Robustness of sepsis-3 criteria in critically ill patients

Diana M Verboom, Jos F Frencken, David S Y Ong, Janneke Horn, Tom van der Poll, Marc J M Bonten, Olaf L Cremer, Peter M C Klein Klouwenberg, Diana M Verboom, Jos F Frencken, David S Y Ong, Janneke Horn, Tom van der Poll, Marc J M Bonten, Olaf L Cremer, Peter M C Klein Klouwenberg

Abstract

Background: Early recognition of sepsis is challenging, and diagnostic criteria have changed repeatedly. We assessed the robustness of sepsis-3 criteria in intensive care unit (ICU) patients.

Methods: We studied the apparent incidence and associated mortality of sepsis-3 among patients who were prospectively enrolled in the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) cohort in the Netherlands, and explored the effects of minor variations in the precise definition and timing of diagnostic criteria for organ failure.

Results: Among 1081 patients with suspected infection upon ICU admission, 648 (60%) were considered to have sepsis according to prospective adjudication in the MARS study, whereas 976 (90%) met sepsis-3 criteria, yielding only 64% agreement at the individual patient level. Among 501 subjects developing ICU-acquired infection, these rates were 270 (54%) and 260 (52%), respectively (yielding 58% agreement). Hospital mortality was 234 (36%) vs 277 (28%) for those meeting MARS-sepsis or sepsis-3 criteria upon presentation (p < 0.001), and 121 (45%) vs 103 (40%) for those having sepsis onset in the ICU (p < 0.001). Minor variations in timing and interpretation of organ failure criteria had a considerable effect on the apparent prevalence of sepsis-3, which ranged from 68 to 96% among those with infection at admission, and from 22 to 99% among ICU-acquired cases.

Conclusion: The sepsis-3 definition lacks robustness as well as discriminatory ability, since nearly all patients presenting to ICU with suspected infection fulfill its criteria. These should therefore be specified in greater detail, and applied more consistently, during future sepsis studies.

Trial registration: The MARS study is registered at ClinicalTrials.gov (identifier NCT01905033).

Keywords: Critical care; Incidence; Infection; Mortality; Sepsis; Septic shock.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Hypothetical cases showing the influence of variations in organ failure definitions. SOFA = Sequential Organ Failure Assessment. The onset of infection (i.e., start of empirical antibiotic therapy) is day 0. Case 1 does not fulfill the sepsis-3 definition as there is no SOFA score increase of ≥ 2 points within the 4-day (or 2-day) time-window. However, case 1 fulfills the criteria if sepsis is defined by the presence of an absolute SOFA score of ≥ 2 (both in the 4-day and 2-day time-window). Case 2 fulfills the sepsis-3 criteria since there is an increase of ≥ 2 points between day 0 and day 1. In a reduced time-window, there is no increase observed between the day before infection and day of the onset of infection, and sepsis-3 criteria are not met
Fig. 2
Fig. 2
Flowchart. ICU = intensive care unit
Fig. 3
Fig. 3
Venn diagram comparing MARS-sepsis and sepsis-3 definitions. ICU = intensive care unit. Presented as frequencies of patients (%)

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