By Richard R. Watkins, MD, MS, FACP, FIDSA

Associate Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports that he has received research support from Allergan.

SYNOPSIS: A meta-analysis that included 38 studies found the SIRS criteria had a higher sensitivity than qSOFA in predicting short-term mortality from sepsis. SIRS criteria remain useful as a screening tool for sepsis and as a prompt to initiate diagnostic work-up and treatment.

SOURCE: Fernando SM, Tran A, Taljaard M, et al. Prognostic accuracy of the Quick Sequential Organ Failure Assessment for mortality in patients with suspected infection: A systematic review and meta-analysis. Ann Intern Med 2018;168:266-275.

In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock Task Force (Sepsis-3) issued new definitions for sepsis and septic shock.1 Two of the most significant changes were to eliminate the systemic inflammatory response syndrome (SIRS) criteria and to include the quick Sequential Organ Failure Assessment (qSOFA) score as a bedside assessment to rapidly identify patients at increased risk for poor outcomes due to sepsis. These changes have been controversial, particularly regarding the paucity of evidence for qSOFA. Therefore, Fernando and colleagues conducted a meta-analysis to compare the accuracy of the SIRS criteria and qSOFA for predicting mortality (in-hospital, 28-day, or 30-day) in adult patients with sepsis.

Researchers identified 38 studies that met the inclusion criteria for the meta-analysis. Of these, 36.8% were conducted in the United States, 23.7% were conducted in Europe, and 23.7% were conducted in Asia. Most were retrospective cohort studies (24/38, 63.2%) and none were randomized controlled trials.

The pooled sensitivity of qSOFA was 60.8% (95% confidence interval [CI], 51.4-69.4%) and the specificity was 72% (95% CI, 63.4-79.2%). The estimated diagnostic odds ratio was 3.98 (95% CI, 3.22-4.92), and the positive and negative predictive values were 2.17 (95% CI, 1.82-2.58) and 0.55 (95% CI, 0.47-0.63), respectively. The sensitivity for the SIRS criteria was 88.1% (95% CI, 82.3-92.1%), and the specificity was 25.8% (95% CI, 17.1-36.9%). The diagnostic odds ratio was 2.57 (95% CI, 2.12-3.11), and the positive and negative predictive values were 1.19 (95% CI, 1.09-1.29) and 0.46 (95% CI, 0.40-0.54), respectively.

The sensitivities for qSOFA and the SIRS criteria varied considerably based on patient location. In patients outside the intensive care unit (ICU), qSOFA sensitivity was 51.2 (95% CI, 43.6-58.7) and dropped to 46.7 (95% CI, 38.3-55.2) for patients in the emergency department (ED). By contrast, the sensitivity of the SIRS criteria for patients outside the ICU was 82.2 (95% CI, 74.5-87.9) and in the ED was 83.6 (95% CI, 75.9-89.1).

COMMENTARY

During the past several years, early recognition and prompt treatment have become well recognized as the keys to improving outcomes in sepsis. However, the goal of early recognition is challenging because there is not a gold standard diagnostic test for sepsis or a set of specific signs and symptoms.

Since the publication of Sepsis-3 in 2016, there has been widespread interest in using qSOFA as a screening tool. The qSOFA is a two-minute assessment that can be conducted at the patient’s bedside. The assessment uses fulfillment of two or more criteria (respiratory rate ≥ 22 breaths/minute, altered mental status, and systolic blood pressure ≤ 100 mmHg) to identify patients at high risk of short-term mortality from sepsis. All screening tests must have a high sensitivity for the condition they are assessing to avoid missing potential cases. Fernando and colleagues have shown that, despite their exclusion from Sepsis-3, the SIRS criteria likely are superior to qSOFA for screening patients suspected to have sepsis.

Indeed, the appropriateness of using qSOFA instead of the SIRS criteria has been questioned recently.2 It is notable that the authors of Sepsis-3 warned that qSOFA was not created to replace the SIRS criteria in screening for sepsis, but rather was designed as an early warning tool to identify patients at high risk for death and who need an escalation of care.1 One of the criteria in qSOFA is hypotension, which, in the setting of infection, usually indicates that clinical decompensation already has occurred. Thus, it is preferable that such patients be identified earlier in their clinical course before hypotension develops.

There are some important limitations to the study. As with all meta-analyses, the results are affected by the quality of the studies on which it is based. Of the 14 studies described as prospective, in fact only three were performed specifically to assess qSOFA. Moreover, the timing of when the scores were determined in relation to when cultures were taken and antibiotics started was not described. Finally, many of the qSOFA studies were performed on specific patient populations (e.g., patients with neutropenic fever or community-acquired pneumonia), yet the tool has been recommended for all adults with suspected sepsis. Whether this is an appropriate indication needs to be investigated further.

The study by Fernando and colleagues is useful because it cautions physicians not to put too much faith in qSOFA, and that the SIRS criteria remain clinically relevant. Perhaps the most prudent recommendation would be to use both qSOFA and the SIRS criteria, along with clinical judgment, to identify patients with early sepsis. Further studies on this combined approach would be beneficial.

REFERENCES

  1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-810.
  2. Sartelli M, Kluger Y, Ansaloni L, et al. Raising concerns about the Sepsis-3 definitions. World J Emerg Surg 2018;13:6.