Diagnostic utility of B-type natriuretic peptide in critically ill patients with pulmonary edema: a prospective cohort study

Abstract

Introduction
Distinguishing pulmonary edema due to acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) from hydrostatic or cardiogenic edema is challenging in critically ill patients. B-type natriuretic peptide (BNP) can effectively identify congestive heart failure in the emergency room setting but, despite increasing use, its diagnostic utility has not been validated in the intensive care unit (ICU).

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Methods
We performed a prospective, blinded cohort study in the medical and surgical ICUs at the University of Chicago Hospitals. Patients were eligible if they were admitted to the ICU with respiratory distress, bilateral pulmonary edema and a central venous catheter suggesting either high-pressure (cardiogenic) or low-pressure (ALI/ARDS) pulmonary edema. BNP levels were measured within 48 hours of ICU admission and development of pulmonary edema and onward up to three consecutive days. All levels were drawn simultaneously with the measurement of right atrial or pulmonary artery wedge pressure. The etiology of pulmonary edema ├óÔé¼ÔÇ£ cardiogenic or ALI/ARDS ├óÔé¼ÔÇ£ was determined by three intensivists blinded to BNP levels.

Results
We enrolled a total of 54 patients (33 with ALI/ARDS and 21 with cardiogenic edema). BNP levels were lower in patients with ALI/ARDS than in those with cardiogenic edema (496 ± 439 versus 747 ± 476 pg/ml, P = 0.05). At an accepted cutoff of 100 pg/ml, specificity for the diagnosis of ALI/ARDS was high (95.2%) but sensitivity was poor (27.3%). Cutoffs at higher BNP levels improved sensitivity at considerable cost to specificity. Invasive measures of filling pressures correlated poorly with initial BNP levels and subsequent day BNP values fluctuated unpredictably and without correlation with hemodynamic changes and net fluid balance.

Conclusion
BNP levels drawn within 48 hours of admission to the ICU do not reliably distinguish ALI/ARDS from cardiogenic edema, do not correlate with invasive hemodynamic measurements, and do not track predictably with changes in volume status on consecutive daily measurements.

Introduction
Early implementation of a lung protective ventilation strategy can improve survival from acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) [1]. However, a recent survey of intensive care units (ICUs) found that a lack of physician recognition of ALI/ARDS was a major barrier to the initiation of lung-protective ventilation [2]. Attributing pulmonary edema to volume overload or congestive heart failure may explain some of this underdiagnosis. The American├óÔé¼ÔÇ£European Consensus Conference definition of ALI/ARDS requires the exclusion of left atrial hypertension [3]. However, advanced age and comorbidities can make this difficult in critically ill patients. Pulmonary artery catheters reliably measure left atrial pressure, but placement can be time-consuming and a recent multicenter randomized trial found no benefit with their routine use in ALI/ARDS [4]. Echocardiography provides noninvasive assessment of left ventricular dysfunction but requires an experienced operator and is limited by lack of universal accessibility and added cost.

B-type natriuretic peptide (BNP), a rapidly-assayed, serum biomarker, has been found to be effective in distinguishing congestive heart failure (CHF) from other causes of dyspnea in the emergency or urgent care setting [5-7]. Ease, low cost, and objectivity have led to widespread incorporation of BNP into the clinical evaluation of CHF. Anecdotal experience also suggests an increasing use of BNP by physicians in the ICU; however, although extrapolation to other clinical settings is tempting, appropriate validation is lacking.

Jefic and colleagues found that levels of BNP correlated with severity of left ventricular dysfunction but did not reliably distinguish high from low pulmonary capillary wedge pressure (PCWP) causes of respiratory failure in critically ill patients [8]. In addition, BNP levels can be markedly, but similarly, increased in both cardiogenic and septic shock despite significant differences in hemodynamic measures [9-11]. Conversely, Rana and colleagues found that a BNP level of less than 250 pg/ml had a high specificity for ALI/ARDS and was comparable to measuring PCWP and superior to troponin levels and echocardiography for distinguishing between ALI/ARDS and cardiogenic edema [12].

There are many possible explanations for these discrepancies. Coexisting cardiac and other organ dysfunction, rapid changes in volume status, variable bioavailability [13] and burst synthesis of BNP [14,15] may all confound interpretation of BNP levels in critically ill patients. Given the potential for confounding by coexisting or overlapping conditions of lung injury and hydrostatic pulmonary edema, we performed a prospective clinical trial of the diagnostic utility of BNP in selected patients with convincing evidence of either ALI/ARDS or cardiogenic pulmonary edema.

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References
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