Physician agreement on the diagnosis of sepsis in the intensive care unit: estimation of concordance and analysis of underlying factors in a multicenter cohort

Bert K Lopansri,Thomas D Yager,Mark Yoder,Richard E Rothman,Franco R D’Alessio,Richard B Brandon,Mangala Narasimhan,Emily Gilbert,Venkataramana K Sidhaye,John P Burke,Roslyn A Brandon,Jared A Greenberg,Majid Afshar,Leo Mchugh,Dayle Sampson,Greg S Martin,Jorge P Parada,Stella Hahn,Adey Tsegaye,Mitchell M Levy ,Russell R Miller ,Gourang Patel ,Therese Seldon ,Paul H Mayo ,Annette Esper ,R.a Balk ,Steven M Opal ,Antony Rapisarda,Jordan A Kempker

doi:10.1186/s40560-019-0368-2

Abstract

BackgroundDifferentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting.MethodsWe conducted a post hoc analysis of previously collected data from a prospective, observational trial (N = 249 subjects) in intensive care units at seven US hospitals, in which physicians at different stages of patient care were asked to make diagnostic calls of either SIRS, sepsis, or indeterminate, based on varying amounts of available clinical information (clinicaltrials.gov identifier: NCT02127502). The overall percent agreement and the free-marginal, inter-observer agreement statistic kappa (κfree) were used to quantify agreement between evaluators (attending physicians, site investigators, external expert panelists). Logistic regression and machine learning techniques were used to search for significant variables that could explain heterogeneity within the indeterminate and SIRS patient subgroups.ResultsFree-marginal kappa decreased between the initial impression of the attending physician and (1) the initial impression of the site investigator (κfree 0.68), (2) the consensus discharge diagnosis of the site investigators (κfree 0.62), and (3) the consensus diagnosis of the external expert panel (κfree 0.58). In contrast, agreement was greatest between the consensus discharge impression of site investigators and the consensus diagnosis of the external expert panel (κfree 0.79). When stratified by infection site, κfree for agreement between initial and later diagnoses had a mean value + 0.24 (range − 0.29 to + 0.39) for respiratory infections, compared to + 0.70 (range + 0.42 to + 0.88) for abdominal + urinary + other infections. Bioinformatics analysis failed to clearly resolve the indeterminate diagnoses and also failed to explain why 60% of SIRS patients were treated with antibiotics.ConclusionsConsiderable uncertainty surrounds the differential clinical diagnosis of sepsis vs. SIRS, especially before organ damage has become highly evident, and for patients presenting with respiratory clinical signs. Our findings underscore the need to provide physicians with accurate, timely diagnostic information in evaluating possible sepsis.

Highlights

Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians
Considerable uncertainty surrounds the differential clinical diagnosis of sepsis vs. SIRS, especially before organ damage has become highly evident, and for patients presenting with respiratory clinical signs
We studied physician agreement in patients admitted to intensive care unit (ICU) for the task of performing this differential diagnosis

Summary

Introduction

Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. A physician may first begin to suspect sepsis in the early stages of the disease, before organ damage is evident, when clinical signs can be either absent, varied, or clinically indistinguishable from systemic inflammation due to non-infectious causes. For patients suspected of sepsis, clinical microbiology tests may be negative but when positive often require two or more days to produce actionable results. These microbiologic data suffer from significant numbers of false-positives and false-negatives when attempting to identify the actual microbial cause of sepsis [2, 3]. Inaccuracies in early sepsis diagnosis could have significant potential consequences for patients including excessive use of empiric, broadspectrum antibiotics, inappropriate management, longterm morbidity, or death [6,7,8]

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