**4. Conclusion**

In this chapter we have outlined some biological markers established in the literature and that have recognized clinical relevance for sepsis, such as CRP [18],

**19**

**Author details**

São Paulo, Brazil

Mike Yoshio Hamasaki\*

provided the original work is properly cited.

*New Biomarkers of Sepsis with Clinical Relevance DOI: http://dx.doi.org/10.5772/intechopen.82156*

were not mentioned in this chapter.

presenting a sensitivity of 75% and specificity of 85% [35].

that the treatment of this disease is increasingly early and efficient.

haptoglobin).

lactate [11], BNP [24], and procalcitonin [28]. In addition, we also present some biomarkers that we believe are promising for the disease (sRAGE, NO, and

The choice of the promising biomarkers cited in this chapter considered the clinical relevance of each of them (demonstrated by several studies) and our experience in the field. However, we recognize that there is a broad spectrum of quality papers published in the area of biomarkers for sepsis and that unfortunately those

Among the new research targets, we believe that sRAGE may be one of the most promising ones in severe sepsis. Our group demonstrated that this soluble receptor can be used as a tool to define the death prognosis of patients with septic shock,

In conclusion, it is noticeable that the currently used methods, even effective ones, require optimization. In this sense, one of the alternatives is combining biological markers, such as those exposed in this chapter, in order to increase the sensitivity and specificity of the diagnosis and prognosis of patients with sepsis, so

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Escola da Saúde do Centro Universitário das Faculdades Metropolitanas Unidas,

Débora Maria da Gomes Cunha, Guilherme Galdino da Silva and

\*Address all correspondence to: mike.yoha@gmail.com

*New Biomarkers of Sepsis with Clinical Relevance DOI: http://dx.doi.org/10.5772/intechopen.82156*

*Clinical Management of Shock - The Science and Art of Physiological Restoration*

ized, the multiplex assay may be useful in the clinic.

**3.5 Biomarker combinations**

accuracy in the prognosis of the patients.

related to high patient mortality [75].

of septic patients.

Accordingly, the cytokine profile in the septic patient could provide information about the stage of the disease and the patient's prognosis, contributing to a better intervention. In addition, we currently have a multiplex assay that simultaneously measures multiple cytokines with small plasma samples; however, this information should be interpreted with caution since the dosages of some cytokines in septic patients appear unclear in the literature needing to be standardized. Once standard-

As previously seen, no biomarker has 100% sensitivity or specificity capable of predicting the clinical outcome for the patient with sepsis. Studies have shown that combining biomarkers may facilitate diagnosis and predict the outcome more faithfully. As above mentioned, Guo demonstrated that the combination among lactate, CRP and BNP, or NT-proBNP has greater specificity for prognosis than isolated lactate dosage, being 100 and 69.23%, respectively [15]. Yu and colleagues [45] also showed that combining NO with SAA is an important tool to improve the prognosis

Clinical scores are not effective in early identification of infection in critically ill patients; however, combining these scores with biomarkers allows an early and accurate identification of sepsis. For example, Yoo and co-workers found that combining Modified Early Warning Score (MEWS), a tool for monitoring sepsis, with blood lactate levels was efficient for early identification of the disease [69]. The same was found by Bozza et al. [70] and Oberholzer et al. [71] when they combined the levels of MPC-1 or IL-6 with APACHE II, respectively, and found greater

Other biomarkers aforementioned are also more accurate when combined. Han et al. showed that the association with CRP and PCT is an important tool to differentiate bacterial sepsis from other possible types of infection in critically ill patients [72]. Angeletti et al. [73] also showed that the combination among PCT, Tumor Necrosis Factor-α (TNF-α), and the adrenomedullin hormone fragment may help in the prior diagnosis and prognosis of septic patients, thus optimizing treatment of patients.

As mentioned above, IL-6, IL10, and IL-8 cytokines may also be altered in septic

patients. In this way, combining cytokine dosage with another biomarker may improve the diagnosis. For example, it has been shown that combining CRP dosage with IL8 and IL2 was useful in the diagnosis of neonatal sepsis [74]. Another study with adult septic patients measured TNF, IL6, and IL10 and demonstrated that combining IL6 (pro-inflammatory) with IL10 (anti-inflammatory) cytokines was useful in establishing the prognosis. Moreover, high levels of IL-6 and IL-10 were

Another combination has been demonstrated by Wong and colleagues who showed that interleukin-27 (IL-27) when combined with PCT can improve the diagnostic accuracy in septic patients when compared to each biomarker alone [76]. In 2012, Andaluz-Ojeda et al. [66] using the multiplex assay demonstrated that combining pro—IL-6 and IL-8—and anti-inflammatory cytokine—IL10 and MCP-1—levels was more predictive than analyzing each cytokine separately. Furthermore, high levels of these cytokines were positively correlated with the patient's mortality rate.

In this chapter we have outlined some biological markers established in the literature and that have recognized clinical relevance for sepsis, such as CRP [18],

**18**

**4. Conclusion**

lactate [11], BNP [24], and procalcitonin [28]. In addition, we also present some biomarkers that we believe are promising for the disease (sRAGE, NO, and haptoglobin).

The choice of the promising biomarkers cited in this chapter considered the clinical relevance of each of them (demonstrated by several studies) and our experience in the field. However, we recognize that there is a broad spectrum of quality papers published in the area of biomarkers for sepsis and that unfortunately those were not mentioned in this chapter.

Among the new research targets, we believe that sRAGE may be one of the most promising ones in severe sepsis. Our group demonstrated that this soluble receptor can be used as a tool to define the death prognosis of patients with septic shock, presenting a sensitivity of 75% and specificity of 85% [35].

In conclusion, it is noticeable that the currently used methods, even effective ones, require optimization. In this sense, one of the alternatives is combining biological markers, such as those exposed in this chapter, in order to increase the sensitivity and specificity of the diagnosis and prognosis of patients with sepsis, so that the treatment of this disease is increasingly early and efficient.
