Although wall stress is thought to be the major stimulus for BNP release, data from the abovementioned studies in critically ill patients and also more recent data obtained from patients with CHF refute the hypothesis that BNP level could serve as a reliable indicator for PCWP. Volume resuscitation could theoretically cause BNP release by the elevation of both left-sided and right-sided filling pressures. In fact, a recently published case report demonstrated that acute fluid loading was followed by an increase in both right-ventricular end-diastolic diameter and BNP. But only few studies have addressed this issue, and only limited conclusions can be drawn at the moment. Charpentier and coworkers reported that patients with an LV-FAC of < 0.5 had significantly higher BNP levels and also had received significantly more fluids during the first 24 h than those with an LVFAC of > 0.5. In contrast, Roch and coworkers found that in a multivariate analysis fluid loading was not a significant predictor of a high NT-proBNP level. Whereas the correlation between BNP level and PCWP has been found to be weak or even absent, few data exist on the effect of fluid loading on BNP levels, and the relationships among right ventricular dimension, central venous pressure, and BNP level, and thus fluid loading could still have an effect on BNP levels. so
It has been well-recognized that in a subgroup of CHF patients BNP levels remain high despite a significant fall in PCWP following therapy, and that patients with high pre-hospital discharge BNP levels are at high risk of readmission after decompensated CHF. This phenomenon, which is called BNP memory by some authors, along with the weak correlation between BNP and PCWP, suggests that beyond left ventricular filling pressures other stimuli might account for BNP release, including right ventricular strain, renal failure, catecholamine therapy, and cytokine up-regulation.
In patients with chronic right ventricular overload (ie, volume overload due to atrial septal defect or pressure overload due to primary or thromboembolic pulmonary hypertension), BNP level has been shown to increase depending on the extent of right ventricular dysfunction. Acute right ventricular overload following pulmonary embolism can also lead to BNP release, and the degree of BNP elevation is predictive of the occurrence of right ventricular failure in this setting. In patients with sepsis, pulmonary vascular resistance can increase markedly due to associated acute lung injury or ARDS, and even if submitted to protective ventilatory support, acute cor pulmonale develops in 25% of patients with ARDS, which is probably associated with BNP release.