New insights into the mechanisms involved in B-type natriuretic peptide elevation and its prognostic value in septic patients

Abstract

Introduction: Elevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.

Methods: In this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.

Results: A total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).

Conclusions: The severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.

Figure 1

Five-day B-type natriuretic peptide kinetics in patients with septic shock (N = 30), severe sepsis (N = 12) and hemorrhagic shock (N = 11). Circles and vertical lines indicate mean B-type natriuretic peptide (BNP) values and standard deviations (SD), respectively. BNP kinetics are indicated by the corresponding mean regression lines for septic shock (solid line), severe sepsis (dashed line) and hemorrhagic shock (dotted line). Septic shock’s mean regression line represents greater mean intercept and steeper mean slope than severe sepsis and hemorrhagic shock regression lines (1,312.6 vs. 333.5 pg/ml and 74.7 pg/ml, respectively, P < 0.001; and −78.1 pg/ml/day vs. −13.4 and −9.6 pg/ml/day, respectively, P ≤ 0.029). Intercept of the regression line, BNP value where the regression line crosses the y-axis at theoretical day 0; Slope of the regression line, Rate at which BNP values change day after day. Black hooks: Bonferroni's subgroup analysis between lines' mean intercepts. Gray hooks: Bonferroni's subgroup analysis between lines' mean slopes.

Figure 2

Daily B-type natriuretic peptide measurements and 5-day B-type natriuretic peptide kinetics in patients with overall critical sepsis (left) and septic shock (right), divided by 28-day mortality. Bars and vertical lines indicate mean B-type natriuretic peptide (BNP) values and standard deviations (SD), respectively. Significant BNP differences on any study day (P < 0.05) are marked with asterisks. Five-day BNP kinetics are indicated by the corresponding mean regression lines (gray in survivors and black in nonsurvivors). Mean regression lines represent similar mean intercepts, yet significantly steeper mean slopes in survivors than in nonsurvivors, either in overall critical sepsis patients (P = 0.001) or in septic shock patients (P = 0.002). The intercept of the regression line is the BNP value where the regression line crosses the y-axis on theoretical day 0. The slope of the regression line is the rate at which BNP values change day after day.