Sepsis Mimics in the ICU: A Qualitative Study of Physicians' Diagnostic Experiences in Japan

Sepsis mimics are non-infectious conditions that resemble sepsis, leading to diagnostic uncertainty, delayed disease-specific therapy, and unnecessary antibiotics.

We conducted semi-structured online interviews with seven physicians with experience in adult general intensive care unit (ICU) practice in Japan (October-December 2023) and analyzed data using Reflexive Thematic Analysis.

Four themes were generated: (1) Spectrum-participants described sepsis mimics as spanning hematologic malignancy, autoimmune/inflammatory disease, endocrine/metabolic crises, drug/toxic states, and other acute non-infectious conditions. (2) Diagnostic challenges-participants described phenotypic overlap, missing or fragmented history, organizational barriers to definitive testing in unstable patients, competing pathophysiology, and diagnostic masking by early corticosteroids. (3) Therapeutic and diagnostic strategies-participants described a sepsis-oriented initial approach with broad antibiotics and organ support, followed by reactive re-evaluation for nonresponse or early parallel work-up for selected mimics. (4) Triggers for re-evaluation-participants described reconsidering sepsis when the clinical course or physiology diverged from expectations, including discrepant hemodynamics, atypical fever patterns, focal physical signs, and metabolic abnormalities not readily explained by presumed infection.

Sepsis mimics were described as diagnostically challenging in ICU practice because clinical trajectories can initially resemble sepsis and because diagnostic work-up is shaped by local organizational constraints. By mapping clinicians' reasoning processes and re-evaluation cues, our findings provide a framework for understanding diagnostic uncertainty and may inform educational efforts and future research on timely recognition of sepsis mimics.