Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients

Andrew Rhodes1, Stephen J Wort1, Helen Thomas2, Paul Collinson2, E David Bennett1
1Intensive Care Unit, St Georges's Hospital, London, UK
2Department of Chemical Pathology, St Georges's Hospital, London, UK

Tóm tắt

Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis. Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human β-haemoglobin gene. Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65–362) ng/ml versus 74 (46–156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185–430) ng/ml versus 71 (46–113) ng/ml, P < 0.001) or in hospital (260 (151–380) ng/ml versus 68 (47–103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0–1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU. Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.

Từ khóa


Tài liệu tham khảo

Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abouhamze A, Pribble JP, Moldawer LL: Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock 2005, 23: 488-493.

Pettila V, Hynninen M, Takkunen O, Kuusela P, Valtonen M: Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis. Intensive Care Med 2002, 28: 1220-1225. 10.1007/s00134-002-1416-1

Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL: C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003, 123: 2043-2049. 10.1378/chest.123.6.2043

Rhodes A, Tilley R, Barnes S, Boa F, Grounds RM, Collinson P, Bennett ED: A prospective study into the use of NT-proBNP measurements in critically ill patients. Clin Intensive Care 2004, 15: 31-36. 10.1080/09563070410001703923

Ammann P, Pfisterer M, Fehr T, Rickli H: Raised cardiac troponins. BMJ 2004, 328: 1028-1029. 10.1136/bmj.328.7447.1028

Rainer TH, Wong LK, Lam W, Yuen E, Lam NY, Metreweli C, Lo YM: Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clin Chem 2003, 49: 562-569. 10.1373/49.4.562

Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R: DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 2001, 61: 1659-1665.

Wu TL, Zhang D, Chia JH, Tsao KH, Sun CF, Wu JT: Cell-free DNA: measurement in various carcinomas and establishment of normal reference range. Clin Chim Acta 2002, 321: 77-87. 10.1016/S0009-8981(02)00091-8

Tsumita T, Iwanagam M: Fate of injected deoxyribosnucleic acid in mice. Nature 1963, 198: 1088-1089.

Lau TW, Leung TN, Chan LY, Lau TK, Chan KC, Tam WH, Lo YM: Fetal DNA clearance from maternal plasma is impaired in preeclampsia. Clin Chem 2002, 48: 2141-2146.

Chang CP, Chia RH, Wu TL, Tsao KC, Sun CF, Wu JT: Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin Chim Acta 2003, 327: 95-101. 10.1016/S0009-8981(02)00337-6

Lo YM, Rainer TH, Chan LY, Hjelm NM, Cocks RA: Plasma DNA as a prognostic marker in trauma patients. Clin Chem 2000, 46: 319-323.

Marshall JC, Vincent JL, Guyatt G, Angus DC, Abraham E, Bernard G, Bombardier C, Calandra T, Jorgensen HS, Sylvester R, Boers M: Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the International Sepsis Forum. Crit Care Med 2005, 33: 1708-1716. 10.1097/01.CCM.0000174478.70338.03

Hehlgans T, Pfeffer K: The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 2005, 115: 1-20. 10.1111/j.1365-2567.2005.02143.x

Martins GA, Kawamura MT, Carvalho Mda G: Detection of DNA in the plasma of septic patients. Ann NY Acad Sci 2000, 906: 134-140.

Zeerleder S, Zwart B, Wuillemin WA, Aarden LA, Groeneveld AB, Caliezi C, van Nieuwenhuijze A, van Mierlo GJ, Eerenberg AJ, Lammle B, Hack CE: Elevated nucleosome levels in systemic inflammation and sepsis. Crit Care Med 2003, 31: 1947-1951. 10.1097/01.CCM.0000074719.40109.95

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-710.

Bone RC: Let's agree on terminology: definitions of sepsis. Crit Care Med 1991, 19: 973-976.

Wijeratne S, Butt A, Burns S, Sherwood K, Boyd O, Swaminathan R: Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients. Ann NY Acad Sci 2004, 1022: 232-238. 10.1196/annals.1318.036

Lichtenstein A, Melkonyan H, Tomei L, Umansky S: Circulating nucleic acids and apoptosis. Ann NY Acad Sci 2001, 945: 239-249.

Anker P, Mulcahy H, Chen XQ, Stroun M: Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev 1999, 18: 65-73. 10.1023/A:1006260319913

Li CN, Hsu HL, Wu TL, Tsao KC, Sun CF, Wu JT: Cell-free DNA is released from tumor cells upon cell death: a study of tissue cultures of tumor cell lines. J Clin Lab Anal 2003, 17: 103-107. 10.1002/jcla.10081

Stroun M, Maurice P, Vasioukhin V, Lyautey J, Lederrey C, Lefort F, Rossier A, Chen XQ, Anker P: The origin and mechanism of circulating DNA. Ann NY Acad Sci 2000, 906: 161-168.

Hahn S, Zhong XY, Holzgreve W: Quantification of circulating DNA: in the preparation lies the rub. Clin Chem 2001, 47: 1577-1578.