Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome.
BACKGROUND
Hemolysis can be induced in sepsis via various mechanisms, its pathophysiological importance has been demonstrated in experimental sepsis. However, no data on free hemoglobin concentrations in human sepsis are available. In the present study we measured free hemoglobin in patients with severe sepsis as well as in postoperative patients using four methods. It was our aim to determine the potential value of free hemoglobin as a biomarker for diagnosis and outcome of severe sepsis in critical illness.


METHODS
Plasma concentration of free hemoglobin was determined in patients with severe sepsis (n = 161) and postoperative patients (n = 136) on day 1 of diagnosis and surgery. For the measurement of free hemoglobin, an enzyme linked immunosorbent assay and three spectrophotometric algorithms were used. Moreover, SAPS II- and SOFA scores as well as procalcitonin concentration and outcome were determined. Kaplan-Meier analysis was performed and odds ratios were determined after classification of free hemoglobin concentrations in a high and low concentration group according to the median. For statistical evaluation the Mann-Whitney test and logistic regression analysis were used.


RESULTS
In non-survivors of severe sepsis, free hemoglobin concentration was twice the concentration compared to survivors. Thirty-day survival of patients, as evidenced by Kaplan-Meier analysis, was markedly lower in patients with high free hemoglobin concentration than in patients with low free hemoglobin concentration. Best discrimination of outcome was achieved with the spectrophotometric method of Harboe (51.3% vs. 86.4% survival, p < 0.001; odds ratio 6.1). Multivariate analysis including free hemoglobin, age, SAPS II- and SOFA-score and procalcitonin demonstrated that free hemoglobin, as determined by all 4 methods, was the best and an independent predictor for death in severe sepsis (p = 0.022 to p < 0.001). Free hemoglobin concentrations were not significantly different in postoperative and septic patients in three of four assays. Thus, free hemoglobin can not be used to diagnose severe sepsis in critical illness.


CONCLUSIONS
Free hemoglobin is an important new predictor of survival in severe sepsis.
Michael
M
Adamzik
Tim
T
Hamburger
Frank
F
Petrat
Jürgen
J
Peters
Herbert
H
de Groot
Matthias
M
Hartmann
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D004797:Enzyme-Linked Immunosorbent Assay; D017707:Erythrocyte Transfusion; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood; D012307:Risk Factors; D018805:Sepsis / Q000097:blood* / Q000401:mortality*; D013053:Spectrophotometry / Q000379:methods; D015996:Survival Rate
D015415:Biomarkers; C000606589:CALCA protein, human; D006454:Hemoglobins; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide