**5. The peripheral hemodynamic monitoring**

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 systemic circulation; therefore, lactic acidosis (>2.5 mmol/L) is a late sign of low cardiac output syndrome. Consequently, the concentration of lactic acid in the systemic blood rises after the reanimation. Moreover, the production of lactic acid is increased in the case of adrenaline treatment, which increases glycogenolysis and glycolysis in the liver [44]. The plasma concentration of the lactic acid is associated with the stage of the disease and a higher mortality in neonates [45].

isotope of xenon [51]—have been developed. Regional blood flow to peripheral organs can be measured using Doppler ultrasound [52]. The method is based on measuring the blood flow velocity through the blood vessel. The product of the flow rate and maximum vessel diam‐ eter allows us to evaluate blood flow in the vessel, and if the vessel supplies the oxygen and nutrients to the organ we can estimate the blood flow to the organ. Blood flow to the brain can also be measured using magnetic resonance imaging (MRI) techniques. Blood flow to the brain is supplied by four arteries in the neck; hence, it can be evaluated using a scan through the arteries: the cross section of the vessels is multiplied by the blood flow velocity. The blood flow velocity is measured by the loss of magnetization caused by the fresh blood flowing into the plane of imaging (imaging with phase contrast) [28]. For quantitative measurement of the flow, a contrast agent containing gadolinium can be used [53]. The blood flow in each blood vessel can be measured with an electromagnetic flowmeter: the moving particles‐ions are deflected to right angles to the direction of movement in an electric field and by that deflec‐ tion the electric current is measured. Blood flow can also be measured by thermodilution method: the faster the blood flow, the cooler the tip of the heated sensor. Using the plethys‐

Frequently used noninvasive and continuous method for the indirect assessment of blood flow in various organs is the spectroscopy in the near‐infrared spectrum [54–56]. The method is based on the principle of different absorption patterns of oxyhemoglobin and deoxyhemo‐ globin. It measures the index of tissue oxygenation and enables the calculation of the extrac‐ tion of oxygen of the tissues in the target organ. If we assume that changes in the regional tissue oxygenation are not accompanied by changes in the arterial blood oxygen saturation

), oxygen consumption, the amount of blood in the arteries and veins, and hemoglobin concentration, then the measured tissue oxygenation can be used to assess organ perfusion. NIRS optodes can be placed practically anywhere on the surface of the body, they measure tissue oxygenation approximately 4 cm below the surface (in the brain, kidneys, intestines,

Microcirculation encompasses arterioles, capillaries, arteriolar‐venous connections, venules, and lymphatic vessels. It supplies the target organs with oxygen and nutrients. Capillary fill‐ ing or opening depends on the tone of arterioles and precapillary sphincters, whose diameter changes in parallel to the contractions/relaxations of smooth muscle in the vessel wall. The

norepinephrine, and endothelin‐1), myogenic mechanism, local metabolites, and the para‐ sympathetic nervous system affect the tone of smooth muscles. Blood flow in the microcircu‐ lation reflects the function of the central elements of the blood flow and is thus the ultimate indicator of cardiovascular efficiency. Microcirculation in individual organs also operates globally and represents one of the largest virtual organs in the body. In adults, it is estimated that 5% of the total blood volume is located in the capillaries, which may increase its capacity

S), vasoconstrictors (epinephrine,

Hemodynamic Monitoring in Neonates http://dx.doi.org/10.5772/intechopen.69215 37

mography, the displaced blood volume from the vessels is measured [38].

(SaO<sup>2</sup>

liver, and muscle) [57].

to fourfold [58].

**5.2. Microcirculation monitoring in the neonate**

humoral factors, endothelial vasodilators (NO, CO, and H<sup>2</sup>

Noninvasively, the peripheral perfusion may be assessed by the perfusion index [46]. It is based on an analysis of the pulse oximetry signal. The perfusion index is the ratio between pul‐ satile and non‐pulsatile pulse oximetry signal (AC/DC × 100). It reflects the difference between the amount of blood in the tissue between systole and diastole. The perfusion index correlates well with the capillary refill time, the surface‐core body temperature difference [47], and also the severity of the disease in neonates [48].

Assessing the function of peripheral organs is another way of assessing the peripheral hemo‐ dynamics. Using amplitude‐integrated electroencephalogram (aEEG), we assess the brain function. Observing respiratory rate and pattern indicates the lung function and myocardial contractility indicates the heart function. By measuring the urine output and cleared sub‐ stances, we assess the renal function. Measurement of diuresis in the neonate for hemody‐ namic monitoring has many caveats, especially in premature neonates, since immature renal tubules are not able to concentrate the urine. Moreover, the accurate monitoring of diure‐ sis is an invasive method. Laboratory measurements of liver enzymes, clotting factors, and ammonia concentration assess liver function, and measurements of muscle enzyme assess the muscle function [49].

The peripheral monitors enable measuring the micro‐vascular blood flow to the periph‐ eral organs by perfusion index and laser‐Doppler method and regional tissue oxygenation by NIRS.

#### **5.1. The regional blood flow monitoring in the peripheral organs in the neonate**

Regional blood flow is a complex and dynamic variable that changes depending on the func‐ tional activity of the body. In pathological conditions, like, for example, a sudden change in blood pressure or hypoxia, blood flow through the body can change very quickly. Like CO also the regional blood flow is measured in mL/min and expressed either normalized by body weight either by 100 g of tissue, or as a percentage of the CO. Assessing and measuring the blood flow is not a part of the permanent clinical practice in neonatal intensive care units, because the methods are generally complicated, inaccurate, invasive, and expensive, and cur‐ rently their use is not showing clinical welfare for sick newborns.

With the help of the abovementioned physical principles and listed methods for CO monitor‐ ing, it is also possible to estimate the regional blood flow in peripheral organs. Using Fick's law, we can calculate blood flow through the peripheral organ, knowing its oxygen con‐ sumption. By applying this principle, several methods for the evaluation of blood flow in the brain—through the inhalation of 15% nitrous oxide [50] and the clearance of a radioactive isotope of xenon [51]—have been developed. Regional blood flow to peripheral organs can be measured using Doppler ultrasound [52]. The method is based on measuring the blood flow velocity through the blood vessel. The product of the flow rate and maximum vessel diam‐ eter allows us to evaluate blood flow in the vessel, and if the vessel supplies the oxygen and nutrients to the organ we can estimate the blood flow to the organ. Blood flow to the brain can also be measured using magnetic resonance imaging (MRI) techniques. Blood flow to the brain is supplied by four arteries in the neck; hence, it can be evaluated using a scan through the arteries: the cross section of the vessels is multiplied by the blood flow velocity. The blood flow velocity is measured by the loss of magnetization caused by the fresh blood flowing into the plane of imaging (imaging with phase contrast) [28]. For quantitative measurement of the flow, a contrast agent containing gadolinium can be used [53]. The blood flow in each blood vessel can be measured with an electromagnetic flowmeter: the moving particles‐ions are deflected to right angles to the direction of movement in an electric field and by that deflec‐ tion the electric current is measured. Blood flow can also be measured by thermodilution method: the faster the blood flow, the cooler the tip of the heated sensor. Using the plethys‐ mography, the displaced blood volume from the vessels is measured [38].

Frequently used noninvasive and continuous method for the indirect assessment of blood flow in various organs is the spectroscopy in the near‐infrared spectrum [54–56]. The method is based on the principle of different absorption patterns of oxyhemoglobin and deoxyhemo‐ globin. It measures the index of tissue oxygenation and enables the calculation of the extrac‐ tion of oxygen of the tissues in the target organ. If we assume that changes in the regional tissue oxygenation are not accompanied by changes in the arterial blood oxygen saturation (SaO<sup>2</sup> ), oxygen consumption, the amount of blood in the arteries and veins, and hemoglobin concentration, then the measured tissue oxygenation can be used to assess organ perfusion. NIRS optodes can be placed practically anywhere on the surface of the body, they measure tissue oxygenation approximately 4 cm below the surface (in the brain, kidneys, intestines, liver, and muscle) [57].

#### **5.2. Microcirculation monitoring in the neonate**

in systemic circulation; therefore, lactic acidosis (>2.5 mmol/L) is a late sign of low cardiac output syndrome. Consequently, the concentration of lactic acid in the systemic blood rises after the reanimation. Moreover, the production of lactic acid is increased in the case of adrenaline treatment, which increases glycogenolysis and glycolysis in the liver [44]. The plasma concentration of the lactic acid is associated with the stage of the disease and a higher

Noninvasively, the peripheral perfusion may be assessed by the perfusion index [46]. It is based on an analysis of the pulse oximetry signal. The perfusion index is the ratio between pul‐ satile and non‐pulsatile pulse oximetry signal (AC/DC × 100). It reflects the difference between the amount of blood in the tissue between systole and diastole. The perfusion index correlates well with the capillary refill time, the surface‐core body temperature difference [47], and also

Assessing the function of peripheral organs is another way of assessing the peripheral hemo‐ dynamics. Using amplitude‐integrated electroencephalogram (aEEG), we assess the brain function. Observing respiratory rate and pattern indicates the lung function and myocardial contractility indicates the heart function. By measuring the urine output and cleared sub‐ stances, we assess the renal function. Measurement of diuresis in the neonate for hemody‐ namic monitoring has many caveats, especially in premature neonates, since immature renal tubules are not able to concentrate the urine. Moreover, the accurate monitoring of diure‐ sis is an invasive method. Laboratory measurements of liver enzymes, clotting factors, and ammonia concentration assess liver function, and measurements of muscle enzyme assess the

The peripheral monitors enable measuring the micro‐vascular blood flow to the periph‐ eral organs by perfusion index and laser‐Doppler method and regional tissue oxygenation

Regional blood flow is a complex and dynamic variable that changes depending on the func‐ tional activity of the body. In pathological conditions, like, for example, a sudden change in blood pressure or hypoxia, blood flow through the body can change very quickly. Like CO also the regional blood flow is measured in mL/min and expressed either normalized by body weight either by 100 g of tissue, or as a percentage of the CO. Assessing and measuring the blood flow is not a part of the permanent clinical practice in neonatal intensive care units, because the methods are generally complicated, inaccurate, invasive, and expensive, and cur‐

With the help of the abovementioned physical principles and listed methods for CO monitor‐ ing, it is also possible to estimate the regional blood flow in peripheral organs. Using Fick's law, we can calculate blood flow through the peripheral organ, knowing its oxygen con‐ sumption. By applying this principle, several methods for the evaluation of blood flow in the brain—through the inhalation of 15% nitrous oxide [50] and the clearance of a radioactive

**5.1. The regional blood flow monitoring in the peripheral organs in the neonate**

rently their use is not showing clinical welfare for sick newborns.

mortality in neonates [45].

36 Selected Topics in Neonatal Care

muscle function [49].

by NIRS.

the severity of the disease in neonates [48].

Microcirculation encompasses arterioles, capillaries, arteriolar‐venous connections, venules, and lymphatic vessels. It supplies the target organs with oxygen and nutrients. Capillary fill‐ ing or opening depends on the tone of arterioles and precapillary sphincters, whose diameter changes in parallel to the contractions/relaxations of smooth muscle in the vessel wall. The humoral factors, endothelial vasodilators (NO, CO, and H<sup>2</sup> S), vasoconstrictors (epinephrine, norepinephrine, and endothelin‐1), myogenic mechanism, local metabolites, and the para‐ sympathetic nervous system affect the tone of smooth muscles. Blood flow in the microcircu‐ lation reflects the function of the central elements of the blood flow and is thus the ultimate indicator of cardiovascular efficiency. Microcirculation in individual organs also operates globally and represents one of the largest virtual organs in the body. In adults, it is estimated that 5% of the total blood volume is located in the capillaries, which may increase its capacity to fourfold [58].

Microcirculation in the newborn can be assessed using a variety of methods, the most commonly used is the evaluation of flow by laser‐Doppler method, video microscopy (dynamic capillaroscopy), and xenon clearance techniques [59]. Flow measurement by laser‐Doppler method is based on the fact that the frequency of the light beam, which passes through the tissue, changes as a result of reflection from the moving parts—red blood cells (the Doppler effect). The flow is proportional to the concentration and speed of moving red blood cells in the microcirculation. Since the flow in microcirculation is highly variable, we usually assess microcirculatory response to some of the challenge tests and monitor the dynamics of change. The most commonly used provocation meth‐ ods are the postocclusive reactive hyperemia (hyperemia after a transitional cuffing of the proximal artery), thermal methods (local heating or cooling), and iontophoresis of vasoactive substances [60, 61]. In the first days after birth, the blood flow is very fragile and the peripheral blood flow in the microcirculation is unstable. The myogenic and nervous controls of skin blood flow enable thermoregulation. The blood flow to the skin in the first days after birth is reduced. The blood flow is related to gestational and post‐ natal age and the incidence of morbidity and cardiovascular function [62]. The deterio‐ ration of peripheral blood flow regulation in microcirculation causes vasodilation and decreased peripheral vascular resistance and contributes to the vulnerability of blood flow. The peripheral blood flow in the first days after birth differs in boys and girls; boys have stronger vasodilation; the mechanism is possibly associated with an increased incidence of hypotension in newborn males [63].

**Author details**

Ljubljana, Ljubljana, Slovenia

trics. 2016;**178**:81‐6.e2

1997;**25**(6):634‐636

2000;**82**(3):F182–F187

\* and Štefan Grosek2,3

Medical Center Ljubljana, Ljubljana, Slovenia

\*Address all correspondence to: petja\_fister@yahoo.com

identifiable cause. Hospital Pediatrics. 2016;**6**(5):255‐260

Fetal and Neonatal Medicine. 2015;**20**(4):225‐231

challenges. Journal of Perinatology. 2010;**30**(Suppl):S38‐S45

1 Department of Neonatology, University Children's Hospital, University Medical Center

Hemodynamic Monitoring in Neonates http://dx.doi.org/10.5772/intechopen.69215 39

2 Department of Pediatric Surgery and Intensive Therapy, Surgical Service, University

[1] Ziegler KA, Paul DA, Hoffman M, Locke R. Variation in NICU admission rates without

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[3] Kluckow M, Hooper SB. Using physiology to guide time to cord clamping. Seminars in

[4] Pinsky MR, Payen D. Functional hemodynamic monitoring. Critical Care. 2005;**9**(6):

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[6] Soleymani S, Borzage M, Seri I. Hemodynamic monitoring in neonates: Advances and

[7] Kluckow M, Evans N. Superior vena cava flow in newborn infants: A novel marker of systemic blood flow. Archives of Diseases in Childhood—Fetal and Neonatal Edition.

[8] Evans N, Kluckow M, Simmons M, Osborn D. Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants. Archives of Diseases in Childhood—Fetal and Neonatal Edition. 2002;**87**(3):F181‐F184

[9] Copetti R, Cattarossi L, Macagno F, Violino M, Furlan R. Lung ultrasound in respiratory distress syndrome: A useful tool for early diagnosis. Neonatology. 2008;**94**(1):52‐59

3 Department of Pediatrics, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia

Petja Fister<sup>1</sup>

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