Article, Emergency Medicine

Biomarkers in the early diagnosis of sepsis: the quest continues

Journal logoImprint logoAmerican Journal of Emergency Medicine 33 (2015) 1671

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www. elsevier. com/ locate/ajem

Controversies

Biomarkers in the early diagnosis of sepsis: the quest continues?

Salim Surani, MD a,b, Joseph Varon, MD c,d,e,?

a Texas A&M University, Corpus Christi, TX, USA

b University of North Texas, Corpus Christi, TX, USA

c The University of Texas Health Science Center at Houston, Houston, TX, USA

d The University of Texas Medical Branch at Galveston, Houston, TX, USA

e University General Hospital, Houston, TX, USA

Sepsis remains one of the leading causes of death among hospital- ized patients [1]. The emergency department (ED) is the portal of entry for many of these patients. In the acute care setting, a variety of clinical trials have attempted to identify the ideal diagnostic test, which can help the early detection of sepsis. Biomarkers and polymer- ase chain reaction assays have been used to help differentiate between the systemic inflammatory response syndrome and sepsis [2]. Of them, procalcitonin has been shown to be a reliable biomarker that can help detect sepsis as early as 8 hours after its onset [3]. However, the cost of PCT testing and the need for separate laboratory equipment have hampered its use. Procalcitonin has been shown to be more sensi- tive than C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell count in patients with sepsis [4].

Others have used other less expensive alternatives, such as the delta neutrophil index (DNI) as an early detector of sepsis. The DNI can be easily obtained from the routine Laboratory analysis. Kim et al [5] showed that the DNI predicts sepsis comparative to PCT and better than CRP. In some studies, combinations of different biomarkers have been found useful in predicting sepsis and survival. Debiane et al [6] found that proadrenomedullin and PCT were superior to CRP in re- sponse to antimicrobial therapy in patients with sepsis. interleukin 6 combined with PCT has also been shown to predict positive blood cul- tures among patients with sepsis [7].

Some authors have argued that scoring systems are better predictors in the ED when compared to biomarkers in determining if a patient has sepsis. The Mortality in the Emergency Department Sepsis (MEDS) score has been shown to have better prognostic value when compared with CRP, PCT, interleukin 6, and lactate [8,9].

In this issue of The American Journal of Emergency Medicine, Gao et al

[10] tried to determine the feasibility of using a newer biomarker in the evaluation of patients with sepsis. These investigators evaluated the prognostic value of myeloid-related protein complex (MRP) 8/14, 2 calcium-binding proteins of the S-100 family, in patients with sepsis. The results of this small clinical trial were quite impressive. The area under the curve for MRP 8/14 in patients with sepsis was 0.901, with sensitivity and specificity of 83.1% and 88.5%. In addition, these investi- gators showed that MRP 8/14 was better in predicting 28-day sepsis mortality when compared to the Mortality in the Emergency Department

? Conflicts of interest: None.

* Corresponding author at: 2219 Dorrington Street, Houston, TX 77030, USA. Tel.: +1 713 669 1670; fax: +1 713 669 1671.

E-mail address: [email protected] (J. Varon).

Sepsis score. In addition, those patients with sepsis and renal insufficien- cy had higher MRP 8/14 levels than those patients who did not have evidence of kidney injury. The primary putative effect of MRP-8 and MRP-14 in the setting of sepsis is the regulation of leukocyte migration.

Although the results of this study are encouraging, there are still a variety of questions that will need to be addressed. In particular, the availability of the assay, turnaround time, and cost will need to be ad- dressed in the very near future. Clinicians will also have to understand the limitations of this bioassay in patients with renal insufficiency. Myeloid-related protein complex 8/14 is interesting and likely to be useful in the ED; however, it is not ready for primetime yet.

Biomarkers remain an important tool in the ED. They may be able to identify the presence or absence of sepsis and present an index of sever- ity of illness. In the hospital setting, these biomarkers may also aid in prognostication, guide antibiotic therapy, and evaluate the response to the therapeutic interventions in sepsis. The quest for predicting sepsis complications and the development of Multiorgan dysfunction contin- ue. Further clinical trials aimed at validating some of these markers are needed. We applaud the efforts of Dr Gao and associates in trying to identify one such biomarker.

References

  1. Marik P, Varon J. Sepsis: state-of-the-art. Dis Mon 2001;42:462-532.
  2. Bloos F. Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays. Methods Mol Biol 2015;1237:247-60.
  3. Zuno C, Varon J. The value of procalcitonin in pulmonary infections. Curr Respir Med

    Rev 2013;9:1-2.

    Leli C, Cardaccia A, Ferranti M, Cesarini A, D’Alo F, Ferri C, et al. Procalcitonin better than C-reactive protein, erythrocyte sedimentation rate, and white blood cell count in predicting DNAemia in patients with sepsis. Scand J Infect Dis 2014;46:745-52.

  4. Kim H, Kim Y, Lee HK, Kim KH, Yeo CD. Comparison of the delta neutrophil index with procalcitonin and C-reactive protein in sepsis. Clin Lab 2014;60:2015-21.
  5. Debiane L, Hachem RY, Al Wohoush I, Shomali W, Bahu RR, Jiang Y, et al. The utility of proadrenomedullin and procalcitonin in comparison to C-reactive protein as pre- dictors of sepsis and Bloodstream infections in critically ill patients with cancer. Crit Care Med 2014;42:2500-7.
  6. Naffaa M, Makhoul BF, Tobia A, Kaplan M, Aronson D, Azzam ZS, et al. Procalcitonin and interleukin 6 for predicting Blood culture positivity in sepsis. Am J Emerg Med 2014;32:448-51.
  7. Putra BE, Tiah L. The mortality in emergency department sepsis score as a predictor of 1-month mortality among adult patients with sepsis. Weighing the evidence. ISRN Emerg Med 2013;2013(896802):1-6.
  8. Varon J, Acosta P. Is the Mortality in the Emergency Department Sepsis score a reli- able Predictive tool for the ED physician? Am J Emerg Med 2008;26:693-4.
  9. Gao S, Yang Y, Fu Y, Guo W, Liu G. Diagnostic and prognostic value of myeloid-related protein complex 8/14 for sepsis. Am J Emerg Med 2015 Jun 17. pii: S0735- 6757(15)00502-1. http://dx.doi.org/10.1016/j.ajem.2015.06.025. [Epub ahead of print].

    http://dx.doi.org/10.1016/j.ajem.2015.08.008

    0735-6757/(C) 2015

Leave a Reply

Your email address will not be published. Required fields are marked *