Sepsis mimics in the Intensive Care Unit: A qualitative study of intensivists’ diagnostic experiences in Japan

Background Sepsis mimics can present with the same shock, fever, and organ dysfunction as sepsis, creating diagnostic uncertainty, delays in disease-specific therapy, and unnecessary antibiotics. How intensivists navigate these syndromes at the bedside is not well described. Methods A qualitative study design was employed. Semi-structured interviews exploring experiences with sepsis mimics were conducted with seven physicians (intensivists, emergency physicians, or general internists) with substantial ICU experience working in adult general ICUs in Japan. Data were collected online from October to December 2023. Data were analyzed using Reflexive Thematic Analysis (Braun & Clarke). Results Analysis generated four themes. (1) Spectrum: Sepsis mimics were relatively common and spanned hematologic malignancy, autoimmune/inflammatory disease, endocrine/metabolic crises, drug/toxic states, and other non-infectious SIRS-like conditions. Their diagnostic difficulty was heterogeneous, with some mimics usually recognized early and others repeatedly diagnosed only late or post-mortem. (2) Diagnostic challenges: These centered on phenotypic overlap with sepsis, unavailable or fragmented history, organizational barriers to definitive testing in unstable patients, competing pathophysiology, and diagnostic masking by early corticosteroids. (3) Strategies: Clinicians used a sepsis-first safety net with broad antibiotics and organ support, followed either by reactive re-evaluation for nonresponse or by early parallel work-up to secure mimic-specific tests before steroid administration. (4) Triggers: Re-evaluation was prompted when the clinical course or physiology diverged from clinicians’ expectations of typical sepsis, including discrepant hemodynamics, atypical temporal patterns of fever, focal physical signs, and metabolic abnormalities that felt disproportionate to presumed infection. Conclusions In ICUs, sepsis mimics are clinically important yet difficult to recognize because of both phenotypic overlap with sepsis and context-dependent constraints. While a sepsis-first approach preserves safety, our findings suggest that early parallel evaluation may help shorten time to the correct diagnosis. These insights support targeted debiasing education, multidisciplinary diagnostic pathways, and quantitative studies to clarify epidemiology and the timing-sensitive harms of delayed recognition.