Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Cerebral tissue oxygen saturation is associated with N-terminal probrain natriuretic peptide in preterm infants on their first day of life Corinna Binder-Heschl1,2,3, Berndt Urlesberger1,2,3, Martin Koestenberger4, Bernhard Schwaberger1,2,3, Georg M. Schm€olzer3,5,6, Gerhard Pichler ([email protected])1,2,3 1.Research Unit for Cerebral Development and Oximetry, Medical University of Graz, Graz, Austria 2.Research Unit for Neonatal Micro- and Macrocirculation, Medical University of Graz, Graz, Austria 3.Division of Neonatology, Department of Pediatrics, Medical University, Graz, Austria 4.Division of Cardiology, Department of Pediatrics, Medical University of Graz, Graz, Austria 5.Division of Neonatology, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada 6.Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta Health Services, Edmonton, AB, Canada
Keywords Cardiac biomarker, Cardiac output, Cerebral tissue oxygen saturation, N-terminal probrain natriuretic peptide, Preterm neonates Correspondence Gerhard Pichler, MD, Department of Pediatrics, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria. Tel: +43/316/385/80520 | Fax: +43/316/385/12678 | Email: [email protected] Received 8 July 2014; revised 24 September 2014; accepted 13 October 2014. DOI:10.1111/apa.12828
ABSTRACT Aim: This prospective observational study investigated if N-terminal probrain natriuretic peptide (NT-proBNP), a cardiac biomarker, correlated with cerebral tissue oxygen saturation (crSO2) in preterm infants on their first day of life. Methods: Using near infrared spectroscopy (NIRS), crSO2 was measured on the right forehead of preterm infants for 24 h. We also recorded arterial oxygen saturation (SpO2) and calculated fractional tissue oxygen extraction (cFTOE) values. At the end of the NIRS measurement, blood was taken to analyse NT-proBNP. Mean values for the 24-h period were calculated for crSO2, cFTOE, SpO2 and these values were correlated to NT-proBNP. An echocardiography was performed in all infants during the measurement period. Results: We analysed 35 preterm neonates (33 2 weeks, 1965 523 g). NIRS measurements started at 3 1 h and blood samples were taken at 24 5 h postnatal. Echocardiography showed an open ductus arteriosus in all infants. Mean NT-proBNP was 4978 3566 pg/mL, crSO2 was 76 8%, and cFTOE was 0.20 0.08. NT-proBNP correlated negatively with crSO2 (r = 0.75; p ≤ 0.001) and positively with cFTOE (r = 0.731; p ≤ 0.001). Conclusion: These results emphasise that crSO2 is influenced by cardiac function, in addition to oxygen consumption, arterial oxygen saturation and vascular resistance, and this can be measured by NT-proBNP.
INTRODUCTION N-terminal probrain natriuretic peptide (NT-proBNP) is a cardiovascular hormone synthesised by the human body and released in response to cardiac stress, pressure or volume overload, ventricular wall expansion or increased wall tension (1). The main part of synthesis and secretion is located in the cardiac ventricles (1). NT-proBNP and brain natriuretic peptide (BNP) are split products from the inactive precursor proBNP, with a half-life of about 60 min and 20 min, respectively (2). Natriuretic peptides do not cross the placenta, which means that the regulation of these markers is intrinsically controlled by the foetus or newborn infant (3).
Adult studies have reported that NT-proBNP and BNP are useful diagnostic biomarkers of congestive heart failure, acute coronary syndrome and acute respiratory distress syndrome and are able to predict mortality and morbidity (4–6). In the neonatal population, the majority of studies have investigated potential associations between
Key notes
Abbreviations BNP, Brain natriuretic peptide; cFTOE, Cerebral fractional tissue oxygen extraction; crSO2, Cerebral tissue oxygen saturation; NIRS, Near infrared spectroscopy; NT-proBNP, N-terminal probrain natriuretic peptide; SpO2, Peripheral arterial oxygen saturation.
32
Minimal changes in cardiac function, which result in inadequate left ventricular output, may compromise cerebral blood flow and cerebral tissue oxygen saturation (crSO2). Our study found that N-terminal probrain natriuretic peptide, a cardiac biomarker synthesised in response to cardiac pressure or volume overload, was significantly associated with crSO2 in preterm infants with normal echocardiography. This result emphasises the fact that crSO2 is influenced by even subtle changes is cardiac function.
©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 32–37
Binder-Heschl et al.
NT-proBNP or BNP and the presence of a patent ductus arteriosus. These studies suggest that NT-proBNP or BNP increase as the diameter of the ductus arteriosus increases (7–11). An open ductus arteriosus has been associated with a lower cerebral tissue oxygen saturation (crSO2), measured with near infrared spectroscopy (NIRS) (12). crSO2 is influenced by peripheral arterial oxygen saturation (SpO2), regional oxygen consumption and cerebral blood flow. Cerebral blood flow is itself affected by total peripheral vascular resistance and cardiac function. NT-proBNP is a marker that allows us to determine the cardiac function, or rather cardiac output, to a certain extent. The aim of this study was to assess whether NT-proBNP, as a marker of cardiac function/output, correlated with crSO2 in preterm infants on their first day of life.
MATERIAL AND METHODS Patients This prospective observational study was conducted at the Neonatal Intensive Care Unit, Medical University of Graz, Austria, from September 2011 to June 2013. Preterm infants with a gestational age of 1.4 mm/kg; and (iii) a left pulmonary artery and diastolic flow of >0.2 m/sec. Echocardiography ductus arteriosus assessment was performed from a high left parasternal view using colour Doppler echocardiography. If a ductus arteriosus was present, the minimal internal diameter was averaged from three to five measurements and the maximum and mean velocity of both shunt directions was measured. Therefore, the pulsed Doppler gate was placed in the pulmonary end of the ductus arteriosus to show the flow pattern of the shunt. Assessment of the tricuspid annular plane systolic excursion was performed by a two-dimensional echocardiograph-guided M-mode from the apical four-chamber view with the cursor placed at the free wall of the tricuspid annulus (14). Care was taken to align the sample volume as vertically as possible with respect to the cardiac apex. Angle correction and respiratory gating were not used. Maximal tricuspid annular plane systolic excursion was determined by the total excursion of the tricuspid annulus, from its highest position, after atrial ascent, to the lowest point of descent during ventricular systole. Study protocol During the measurements, all infants were nursed in an incubator to control air temperature and humidity. Respiratory support was provided according to the European Consensus Guidelines (15). NIRS measurements were continuously recorded over 24 h at a sample rate of 8-sec (0.13 Hz). At the end of the NIRS measurement (6 h), the NT-proBNP was measured by collecting a venous or arterial blood sample into a lithium heparin tube. The NTproBNP assay was performed with the Cobas 8000 (Roche Diagnostics, Mannheim, Germany). Data collection and statistical analyses In addition to crSO2 and SpO2, we calculated cerebral fractional tissue oxygen extraction (cFTOE) for each hour of the NIRS measurement [(SpO2-crSO2)/ SpO2] (16). Mean values (SD) of crSO2, cFTOE, SpO2, heart rate and mean blood pressure were calculated for the 24-h period. The data are presented as mean standard deviation (SD) for normally distributed continuous variables and median interquartile range (IQR) when the distribution was skewed. Pearson correlations were used to assess correlations between NT-proBNP and crSO2, cFTOE and routine monitoring parameters. A p-value of
REGULAR ARTICLE
Cerebral tissue oxygen saturation is associated with N-terminal probrain natriuretic peptide in preterm infants on their first day of life Corinna Binder-Heschl1,2,3, Berndt Urlesberger1,2,3, Martin Koestenberger4, Bernhard Schwaberger1,2,3, Georg M. Schm€olzer3,5,6, Gerhard Pichler ([email protected])1,2,3 1.Research Unit for Cerebral Development and Oximetry, Medical University of Graz, Graz, Austria 2.Research Unit for Neonatal Micro- and Macrocirculation, Medical University of Graz, Graz, Austria 3.Division of Neonatology, Department of Pediatrics, Medical University, Graz, Austria 4.Division of Cardiology, Department of Pediatrics, Medical University of Graz, Graz, Austria 5.Division of Neonatology, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada 6.Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta Health Services, Edmonton, AB, Canada
Keywords Cardiac biomarker, Cardiac output, Cerebral tissue oxygen saturation, N-terminal probrain natriuretic peptide, Preterm neonates Correspondence Gerhard Pichler, MD, Department of Pediatrics, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria. Tel: +43/316/385/80520 | Fax: +43/316/385/12678 | Email: [email protected] Received 8 July 2014; revised 24 September 2014; accepted 13 October 2014. DOI:10.1111/apa.12828
ABSTRACT Aim: This prospective observational study investigated if N-terminal probrain natriuretic peptide (NT-proBNP), a cardiac biomarker, correlated with cerebral tissue oxygen saturation (crSO2) in preterm infants on their first day of life. Methods: Using near infrared spectroscopy (NIRS), crSO2 was measured on the right forehead of preterm infants for 24 h. We also recorded arterial oxygen saturation (SpO2) and calculated fractional tissue oxygen extraction (cFTOE) values. At the end of the NIRS measurement, blood was taken to analyse NT-proBNP. Mean values for the 24-h period were calculated for crSO2, cFTOE, SpO2 and these values were correlated to NT-proBNP. An echocardiography was performed in all infants during the measurement period. Results: We analysed 35 preterm neonates (33 2 weeks, 1965 523 g). NIRS measurements started at 3 1 h and blood samples were taken at 24 5 h postnatal. Echocardiography showed an open ductus arteriosus in all infants. Mean NT-proBNP was 4978 3566 pg/mL, crSO2 was 76 8%, and cFTOE was 0.20 0.08. NT-proBNP correlated negatively with crSO2 (r = 0.75; p ≤ 0.001) and positively with cFTOE (r = 0.731; p ≤ 0.001). Conclusion: These results emphasise that crSO2 is influenced by cardiac function, in addition to oxygen consumption, arterial oxygen saturation and vascular resistance, and this can be measured by NT-proBNP.
INTRODUCTION N-terminal probrain natriuretic peptide (NT-proBNP) is a cardiovascular hormone synthesised by the human body and released in response to cardiac stress, pressure or volume overload, ventricular wall expansion or increased wall tension (1). The main part of synthesis and secretion is located in the cardiac ventricles (1). NT-proBNP and brain natriuretic peptide (BNP) are split products from the inactive precursor proBNP, with a half-life of about 60 min and 20 min, respectively (2). Natriuretic peptides do not cross the placenta, which means that the regulation of these markers is intrinsically controlled by the foetus or newborn infant (3).
Adult studies have reported that NT-proBNP and BNP are useful diagnostic biomarkers of congestive heart failure, acute coronary syndrome and acute respiratory distress syndrome and are able to predict mortality and morbidity (4–6). In the neonatal population, the majority of studies have investigated potential associations between
Key notes
Abbreviations BNP, Brain natriuretic peptide; cFTOE, Cerebral fractional tissue oxygen extraction; crSO2, Cerebral tissue oxygen saturation; NIRS, Near infrared spectroscopy; NT-proBNP, N-terminal probrain natriuretic peptide; SpO2, Peripheral arterial oxygen saturation.
32
Minimal changes in cardiac function, which result in inadequate left ventricular output, may compromise cerebral blood flow and cerebral tissue oxygen saturation (crSO2). Our study found that N-terminal probrain natriuretic peptide, a cardiac biomarker synthesised in response to cardiac pressure or volume overload, was significantly associated with crSO2 in preterm infants with normal echocardiography. This result emphasises the fact that crSO2 is influenced by even subtle changes is cardiac function.
©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 32–37
Binder-Heschl et al.
NT-proBNP or BNP and the presence of a patent ductus arteriosus. These studies suggest that NT-proBNP or BNP increase as the diameter of the ductus arteriosus increases (7–11). An open ductus arteriosus has been associated with a lower cerebral tissue oxygen saturation (crSO2), measured with near infrared spectroscopy (NIRS) (12). crSO2 is influenced by peripheral arterial oxygen saturation (SpO2), regional oxygen consumption and cerebral blood flow. Cerebral blood flow is itself affected by total peripheral vascular resistance and cardiac function. NT-proBNP is a marker that allows us to determine the cardiac function, or rather cardiac output, to a certain extent. The aim of this study was to assess whether NT-proBNP, as a marker of cardiac function/output, correlated with crSO2 in preterm infants on their first day of life.
MATERIAL AND METHODS Patients This prospective observational study was conducted at the Neonatal Intensive Care Unit, Medical University of Graz, Austria, from September 2011 to June 2013. Preterm infants with a gestational age of 1.4 mm/kg; and (iii) a left pulmonary artery and diastolic flow of >0.2 m/sec. Echocardiography ductus arteriosus assessment was performed from a high left parasternal view using colour Doppler echocardiography. If a ductus arteriosus was present, the minimal internal diameter was averaged from three to five measurements and the maximum and mean velocity of both shunt directions was measured. Therefore, the pulsed Doppler gate was placed in the pulmonary end of the ductus arteriosus to show the flow pattern of the shunt. Assessment of the tricuspid annular plane systolic excursion was performed by a two-dimensional echocardiograph-guided M-mode from the apical four-chamber view with the cursor placed at the free wall of the tricuspid annulus (14). Care was taken to align the sample volume as vertically as possible with respect to the cardiac apex. Angle correction and respiratory gating were not used. Maximal tricuspid annular plane systolic excursion was determined by the total excursion of the tricuspid annulus, from its highest position, after atrial ascent, to the lowest point of descent during ventricular systole. Study protocol During the measurements, all infants were nursed in an incubator to control air temperature and humidity. Respiratory support was provided according to the European Consensus Guidelines (15). NIRS measurements were continuously recorded over 24 h at a sample rate of 8-sec (0.13 Hz). At the end of the NIRS measurement (6 h), the NT-proBNP was measured by collecting a venous or arterial blood sample into a lithium heparin tube. The NTproBNP assay was performed with the Cobas 8000 (Roche Diagnostics, Mannheim, Germany). Data collection and statistical analyses In addition to crSO2 and SpO2, we calculated cerebral fractional tissue oxygen extraction (cFTOE) for each hour of the NIRS measurement [(SpO2-crSO2)/ SpO2] (16). Mean values (SD) of crSO2, cFTOE, SpO2, heart rate and mean blood pressure were calculated for the 24-h period. The data are presented as mean standard deviation (SD) for normally distributed continuous variables and median interquartile range (IQR) when the distribution was skewed. Pearson correlations were used to assess correlations between NT-proBNP and crSO2, cFTOE and routine monitoring parameters. A p-value of
