Plasma cell-free DNA in patients needing mechanical ventilation

Abstract

Introduction: Concentrations of plasma cell-free DNA are increased in various diseases and have shown some prognostic value in many patient groups, including critically ill patients. Pathophysiological processes behind the need for mechanical ventilation and the treatment itself could raise plasma levels of cell-free DNA. We evaluated levels of plasma cell-free DNA and their prognostic value in patients needing mechanical ventilation.

Methods: We studied prospectively 580 mechanically ventilated critically ill patients. Blood samples were taken at study admission (Day 0) and on Day 2. Plasma cell-free DNA concentrations were measured by real-time quantitative PCR assay for the β-globin gene and are expressed as genome equivalents (GE)/ml.

Results: Median (interquartile range, IQR) plasma cell-free DNA concentration was 11,853 GE/ml (5,304 to 24,620 GE/mL) at study admission, and 11,610 GE/mL (6,411 to 21,558 GE/mL) on Day 2. Concentrations at admission were significantly higher in 90-day non-survivors than survivors, 16,936 GE/mL (7,262 to 46,866 GE/mL) versus 10,026 GE/mL (4,870 to 19,820 GE/mL), P < 0.001. In a multivariate logistic regression analysis plasma cell-free DNA concentration over 16,000 GE/ml remained an independent predictor of 90-day mortality (adjusted odds ratio 2.16, 95% confidence interval CI 1.37 to 3.40). Positive likelihood ratio of plasma cell-free DNA at admission for the prediction of 90-day mortality was 1.72 (95% CI 1.40 to 2.11).

Conclusions: Plasma levels of cell-free DNA were significantly higher in non-survivors than survivors. Plasma DNA level at baseline was an independent predictor of 90-day mortality. However, its clinical benefit as a prognostic marker seems to be limited.

Figure 1

Flowchart of study patients. (A) Blood sample at study admission (Day 0); (B) blood sample at Day 2.

Figure 2

Plasma cell-free DNA at admission in 90-day non-survivors and survivors according to operative status. Data are presented as median values (lines) with 25^th and 75^th (boxes) and 5th and 95th percentiles (whiskers). Sample A obtained at admission. GE, genome equivalents; NS, non-significant.

Figure 3

Plasma cell-free DNA at admission according to baseline PaO₂/FiO₂-ratio based on SOFA cut-offs. Data are presented as median values (lines) with 25^th and 75^th percentiles (boxes) and 5^th and 95^th percentiles (whiskers). Sample A obtained at admission. Comparison between groups by Kruskal-Wallis test (P < 0.001). Post hoc analyses between groups by Mann-Whitney test (P < 0.01 considered significant due to multiple comparisons). GE, genome equivalents; NS, non-significant; SOFA, Sequential Organ Failure Assessment.

Figure 4

Kaplan-Meier survival curves for 90-day mortality according to plasma cell-free DNA cut-off point at admission. Sample A obtained at admission. GE, genome equivalents.