B-type natriuretic levels in critically ill patients: critically misleading?

Abstract

Although B-type natriuretic peptide (BNP) has been used for the diagnosis of congestive heart failure in many clinical settings, its diagnostic role in critically ill patients remains uncertain. The body of literature suggests that BNP and N-terminal pro-BNP levels are not useful for the diagnosis of systolic or diastolic heart failure in the critically ill, including in patients with brain hemorrhage, due to poor specificity. However, these cardiac peptides may have a more promising prognostic role in this patient population.

Full text

Page 1

Available online http://ccforum.com/content/13/4/163
Page 1 of 2
(page number not for citation purposes)
Abstract
Although B-type natriuretic peptide (BNP) has been used for the
diagnosis of congestive heart failure in many clinical settings, its
diagnostic role in critically ill patients remains uncertain. The body
of literature suggests that BNP and N-terminal pro-BNP levels are
not useful for the diagnosis of systolic or diastolic heart failure in
the critically ill, including in patients with brain hemorrhage, due to
poor specificity. However, these cardiac peptides may have a more
promising prognostic role in this patient population.
In the previous issue of Critical Care, Meaudre and colleagues
measured bedside rapid assay B-type natriuretic peptide
(BNP) levels daily, and performed bedside echocardiography
in patients admitted to hospital for subarachnoid hemorrhage
(SAH) [1]. They found that BNP levels rose in 25/31 (81%)
patients, peaking at day 2 (at a mean of 126 ng/ml) and
tapering off by day 7. Importantly, BNP levels did not
correlate with left ventricular (LV) filling pressure as estimated
by echocardiography. BNP levels did correlate with cardiac
troponin I levels at day 2 and day 3 (R = 0.63, P <0.001 and
R = 0.44, P = 0.05, respectively). The authors therefore
concluded that BNP cannot estimate LV filling pressure in
SAH patients but does correlate with myocardial necrosis as
assessed by cardiac troponin I levels in these patients
without prior hypertensive or cardiac disease.
What is the mechanism of BNP release in such patients? As
Meaudre and colleagues mention, intramyocardial norepi-
nephrine release, possibly resulting in myocardial necrosis,
appears to be a plausible mechanism of BNP release – and
perhaps explains the correlation of BNP with troponin I levels
[1,2]. It should be noted that BNP levels, putatively
correlating with intramyocardial norepinephrine levels, do not
necessarily correlate with serum norepinephrine levels, which
makes sense given the lack of clinically detectible myocardial
injury (lack of decrease in LV ejection fraction, lack of new
wall motion abnormalities) in these patients [1,2].
There are several important caveats – many of which the
authors mention – that must be considered when interpreting
Meaudre and colleagues’ data. First, all patients with known
hypertensive or cardiomyopathic disease were excluded from
the study. The extent of neurocardiogenic injury associated
with SAH in patients with known cardiovascular disease is
therefore unknown and could arguably be more serious.
Second, although echocardiographic diagnosis of the LV filling
pressure has significant precedent and is clinically useful [3],
the diagnosis remains inferior to direct hemodynamic data from
right or left heart catheterization, which was not performed in
this study. Third, and importantly, the 6/37 (16%) patients with
SAH who died prior to the day 7 follow-up studies were
excluded from the final analysis, and consequently it is
unknown whether BNP or troponin I levels had any prognostic
or mechanistic effect in these expired patients.
What is the significance of these findings? These data add to
the growing body of evidence that BNP (and N-terminal pro-
BNP) are poor predictors of LV filling pressure in critically ill
patients. In critical care patients with indwelling pulmonary
artery catheters, it has previously been demonstrated that
BNP levels have a weak correlation (R = 0.32) with the
pulmonary capillary wedge pressure [3]. In another study of
40 critical care patients, both BNP (R = 0.40) and N-terminal
pro-BNP (R = 0.32) had weak correlations with the pulmonary
capillary wedge pressure and were dependent on renal
function [4]. Another group has shown that, in 249 critically ill
patients, those with congestive heart failure confirmed by
invasive hemodynamic measurements had BNP and
N-terminal pro-BNP levels comparable with patients with
sepsis and without congestive heart failure [5]. Yet another
Commentary
B-type natriuretic levels in critically ill patients:
critically misleading?
Hisham Dokainish
Department of Medicine, Baylor College of Medicine, 6620 Main Street, 11A.08, Houston, TX 77030, USA
Corresponding author: Hisham Dokainish, hishamd@bcm.edu
Published: 13 July 2009
This article is online at http://ccforum.com/content/13/4/163
© 2009 BioMed Central Ltd
Critical Care 2009, 13:163 (doi:10.1186/cc7938)
See related research by Meaudre et al., http://ccforum.com/content/13/3/R76
BNP = B-type natriuretic peptide; LV = left ventricular; SAH = subarachnoid hemorrhage.

Page 2

Critical Care Vol 13 No 4Dokainish
Page 2 of 2
(page number not for citation purposes)
study showed that BNP levels were increased in critically ill
patients with severe sepsis or septic shock regardless of the
presence or absence of heart failure [6]. The body of
evidence therefore indicates that BNP and N-terminal pro-
BNP should not be used to diagnose systolic or diastolic
heart failure in critically ill patients.
Is this the death knell, then, for the use of BNP in critical
care? From a diagnostic point of view, yes – BNP and
N-terminal pro-BNP levels do not provide useful, cardiac-
specific information given that sepsis, trauma or congestive
heart failure can result in similar BNP levels in critically ill
patients [6-8]. From the prognostic point of view, however,
the role for cardiac peptides could be more promising. While
one study in patients with sepsis showed that BNP levels did
not predict inhospital mortality or length of stay [6], two other
studies in unselected critically ill patients showed that
hospital nonsurvivors had significantly higher NT-pro-BNP
values than hospital survivors [7,8]. A potentially important
prognostic role therefore remains for cardiac peptides in
critically ill patients, an area that requires further study;
however, the diagnostic role of BNP and N-terminal pro-BNP
in such patients appears to be very limited indeed.
Competing interests
The author declares that they have no competing interests.
References
1. Meaudre E, Jego C, Kenane N, Montcriol A, Boret H, Goutorbe P,
Habib G, Palmier B: B-type natriuretic peptide release and left
ventricular filling pressure assessed by echocardiographic
study after subarachnoid hemorrhage: a prospective study in
non-cardiac patients. Crit Care 2009, 13:R76.
2. Banki NM, Kopelnik A, Dae MW, Miss J, Tung P, Lawton MT,
Drew BJ, Foster E, Smith W, Parmley WW, Zaroff JG: Acute neu-
rocardiogenic injury after subarachnoid hemorrhage. Circula-
tion 2005, 112:3314-3319.
3.Dokainish H, Zoghbi WA, Lakkis NM, Al-Bakshy F, Dhir M,
Quinones MA, Nagueh SF: Optimal non-invasive assessment
of LV filling pressures: a comparison of tissue Doppler
echocardiography and BNP in patients with pulmonary artery
catheters. Circulation 2004, 109:2432-2439.
4.Forfia PR, Watkins SP, Rame JE, Stewart KJ, Shapiro EP: Rela-
tionship between B-type natriuretic peptides and pulmonary
capillary wedge pressure in the intensive care unit. J Am Coll
Cardiol 2005, 45:1667-1671.
5.Rudiger A, Gasser S, Fischler M, Hornemann T, von Eckardstein
A, Maggiorini M: Comparable increase of B-type natriuretic
peptide and amino-terminal pro-B-type natriuretic peptide
levels in patients with severe sepsis, septic shock, and acute
heart failure. Crit Care Med 2006, 34:2140-2144.
6.McLean AS, Huang SJ, Hyams S, Poh G, Nalos M, Pandit R, Balik
M, Tang B, Seppelt I: Prognostic values of B-type natriuretic
peptide in severe sepsis and septic shock. Crit Care Med
2007, 35:1019-1026.
7.Kotanidou A, Karsaliakos P, Tzanela M, Mavrou I, Kopterides P,
Papadomichelakis E, Theodorakopoulou M, Botoula E, Tsangaris I,
Lignos M, Ikonomidis I, Ilias I, Armaganidis A, Orfanos SE,
Dimopoulou I: Prognostic importance of increased plasma
amino-terminal pro-brain natriuretic peptide levels in a large
noncardiac, general intensive care unit population. Shock
2009, 31:342-347.
8.Meyer B, Huelsmann M, Wexberg P, Delle Karth G, Berger R,
Moertl D, Szekeres T, Pacher R, Heinz G: N-terminal pro-B-type
natriuretic peptide is an independent predictor of outcome in
an unselected cohort of critically ill patients. Crit Care Med
2007, 35:2268-2273.