Sepsis has consistently challenged clinicians. The discovery of antibiotics marked a major advance in the treatment of sepsis, yet germ theory alone did not fully explain its pathogenesis: many patients with sepsis continued to die even after antibiotic treatment had successfully eradicated the causative pathogen. It is now understood that the dysregulated host response, rather than the pathogen itself, drives the pathogenesis of sepsis.
In 2016, the Sepsis-3 Task Force defined sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. This definition shifted both clinical practice and research away from focusing on infection alone and towards recognising the host response as a central therapeutic target.
Sepsis was once regarded primarily as an overwhelming inflammatory condition driven by excessive cytokine release. It is now recognised as a far more complex dysregulated immune response involving both hyperinflammation and prolonged immune suppression, including lymphopenia and immunoparalysis. While earlier therapeutic approaches concentrated largely on suppressing inflammation, current research increasingly examines how sepsis-induced immune dysfunction contributes to secondary and opportunistic infections, and whether immune-targeted therapies may improve outcomes in selected patients.
In a lightning talk session at Euroanaesthesia 2026, speakers presented emerging therapeutic strategies to modulate the immune response in septic patients. They discussed approaches to tailoring treatment for specific patient groups, including those with immunoparalysis or oncology-related sepsis, and examined methods for stratifying patients according to their risk of developing opportunistic infections.
Prof Mervyn Singer, University College London, UK, reviewed the rationale for corticosteroid use, discussed efforts to identify patients most likely to benefit, and addressed the challenges surrounding optimal dosing regimens and treatment duration.
Dr Giorgia Montrucchio, intensivist, Città della Salute e della Scienza Hospital and University of Turin, Italy, examined the current evidence for therapeutic plasma exchange (TPE), including practical implementation and patient selection criteria. TPE shows considerable potential to rapidly eliminate circulating injurious mediators while simultaneously replacing essential plasma proteins that have already been consumed.
Dr Krisztina Madách, Semmelweis University, Budapest, Hungary, explored why some patients who survive the initial cytokine storm of sepsis later succumb to secondary infections caused by immunoparalysis. She discussed the complex cellular and microbiological mechanisms underlying this condition, approaches to patient stratification using validated biomarkers, and the evolving field of precision immunotherapy, including cytokines, growth factors, checkpoint inhibitors, and microbiome restoration.
Prof Elie Azoulay, Paris-Cité University and Director of the Intensive Care Department, Hôpital Saint-Louis, discussed how patients with haematological malignancies and cancer may particularly benefit from tailored approaches to sepsis management. He highlighted the specific challenges involved in treating these patients, their key vulnerabilities, innovations in management that have contributed to improved outcomes, and the growing evidence supporting targeted therapeutic strategies.
Source: Euroanaesthesia 2026
Image Credit: iStock
