B-type NAtriuretic Peptide In Critically Ill : A Multicentric Diagnostic Study (B-rAPID)
B-type NAtriuretic Peptide In Critically Ill : A Multicentric Diagnostic Study (B-rAPID)
Difficulty in breathing or increased rate of breathing are common causes of admission to
 intensive care unit. This may be due to heart failure, or other causes such as infection in
 the lungs. Treating doctors usually perform Chest X-ray, ECG, and other tests to know if
 breathlessness is due to heart failure or other cause. Doctors also give medicines to treat
 heart failure, or other conditions of the lungs based on the symptoms and investigation
 results. BNP is released by heart which is not functioning well. However BNP levels are also
 high in case of severe infection.Hence there is equipoise in utility of BNP measurements
 among critically ill patients, and it is not a current standard of care. The current cost of
 this test (about 1000 rupees per measurement) is high, and hence its utility needs to be
 carefully examined before a widespread use. The investigators intend to test the hypothesize
 that that on-admission BNP measurements, help clinicians identify CHF early, which may modify
 therapeutic decisions, and improve outcomes. The current study is designed with an objective
 to determine if on-admission BNP value and availability of its test results to treating
 physicians will reduce in-hospital, and 30-day mortality and in-hospital morbidity.
There usually remains a diagnostic uncertainty as differentiation between cardiogenic or
 non-cardiogenic cause of dyspnea. Often there are multiple underlying etiologies for acute
 onset dyspnea, and their evaluation leads to diagnostic delays, and hence longer hospital
 stay. While various clinical symptoms, signs and imaging based investigations are used in
 this differentiation, their accuracy remains low, and overlapping features preclude such
 differentiation. Echocardiography is an important adjunct in making such differentiation, but
 operator skill, and lack of availability of this technique at point of care are barriers in
 use of this modality. 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 settings. Recently this test has become
 available at point of care (Alere Heart-Check). Ease, low cost, and objectivity in
 measurement of BNP has led to widespread incorporation of BNP and its precursor NT-pro-BNP
 into the clinical evaluation of CHF.

 Circulating levels of BNP/NT-proBNP are normally very low in healthy individuals. In response
 to increased myocardial wall stress due to volume- or pressure-overload states (such as in
 CHF), the BNP gene is activated in cardiomyocytes. This results in the production of an
 intracellular precursor propeptide (proBNP108); further processing of this propeptide results
 in release of the biologically inert aminoterminal fragment (NT-proBNP) and the biologically
 active BNP.Various studies have been performed to determine cut-off level to make a
 differentiation between presence or absence of CHF using this test. BNP level below 50pg/ml
 rules out CHF with a negative predictive value of 96%. (3) In the same study by Maisel et al
 the diagnostic accuracy of B-type natriuretic peptide to rule in CHF at a cutoff of 100 pg
 per milliliter or more was 83.4 percent. However subsequent studies have instead suggested a
 multiple cut-point strategy (Less than 100pg/ml rules out CHF (NPV 90%), more than 400 pg/ml
 rules in CHF (91% specificity) while intermediate values representing a grey zone.
 Individuals with renal dysfunction have elevated BNP levels, and a lower cut-off to exclude
 CHF in such patients is 200pg/ml. Individuals with a high BMI have falsely low levels and a
 BMI adjusted correction is used (Lower cut-off of 54pg/mL if BMI >35kg/m2). The levels of BNP
 as well as NT-Pro-BNP have similar elevations in CHF, later being three times as much higher.
 (1) Use of BNP to differentiate CHF from other causes of dyspnea, (4) and ease in its
 measurement has resulted in increase in its use in intensive care settings, as point-of-care
 testing has a potential to change outcomes. However when the test is used in this setting,
 very high BNP levels were detected in critically ill patients with sepsis and shock. In
 patients with shock, levels below 1200pg/ml had a negative predictive value of 92% for
 cardiogenic shock. Such high levels in patients with compromised systolic function have
 questioned utility of this measure to distinguish between CHF and other causes in critical
 care settings. It is debated that in critically ill patients, coexisting other organ
 dysfunction, rapid changes in volume status, variable bioavailability and burst synthesis of
 BNP may all confound interpretation of BNP levels. However despite this confounding, even in
 critically ill patients higher values are associated with adverse prognosis, and very low
 levels (less than 100pg/ml) will mean a preserved left ventricular function. Thus, while it
 is known that BNP really gives useful information, not already available from other clinical,
 radiologic and biochemical measurements, what the investigators do not know is if the test
 results become available in an intensive care unit setting, will it help treating physicians
 to make meaningful clinical decisions.

 Given above considerations, there is equipoise in utility of BNP measurements among
 critically ill patients, and it is not a current standard of care. The current cost of this
 test (about 1000 rupees per measurement) is high, and hence its utility needs to be carefully
 examined before a widespread use. The investigators intend to test the hypothesize that that
 on-admission BNP measurements, help clinicians identify CHF early, which may modify
 therapeutic decisions, and improve outcomes. The current study is designed with an objective
 to determine if on-admission BNP value and availability of its test results to treating
 physicians will reduce in-hospital, and 30-day mortality and in-hospital morbidity.
Inclusion Criteria:

 We will include all consecutive patients admitted to intensive care units in participating
 sites with all of the following features:

 -  Adult aged 18 years or more

 -  Acute onset dyspnea (duration 3 days or less) , defined as respiratory rate of 20 or
 more.

 -  Treating physician considers patient to be critically ill so as to warrant care in
 intensive care unit.

 Exclusion Criteria:

 Patients for whom consent is not obtained will be excluded from the study