Impaired plasma B-type natriuretic peptide clearance in human septic shock

High B-type natriuretic peptide (BNP) levels are reported in the context of septic shock. We hypothesized that high BNP levels might be related to an alteration in BNP clearance pathway, namely neutral endopeptidase (NEP) 24.11. NEP 24.11 activity was measured in septic shock and in cardiogenic shock patients. We further evaluated whether baseline plasma BNP can predict fluid responsiveness and whether BNP can still be released in plasma despite high initial BNP levels, in response to overloading.

Prospective observational study. Patients in severe sepsis (S) or in septic shock (SS) needing a fluid challenge were included. Stroke volume (SV) and BNP were measured before (SV1, BNP1) and 45 mins after (SV2, BNP2) a standardized fluid challenge. DeltaBNP was defined as the difference between BNP2 and BNP1. NEP 24.11 activity was determined by fluorometry in 12 SS and 4 S patients before fluid challenge and in 5 cardiogenic shock patients.

Twenty-three patients (61 +/- 18 years old, Simplified Acute Physiology Score II: 54 +/- 21; 19 SS, 4 S; BNP1: 1371 +/- 1434 pg/mL) were studied. BNP1 concentrations were significantly higher in SS than in S (1643 +/- 1437 vs. 80 +/- 35 pg/mL; p = 0.002). There was no correlation between baseline BNP and fluid responsiveness. Nine of the 11 patients with BNP1 >1000 pg/mL were fluid responders. DeltaBNP was greater in fluid nonresponders than in fluid responders (22 +/- 27% vs. 6 +/- 11%, p = 0.028). Plasma BNP was higher in SS than in cardiogenic shock patients (1367 +/- 1438 vs. 750 +/- 346 respectively; p = 0.027). NEP 24.11 activity was lower in SS than in S patients (0.10 +/- 0.06 nmole/mL/min vs. 0.50 +/- 0.22 nmole/mL/min, p <0.0001) cardiogenic shock patients (0.10 +/- 0.06 nmole/mL/min vs. 0.58 +/- 0.19 nmole/mL/min; p = 0.002).

High levels of BNP might be related to an alteration in BNP clearance. During sepsis, high BNP levels are not predictive of fluid nonresponsiveness. Nevertheless, in fluid nonresponders, acute ventricular stretching can result in further BNP release.