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Correspondence |

Characterizing Systemic Immune Dysfunction Syndrome to Fill in the Gaps of SEPSIS-2 and SEPSIS-3 Definitions FREE TO VIEW

Jesús F. Bermejo-Martin, MD, PhD; Eduardo Tamayo, MD, PhD; David Andaluz-Ojeda, MD, PhD; Marta Martín-Fernández, MSc; Raquel Almansa, PhD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

OTHER CONTRIBUTIONS: We appreciate the support from Consejería de Sanidad de Castilla y León and Instituto de Salud Carlos III for maintaining our research program on sepsis (grants EMER 07/050, PI13/02110, and PI16/01156).

aGrupo de Investigación Clínica en Infección e Inmunidad, Hospital Clínico Universitario/IECSCYL, Valladolid, Spain

bServicio de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain

cServicio de Medicina Intensiva, Hospital Clínico Universitario, Valladolid, Spain

CORRESPONDENCE TO: Jesús F. Bermejo-Martin, MD, PhD, Grupo de Investigación Clínica en Infección e Inmunidad (ICÏ), Hospital Clínico Universitario/ IECSCYL, Avda Ramón y Cajal 3, 47005 Valladolid. Spain


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(2):518-519. doi:10.1016/j.chest.2016.11.047
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We read with interest Dr Simpson’s editorial entitled “New Sepsis Criteria: A Change We Should Not Make” in a recent issue of CHEST (May 2016). The author argues against clinical implementation of the SEPSIS-3 guidelines for defining sepsis. SEPSIS-3 has solved a major problem of SEPSIS-2, which required the presence of systemic inflammatory response syndrome (SIRS) + suspected infection to define sepsis. For most physicians, the term “sepsis” is usually reserved for patients with a severe infection deserving critical care. Using the SEPSIS-2 criteria would “overestimate” the number of cases of this disease by considering uncomplicated infection as sepsis. Conversely, the SEPSIS-2 definition excludes a number of patients with potentially deleterious infection because SIRS is absent in one of eight patients with infection and organ dysfunction. We agree with Dr Simpson that the lethality of sepsis demands a screening mechanism exhibiting high sensitivity, but in our opinion, specificity does not have to be sacrificed. It is clear that the SEPSIS-2 and SEPSIS-3 definitions leave in “no men’s land” those patients with an infection and a potential complicated outcome neither fulfilling the criteria of SIRS nor showing signs of organ failure at clinical presentation.

The existence of a dysregulated host response to infection is now considered a central pathogenic event in this disease and correlates with the extent of organ failure. We propose to better characterize those features of immunologic dysfunction conferring risk of organ failure and death in infected patients, to build the concept of systemic immune dysfunction syndrome (SIDS) for early identification of sepsis. Some of these features are well known (eg, low levels of human leukocyte antigen-DR expression in monocytes, depressed T CD4/CD8 immunity, relative increase in regulatory T cells, absence of increment of neutrophil concentration in blood over the upper limit of normality [8,000 cells/mm3], increased immature forms of these cells, low levels of immunoglobulins), but large prospective studies must be developed to further characterize them.

This effort would attempt to generate a form of “SEPSIS 2.5” definition, which would consider sepsis as “an infection in the presence of SIDS” (Fig 1), indicating a potential complicated outcome in patients experiencing an infection. These patients would require close monitoring of blood pressure, lactate levels, presence of altered mentation, and tachypnea; active microbiological testing; admission to the hospital/ICU; and early treatment with systemic antibiotics., As a result, the concept of SIDS could help obtain a better balance between sensitivity and specificity in the diagnosis of sepsis.

Figure Jump LinkFigure 1 SIDS would indicate a potential complicated outcome in patients experiencing an infection. Left, Gaps not covered by SEPSIS-2 or SEPSIS-3 definitions. A = presence of infection with organ failure (Sequential Organ Failure Assessment score ≥ 2) but with no SIRS. B = presence of infection with no organ failure at clinical diagnosis, with no SIRS, but at risk of complications based on the immunologic profile (SIDS). C = presence of infection with SIRS and no organ failure at clinical diagnosis but at risk of complications based on the immunologic profile (SIDS). Right, The presence of SIDS + infection would define sepsis. SIDS = systemic immune dysfunction syndrome; SIRS = systemic inflammatory response syndrome.Grahic Jump Location

References

Simpson S.Q. . New sepsis criteria: a change we should not make. Chest. 2016;149:1117-1118 [PubMed]journal. [CrossRef] [PubMed]
 
Vincent J.L. .Opal S.M. .Marshall J.C. .Tracey K.J. . Sepsis definitions: time for change. Lancet Lond Engl. 2013;381:774-775 [PubMed]journal. [CrossRef]
 
Bermejo-Martin J.F. .Andaluz-Ojeda D. .Almansa R. .et al Defining immunological dysfunction in sepsis: a requisite tool for precision medicine. J Infect. 2016;72:525-536 [PubMed]journal. [PubMed]
 
Almansa R. .Wain J. .Tamayo E. .et al Immunological monitoring to prevent and treat sepsis. Crit Care Lond Engl. 2013;17:109- [PubMed]journal. [CrossRef]
 
Bermejo-Martin J.F. .Andaluz-Ojeda D. .Almansa R. .Eiros J.M. .Tamayo E. . Preventing sepsis. Lancet Infect Dis. 2015;15:1259-1260 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 SIDS would indicate a potential complicated outcome in patients experiencing an infection. Left, Gaps not covered by SEPSIS-2 or SEPSIS-3 definitions. A = presence of infection with organ failure (Sequential Organ Failure Assessment score ≥ 2) but with no SIRS. B = presence of infection with no organ failure at clinical diagnosis, with no SIRS, but at risk of complications based on the immunologic profile (SIDS). C = presence of infection with SIRS and no organ failure at clinical diagnosis but at risk of complications based on the immunologic profile (SIDS). Right, The presence of SIDS + infection would define sepsis. SIDS = systemic immune dysfunction syndrome; SIRS = systemic inflammatory response syndrome.Grahic Jump Location

Tables

References

Simpson S.Q. . New sepsis criteria: a change we should not make. Chest. 2016;149:1117-1118 [PubMed]journal. [CrossRef] [PubMed]
 
Vincent J.L. .Opal S.M. .Marshall J.C. .Tracey K.J. . Sepsis definitions: time for change. Lancet Lond Engl. 2013;381:774-775 [PubMed]journal. [CrossRef]
 
Bermejo-Martin J.F. .Andaluz-Ojeda D. .Almansa R. .et al Defining immunological dysfunction in sepsis: a requisite tool for precision medicine. J Infect. 2016;72:525-536 [PubMed]journal. [PubMed]
 
Almansa R. .Wain J. .Tamayo E. .et al Immunological monitoring to prevent and treat sepsis. Crit Care Lond Engl. 2013;17:109- [PubMed]journal. [CrossRef]
 
Bermejo-Martin J.F. .Andaluz-Ojeda D. .Almansa R. .Eiros J.M. .Tamayo E. . Preventing sepsis. Lancet Infect Dis. 2015;15:1259-1260 [PubMed]journal. [CrossRef] [PubMed]
 
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