. Université Paris Cité, Institute of Psychiatry and Neurosciences of Paris (IPNP), INSERM U1266, Stroke Team, Paris, France.
Bourhy L0000-0002-0779-8591Nervous System Development and Homeostasis Laboratory, The Francis Crick Institute, London, UK.
Cunningham C0000-0003-1423-5209School of Biochemistry and Immunology Trinity Biomedical Sciences Institute, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Ehler J0000-0001-7866-9781Department of Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany.
Girard TD0000-0002-9833-4871Center for Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) in the Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Gofton TE0000-0001-9001-4884Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Hermann B0000-0001-9071-3415Université Paris Cité, Institute of Psychiatry and Neurosciences of Paris (IPNP), INSERM U1266, Stroke Team, Paris, France. Medical ICU, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre-Université Paris Cité, Paris, France.
Jiwaji Z0000-0002-3129-1168UK Dementia Research Institute at University of Edinburgh, University of Edinburgh, Edinburgh, UK. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.
Mazeraud A0000-0001-8473-7779Université Paris Cité, Institute of Psychiatry and Neurosciences of Paris (IPNP), INSERM U1266, Stroke Team, Paris, France. Neuro-Anesthesiology and Intensive Care Medicine, Anesthesia and Intensive Care Department GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France.
Neeham E0000-0001-7042-7462Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Rosa RG0000-0001-7881-9866Serviço de Medicina Interna, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil. Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Singer M0000-0002-1042-6350Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Slooter AJC0000-0003-0804-8378Department of Psychiatry, and Research School of Behavioural and Cognitive Neurosciences (BCN), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Department of Intensive Care Medicine, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Department of Neurology, UZ Brussel and Vrije Universiteit Brussel, Brussels, Belgium.
Sonneville R0000-0003-0245-309XUniversité Paris Cité, IAME, INSERM U1137, 75018, Paris, France. APHP.Nord, Médecine Intensive Réanimation, Hôpital Bichat-Claude Bernard, Paris, France.
Stevens RD0000-0001-5984-7837Departments of Anesthesiology and Critical Care Medicine, Neurology, Biomedical Engineering, Johns Hopkins University, Baltimore, USA.
Taccone FS0000-0003-0830-1628Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium.
Sharshar T0000-0003-2276-0951Université Paris Cité, Institute of Psychiatry and Neurosciences of Paris (IPNP), INSERM U1266, Stroke Team, Paris, France. t.sharshar@ghu-paris.fr. Neuro-Anesthesiology and Intensive Care Medicine, Anesthesia and Intensive Care Department GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France. t.sharshar@ghu-paris.fr.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

42301312