Emerg Med J. 2025 Nov 28:emermed-2025-214894. doi: 10.1136/emermed-2025-214894. Online ahead of print.
BACKGROUND: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines sepsis as a life-threatening organ dysfunction due to a dysregulated host response to infection. Measuring a dysregulated host response is difficult in practice, so patients with organ dysfunction due to other causes, such as an underlying comorbidity or the direct effects of infection, may be diagnosed with sepsis. We aimed to characterise patients diagnosed with sepsis and meeting the Sepsis-3 criteria according to whether organ dysfunction was potentially due to a dysregulated immune response or an alternative cause.
METHODS: We undertook a single-centre, retrospective, observational study of patients admitted to hospital with sepsis between 1 January 2022 and 31 December 2022. We reviewed clinical, laboratory and imaging records to determine whether cases met Sepsis-3 criteria and whether organ dysfunction was more likely to be due to a dysregulated immune response or an identifiable alternative explanation.
RESULTS: We analysed 373 cases, of whom 303 (81.2%) fulfilled the Sepsis-3 criteria. Of these, 78 (25.7%, 95% CI 21.4% to 30.0%) had an alternative explanation for their organ dysfunction, with 28 (9.2%) due to exacerbation of a comorbidity, 42 (13.9%) direct effects of infection and 8 (2.6%) involving evidence of respiratory dysfunction based on ‘normal’ oxygen saturation measurements. Patients with an alternative explanation for their organ dysfunction tended to be less acutely ill (median (IQR) National Early Warning Score 5 (3-8) vs 7 (5-10), p<0.001) and have lower in-hospital mortality (19.2% vs 34.7%, p=0.011) than those who were more likely to have a dysregulated host response.
CONCLUSION: Around a quarter of patients diagnosed with sepsis and meeting the Sepsis-3 criteria were unlikely to have a dysregulated immune response causing their organ dysfunction. Focusing sepsis diagnosis on those most likely to have a dysregulated immune response could identify patients who are most likely to benefit from sepsis treatment and could improve sepsis care.
PubMed:41314776 | DOI:10.1136/emermed-2025-214894