Introduction
Materials and methods
Results
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
√ | C (m) | √ | Higher in septic shock than in sepsis | |
√ | C | √ | No difference between survivors and non-survivors at 28 days | |
√ | A | √ | Correlation with SOFA score | |
√ | A | Increased in septic compared with non-septic individuals | ||
IL-2 [58] | B | √ | Increased in parallel with disease severity | |
IL-4 [59] | C (s) | √ | Increased levels associated with development of sepsis | |
√ | B | √* | Distinguished between survivors and non-survivors at 28 days | |
B | √*** | Prediction of MOF, DIC | ||
√ | B | √** | Higher in septic shock than sepsis, distinguished between survivors and non-survivors at 28 days | |
√ | C | √ | Predictive of lethal outcome from postoperative sepsis | |
√ | B | √ | Higher in septic shock than sepsis | |
√ | B(s) | √ | Distinguished between survivors and non-survivors at 28 days | |
√ | A | √ | Increased in sepsis compared with healthy controls | |
√ | A | √** | Distinguished between survivors and non-survivors at 28 days | |
√ | B | √* | Distinguished between survivors and non-survivors at 28 days | |
Osteopontin [75] | B | Increased in sepsis compared with healthy controls | ||
√ | B | Increased in sepsis compared with healthy controls | ||
√ | C | √ | Distinguished between survivors and non-survivors at 28 days in patients with septic shock |
Sepsis Marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
√ | A | Decreased in septic shock compared with healthy controls | ||
√ | B(s) | √ | Correlation with SOFA score | |
CD11c [84] | A | Decreased in septic shock compared with healthy controls | ||
CD14 (cellular and soluble) [85] | C | √ | Distinguished between survivors and non-survivors at 28 days | |
CD18 [86] | √ | |||
CD25 (cellular and soluble) [87] | A | Distinguished between survivors and non-survivors at 28 days | ||
CD28 (soluble) [88] | B | √ | Distinguished between survivors and non-survivors at 28 days | |
CD40 (cellular and soluble) [89] | B | √ | Distinguished between survivors and non-survivors at 28 days | |
CD48 [90] | B | Increased in sepsis compared with healthy controls | ||
CD64 [91] | B | √ | Correlation with APACHE II and SOFA scores | |
CD69 [92] | A | Increased in sepsis compared with healthy controls | ||
CD80 [88] | B | √ | Predicted development of septic shock | |
CD163 (soluble) [93] | C | √ | Distinguished between survivors and non-survivors at 28 days | |
mHLA-DR (soluble) [94] | C | √* | Distinguished between survivors and non-survivors at 28 days in patients with septic shock |
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
CC chemokine receptor (CCR) 2 [95] | √ | |||
CCR 3 [96] | C | √ | Distinguished between survivors and non-survivors at 28 days | |
C5L2 [97] | √ | B | √ | Predicted development of MOF |
CRTh2 [98] | C | √ | Distinguished between survivors and non-survivors at 28 days | |
Fas receptor (soluble) [99] | B(m) | √ | Predicted development of MOF | |
Fc-gamma RIII [100] | A | √ | Increased in sepsis compared with healthy controls, correlated with APACHE II score | |
√ | C | √ | Correlated with APACHE II score | |
GP130 [103] | A | Increased in sepsis compared with healthy controls | ||
IL-2 receptor (soluble) [104] | C | √ | Predicted development of septic shock | |
√ | B | Distinguished between survivors and non-survivors at 28 days | ||
RAGE (soluble) [107] | B | √* | Distinguished between survivors and non-survivors at 28 days | |
ST2 (soluble, IL-1 receptor) [108] | A(s) | √ | Increased in sepsis compared with healthy controls | |
Toll-like receptor (TLR) 2 and 4 [109] | √ | B | √ | Increased in septic compared with non-septic critically ill patients |
Transient receptor potential vanilloid (TRPV)1 [110] | √ | |||
√ | C | √ | Distinguished between survivors and non-survivors at 28 days | |
TNF-receptor (soluble) [113] | B | Predicted development of MOF | ||
Urokinase type plasminogen activator receptor (uPAR) (soluble) [114] | C(m) | √ | Distinguished between survivors and non-survivors at 28 days |
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
Antithrombin [115] | √ | B | √** | Distinguished between survivors and non-survivors at 28 days |
Activated partial thromboplastin time (aPTT) [35] | C | √ | Correlated with MOF score in patients with sepsis and DIC, high negative predictive value | |
D-dimers, TAT, F1.2, PT [116] | C | √ | Distinguished between survivors and non-survivors at 28 days, correlated with APACHE II score | |
Fibrin [36] | C | Increased in patients with Gram-negative bacteremia | ||
PF-4 [117] | A | √ | Predicted response to therapy | |
B | √ | Distinguished between survivors and non-survivors at 28 days, predicted development of MOF | ||
√ | C | √* | Distinguished between survivors and non-survivors at 28 days | |
√ | C | √ | Predicted development of MOF, DIC, and response to therapy |
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
√ | B | √ | Decreased in septic patients with DIC compared with no DIC | |
Angiopoietin (1 and 2) [126] | B | √ | Distinguished between survivors and non-survivors at 28 days | |
√ | B | √ | Predicted development of septic shock | |
√ | B(s) | √* | Distinguished between survivors and non-survivors at 28 days | |
Endothelial progenitor cells (cEPC) [131] | B | √ | Distinguished between survivors and non-survivors at 28 days | |
Intracellular adhesion molecule (ICAM)-1 (soluble) [38] | √ | B(m) | √ | |
Laminin [132] | A | Increased in sepsis compared with non-infected controls | ||
√ | C | √* | Distinguished between survivors and non-survivors at 28 days | |
Platelet-derived growth factor (PDGF)-BB [135] | B | √ | Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis | |
√ | C | √ | Predicted development of MOF, correlated with SAPS score | |
L-Selectin (soluble) [137] | C | √* | Distinguished between survivors and non-survivors at 28 days | |
P-Selectin [138] | √ | |||
√ | C | Predicted development of MOF | ||
√ | A | √ | Distinguished between survivors and non-survivors at 28 days, predicted development of MOF | |
B(m) | √ | Distinguished between survivors and non-survivors at 28 days, predicted development of acute lung injury |
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
B | √* | Predicted development of septic shock | ||
Anandamide [147] | √ | A | Increased in sepsis compared with healthy controls | |
√ | B | Increased in sepsis compared with healthy controls | ||
2-arachidonoylglycerol [150] | A | Increased in sepsis compared with healthy controls | ||
Copeptin [151] | C(m) | √* | Distinguished between survivors and non-survivors at 28 days, correlated with APACHE II score | |
C-type natriuretic peptide (CNP) [152] | A | Increased in patients with septic shock compared with healthy controls | ||
√ | A(m) | √ | Distinguished between survivors and non-survivors at 28 days | |
Elastin [155] | B | Decreased in sepsis compared with healthy controls | ||
√ | C(s) | √ | Distinguished between survivors and non-survivors at 28 days, correlated with APACHE II score | |
47 kD HK [158] | B(m) | Correlated with severity of sepsis | ||
√ | A | Increased in sepsis compared with healthy controls | ||
√ | B | √ | Predicted development of septic shock | |
√ | C(s) | √ | Distinguished between survivors and non-survivors at 28 days (predictive only in the late phase of sepsis, 2 days before death) | |
A | Increased in sepsis compared with non-septic critically ill patients | |||
√ | A | Increased in tissue samples from patients with peritonitis compared with no peritonitis |
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
C | √* | Distinguished between survivors and non-survivors at 28 days | ||
B | √** | Distinguished between survivors and non-survivors at 28 days, correlated to APACHE II score | ||
Carbomyl phosphate synthase (CPS)-1 [173] | √ | |||
√ | B | √ | Distinguished between survivors and non-survivors at 28 days, correlated with SOFA score | |
Filterable cardiodepressant substance (FCS) [178] | √ | |||
Gc-globulin [179] | C(s) | Predicted development of MOF | ||
Glial fibrillary acidic protein (GFAP) [180] | B | √ | Increased in septic shock compared with healthy controls | |
alpha glutathione S-transferase (GST) [181] | √ | |||
√ | C(m) | Predicted response to therapy | ||
√ | A | √ | Correlated with SAPS II score | |
Myocardial angiotensin II [186] | √ | |||
NSE [187] | B | √ | Correlated with SOFA scores | |
Pancreatitis-associated protein-I [188] | √ | |||
Pre B cell colony-enhancing factor (PBEF) [189] | A | Increased in sepsis compared with healthy controls | ||
√ | B | √ | Distinguished between survivors and non-survivors at 28 days, correlated with SOFA score | |
√ | A | Increased in sepsis compared with healthy controls | ||
Troponin [193] | B | √ | Distinguished between survivors and non-survivors at 28 days, correlated with APACHE II score |
Sepsis Marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
√ | B(s) | √ | Correlated with CRP in patients with septic shock | |
A | √ | Predicted liver dysfunction in patients with sepsis | ||
C | √* | Predicted response to therapy | ||
Ferritin [200] | B(m) | √ | Distinguished between survivors and non-survivors at 28 days, correlated with SOFA score | |
√ | B | √ | Distinguished between survivors and non-survivors at 28 days, correlated with SOFA score | |
Hepcidin [203] | B | Incraesed in sepsis compared with healthy controls and patients with chronic renal failure | ||
√ | C(s) | √ | Higher in sepsis compared with no sepsis, no prognostic value | |
√ | C | √* | Increased in infected compared with non-infected patients | |
C | √ | Distinguished between survivors and non-survivors at 28 days, correlated with APACHE II score |
Sepsis marker | Evaluated in experimental studies | Evaluated in clinical studies | Evaluated as a prognostic factor | Comment |
---|---|---|---|---|
√ | ||||
Albumin [209] | √ | |||
Anti-endotoxin core antibodies (EndoCab) [210] | A | √ | Distinguished between survivors and non-survivors at 28 days | |
C | √ | Distinguished between survivors and non-survivors at 28 days | ||
Bcl-2 [214] | A | √ | Distinguished between survivors and non-survivors at 28 days | |
Beta-thromboglobulin [215] | B | √ | Predicted response to therapy | |
Caspase-1 [216] | A | Increased in septic shock compared with healthy controls | ||
Ceramide [217] | B | √** | Predicted development of MOF | |
Cholesterol [218] | C | √ | Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis | |
B(m) | √ | Distinguished between survivors and non-survivors at 28 days | ||
Terminal complement complex [221] | √ | |||
√ | B | √ | Distinguished between survivors and non-survivors at 28 days, correlated with SOFA score | |
Dipeptidylpeptidase [224] | B | Decreased in sepsis compared with healthy controls | ||
Diiodotyrosine (DIT) [225] | C | √ | Increased in sepsis compared with non-septic critically ill | |
√ | A(s) | √ | Correlated with SAPS score, predicted response to therapy | |
√ | C(s) | √ | Predicted response to therapy in patients with joint infections | |
C | √ | Predicted response to therapy | ||
Erythropoietin [232] | A | √ | Distinguished between survivors and non-survivors at 28 days in patients with septic shock, correlated with lactate levels | |
F2 isoprostanes [233] | B(m) | √ | Increased in infected diabetic patients compared with non-infected diabetics | |
Fatty acid amide hydrolase [234] | A | √ | Decreased in sepsis compared with healthy controls | |
Free DNA [235] | B | √* | Distinguished between survivors and non-survivors at 28 days | |
B | √** | Distinguished between survivors and non-survivors at 28 days | ||
Gelsolin [238] | B(s) | √ | Distinguished between survivors and non-survivors at 28 days | |
√ | ||||
Growth arrest specific protein (Gas) 6 [241] | B | √ | Correlated with APACHE II score in patients with severe sepsis | |
√ | C(s) | Increased in sepsis compared with healthy controls | ||
HDL cholesterol | C | √** | Distinguished between survivors and non-survivors at 28 days, predicted polonged ICU length of stay | |
HLA-G5 protein (soluble) [246] | C(m) | √* | Distinguished between survivors and non-survivors at 28 days in patients with septic shock | |
H2S [247] | √ | |||
√ | B | Distinguished between survivors and non-survivors at 28 days in patients with septic shock | ||
Hydrolytic IgG antibodies [250] | B | √ | Distinguished between survivors and non-survivors at 28 days, correlation with SAPS II score | |
Inter-alpha inhibitor proteins (IalphaIp) [251] | C | √ | Predicted development of MOF | |
Intracellular nitric oxide in leukocyte [252] | B | √ | Negatively correlated with SOFA score | |
IP-10 [30] | C | Increased in sepsis compared with healthy controls | ||
C | √ | Distinguished between survivors and non-survivors at 28 days, predicted response to therapy | ||
√ | C(s) | Predicted response to therapy | ||
√ | B | √ | No prognostic value, higher in septic than in non-septic ICU patients | |
Serum lysozyme (enzyme activity) [258] | B(s) | Increased in sepsis compared with healthy controls | ||
Matrix-metalloproteinase (MMP)-9 [259] | B | Increased in severe sepsis compared with healthy controls | ||
Microparticles (cell derived) [252] | B | √ | Distinguished between survivors and non-survivors at 28 days, correlation with SOFA score | |
Neurotensin [260] | √ | |||
Nitrate excretion (urinary and expired) [261] | √ | |||
Nociceptin/orphanin FQ (N/OFQ) [262] | A | √ | Distinguished between survivors and non-survivors at 28 days | |
NF-κB (activity and expression) [263] | B | √** | Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis, correlation with APACHE II score | |
Nucleosomes [264] | C | Distinguished between survivors and non-survivors at 28 days | ||
Peptidoglycan [265] | B(s) | √ | Increased in sepsis compared with healthy controls | |
PlGF [266] | √ | |||
A | √ | Distinguished between survivors and non-survivors at 28 days, predicted development of MOF | ||
Plasma fibronectin [270] | B | √ | Increased in sepsis compared with healthy controls | |
Plasmin alpha2-antiplasmin complex [271] | C | Predicted development of MOF | ||
Renin [272] | B | √ | Correlation with lactate levels in patients with septic shock | |
Resistin [273] | C | √ | Correlation with APACHE II score in patients with severe sepsis | |
Selenium [274] | C | √ | Correlation with APACHE II in patients with severe sepsis | |
Selenoprotein P [275] | B | Decraesed in sepsis compared with healthy controls | ||
Serum bicarbonate [276] | A(m) | √ | Predicted development of septic shock in neutropenic patients | |
Sphingomyelinase (enzyme activity) [277] | A | Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis | ||
Sulfite [278] | √ | B(m) | √ | Predicted response to therapy |
√ | A(m) | Distinguished between survivors and non-survivors at 28 days | ||
TIMP-1 and 2 [259] | B | √* | Distinguished between survivors and non-survivors at 28 days | |
TIMP-3 [281] | √ | |||
Uric acid [282] | C(s) | √ | Decreased in postoperative patients with sepsis compared with those with no sepsis | |
Urinary 8-OhdG [283] | C | √ | Distinguished between survivors and non-survivors at 28 days | |
Urinary bilirubin oxidative metabolites (BOMs) [284] | A | √ | Correlation with APACHE II score | |
Annexin V binding [285] | √ | B(s) | Increased in sepsis compared with healthy controls | |
Xanthine oxidase (activity) [286] | C | √ | Distinguished between survivors and non-survivors at 28 days |
Sepsis biomarker | Clinical study | Type of measurement | Outcome | |
---|---|---|---|---|
1 | aPTT**[35] |
C
|
c
| High negative predictive value |
2 | CD11b***[33] |
B
|
s
| Higher values in neonates with sepsis than in those with possible infection |
3 | CD25[87] |
A
|
s
| Distinguished between sepsis and SIRS |
4 |
C
|
s
| Low sensitivity and specificity to distinguish between viral and bacterial infections | |
5 | Complement (C3, C4, C5a)[219] |
B
|
s
| Distinguished between sepsis and SIRS |
6 | EA complex[230] |
C
|
s
| Diagnosis of sepsis, increased earlier than CRP |
7 | ELAM-1 (cellular and soluble)[129] |
C(s)
|
c
| Increased in trauma patients with sepsis compared with no sepsis |
8 | Endocan [127] |
B
|
s
| Distinguished between sepsis and SIRS |
9 | E-Selectin (cellular and soluble)[136] |
B
|
s
| Distinguished between sepsis and SIRS |
10 | Fibrin degradation products[36] |
B
|
s
| High negative predictive value |
11 | Gas6[241] |
B
|
s
| Higher values in patients with severe sepsis compared with patients with organ failure but no sepsis |
12 | G-CSF[237] |
C
|
s
| Distinguished between sepsis and SIRS |
13 | Gelsolin[238] |
B(s)
|
c
| Higher in septic patients compared with patients without sepsis |
14 | IL-1 receptor antagonist[55] |
C
|
s
| Early diagnosis of sepsis before symptoms in newborns |
15 | IL-8*[61] |
C
|
s
| Higher in septic neutropenic patients compared with febril neutropenic patients without sepsis |
16 | IL-10[65] |
A
|
s
| Higher in septic shock compared with cardiogenic shock |
17 | IL-12***[29] |
C
|
s
| Diagnosis of sepsis in pediatric patients |
18 | IL-18[70] |
B(s)
|
s
| Distinguished between Gram-positive and Gram-negative sepsis. Higher in trauma patients with sepsis than in those without |
19 | IP-10***[30] |
C
|
s
| Early diagnosis of sepsis in newborns |
20 | Laminin[38] |
A
|
s
| Distinguished between Candida sepsis and bacterial sepsis |
21 | LBP[204] |
C
|
s
| Distinguished between Gram-positive sepsis and Gram-negative |
22 | MCP-1[61] |
C
|
s
| Distinguished between sepsis and SIRS in neutropenic pediatric patients |
23 | NO, nitrate, nitrite[161] |
B
|
s
| Higher in septic shock compared with cardiogenic shock |
24 | Osteopontin[75] |
B
|
s
| Distinguished between sepsis and SIRS |
25 | PAI-1[118] |
B
|
s
| Higher in patients with sepsis and DIC compared with no-septic patients with DIC |
26 | Pentraxin 3[207] |
C
|
s
| Distinguished between septic shock and SIRS |
27 | Peptidoglycan[262] |
B(s)
|
c
| Higher in postoperative patients with infection compared with no-infected postoperative patients |
28 | pFN[270] |
B
|
s
| Distinguished between sepsis and SIRS |
29 | PLA2-II (soluble)***[31] |
B
|
s
| Distinguished between bacteremic and non-bacteremic infections |
30 | Serum lysozyme (enzyme activity)[258] |
B
|
s
| Distinguished between sepsis and organ rejection in transplanted patients |
31 | ST2 (soluble)[108] |
A
|
s
| Higher in septic patients compared with those with no sepsis |
32 | Surfactant protein (A, B, C, D)[192] |
B
|
s
| Early diagnosis of ARDS in septic patients |
33 |
C
|
s
| Distinguished between sepsis and SIRS, diagnosed pneumonia | |
34 | Troponin[193] |
B
|
s
| Diagnosis of myocardial dysfunction in septic patients |