Table 9

Other biomarkers identified in the literature search (with some selected references)

Sepsis marker

Evaluated in experimental studies

Evaluated in clinical studies

Evaluated as a prognostic factor

Comment


Alpha2 macroglobulin [196,208]

Albumin [209]

Anti-endotoxin core antibodies (EndoCab) [210]

A

Distinguished between survivors and non-survivors at 28 days

Apolipoprotein CI [211-213]

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

Complement (C3, C4, C5a levels) [219,220]

B(m)

Distinguished between survivors and non-survivors at 28 days

Terminal complement complex [221]

Dendritic cell [222,223]

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

Eicosanoid [226,227]

A(s)

Correlated with SAPS score, predicted response to therapy

Elastase [228,229]

C(s)

Predicted response to therapy in patients with joint infections

Elastase-a1-antitrypsin complex [230,231]

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

G-CSF and GM-CSF [236,237]

B

√**

Distinguished between survivors and non-survivors at 28 days

Gelsolin [238]

B(s)

Distinguished between survivors and non-survivors at 28 days

Ghrelin [239,240]

Growth arrest specific protein (Gas) 6 [241]

B

Correlated with APACHE II score in patients with severe sepsis

Heat shock protein (HSP)70, 72, 73, 90 and 32 [242-245]

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]

Hyaluronan [248,249]

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

Lactate [253,254]

C

Distinguished between survivors and non-survivors at 28 days, predicted response to therapy

Lactoferrin [255,256]

C(s)

Predicted response to therapy

Leptin [240,257]

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]

Plasma amino acids [267-269]

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

Transforming growth factor (TGF)-β1 [279,280]

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


*sensitivity and specificity of less than 90%; **sensitivity of more than 90% but specificity of less than 90%; A, Clinical study with less than 20 patients; B, Clinical study with 20 to 50 patients; C, Clinical study with more than 50 patients; (s), surgical patients only; (m), medical patients only.

APACHE: acute physiology and chronic health evalution; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocyte-macrophage colony stimulating factor; MOF: multiple organ failure; NF-κB: nuclear factor kappa B; PlGF: placental growth factor; SAPS: simplified acute physiology score; SOFA: sequential organ failure assessment; TIMP: tissue inhibitor of metalloproteinase.

Pierrakos and Vincent Critical Care 2010 14:R15   doi:10.1186/cc8872

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