**4. The central hemodynamic monitoring**

The central hemodynamic monitoring assesses the blood flow and the blood pressure in the heart and major vessels. The heart function and by that the stroke volume (SV) are determined by the preload—the venous filling, contractility of the heart muscle, and the afterload—which can be estimated only partially with the pressure in the aorta. The CO is the product of the SV and the heart rate (HR). Neonates increase their CO mainly by increasing the HR as they can‐ not sufficiently increase the SV. The HR is influenced by the body temperature, catecholamine secretion, and the autonomic nervous system.

#### **4.1. The preload assessment**

as possible and many new techniques have been applied in this vulnerable population to measure the central (arterial blood pressure and systemic blood flow) and peripheral hemodynamic parameters (peripheral vascular resistance). Arterial blood pressure is mea‐ sured either noninvasively by sphygmomanometer or invasively through arterial catheters. Systemic blood flow is noninvasively assessed by echocardiography, cardiac magnetic reso‐ nance, electrical cardiometry, and arterial pulse waveform analysis. Invasive methods for measuring the systemic blood flow are applied through centrally inserted vascular cath‐ eters. It is not known whether laser‐Doppler and spectroscopy in the near‐infrared spec‐ trum (near‐infrared spectroscopy, NIRS) can reliably monitor peripheral vascular resistance

**Figure 1.** Assessment of hemodynamic status in neonatal intensive care unit. Adapted from Ref. [64]. aEEG, amplitude‐ integrated electroencephalogram; BGA, blood gas analysis; ECG, electrocardiogram; NIRS, near‐infrared spectroscopy;

PICCO, pulse‐induced contour cardiac output.

(**Figure 1**) [6].

30 Selected Topics in Neonatal Care

Clinically, the preload can be assessed visually assessing the jugular venous pressure, which is rarely possible in neonates with short neck. Using the hand pressure on the liver or eleva‐ tion of the legs increases preload and is a simple method of assessing preload but less used in the NICU. The venous filling in neonates can be measured by inferior vena cava (IVC) diameter, and its collapsibility during respiration indicates volume responsiveness [7, 8]. IVC assessment is not an accurate marker of volume status and fluid responsiveness in cases of (1) increased right atrial pressure, (2) tricuspid or pulmonary valve regurgitation, (3) pulmo‐ nary hypertension, or (4) right ventricular dysfunction. Another method for assessing volume status of a neonate is lung ultrasonography (US) [9, 10]. Sonographic visualization of B‐lines and measurement of extravascular lung water may aid diagnosing early volume overload in neonate. In a neonate with RDS after receiving surfactant, the B‐lines are still visible [11].

#### **4.2. Cardiac output**

The measurement of CO is the most important parameter of the central hemodynamic moni‐ toring, assessing the perfusion of organs. It is vital for the etiopathogenic diagnosis of low cardiac output syndrome, being due to either hypovolemia, myocardial dysfunction, vasodila‐ tation, tamponade, pneumothorax, obstructive shock, pulmonary hypertension, or acute RDS. CO should be measured in the following clinical conditions: congenital and acquired heart diseases, shock, multiple organ failure, cardiopulmonary interactions during mechanical ven‐ tilation, clinical research, and assessment of new therapies [12]. The following three questions guide us in the interpretation of the adequacy of CO: (1) Is the delivery of oxygen adequate to meet the metabolic need of the patient? (2) Is oxygen delivery occurring with an adequate perfusion pressure? (3) Is the patient able to utilize the oxygen delivered, and if not, why so? [13]. Not only the measurement but also adequacy of CO and oxygen delivery is important, reflecting in clinical (capillary refill and core‐peripheral temperature difference) and labora‐ tory (lactic acid) parameters. But caveat is needed; normal values do not mean that regional perfusion is adequate, as well as abnormal values do not provide us with etiologic clue.

Clinically, CO with the systemic blood flow and perfusion can indirectly noninvasively be assessed by palpating the peripheral pulses and heart rate, capillary refill time, and measuring the peripheral‐core temperature difference [14]. None of clinical methods for the evaluation of CO is definitely reliable [15]. The HR in neonate is affected by many factors and so it is not necessarily a good indicator of hemodynamic status. In hypovolemic state, the immature heart muscle and the autonomic nervous system impact the cardiovascular response differ‐ ently in neonates in comparison to adults. The capillary refill time is affected by the pres‐ sure technique, variability among investigators, ambient temperature, drugs, and maturity of neonatal skin. The capillary refill time of >3 s has 55% sensitivity and 81% specificity for the prediction of the low systemic blood flow [16].

of the venous return to the heart through the SVC. The flow in the SVC is normally between 30 and 50% of the total systemic blood flow. Similarly, to assess the pulmonary blood flow, the

Hemodynamic Monitoring in Neonates http://dx.doi.org/10.5772/intechopen.69215 33

Measuring the ejection fraction (EF) and fractional shortening (FS) in hemodynamic monitor‐ ing of the newborn is not very useful measurement, except in the case of severe myocardial dysfunction, when measurements are not really necessary, since the poor contractility of the heart muscle is obvious. We calculate them on the basis of measurement differences in dimen‐ sions of left ventricle in the long axis between diastole and systole. The problem of measure‐ ment in neonates is that the anterior wall of the ventricle is relatively stiff in comparison to the posterior and lateral wall of the left ventricle. To avoid this, they proposed measuring the dimensions of the left ventricle in short axis [22]. Two new US methods for assessing cardiac function are the measurement of diastolic function and tissue Doppler US. Diminished dia‐ stolic relaxation effects systolic function of the heart muscle, and thus the SV and CO. We may assess the diastolic function from the shape of Doppler wave of the inflow of blood into the ventricle. The filling of the ventricle has two phases: early ventricular filling during relaxation (E wave) and late active ventricular filling due to atrial systole (A wave). In a healthy neo‐ nate, 80% of the blood fills the left ventricle early in diastole, so the predominance of A wave indicates impaired diastolic function [23]. But when assessing impaired diastolic function, we have to be aware that diastolic function in premature and mature infants is already impaired because of immature contractile system of cardiac muscles [22]. The method of tissue Doppler echocardiography detects low frequency of high energy resulting from the movement of the ventricular wall which cannot be assessed by the standard Doppler investigation. In the four‐ chamber view of the heart in the longitudinal axis, we observe three different variables of ventricular wall motion: velocity, acceleration, and displacement [24]. Even if the method is advantageously used in adult patients, their clinical utility in the treatment of sick newborns

Cardiovascular magnetic resonance (CMR) imaging is a method of nuclear magnetic resonance based on the spinning of hydrogen nuclei in a magnetic field, which are most numerous in the human body. CMR is the gold standard for the assessment of CO. Special expensive equip‐ ment, trained personnel, sedation, and transportation of a neonate are needed to perform CMR. In adults, CMR is used to assess the function of the ventricles, in complex congenital heart disease and cardiomyopathy. Compared with adults, it is necessary to increase the image reso‐ lution in neonates, both spatially (because of the size of the heart), as well as the time (due to the relatively high heart rate of newborn). The essential advantages of this method are detailed assessment of CO, cardiovascular anatomy, and good repeatability. CMR cannot measure the oxygen need and consumption [26]. Images obtained by CMR in real time have lower quality. Kino CMR enables improved anatomy imaging and the ventricular wall motion, by which the heart is imaged at specific phases of the cardiac cycle, depending on the electrocardiographic (ECG) recording. This creates a series of images that can be played as a movie (kino). End‐dia‐ stolic and end‐systolic endocardial and epicardial borders are followed and we reconstruct three‐dimensional models of ventricles: end‐systolic and end‐diastolic volume, ejection frac‐ tion, and SV. CMR with a phase contrast allows the measurement of blood flow to the heart throughout the cardiac cycle [27]. This method quantifies the flow in IVC and descendent aorta,

blood flow velocity in the left pulmonary artery is measured [21].

is not yet fully understood [25].

Noninvasive methods that are used in clinical practice to assess neonatal CO are echocar‐ diography, cardiac magnetic resonance, electrical cardiometry, and arterial pulse waveform analysis. Functional echocardiography (fECHO) enables visualization of the shape and size of the chambers of the heart, the heart valves, contractility, and relaxation of the heart muscle. Various forms of Doppler echocardiography, such as color, continuous and pulsed Doppler echocardiography, enable the determination of both the blood flow direction and velocity. By assessing the velocity of blood flow, two more parameters can be calculated: the difference in pressure above and below the narrowing with the modified Bernoulli's equation and the blood flow through the blood vessel diameter and a mean flow velocity of the blood [17].

fECHO is daily used in the neonatal intensive medicine and constitutes an important part of an integrated bedside hemodynamic monitoring of a neonate. An appropriate training and experience is necessary for performing fECHO; so the obtained measurements are accurate and reliable. It should be noted that fECHO is not a substitute for formal echocardiographic assessment of the neonate by a pediatric cardiologist, especially if the newborn is suspected to have CHD or the latter has already been diagnosed [18, 19]. fECHO enables discontinuous hemodynamic assessment of neonate in real time. With fECHO, we can estimate the central venous pressure, and thus the volume of blood, and the contractility and filling of the right and left cavities, pulmonary arterial pressure, and the SV of the both ventricles, thereby CO. With neonatal fECHO, we can assess the presence, direction, and measure the blood flow velocity through the shunts, such as persistent ductus arteriosus (PDA) and open foramen ovale, the pressure in the pulmonary artery and the superior vena cava (SVC) and thereby assess heart function. The drawback is the limited accuracy of the measurements (10% with a single investigator and 20% among various investigators). Acquired measurements also depend on the blood flow: from the transitional to neonatal, shunts through connections between the pulmonary and systemic blood flow and immaturity or lability of the lung vas‐ culature, and thus the pressure in the pulmonary artery [20].

fECHO is helpful in the treatment of neonates with cardiovascular instability, PDA, persistent pulmonary hypertension, preterm premature rupture of membranes, perinatal asphyxia, sep‐ sis, and general management in intensive care for a sick neonate. In the case of hemodynami‐ cally significant PDA, fECHO has significant limitations in measuring CO. Significant left‐right shunting through PDA apparently increases SV of the left ventricle, which is a measure of pul‐ monary blood flow; outflow from the right ventricle is a measure of the systemic blood flow. Similarly, the measurement of flow from the right ventricle is affected by the presence of left‐ right atrial shunting which apparently increases SV and the outflow from the right ventricle. For this reason, the assessment of the systemic blood flow is made through the measurement of the venous return to the heart through the SVC. The flow in the SVC is normally between 30 and 50% of the total systemic blood flow. Similarly, to assess the pulmonary blood flow, the blood flow velocity in the left pulmonary artery is measured [21].

of CO is definitely reliable [15]. The HR in neonate is affected by many factors and so it is not necessarily a good indicator of hemodynamic status. In hypovolemic state, the immature heart muscle and the autonomic nervous system impact the cardiovascular response differ‐ ently in neonates in comparison to adults. The capillary refill time is affected by the pres‐ sure technique, variability among investigators, ambient temperature, drugs, and maturity of neonatal skin. The capillary refill time of >3 s has 55% sensitivity and 81% specificity for the

Noninvasive methods that are used in clinical practice to assess neonatal CO are echocar‐ diography, cardiac magnetic resonance, electrical cardiometry, and arterial pulse waveform analysis. Functional echocardiography (fECHO) enables visualization of the shape and size of the chambers of the heart, the heart valves, contractility, and relaxation of the heart muscle. Various forms of Doppler echocardiography, such as color, continuous and pulsed Doppler echocardiography, enable the determination of both the blood flow direction and velocity. By assessing the velocity of blood flow, two more parameters can be calculated: the difference in pressure above and below the narrowing with the modified Bernoulli's equation and the blood flow through the blood vessel diameter and a mean flow velocity of the blood [17].

fECHO is daily used in the neonatal intensive medicine and constitutes an important part of an integrated bedside hemodynamic monitoring of a neonate. An appropriate training and experience is necessary for performing fECHO; so the obtained measurements are accurate and reliable. It should be noted that fECHO is not a substitute for formal echocardiographic assessment of the neonate by a pediatric cardiologist, especially if the newborn is suspected to have CHD or the latter has already been diagnosed [18, 19]. fECHO enables discontinuous hemodynamic assessment of neonate in real time. With fECHO, we can estimate the central venous pressure, and thus the volume of blood, and the contractility and filling of the right and left cavities, pulmonary arterial pressure, and the SV of the both ventricles, thereby CO. With neonatal fECHO, we can assess the presence, direction, and measure the blood flow velocity through the shunts, such as persistent ductus arteriosus (PDA) and open foramen ovale, the pressure in the pulmonary artery and the superior vena cava (SVC) and thereby assess heart function. The drawback is the limited accuracy of the measurements (10% with a single investigator and 20% among various investigators). Acquired measurements also depend on the blood flow: from the transitional to neonatal, shunts through connections between the pulmonary and systemic blood flow and immaturity or lability of the lung vas‐

fECHO is helpful in the treatment of neonates with cardiovascular instability, PDA, persistent pulmonary hypertension, preterm premature rupture of membranes, perinatal asphyxia, sep‐ sis, and general management in intensive care for a sick neonate. In the case of hemodynami‐ cally significant PDA, fECHO has significant limitations in measuring CO. Significant left‐right shunting through PDA apparently increases SV of the left ventricle, which is a measure of pul‐ monary blood flow; outflow from the right ventricle is a measure of the systemic blood flow. Similarly, the measurement of flow from the right ventricle is affected by the presence of left‐ right atrial shunting which apparently increases SV and the outflow from the right ventricle. For this reason, the assessment of the systemic blood flow is made through the measurement

prediction of the low systemic blood flow [16].

32 Selected Topics in Neonatal Care

culature, and thus the pressure in the pulmonary artery [20].

Measuring the ejection fraction (EF) and fractional shortening (FS) in hemodynamic monitor‐ ing of the newborn is not very useful measurement, except in the case of severe myocardial dysfunction, when measurements are not really necessary, since the poor contractility of the heart muscle is obvious. We calculate them on the basis of measurement differences in dimen‐ sions of left ventricle in the long axis between diastole and systole. The problem of measure‐ ment in neonates is that the anterior wall of the ventricle is relatively stiff in comparison to the posterior and lateral wall of the left ventricle. To avoid this, they proposed measuring the dimensions of the left ventricle in short axis [22]. Two new US methods for assessing cardiac function are the measurement of diastolic function and tissue Doppler US. Diminished dia‐ stolic relaxation effects systolic function of the heart muscle, and thus the SV and CO. We may assess the diastolic function from the shape of Doppler wave of the inflow of blood into the ventricle. The filling of the ventricle has two phases: early ventricular filling during relaxation (E wave) and late active ventricular filling due to atrial systole (A wave). In a healthy neo‐ nate, 80% of the blood fills the left ventricle early in diastole, so the predominance of A wave indicates impaired diastolic function [23]. But when assessing impaired diastolic function, we have to be aware that diastolic function in premature and mature infants is already impaired because of immature contractile system of cardiac muscles [22]. The method of tissue Doppler echocardiography detects low frequency of high energy resulting from the movement of the ventricular wall which cannot be assessed by the standard Doppler investigation. In the four‐ chamber view of the heart in the longitudinal axis, we observe three different variables of ventricular wall motion: velocity, acceleration, and displacement [24]. Even if the method is advantageously used in adult patients, their clinical utility in the treatment of sick newborns is not yet fully understood [25].

Cardiovascular magnetic resonance (CMR) imaging is a method of nuclear magnetic resonance based on the spinning of hydrogen nuclei in a magnetic field, which are most numerous in the human body. CMR is the gold standard for the assessment of CO. Special expensive equip‐ ment, trained personnel, sedation, and transportation of a neonate are needed to perform CMR. In adults, CMR is used to assess the function of the ventricles, in complex congenital heart disease and cardiomyopathy. Compared with adults, it is necessary to increase the image reso‐ lution in neonates, both spatially (because of the size of the heart), as well as the time (due to the relatively high heart rate of newborn). The essential advantages of this method are detailed assessment of CO, cardiovascular anatomy, and good repeatability. CMR cannot measure the oxygen need and consumption [26]. Images obtained by CMR in real time have lower quality. Kino CMR enables improved anatomy imaging and the ventricular wall motion, by which the heart is imaged at specific phases of the cardiac cycle, depending on the electrocardiographic (ECG) recording. This creates a series of images that can be played as a movie (kino). End‐dia‐ stolic and end‐systolic endocardial and epicardial borders are followed and we reconstruct three‐dimensional models of ventricles: end‐systolic and end‐diastolic volume, ejection frac‐ tion, and SV. CMR with a phase contrast allows the measurement of blood flow to the heart throughout the cardiac cycle [27]. This method quantifies the flow in IVC and descendent aorta, which indicates the systemic perfusion in the premature neonate. Similarly, we can measure the flow in the internal carotid and basilar arteries and thus the blood flow in the brain [28].

the lungs [36]. In neonates with a healthy alveolar‐capillary membrane, the partial pressure of

Stewart principle is a method of dilution of the indicator and provides calculation of the CO on the basis of change in the concentration of the dye (lithium‐based dilution devices) or a change in the temperature of the solution (thermodilution‐based devices). We inject a known amount/temperature of a substance proximally and measure its concentration/temperature

and a known quantity of the injected substance [38]. Clinically, a known amount of dye or isotope is injected rapidly into a large central vein, or the right side of the heart. We measure the concentration of dye or isotope in arterial blood: the larger the CO the greater the dilu‐ tion. The most common indicator is a small volume of cold saline; we calculate flow from the temperature change. The average blood flow through an organ can also be calculated from the change in the volume of the hollow body in time: *dV*/*dt* (volume of a cavity is imaged within

Arterial blood pressure in the newborn can be measured noninvasively using appropriate cuffs or through the invasive arterial catheters. In principle, the matching of both methods is good [39]. We currently do not know what the normal arterial blood pressure is for a given gestational and postnatal age. Also, we do not know what the value of blood pressure is when the blood flow to vital organs is diminished and the auto‐regulatory mechanisms in the brain fail. Thus, neonatal hypotension is not precisely defined. In addition, there is currently no evidence that the treatment of hypotension has significant impact on the clinical outcome in neonates [40–42]. Global perfusion pressure is measured via invasive arterial blood pressure monitoring. However, "adequate" blood pressure does not signify an "adequate" CO; therefore, an increase in blood pressure does not necessary mean an increment of CO. However, without measuring CO we can only assume that adequate mean blood pressure means also adequate CO, which is not always true. Second, the increase in blood pressure does not always mean the elevation of CO (failing myocardium poorly responds to a high vascular resistance). In neonates, the threshold heart rates and perfusion pressure are different depending on gestational and post‐

Hemodynamic failure results in low cardiac output syndrome with inadequacy of oxygen and nutrients delivered to peripheral tissues and cells. Clinically, peripheral perfusion of organs can be assessed by observing the skin color of a neonate. The method is vastly sub‐ jective. A laboratory method of defining the peripheral perfusion is the measurement of the concentration of lactic acid in the peripheral blood. In case of lowered peripheral perfusion tissue hypoxia occurs, which leads to anaerobic metabolism and lactic acid formation. Lactic acid is present in the less perfused tissues and therefore it is primarily not present centrally

∫

in the exhaled air [37].

Hemodynamic Monitoring in Neonates http://dx.doi.org/10.5772/intechopen.69215 35

*cdt*) from the time profile (integral) curve

in arterial blood is equal to the partial concentration of CO<sup>2</sup>

a specified time sequence: by ultrasound, magnetic resonance, X‐ray).

distally. We calculate the total flow rate (*Q* = *m*/

menstrual age of premature neonates [42, 43].

**5. The peripheral hemodynamic monitoring**

**4.3. Arterial blood pressure**

CO<sup>2</sup>

Electrical impedance cardiometry is the only available method that enables continuous nonin‐ vasive monitoring of SV and CO in a neonate [29, 30]. The method is based on a model of the electrical velocimetry, using four‐surface ECG electrodes attached to the left side of the neck (two electrodes), and to the chest (two electrodes). Alternating electric current (AC) of constant amplitude flows through the pair of external electrodes toward the direction of the aorta. The ratio of the current and measured voltage is equal to the conductivity (or bioimpedance). Each tissue in the chest has its bioimpedance: that of the blood is very low, whole bone and lungs, filled with air, have high bioimpedance. Moreover, bioimpedance of bone is static, and bio‐ impedance of the lungs, which are filled and emptied of air, and of the heart and large blood vessels, which are filled with blood, is dynamic, in accordance with the respiratory or cardiac cycle. In case of sudden acceleration of blood flow into the aorta in systole, the conductivity dra‐ matically increases. Electrical bioimpedance of the chest is strongly increased with every heart‐ beat. The neonate's movement causes artifacts in measuring the electrical impedance [31, 32].

Arterial pulse waveform analysis is a relatively good method for monitoring the dynamics of arterial blood pressure and assessment of CO. It is based on the analysis of the curve of arte‐ rial pulse waveform derived from arterial catheter and on the fact that the pulse pressure is proportional to SV [33]. The arterial pulse waveform changes in the case of arrhythmia, shock, or hypothermia, when it comes to peripheral vasoconstriction. Typically, the devices for cal‐ culating the SV and CO are based on the analysis of arterial pulse waveform, and require peri‐ odic, and in advance calibrations. An additional limitation of the method is that it assumes a constant rate of systemic vascular resistance [34]. So far, the methods of arterial pulse wave analysis have not been studied in neonates.

Invasive methods for assessing the CO have been developed in adults, and then applied in sick neonates, where their use is limited. Limitations of these methods are the invasive‐ ness, complexity, and relatively long process (need for central vascular approach and taking sequential blood samples for laboratory analysis), for which reason they are seldom used in practice. Invasive methods for estimating average CO over time are based on a few physical principles. Fick's law is the law of mass/mass flow conservation. The amount of oxygen in the pulmonary artery and the amount of oxygen in the capillaries, flowing from the alveoli, is equal to the concentration of oxygen in the pulmonary vein [35].

Clinically, the O<sup>2</sup> consumption can be measured by measuring the concentration of oxygen in the inhaled and exhaled air and pulmonary ventilation. Consumption is estimated as the difference between the amount of oxygen in the inhaled and exhaled air. The concentration of oxygen in the peripheral arteries is the same as in the pulmonary veins. Pulmonary arteries have mixed venous blood. Samples for the analysis of O<sup>2</sup> are obtained from the pulmonary artery or the right ventricle through the cardiac catheter. Thus, we can calculate the CO (CO = O<sup>2</sup> consumption/AVΔO<sup>2</sup> ). Neonates compensate the reduced release of oxygen from fetal hemoglobin in tissues with higher hemoglobin concentrations, a larger volume of blood per unit of body weight, and increased CO. Instead of measuring O<sup>2</sup> consumption, we can measure the formation of CO<sup>2</sup> using capnography and assume that it is equal to the exchange of CO<sup>2</sup> in the lungs [36]. In neonates with a healthy alveolar‐capillary membrane, the partial pressure of CO<sup>2</sup> in arterial blood is equal to the partial concentration of CO<sup>2</sup> in the exhaled air [37].

Stewart principle is a method of dilution of the indicator and provides calculation of the CO on the basis of change in the concentration of the dye (lithium‐based dilution devices) or a change in the temperature of the solution (thermodilution‐based devices). We inject a known amount/temperature of a substance proximally and measure its concentration/temperature distally. We calculate the total flow rate (*Q* = *m*/∫*cdt*) from the time profile (integral) curve and a known quantity of the injected substance [38]. Clinically, a known amount of dye or isotope is injected rapidly into a large central vein, or the right side of the heart. We measure the concentration of dye or isotope in arterial blood: the larger the CO the greater the dilu‐ tion. The most common indicator is a small volume of cold saline; we calculate flow from the temperature change. The average blood flow through an organ can also be calculated from the change in the volume of the hollow body in time: *dV*/*dt* (volume of a cavity is imaged within a specified time sequence: by ultrasound, magnetic resonance, X‐ray).

#### **4.3. Arterial blood pressure**

which indicates the systemic perfusion in the premature neonate. Similarly, we can measure the flow in the internal carotid and basilar arteries and thus the blood flow in the brain [28].

Electrical impedance cardiometry is the only available method that enables continuous nonin‐ vasive monitoring of SV and CO in a neonate [29, 30]. The method is based on a model of the electrical velocimetry, using four‐surface ECG electrodes attached to the left side of the neck (two electrodes), and to the chest (two electrodes). Alternating electric current (AC) of constant amplitude flows through the pair of external electrodes toward the direction of the aorta. The ratio of the current and measured voltage is equal to the conductivity (or bioimpedance). Each tissue in the chest has its bioimpedance: that of the blood is very low, whole bone and lungs, filled with air, have high bioimpedance. Moreover, bioimpedance of bone is static, and bio‐ impedance of the lungs, which are filled and emptied of air, and of the heart and large blood vessels, which are filled with blood, is dynamic, in accordance with the respiratory or cardiac cycle. In case of sudden acceleration of blood flow into the aorta in systole, the conductivity dra‐ matically increases. Electrical bioimpedance of the chest is strongly increased with every heart‐ beat. The neonate's movement causes artifacts in measuring the electrical impedance [31, 32]. Arterial pulse waveform analysis is a relatively good method for monitoring the dynamics of arterial blood pressure and assessment of CO. It is based on the analysis of the curve of arte‐ rial pulse waveform derived from arterial catheter and on the fact that the pulse pressure is proportional to SV [33]. The arterial pulse waveform changes in the case of arrhythmia, shock, or hypothermia, when it comes to peripheral vasoconstriction. Typically, the devices for cal‐ culating the SV and CO are based on the analysis of arterial pulse waveform, and require peri‐ odic, and in advance calibrations. An additional limitation of the method is that it assumes a constant rate of systemic vascular resistance [34]. So far, the methods of arterial pulse wave

Invasive methods for assessing the CO have been developed in adults, and then applied in sick neonates, where their use is limited. Limitations of these methods are the invasive‐ ness, complexity, and relatively long process (need for central vascular approach and taking sequential blood samples for laboratory analysis), for which reason they are seldom used in practice. Invasive methods for estimating average CO over time are based on a few physical principles. Fick's law is the law of mass/mass flow conservation. The amount of oxygen in the pulmonary artery and the amount of oxygen in the capillaries, flowing from the alveoli, is

in the inhaled and exhaled air and pulmonary ventilation. Consumption is estimated as the difference between the amount of oxygen in the inhaled and exhaled air. The concentration of oxygen in the peripheral arteries is the same as in the pulmonary veins. Pulmonary arteries

artery or the right ventricle through the cardiac catheter. Thus, we can calculate the CO (CO

hemoglobin in tissues with higher hemoglobin concentrations, a larger volume of blood per

consumption can be measured by measuring the concentration of oxygen

using capnography and assume that it is equal to the exchange of CO<sup>2</sup>

). Neonates compensate the reduced release of oxygen from fetal

are obtained from the pulmonary

consumption, we can measure

in

analysis have not been studied in neonates.

Clinically, the O<sup>2</sup>

34 Selected Topics in Neonatal Care

consumption/AVΔO<sup>2</sup>

the formation of CO<sup>2</sup>

= O<sup>2</sup>

equal to the concentration of oxygen in the pulmonary vein [35].

have mixed venous blood. Samples for the analysis of O<sup>2</sup>

unit of body weight, and increased CO. Instead of measuring O<sup>2</sup>

Arterial blood pressure in the newborn can be measured noninvasively using appropriate cuffs or through the invasive arterial catheters. In principle, the matching of both methods is good [39]. We currently do not know what the normal arterial blood pressure is for a given gestational and postnatal age. Also, we do not know what the value of blood pressure is when the blood flow to vital organs is diminished and the auto‐regulatory mechanisms in the brain fail. Thus, neonatal hypotension is not precisely defined. In addition, there is currently no evidence that the treatment of hypotension has significant impact on the clinical outcome in neonates [40–42].

Global perfusion pressure is measured via invasive arterial blood pressure monitoring. However, "adequate" blood pressure does not signify an "adequate" CO; therefore, an increase in blood pressure does not necessary mean an increment of CO. However, without measuring CO we can only assume that adequate mean blood pressure means also adequate CO, which is not always true. Second, the increase in blood pressure does not always mean the elevation of CO (failing myocardium poorly responds to a high vascular resistance). In neonates, the threshold heart rates and perfusion pressure are different depending on gestational and post‐ menstrual age of premature neonates [42, 43].
