February 7, 2017

Putting them to the test in the ICU: SOFA, SIRS & qSOFA 


In 2016, a new definition for sepsis and its diagnosis has been recommended by an international task-force of experts [1-3]. Indeed, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Previous evidence showed the poor specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria [4], inappropriately excluded otherwise similar patients with infection, organ failure, and increased mortality. The Sepsis-3 consensus now recommends that diagnosis of sepsis should be now based on the increase of at least 2 points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score in patients with a suspicion of infection. Moreover, the Sepsis-3 introduced the quick SOFA (qSOFA) score, a surrogate for SOFA in settings in which all components of SOFA are not routinely measured (for instance in the emergency department and in the ward). The purpose of the qSOFA was to allow early diagnosis of sepsis in order to allow timely treatment and achieve the goals of resuscitation. However, the data to support such change of mindset on the diagnosis of sepsis were drawn from North American cohorts and a single German cohort. Therefore, external validations of the Sepsis-3 criteria seems desirable. 

The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes and Resource Evaluation (CORE) investigators conducted a large retrospective cohort analysis of over 184,000 patients (age≥17 years) with an infection-related primary admission diagnosis in 182 Australian and New Zealand ICUs for the period 2000-2015. The authors studied the correlation of SOFA, qSOFA, and SIRS criteria (collected within 24 hours of ICU admission) with in-hospital mortality (primary outcome) or with the composite of in-hospital mortality and ICU length of stay (LOS) ≥ 3 days (secondary outcome).

The authors reported an in-hospital mortality of almost 19% – in line with the figures reported in other large studies [6, 7] – and that over half of the patients (~56%) with an infection-related primary admission diagnosis met the composite outcome of in-hospital mortality or ICU-LOS≥ 3 days. A SOFA score increase of ≥ 2 points was noted in 90% of the cohort, 87% manifested ≥ 2 SIRS criteria, while only 54% had a qSOFA score increase of ≥ 2 points. 

The authors report that SOFA had significantly greater discrimination for the primary outcome (in-hospital mortality) than SIRS criteria or qSOFA (AUROC 0.75 vs 0.59 vs 0.61, respectively; all comparisons p values <0.001). Similarly, with regards to the composite secondary endpoint, SOFA score showed better prognostic accuracy (AUROC 0.74 vs 0.61 SIRS vs 0.61 qSOFA, respectively; p<0.001). Moreover, the study findings were consistent also in multiple sensitivity analyses, including the analyses of “mechanically ventilated-only” and “non-ventilated only” patients. Of note, SOFA score showed an incremental increase of in-hospital mortality with higher scores and this was consistent across all deciles of baseline risk.

The authors analysed a large database with a very low incidence of missing data (<1% of scores could not be calculated) and their work provide further support to the new definition of sepsis and to the new diagnostic criteria. 

The importance of early diagnosis cannot be overemphasised, and having a more accurate predictor of critical illness may improve the outcome of sepsis, although more research is needed. Importantly, it is should be noted that very recently Mayr et al. [8] provided shocking preliminary data on the burden of sepsis, showing that sepsis not only a disease with high mortality but also the leading cause of unplanned hospital readmissions and associated costs. Indeed, the authors report an incidence of unplanned 30-day readmission for sepsis of 12.2%, as compared with 1.3% for acute myocardial infarction (AMI), 6.7% for heart failure (HF), 4.6% for COPD and 5.0% for pneumonia. Moreover, sepsis re-hospitalisation was longer than readmissions for AMI, HF, COPD, and pneumonia (7.4 vs 5.7 vs 6.4 vs 6.0 vs 6.7 days, respectively). Similarly, the estimated costs per-readmission was higher for sepsis ($10,070) as compared with the other diagnoses: $8,417 for COPD, $9,051 for heart failure, $9,424 for AMI, and $9,533 for pneumonia.

Although the shift of clinicians’ mindset in the approach to the diagnosis of sepsis with new criteria may take some time, the superiority of the approach using SOFA score seems confirmed and the increased prognostic accuracy may help in early recognition and treatment of sepsis.

Article review submitted by EJRC member Filippo Sanfilippo.

1.    Shankar-Hari M, Phillips GS, Levy ML, et al.: Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:775-787, 2016.
2.    Singer M, Deutschman CS, Seymour CW, et al.: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:801-810, 2016.
3.    Seymour CW, Liu VX, Iwashyna TJ, et al.: Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:762-774, 2016.
4.    Kaukonen KM, Bailey M, Pilcher D, et al.: Systemic inflammatory response syndrome criteria in defining severe sepsis. NEJM 372:1629-1638, 2015.
5.    Raith EP, Udy AA, Bailey M, et al.: Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality Among Adults With Suspected Infection Admitted to the Intensive Care Unit. JAMA 317:290-300, 2017.
6.    Peake SL, Delaney A, Bailey M, et al.: Goal-directed resuscitation for patients with early septic shock. NEJM 371:1496-1506, 2014.
7.    Yealy DM, Kellum JA, Huang DT, et al.: A randomised trial of protocol-based care for early septic shock. NEJM 370:1683-1693, 2014.
8.    Mayr FB, Talisa VB, Balakumar V, et al.: Proportion and Cost of Unplanned 30-Day Readmissions After Sepsis Compared With Other Medical Conditions. JAMA 2017.
9.    Freund Y, Lemachatti N, Krastinova E, et al.: Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department. JAMA 317:301-308, 2017. Find a review of this article here.


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