Drotrecogin alfa (activated) reduces the plasma levels of N-terminal prohormone atrial natriuretic peptide and N-terminal prohormone brain natriuretic peptide as markers of cardiac depression in septic patients

Background

The family of natriuretic peptides comprises several structurally related 22–53 amino acid peptides, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are vasoactive peptides that have vasodilator and diuretic properties and play an important role in cardiovascular homeostasis. The salutary cardiovascular effects of natriuretic peptides suggest that ANP and BNP have a pathophysiological significance in cardiac depression in septic patients. Aim of the present study was to determine plasma levels of the stable N-terminal prohormone forms of ANP (Nt-proANP) and BNP (Nt-proBNP) in septic patients treated with and without Drotrecogin alfa (activated). Troponin I (TNI) as a parameter for cardiac dysfunction was also evaluated.

Patients and methods

Nt-proANP, Nt-proBNP and TNI levels were measured in plasma samples from 40 septic patients at day 1 of severe sepsis and from 25 septic patients treated with Drotrecogin alfa (activated) by ELISA methods. Statistical analysis was performed with the unpaired Students t test.

Results

The mean SAPS II scores from septic patients on day 1 treated with and without Drotrecogin alfa (activated) were comparable (SAPS II score mean = 32). Significantly lower concentrations of NT-proBNP (P = 0.0075) and NT-proANP (P = 0.0366) were measured in the patients treated with Drotrecogin alfa (activated) as compared with the patients not receiving Drotrecogin alfa (activated). TNI values were significantly lower (P < 0.05) in septic patients treated with Drotrecogin alfa (activated) (mean ± SD = 3.3 ± 7.2 ng/ml) as compared with untreated patients (mean ± SD = 0.3 ± 0.97 ng/ml). There was a correlation between NT-proBNP and NT-proANP values (r = 0.6381, P < 0.001). Septic patients with NT-proBNP levels > 1600 fmol/ml have a 3.7-fold higher risk of death than patients with NT-proBNP levels < 1600 fmol/ml (P = 0.05).

Conclusion

Nt-proANP and Nt-proBNP levels are significantly lower in septic patients treated with Drotrecogin alfa (activated). Nt-proBNP can serve as a predictor for survival in septic patients. Drotrecogin alfa (activated) may influence cardiac depression in septic patients by controlling the pathways of NT-proANP and Nt-proBNP production. The beneficial effect of Drotrecogin alfa (activated) on cardiac function is also reflected by lower TNI values in this patient group.