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Transitional hemodynamics and pathophysiology of peri-/intraventricular hemorrhage


Key points

  • A period of systemic and cerebral hypoperfusion in the immediate postnatal period predisposes the extremely preterm infant to peri-/intraventricular hemorrhage (P/IVH).

  • Cardiovascular immaturity and maladaptation after birth contribute to postnatal hypoperfusion.

  • Ventilatory support, especially inappropriately high mean airway pressure, can accentuate the early postnatal hypoperfusion.

  • Following the initial hypoperfusion, a period of improvement in systemic and cerebral perfusion precedes occurrence of P/IVH on the second or third postnatal days. Therefore ischemia-reperfusion is a major hemodynamic contributor to the pathogenesis of P/IVH.

  • Hypercapnia, especially PaCO 2 above low 50s, may increase the risk of P/IVH by potentiating the reperfusion phase via increasing the cerebral blood flow and attenuating autoregulation.

  • Delayed cord clamping is associated with hemodynamic stability and appears to be beneficial in preventing P/IVH by mitigating the risk of hypoperfusion.

  • Cord milking is associated with decreased need for cardiovascular support during the transitional period. However, this procedure is not recommended due to the increased rate of P/IVH found in a recent randomized control trial. Although the mechanism(s) of the development of P/IVH with cord milking is unclear, a rapid change in cerebral blood flow has been postulated.

Introduction

Peri-/intraventricular hemorrhage (P/IVH) is a devastating complication of prematurity that affects about a third of extremely preterm infants (<28 weeks’ gestation). P/IVH is a major risk factor for poor neurodevelopmental outcome, hydrocephalus, and mortality amongst these patients. Although the pathogenesis of P/IVH is complex and likely involves multiple different mechanisms, alteration in cerebral hemodynamics is thought to play a major role. Recent advances in noninvasive monitoring have highlighted the hemodynamic antecedents of P/IVH. This chapter reviews the inherent vulnerabilities of preterm infants during the transitional period and how the interaction between transitional hemodynamics and interventions aimed at supporting respiratory and cardiovascular function can increase the risk of P/IVH.

Fetal and transitional circulation

As the physiology of fetal circulation is discussed in Chapter 1 , we only provide a brief review of its main characteristics pertinent to the topic of this chapter. In utero, the most oxygenated blood, with oxygen saturation of around 75–85%, flows from the umbilical vein through the ductus venosus to the inferior vena cava (IVC). Due to mixing with venous blood from the portal and hepatic circulations in the liver and to some mixing with the venous blood flowing from the lower body in the IVC, the oxygen saturation of blood entering the heart is only about 70%. Of note, blood flowing in from the ductus venosus into the IVC is primarily diverted by the Eustachian valve toward the foramen ovale and into the left atrium. The low flow of poorly oxygenated pulmonary venous return to the left atrium admixing with this flow via the foramen ovale still ensures supply of relatively well-oxygenated blood to the heart and brain with an oxygen saturation around 60%. On the other hand, blood returning from superior vena cava (SVC) and the stream in the IVC, representing blood returning from the lower parts of the body, are preferentially directed to right ventricle. As most of right ventricular output is diverted through the patent ductus arteriosus (PDA) to the systemic circulation, both ventricles contribute to the systemic circulation. Given the low blood flow to the lungs, due to high pulmonary vascular resistance, left ventricular preload is relatively small. As such, during fetal life, the contribution of the right ventricle to systemic blood flow is greater than that of the left ventricle. In the fetus the combined cardiac output is about 400–450 mL/kg/min, with only about 11–25% constituting the pulmonary circulation. , This is in contrast to postnatal circulation, where the left and right cardiac outputs are equal and average about 200 mL/kg/min. The low-resistance placental circulation facilitates the high cardiac output in the fetus by reducing the afterload. At birth, pulmonary vascular resistance drops precipitously as the newborn starts breathing and the lungs become the organ of gas exchange. This increases pulmonary blood flow and changes the ductal flow pattern in a way that progressively directs blood from the right ventricle to the pulmonary circulation. The increased pulmonary blood flow in turn increases left-sided preload and promotes functional closure of the foramen ovale. This, along with the closure of the ductus arteriosus over the following 2–3 days, transforms the circulation to the adult-type (postnatal) circulation, in which the pulmonary and systemic circuits are not functioning as parallel circulations anymore but as circulations in series. Despite its complexity, this transformation occurs smoothly in most term infants. However, in preterm infants, especially those born before 28 weeks’ gestation, this process is hindered by immaturity of the organ systems and is more likely to represent an abnormal cardiorespiratory transition. Accordingly, it is likely to be associated with circulatory compromise, as discussed in detail in this chapter.

Cerebral blood flow

Understanding the evolution of cerebral hemodynamics from fetal circulation through the postnatal transition is critical in understanding the role of abnormal transition in pathogenesis of P/IVH. However, measurement of cerebral blood flow (CBF) is challenging in neonates, especially in preterm infants and during the immediate postnatal period. CBF has been assessed using radioactive xenon clearance, positron emission tomography, Doppler ultrasonography, magnetic resonance imaging, and near-infrared spectroscopy (NIRS). Each of these methods has its own intrinsic limitations. Due to their noninvasive nature and bedside availability, Doppler and NIRS are the most commonly used methods for the assessment of CBF. With Doppler ultrasonography, various surrogates of CBF, such as SVC blood flow and a major cerebral artery blood flow velocity, have been used to characterize intermittent changes in cerebral hemodynamics. On the other hand, NIRS allows for the continuous assessment of regional tissue oxygen saturation (rSO 2 ) or tissue oxygenation index (TOI). Although NIRS does not measure blood flow directly, by considering cerebral regional oxygen saturation (CrSO 2 ), clinical information, and certain other parameters, changes in CBF can be deduced. Considering arterial oxygen saturation (SPO 2 ), the index of cerebral fractional oxygen extraction (CFOE) can be calculated according to the following formula: (SPO 2 – CrSO 2 )/SPO 2 . CrSO 2 has a direct and CFOE an inverse relationship with changes in CBF. In other words, a reduction in CrSO 2 or an increase in CFOE indicates a decrease in CBF provided certain assumptions hold true. These assumptions include no significant changes in SPO 2 (with CrSO 2 ), organ metabolism, hemoglobin, and/or the distribution of blood in tissue among arteries, veins, and capillaries.

Normal changes in CBF

During fetal development, brain blood flow increases both as an absolute value and per gram of tissue. , Animal and human studies have shown a decrease in CBF at and immediately after birth. , The cause of this reduction is unclear but in part may be related to an increase in tissue oxygenation at birth compared to the fetal life. , Interestingly, the progressive change of PDA flow pattern from right to left to left to right during the first few minutes after birth strongly and inversely correlates with middle cerebral artery mean blood flow velocity (MCA-MV), a surrogate of CBF. This suggests a possible role of PDA immediately after birth in reduction of CBF. Alternatively, the changes in PDA flow pattern and reduction in CBF may be independent, and both reflective of the increasing oxygen tension following delivery. More data are needed to elucidate the normal changes in cardiovascular function and cerebral hemodynamics at and immediately after birth, especially in preterm infants.

After the immediate postnatal period, CBF increases rather significantly over the following days and more gradually afterward in both preterm and term infants. Despite the rise in CBF, it remains at only a fraction of the adult value. , Moreover, sick preterm infants have even lower CBF. The low CBF in neonates may be explained by lower brain metabolism; however, cardiovascular maladaptation in preterm infants may also contribute to the observed low CBF.

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