The results of this study can be summarized as follows: (1) serum levels of NT–proBNP are not influenced by tidal volume size in patients without ARDS at onset of mechanical ventilation; (2) serum levels of NT–proBNP are dependent on the development of ARDS; and (3) serum levels of NT–proBNP are dependent on cumulative fluid balances, both in patients with and without HF, and on development of AKI.
Several limitations of our study have to be acknowledged. First, we may not have included a sufficient number of patients to demonstrate a difference in serum levels of NT–proBNP between the randomization groups. Notably, as patients developing ARDS in the conventional tidal volume group were immediately set to lower tidal volume ventilation as soon as ARDS was recognized, we may have limited right ventricular wall stress, possibly influencing serum levels of NT–proBNP. Second, we did not perform pulmonary artery pressure measurements to assess the afterload of the right ventricle. However, this procedure can result in complications as cardiac arrhythmias or lung bleeding. We therefore choose not to perform this procedure in patients who were already compromised by ARDS. Third, our study was performed using the American-European consensus conference ARDS criteria. The ARDS criteria have recently been changed
. In our study patients who developed ARDS all had underlying risk factors
. Furthermore, it is standard practice in our clinic to perform echocardiography in case heart failure is suspected. As all patients were ventilated with at least 5 cm H2O of PEEP, ARDS diagnosis may not have differed significantly in case patients were reviewed based on the Berlin definition.
The incidence of acute cor pulmonale with ARDS seems to have declined with the use of lower tidal volumes. The study by Vieillard-Baron et al. showed a lower incidence of acute cor pulmonale diagnosed by echocardiography
. They suggested that lowering tidal volumes with mechanical ventilation resulted in afterload reduction of the right ventricle, thereby minimizing the incidence of acute cor pulmonale. Their results also suggested that a lower tidal volume may be associated with higher degree of hypercapnia which was significantly associated with presence of acute cor pulmonale. In our study no correlation was found between tidal volume size and serum levels of NT–proBNP. We also did not find any relation between hypercapnia and the level of NT–proBNP. This may have been caused by the two independent determinants of NT–proBNP levels. i.e., the cumulative fluid balance and the presence of kidney injury. Although ARDS is associated with hypercapnia, patients with higher cumulative fluid balance or with AKI were not hypercapnic in most cases.
The relation between tidal volume size and acute cor pulmonale may be different in patients with and without ARDS. Although higher tidal volumes may indeed increase the afterload of the right ventricle, this may be less or even not important in patients without lung disease. However, the effect of conventional tidal volume on the right ventricle and therefore on serum levels of NT–proBNP may have been tempered in our study. In patients who developed ARDS, the tidal volume was immediately set at 6 ml/kg in patients of the conventional tidal volume group. As mentioned above, this may have resulted in less stress on the right ventricle and accordingly lower serum levels of NT–proBNP.
In line with previous studies, serum levels of NT–proBNP correlated with cumulative fluid balance
[17, 18] and the presence of AKI
. Our finding that serum levels of NT–proBNP were associated with both cumulative fluid balance, and AKI and ARDS may disqualify this protein as a suitable biological marker to distinguish between ARDS and acute pulmonary cardiogenic edema or acute pulmonary edema due to circulatory overload. Recent studies have investigated this issue. Rana et al. studied patients with acute pulmonary edema and measured serum levels of NT–proBNP within 24 hours after the onset of the edema
. They found a low serum level of NT–proBNP to be supportive of ARDS. However levels of NT–proBNP were not discriminative in patients with a level above 250 pg/ml. In a study of patients with acute hypoxic respiratory failure and bilateral pulmonary infiltrates, low serum levels of NT–proBNP (< 200 pg/ml) were found to be supportive of ARDS while high serum levels of NT–proBNP (> 1200 mg/ml) were supportive of cardiogenic pulmonary edema
. However, in a study of patients with respiratory distress and bilateral pulmonary edema, Levitt et al. could not find a useful cut–off point for NT–proBNP in diagnosing ARDS
. Finally, in a study of patients with respiratory distress after blood transfusions, Li et al. observed higher serum levels of NT–proBNP in patients with circulatory overload compared to patients with transfusion–associated lung injury, but NT–proBNP had no diagnostic value due to a large range of overlapping values
. All studies bear more of less the same message: in patients with acute respiratory distress, serum levels of NT–proBNP tend to be lower in patients with ARDS as compared to patients with circulatory overload or congestive heart failure.