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Published in: Intensive Care Medicine 9/2007

01-09-2007 | Brief report

Association of cell-free plasma DNA with hospital mortality and organ dysfunction in intensive care unit patients

Authors: Katri Saukkonen, Päivi Lakkisto, Marjut Varpula, Tero Varpula, Liisa-Maria Voipio-Pulkki, Ville Pettilä, Kari Pulkki

Published in: Intensive Care Medicine | Issue 9/2007

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Abstract

Objective

To investigate the concentration of cell-free plasma DNA and its association with organ dysfunction and hospital mortality in intensive care unit patients.

Design and setting

Prospective cohort study in a medical and two medical-surgical intensive care units in a university hospital.

Patients

228 critically ill patients admitted to the ICUs between January 2004 and July 2005.

Measurements and results

Blood samples were collected as soon as possible after ICU admission, the following morning, and 48 h after the second sample. The cell-free plasma DNA was measured by real-time quantitative PCR assay for the β-globin gene. Physiological and mortality data were collected to the clinical database. Hospital mortality rate and SOFA scores were primary outcome measures. The maximum plasma DNA concentrations were correlated significantly with APACHE II points and with maximum SOFA scores. Cell-free plasma DNA concentrations were higher in hospital non-survivors than in survivors (median 9,366 vs. 6,506 GE/ml). Using logistic regression analysis, the maximum plasma DNA was an independent predictor of hospital mortality.

Conclusions

The maximum plasma DNA concentration measured during the first 96 h of intensive care is associated with the degree of organ dysfunction and disease severity. Moreover, the maximum DNA concentration is independently associated with hospital mortality.
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Literature
1.
go back to reference Knaus WA, Drapper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRef Knaus WA, Drapper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRef
2.
go back to reference Vincent J-L, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG, on behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine (1996) The SOFA (Sepsis-Related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710PubMed Vincent J-L, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG, on behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine (1996) The SOFA (Sepsis-Related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710PubMed
3.
go back to reference Vincent J-L, De Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S, on behalf of the Working Group on “Sepsis-related Problems” of the European Society of Intensive Care Medicine (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Crit Care Med 26:1793–1800PubMed Vincent J-L, De Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S, on behalf of the Working Group on “Sepsis-related Problems” of the European Society of Intensive Care Medicine (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Crit Care Med 26:1793–1800PubMed
4.
go back to reference Lo YMD, Rainer TH, Chan LYS, Hjelm NM, Cooks RA (2000) Plasma DNA as a prognostic marker in trauma patients. Clin Chem 46:319–323PubMed Lo YMD, Rainer TH, Chan LYS, Hjelm NM, Cooks RA (2000) Plasma DNA as a prognostic marker in trauma patients. Clin Chem 46:319–323PubMed
5.
go back to reference Rainer TH, Wong LKS, Lam W, Yuen E, Lam NYL, Metreweli C, Lo YMD (2003) Prognostic use of circulating plasma nucleic acid concentration in patients with acute stroke. Clin Chem 49:562–569PubMedCrossRef Rainer TH, Wong LKS, Lam W, Yuen E, Lam NYL, Metreweli C, Lo YMD (2003) Prognostic use of circulating plasma nucleic acid concentration in patients with acute stroke. Clin Chem 49:562–569PubMedCrossRef
6.
go back to reference Chang CP-Y, Chia R-H, Wu T-L, Tsao K-C, Sun C-F, Wu JT (2003) Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin Chim Acta 327:95–101PubMedCrossRef Chang CP-Y, Chia R-H, Wu T-L, Tsao K-C, Sun C-F, Wu JT (2003) Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin Chim Acta 327:95–101PubMedCrossRef
7.
go back to reference Tong Y-K, Lo YMD (2006) Diagnostic developments involving cell-free (circulating) nucleic acids. Clin Chim Acta 363:187–196PubMedCrossRef Tong Y-K, Lo YMD (2006) Diagnostic developments involving cell-free (circulating) nucleic acids. Clin Chim Acta 363:187–196PubMedCrossRef
8.
go back to reference Fournie GJ, Martres F, Pourrat JP, Alary C, Rumeau M (1993) Plasma DNA as cell death marker in elderly patients. Gerontology 39:215–221PubMedCrossRef Fournie GJ, Martres F, Pourrat JP, Alary C, Rumeau M (1993) Plasma DNA as cell death marker in elderly patients. Gerontology 39:215–221PubMedCrossRef
9.
go back to reference Fournie GJ, Courtin JP, Laval F, Chale JJ, Pourrat JP, Pujazon M-C, Lauque D, Carles P (1995) Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours. Cancer Lett 91:221–227PubMedCrossRef Fournie GJ, Courtin JP, Laval F, Chale JJ, Pourrat JP, Pujazon M-C, Lauque D, Carles P (1995) Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours. Cancer Lett 91:221–227PubMedCrossRef
10.
go back to reference Jiang N, Pisetsky DS (2005) The effect of inflammation on the generation of plasma DNA from dead and dying cells in the peritoneum. J Leukoc Biol 77:1–7 Jiang N, Pisetsky DS (2005) The effect of inflammation on the generation of plasma DNA from dead and dying cells in the peritoneum. J Leukoc Biol 77:1–7
11.
go back to reference Wijeratne S, Butt A, Burns S, Sherwood K, Boyd O, Swaminathan R (2004) Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients. Ann NY Acad Sci 1022:232–238PubMedCrossRef Wijeratne S, Butt A, Burns S, Sherwood K, Boyd O, Swaminathan R (2004) Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients. Ann NY Acad Sci 1022:232–238PubMedCrossRef
12.
go back to reference Rhodes A, Wort SJ, Thomas H, Collinson P, Bennett ED (2006) Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients. Crit Care 10:R60PubMedCrossRef Rhodes A, Wort SJ, Thomas H, Collinson P, Bennett ED (2006) Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients. Crit Care 10:R60PubMedCrossRef
13.
go back to reference Saukkonen K, Lakkisto P, Varpula M, Varpula T, Voipio-Pulkki L-M, Pettilä V, Pulkki K (2006) The cell-free plasma DNA in intensive care unit patients: kinetics and association with outcome. Intensive Care Med 32:S142 Saukkonen K, Lakkisto P, Varpula M, Varpula T, Voipio-Pulkki L-M, Pettilä V, Pulkki K (2006) The cell-free plasma DNA in intensive care unit patients: kinetics and association with outcome. Intensive Care Med 32:S142
14.
go back to reference Swinkels DW, Wiegerinck E, Steegers EAP, de Kok JB (2003) Effects of blood-processing protocols on cell-free DNA quantification in plasma. Clin Chem 49:525–526PubMedCrossRef Swinkels DW, Wiegerinck E, Steegers EAP, de Kok JB (2003) Effects of blood-processing protocols on cell-free DNA quantification in plasma. Clin Chem 49:525–526PubMedCrossRef
15.
go back to reference Lo YMD, Tein MSC, Lau TK, Haines CJ, Leung TN, Poon PMK, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62:768–775PubMedCrossRef Lo YMD, Tein MSC, Lau TK, Haines CJ, Leung TN, Poon PMK, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62:768–775PubMedCrossRef
16.
go back to reference Sylvain K, Aurelie H, Marc M, Christophe R (2004) Rapid screening for HLA-B27 by a TaqMan-PCR assay using sequence-specific promoters and a minor groove binder probe, a novel type of a TaqMan probe. J Immunol Methods 287:179–186PubMedCrossRef Sylvain K, Aurelie H, Marc M, Christophe R (2004) Rapid screening for HLA-B27 by a TaqMan-PCR assay using sequence-specific promoters and a minor groove binder probe, a novel type of a TaqMan probe. J Immunol Methods 287:179–186PubMedCrossRef
17.
go back to reference Zhao JR, Bai YJ, Zhang QH, Wan Y, Li D, Yan XJ (2005) Detection of hepatitis B virus DNA by real-time PCR using TaqMan-MGB probe technology. World J Gastroenterol 11:508–510PubMed Zhao JR, Bai YJ, Zhang QH, Wan Y, Li D, Yan XJ (2005) Detection of hepatitis B virus DNA by real-time PCR using TaqMan-MGB probe technology. World J Gastroenterol 11:508–510PubMed
Metadata
Title
Association of cell-free plasma DNA with hospital mortality and organ dysfunction in intensive care unit patients
Authors
Katri Saukkonen
Päivi Lakkisto
Marjut Varpula
Tero Varpula
Liisa-Maria Voipio-Pulkki
Ville Pettilä
Kari Pulkki
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 9/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0686-z

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