Download B-type natriuretic peptide (BNP) and N-terminal

Acta Anaesthesiol Scand 2006; 50: 340—347
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Copyright # Acta Anaesthesiol Scand 2006
ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2005.00963.x
B-type natriuretic peptide (BNP) and N-terminal-proBNP
for heart failure diagnosis in shock or acute respiratory
distress
L. BAL1, S. THIERRY1, E. BROCAS1, A. VAN
and A. TENAILLON1
DE
LOUW1, J. POTTECHER1, S. HOURS1, M. H. MOREAU2, D. PERRIN GACHADOAT1
1
General Intensive Care Unit and 2Biochemistry Department, Sud Francilien Hospital Center, Evry, France
Background: Plasma B-type natriuretic peptide (BNP) assay is
recommended as a diagnostic tool in emergency-room patients
with acute dyspnea. In the intensive care unit (ICU), the utility
of this peptide remains a matter of debate. The objectives of this
study were to determine whether cut-off values for BNP and
N-terminal-proBNP (NT-proBNP) reliably diagnosed right
and/or left ventricular failure in patients with shock or acute
respiratory distress, and whether non-cardiac factors led to an
increase in these markers.
Methods: Plasma BNP and NT-proBNP levels and echocardiographic parameters of cardiac dysfunction were determined in
41 patients within 24 h of the onset of shock or acute respiratory
distress.
Results: BNP and NT-proBNP levels were higher in the 25
patients with heart failure than in the other 16 patients: 491.7 418 pg/ml vs. 144.3 128 pg/ml and 2874.4 2929 pg/ml
vs. 762.7 1128 pg/ml, respectively (P < 0.05). In the diagnosis
of cardiac dysfunction, BNP > 221 pg/ml and NT-proBNP
> 443 pg/ml had 68% and 84% sensitivity, respectively, and
88% and 75% specificity, respectively, but there was a substantial
overlap of BNP and NT-proBNP values between patients with
and without heart failure. BNP and NT-proBNP were elevated,
but not significantly, in patients with isolated right ventricular
dysfunction. Patients with renal dysfunction and normal heart
function had significantly higher levels of BNP (258.6 144 pg/
ml vs. 92.4 84 pg/ml) and NT-proBNP (2049 1320 pg/ml vs.
118 104 pg/ml) than patients without renal dysfunction.
Conclusion: Both BNP and NT-proBNP can help in the diagnosis of cardiac dysfunction in ICU patients, but cannot replace
echocardiography. An elevated BNP or NT-proBNP level merely
indicates the presence of a ‘cardiorenal distress’ and should
prompt further investigation.
B
The evaluation of RV and left ventricular (LV)
function is essential to the diagnosis and management of critically ill patients, and increasingly relies
on echocardiography. Although echocardiography
is a good tool, an experienced echocardiographer
may not be available around the clock, and severe
dyspnea may preclude echocardiography (12, 13).
Recent studies conducted in the intensive care unit
(ICU) have found that plasma BNP elevation is significantly correlated with acute cardiac dysfunction.
However, BNP cut-offs vary across studies, depending on the assay method, type of cardiac dysfunction (isolated LV systolic dysfunction or LV plus
RV dysfunction) and patient characteristics (with
or without renal dysfunction, or all patients vs.
only those with septic shock) (14—16). Until now, in
-TYPE natriuretic peptide (BNP) is secreted by
cardiomyocytes in response to an increase in
transmural ventricular pressure (1—3). Its precursor,
proBNP, is cleaved into an inactive N-terminal portion,
NT-proBNP, and BNP, both of which can be quantified.
Many clinical studies have established that both
markers are useful in the diagnosis of heart failure.
A plasma BNP assay is now widely recommended
as a diagnostic tool in emergency-room patients
with acute dyspnea. A level greater than 100 pg/
ml without renal failure suggests systolic dysfunction as the cause of dyspnea (4—6). A correlation
between BNP and diastolic dysfunction has also
been reported (7—10), and BNP is a marker for
right ventricular (RV) dysfunction in patients with
pulmonary arterial hypertension (11).
340
Accepted for publication 3 October 2005
Key words: brain natriuretic peptide; echocardiography;
intensive care unit; myocardial dysfunction.
#
Acta Anaesthesiologica Scandinavica 50 (2006)
Brain natriuretic peptides in shock or respiratory distress
general ICU patients, only one previous study has
compared simultaneously BNP and NT-proBNP
with hemodynamic variables obtained by pulmonary artery catheterization (17).
The objectives of this study were to determine
whether cut-off values for BNP and NT-proBNP
reliably diagnosed RV and/or LV failure in a heterogeneous population of patients admitted to the ICU
for acute respiratory distress and/or shock, whether
non-cardiac factors led to an increase in these markers
and, finally, whether these markers could be an alternative to echocardiography. To this end, we compared plasma levels of BNP and NT-proBNP with
echocardiographic signs of cardiac dysfunction.
Patients and methods
Patients
Between March and November 2003, patients were
eligible if they were admitted to our general ICU for
acute respiratory distress and/or shock investigated
by echocardiography.
Shock was defined as hypotension (systolic arterial
pressure < 90 mmHg), together with the presence
of perfusion abnormalities, including oliguria, lactic
acidosis and acute alteration of mental status. Acute
respiratory distress was defined as dyspnea with
tachypnea (respiratory rate > 30/min), hypoxemia
(PaO2 with nasal oxygen < 70 mmHg) or the need
for mechanical ventilation. We excluded patients
with conditions known to elevate natriuretic peptide
levels: acute coronary events (as identified by
clinical findings, enzyme levels and electrocardiographic signs), supraventricular arrhythmia, known
chronic heart failure and chronic renal failure (renal
clearance < 50 ml/min). The study was approved by
the Ethics Committee of the French Society of Critical
Care, and written informed consent was obtained
from either the patient or his or her next of kin.
Study design
At ICU admission, all patients received the standard
of care, including volume repletion, vasopressors
and mechanical ventilation, as indicated by their
clinical status. After hemodynamic and respiratory
stabilization, echocardiography and plasma BNP
and NT-proBNP assays were performed at the
same time within 24 h of ICU admission. The following data were recorded for each patient at study
inclusion: age, sex, reason for ICU admission,
Simplified Acute Physiologic Score II, hemodynamic
variables (heart rate, blood pressure, nature and
dosage of vasopressors) and ventilatory variables.
Evaluation of heart function
At our ICU, transthoracic echocardiography (HP
Sonos 2000) is performed routinely in patients with
shock or acute respiratory distress. Transesophageal
echocardiography is also performed when echogenicity is poor. For this study, two echocardiographers
(blind to the BNP and NT-proBNP levels) interpreted the echocardiograms. The echocardiography
variables listed below were recorded.
(a) Systolic function parameters, including left ventricular ejection fraction (LVEF) by Simpson’s
method, shortening fraction and left ventricular
end-diastolic area (LV-EDA).
(b) Diastolic variables based on the transmitral flow
measured by pulse Doppler ultrasonography, with
computation of the ratio of the LV peak E-wave
velocity to the LV peak A-wave velocity (E/A) and
the E-wave deceleration time (EDT).
(c) Cardiac index calculated using the LV outflow tract
method.
(d) Interventricular septum thickness.
(e) Systolic pulmonary arterial pressure (sPAP) as estimated from the tricuspid valve regurgitation flow.
(f) Right ventricular end-diastolic area normalized for
the body surface area (iRV-EDA) and ratio of the
RV to LV areas (iRV-EDA/iLV-EDA).
Systolic LV dysfunction was defined as an LVEF
below 50%. In patients without systolic LV dysfunction,
diastolic dysfunction was defined as transmitral flow
parameters consistent with one of the three patterns of
diastolic dysfunction: impaired relaxation (E/A < 1
and EDT > 240 ms), pseudonormalization(1 < E/
A < 2 and 150 < EDT < 200 ms) or restricted filling
(E/A > 2 and EDT < 150 ms) (18). RV dysfunction
was defined as an iRV-EDA/iLV-EDA ratio greater
than 0.6, with or without septal dyskinesia (19).
Patients with systolic or diastolic LV dysfunction
and/or patients with RV dysfunction were categorized as having heart failure (HFþ); all other patients
were categorized as having no heart failure (HF—).
Plasma assays of BNP and NT-proBNP
Blood samples drawn at the time of echocardiography were immediately centrifuged; the plasma
was separated and stored at 70 C until the assays
were performed at the end of the study. BNP was
measured using the quantitative immunofluorescence assay Triage BNP (Biosite Europe, Velizy,
France) on 5 ml of whole blood drawn in an ethylenediaminetetraacetic acid (EDTA) tube (20). This assay
can detect BNP levels in the 5—5000 pg/ml range.
Values lower than 100 pg/ml are considered to be
341
L. Bal et al.
normal in patients without heart failure. NT-proBNP
was measured using the quantitative immunological
electrochemiluminescence assay proBNP (Roche
Diagnostics GmbH, Mannheim, Germany) on a 5-ml
blood sample drawn in a standard tube (21). This
assay uses two polyclonal antibodies specific for epitopes in the N-terminal portion (1—76) of proBNP, and
detects levels in the 5—35,000 pg/ml range. Normal
values in patients younger than 50 years are 153 and
88 pg/ml in females and males, respectively; normal
values in patients 50—65 years of age are 334 and
227 pg/ml in females and males, respectively.
Troponin Ic assay
The immunofluorescence assay Stratus (Dade
Behring, Newark, USA) was used. Values lower
than 0.03 ng/ml are normal with this assay.
Renal function tests
The serum creatinine level determined at the time
of echocardiography was used to compute renal clearance according to the Cockcroft and Gault formula:
clearance (ml/min) ¼ [R body weight (kg) (140
age)]/serum creatinine (mmol/l), where R is 1.23 in
males and 1.04 in females. Renal failure was defined
as a creatinine clearance of less than 90 ml/min.
Statistics
All values were expressed as the mean standard
deviation. Correlations linking BNP or NT-proBNP
to echocardiography parameters, age and creatinine
clearance were evaluated by linear regression in the
overall study population and in the HFþ and HF—
subgroups. Variables identified with P < 0.05 were
entered into multiple regression to identify factors
independently associated with BNP or NT-proBNP
elevation. The non-parametric Mann—Whitney test
was selected for the comparison of means. Receiver
operating characteristic (ROC) curves were plotted
using heart function status (HFþ or HF—) as the
response variable and the BNP or NT-proBNP
level as the reference criterion. The negative predictive value of each assay was computed on the basis
of these curves. For all tests, P values below 0.05
were considered to be statistically significant.
Results
During the study period, 49 patients met the inclusion criteria. In six patients, echocardiographers
were not present on admission, and blood samples
were not available in two other patients. Therefore,
41 patients were studied. The main characteristics
342
and reasons for admission of the 41 patients
included in the study are reported in Table 1. The
etiology of RV dysfunction was acute respiratory
distress syndrome in seven patients, acute respiratory failure in two patients with chronic obstructive
pulmonary disease and pulmonary embolism in one
patient. Table 2 reports the echocardiography and
laboratory test results.
Plasma BNP (Table 2, Figs 1 and 2)
By univariate analysis, plasma BNP was significantly correlated with age (r ¼ 0.34; P ¼ 0.03), creatinine clearance (r ¼ 0.42; P ¼ 0.01), LVEF (r ¼ 0.64;
P < 0.001), iRV-EDA (r ¼ 0.53; P < 0.001) and sPAP
(r ¼ 0.33; P ¼ 0.04). Two factors were independently correlated with plasma BNP in the multivariate analysis: LVEF (P ¼ 0.02) and iRV-EDA
(P ¼ 0.02). The comparison of patients with and
Table 1
Patient characteristics.
Characteristic
Study population
(n ¼ 41)
Age (years)*
Simplified Acute Physiologic Score II*
Male gender, n (%)
Died, n (%)
Mechanical ventilation, n (%)
Vasoactive drugs, n (%)
Norepinephrine, n (%)
Norepinephrine þ dobutamine, n (%)
Dopamine þ dobutamine, n (%)
Heart failure, n (%)
Pattern of heart failure (25 patients), n (%)
Left ventricular systolic dysfunction
Right ventricular dysfunction
Left and right ventricular dysfunction
Left ventricular diastolic dysfunction
Renal function, n (%)
Creatinine clearance < 90 ml/min
Creatinine clearance 90 ml/min
Reasons for intensive care unit admission,
n (%)
Respiratory failure
Acute respiratory distress
syndrome or pneumonia
Chronic obstructive
pulmonary disease
Cardiogenic pulmonary edema
Shock
Septic
Hypovolemic
Shock and respiratory failure
Septic with acute respiratory distress
syndrome or pneumonia
Pulmonary embolism
52.9 20
48 21
17 (41)
7 (17)
28 (68)
16 (39)
14 (34)
1 (2)
1 (2)
25 (61)
9 (22)
10 (24)
3 (7)
3 (7)
18 (44)
23 (56)
17 (41)
11 (27)
2 (5)
4 (9)
15 (37)
8 (20)
7 (17)
9 (22)
8 (20)
1 (2)
*Results are expressed as mean standard deviation.
Brain natriuretic peptides in shock or respiratory distress
Table 2
Echocardiographic parameters, creatinine clearance, troponin, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic
peptide (NT-proBNP) in the overall population and in patients with (HFþ) and without (HF—) heart failure.
Study population Mean SD
[range] (n ¼ 41)
BNP (pg/ml)
NT-proBNP (pg/ml)
Age (years)
SAPS II
Troponin
Creatinine clearance (ml/min)
LVEF (%)
iRV-EDA (cm2/m2)
RV-EDA/LV-EDA
sPAP (mmHg)
Cardiac index (l/min/m2)
E/A
356.2
2050.3
52.9
48
0.3
113.9
55.2
8.3
0.55
35
2.8
1.2
HF—Mean SD
(n ¼ 16)
375 [4—1870]
2591 [49—11489]
20 [14—86]
21 [10—103]
0.6 [0.1—2.9]
49 [51—248]
12 [20—74]
2.7 [4—17]
0.17 [0.31—1.2]
11 [20—70]
0.7 [1.6—4.6]
0.5 [4—17]
144.3
762.7
46
46
0.25
129.8
61
6.8
0.47
28.8
2.8
1.3
HFþ Mean SD
(n ¼ 25)
128
1128
24
24
0.4
57
8
1.4
0.1
6.4
0.7
0.5
491.7
2874.4
57
49
0.35
103.8
51
9.1
0.61
39.3
2.7
1.1
P*
418
2929
17
20
0.7
41
13
2.9
0.2
12
0.7
0.5
< 0.001
0.003
0.11
0.47
0.72
0.23
0.01
0.006
0.02
0.002
0.84
0.1
E/A, peak velocity of the E-wave/peak velocity of the A-wave of the mitral flow; LV-EDA, left ventricular end-diastolic area; LVEF, left
ventricular ejection fraction; RV-EDA, right ventricular end-diastolic area; SAPS II, Simplified Acute Physiologic Score II; sPAP, systolic
pulmonary artery pressure.
*
Group HF— vs. HFþ.
without heart failure is shown in Table 2 and Fig. 1.
The ROC curve showed that BNP levels greater than
221 pg/ml predicted cardiac dysfunction (HFþ)
with 68% sensitivity, 88% specificity, 89% positive
predictive value and 63% negative predictive value
(Fig. 2).
LVEF (r ¼ 0.58; P < 0.001), cardiac index (r ¼ 0.37;
P ¼ 0.02) and iRV-EDA (r ¼ 0.37; P ¼ 0.03). In the
multivariate analysis, NT-proBNP was independently correlated with age (P ¼ 0.02) and LVEF
(P < 0.001). The comparison of patients with and
100
Plasma NT-proBNP (Table 2, Figs 1 and 2)
By univariate analysis, plasma NT-proBNP was significantly correlated with age (r ¼ 0.34; P ¼ 0.03),
443 pg/ml
80
NTproBNP (pg/ml)
BNP (pg/ml)
Sensitivity
1000
5600
900
800
221 pg/ml
4600
700
60
BNP
proBNP
40
3600
600
500
*
*
2600
400
20
1600
300
200
0
600
100
0
0
–400
HF–
HF+
HF–
HF+
Fig. 1. Mean standard deviation of B-type natriuretic peptide (BNP)
and N-terminal-proBNP (NT-proBNP) in patients with (HFþ) and
without (HF—) heart failure. HFþ: BNP ¼ 491.7 418 pg/ml; NTproBNP ¼ 2874.4 2929 pg/ml; HF—: BNP ¼ 144.3 128 pg/ml;
NT-proBNP ¼ 762.7 1128 pg/ml. *P < 0.05.
20
40
60
100-Specificity
80
100
Fig. 2. Receiver operating characteristic (ROC) curve of B-type
natriuretic peptide (BNP) and N-terminal-pro-BNP (NTproBNP) in patients with and without heart failure as assessed
by echocardiography. ROC curve for BNP (full line): area under
the curve ¼ 0.81; 95% confidence interval ¼ 0.66—0.92. ROC
curve for NT-proBNP (broken line): area under the curve ¼ 0.78;
95% confidence interval ¼ 0.62—0.89. P ¼ 0.54.
343
L. Bal et al.
without heart failure is shown in Table 2 and Fig. 1.
Plasma NT-proBNP levels were not significantly
increased in patients older than 75 years of age
when compared with those in the overall study
population. The ROC curve showed that a plasma
NT-proBNP level greater than 443 pg/ml indicated
cardiac dysfunction (HFþ) with 84% sensitivity,
75% specificity, 84% positive predictive value and
75% negative predictive value (Fig. 2).
There was no difference in plasma BNP and
NT-proBNP levels with regard to vasoactive drugs,
mechanical ventilation and death.
Comparison of BNP and NT-proBNP
There was a good correlation between plasma BNP
and NT-proBNP levels (r ¼ 0.71; P < 0.001). The
ROC curves showed no significant difference
between these two markers for the diagnosis of
cardiac dysfunction (Fig. 2).
Subgroup of patients with heart failure (Fig. 3)
We compared BNP and NT-proBNP levels in patients
with LV dysfunction (systolic and/or diastolic) and
RV dysfunction (iRV-EDA/iLV-EDA > 0.6). RV dysfunction with normal LV function was associated
with a marked but non-significant increase in plasma
BNP; in contrast, the increase was significant in
patients with both LV and RV dysfunction.
RV dysfunction was associated with a non-significant
NT-proBNP increase in patients with or without LV
dysfunction.
4357.7+/–4085*
LVF+RVF+
Renal function was similar in the HFþ and HF—
groups (Table 2). Amongst HF— patients, those with
renal failure had significantly higher BNP levels than
those without. In the HFþ group, in contrast, the
BNP increase associated with renal dysfunction
was not statistically significant. Similarly, linear
regression showed a significant correlation between
BNP and renal function in the HF— group (r ¼ 0.55;
P ¼ 0.03), but not in the HFþ group.
Renal dysfunction was associated with NTproBNP increase in the HF— group, but not in the
HFþ group. Similarly, NT-proBNP was significantly
correlated with creatinine clearance in the HF—
group (r ¼ 0.6; P ¼ 0.01), but not in the HFþ group.
Discussion
In this study, plasma NT-proBNP and BNP levels
were independently associated with cardiac dysfunction. A plasma BNP level of more than 221 pg/ml or a
plasma NT-proBNP level of more than 443 pg/ml
had sensitivity values for cardiac dysfunction of 68%
and 84%, respectively, and specificity values of 87%
and 75%, respectively. These results confirm earlier
reports that plasma BNP and NT-proBNP assays can
assist in the diagnosis of cardiac dysfunction
in patients admitted to general ICUs with lifethreatening hemodynamic or respiratory dysfunction.
Nevertheless, there is a substantial overlap of BNP
2766.3+/–2511*
HF+RF+
628 7+/–505*
1080.7+/–683* **
3466.3+/–2449*
LVF+RVF–
419.2+/–317*
1052.8+/–937
337.9+/–361
LVF–RVF+
NTproBNP
BNP
2991.5+/–3438*
HF+RF–
343.4+/–238*
2049+/–1320*
HF–RF+
258.6+/–144*
NTproBNP
762.7+/–1128
144.3+/–128
LVF–RVF–
0
1000
2000
3000
4000
pg/ml
5000
Fig. 3. Comparison of B-type natriuretic peptide (BNP) and
N-terminal-proBNP (NT-proBNP) levels in patients with or without
left ventricular and/or right ventricular failure. BNP and NTproBNP results are expressed as means in pg/ml. LVF— RVF—,
patients without left or right ventricular failure; LVF— RVFþ,
patients without left ventricular failure and with right ventricular
failure; LVFþRVF—, patients with left ventricular failure and without right ventricular failure; LVFþRVFþ, patients with both left and
right ventricular failure. *P < 0.05 vs. LVF— RVF— patients.
**P < 0.05 vs. LVFþRVF— patients.
344
Comparison of patients with and without renal
dysfunction (Fig. 4)
118+/–104*
92.4+/–84*
HF–RF–
BNP
pg/ml
0
500
1000 1500 2000 2500 3000 3500
Fig. 4. Comparison of B-type natriuretic peptide (BNP) and
N-terminal-proBNP (NT-proBNP) in patients with or without
heart and/or renal failure. BNP and NT-proBNP results are
expressed as means in pg/ml. HF— RF—, patients without heart or
renal failure; HF— RFþ, patients without heart failure and with
renal failure; HFþRF—, patients with heart failure and without
renal failure; HFþRFþ, patients with both heart and renal failure.
*P < 0.05 vs. HF— RF— patients.
Brain natriuretic peptides in shock or respiratory distress
and NT-proBNP values between patients with and
without relevant heart dysfunction (Fig. 1).
McLean et al. (22) found a lower BNP cut-off
(144 pg/ml) for LV and/or RV dysfunction in ICU
patients, although their cardiac dysfunction definitions and BNP assay method were similar to those
used in our study; however, their report supplies
no information on renal function. The cut-off of
NT-proBNP for the diagnosis of cardiac dysfunction
in our study is different from that found by Jefic
et al. (17) (1550 pg/ml); however, in the study
by Jefic et al., RV function was not evaluated, LV
function was measured with a pulmonary artery
catheter (LV dysfunction was defined as an LV
stroke index of less than 35 g/m2) and, finally, the
cohort of patients was different (only hypoxic
respiratory failure).
BNP and NT-proBNP differ in terms of their
secretion and excretion kinetics, their plasma halflives being 22 min and 120 min, respectively (23).
Therefore, theoretically, BNP should be more useful
to detect an acute change in cardiac function.
Nevertheless, both markers can be used to assist in
the diagnosis of cardiac dysfunction in ICU patients,
as they have similar ROC curves. In our population,
with a higher representation of mildly/moderately
reduced LVEF (35—50%), BNP seems to be more
specific but less sensitive than NT-proBNP. In the
study by Jefic et al. (17), NT-proBNP was also more
sensitive than BNP for the diagnosis of LV dysfunction. This can be explained by a different diagnostic
accuracy of BNP and NT-proBNP, with an advantage of BNP in diagnosing more severely impaired
LVEF, as has been described by Mueller et al. (24),
and an advantage for NT-proBNP for milder cardiac
dysfunction, as described by others (17). Another
advantage of NT-proBNP may be that the levels
can be determined in urine, and can be used for a
simple diagnosis of heart failure (25).
LV dysfunction may be the main factor in BNP
and NT-proBNP production. In our study, RV dysfunction alone induced a non-significant BNP
increase. This result can probably be ascribed to
the relatively weaker study population and to the
moderate nature of RV dilation in our population,
with 90% of patients having an iRV-EDA/iLV-EDA
ratio of less than unity (26). In contrast, in patients
with LV systolic dysfunction, concomitant RV dilation was associated with a greater BNP elevation
than was LV systolic dysfunction alone, in keeping
with a report by Mariano-Goulart et al. (27). NTproBNP may be less susceptible than BNP to the
effects of RV dilation.
Amongst the many factors that may influence
BNP and NT-proBNP levels, renal function has
been reported to have the greatest effect on the
cut-offs for these two parameters (28, 29). We
found that BNP and NT-proBNP were higher in
patients with than without renal dysfunction, and
that the difference was significant only for those
patients without cardiac dysfunction. However,
creatinine clearance was not independently associated with BNP or NT-proBNP elevation. Similar
results were found by Jefic et al. (17). In a study of
patients receiving emergency-room care for acute
dyspnea, McCullough et al. (30) determined BNP
cut-offs for different ranges of creatinine clearance
(< 30, 30—60, 60—90 and > 90 ml/min/1.73 m2). In
our study, the exclusion of patients with severe
renal failure (creatinine clearance of less than
50 ml/min) may explain why BNP and NTproBNP levels varied significantly with creatinine
clearance in the HF— group, but not in the HFþ
group. Indeed, the contribution of early renal failure
to the increase in myocardial transmural pressure,
and therefore to BNP (and NT-proBNP) elevation,
is proportionally less marked in patients with
than without cardiac dysfunction (29, 31, 32). NTproBNP is excreted through the kidneys, and it
is therefore not surprising that the levels of this
peptide are higher in patients with renal failure
(22); in contrast, no satisfactory explanation for the
BNP increase associated with renal failure has been
reported to date (17, 29, 30).
Therefore, in our opinion, although plasma NTproBNP and BNP levels were independently associated with cardiac dysfunction in ICU patients,
these markers should not constitute an alternative
to echocardiography for the following reasons.
(a) There is a substantial overlap of both BNP and NTproBNP values between patients with and without
relevant heart disease (33).
(b) In patients with heart failure, the brain natriuretic
peptides could not discriminate between LV, RV, or
LV and RV damage.
(c) The possibility of abnormal values of BNP in
patients with renal dysfunction (often encountered
in these life-threatening conditions) despite preserved LV and RV function.
An elevated BNP or NT-proBNP level merely
indicates the presence of ‘cardiorenal distress’, and
should prompt further investigation.
The limitations of our study must be borne in
mind. Our population was heterogeneous, as
expected for patients admitted to a general ICU.
345
L. Bal et al.
We excluded patients with more severe renal failure,
but the results of our study indicate that these
patients should be specifically investigated. The correlation between BNP or NT-proBNP and invasive
filling pressure was not evaluated because the pulmonary artery catheter is no longer used in our ICU;
however, recent studies have produced disappointing findings in this regard (17, 34). Finally, plasma
levels of natriuretic peptides fluctuate, so that single
measurements should be interpreted with caution
(16).
Conclusion
In patients with acute respiratory or circulatory failure, plasma BNP and NT-proBNP levels can help
in the diagnosis of cardiac dysfunction, but the
wide spectrum of cardiac diseases encountered in
the intensive care population and the presence of
important confounding factors (such as renal failure) limit the interpretation of an isolated elevated
value of these markers in this setting. Brain natriuretic peptides as a diagnostic tool are not well established in the ICU and require further investigations;
they do not constitute an alternative to echocardiography.
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Address:
Stéphane Thierry
Centre Hospitalier Sud Francilien
Site EVRY — Quartier du Canal
91014 Evry
France
e-mail: [email protected];
[email protected]
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