The Relationship Between Systemic Hemodynamic Perturbations and Periventricular-Intraventricular Hemorrhage—A Historical Perspective

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Periventricular-intraventricular hemorrhage (PV–IVH) remains the major cause of injury to the developing brain. Predisposing factors include a germinal matrix with an immature vasculature, a pressure passive cerebral circulation, and hemodynamic perturbations in sick premature infants. Intact cerebral autoregulation has been documented in stable premature infants; however, it functions within a limited blood pressure range and is likely to be absent in the sick hypotensive infant, which increases the risk for PV–IVH with perturbations in blood pressure. The risk for PV–IVH is markedly increased in the absence of antenatal glucocorticoid exposure in the intubated low birthweight infant <1000 g with respiratory distress syndrome; ± other complications. Although surfactant administration reduces the severity of respiratory distress syndrome, it has not led to a reduction in PV–IVH. Early postnatal administration of indomethacin has been associated with a reduction in PV–IVH, although this has not translated into long-term neurocognitive benefits.

Section snippets

Neuropathology

The primary lesion in PV–IVH is bleeding from vessels within the periventricular subependymal germinal matrix (GM) located between the caudate nucleus and thalamus at the level of the foramen of Monro.2, 9 The matrix is a transitional gelatinous region that provides poor support for a large, immature network of blood vessels primarily supplied by Heubner's artery, a branch of the anterior cerebral artery. Venous drainage includes the terminal, choroidal, and thalamostriate veins that lead to

Cerebral Autoregulation and Pressure-Passive Circulation

Cerebral autoregulation is the intrinsic ability of the cerebral blood vessels to maintain relatively constant cerebral blood flow (CBF) over a range of systemic blood pressures. As cerebral perfusion pressure decreases, cerebrovascular resistance also decreases by alterations in the diameter of the precapillary arterioles, maintaining CBF.2, 16, 17 This adaptive ability has a limited capacity and will result in a decrease of CBF when the blood pressure falls below a certain threshold and an

Evaluation of the Cerebral Circulation

Application of the Doppler ultrasound technique in the early 1980s to measure cerebral arterial blood flow velocity (CBFV) through the anterior fontanel facilitated the ability to link systemic events to the pathogenesis of PV–IVH.7 Measurements were obtained from the pericallosal artery (terminal branch of the anterior cerebral artery) as it courses around the genu of the corpus callosum, as well as from the right or left middle cerebral artery transcranially through the coronal suture.

Pathogenesis

The pathogenesis of PV–IVH is complex, and predisposing factors include a combination of vascular, intravascular, and extravascular influences1, 2 (Fig 2). From earlier report, several reasons pointed to a critical role for intravascular factors and specifically perturbations in mean arterial blood pressure (ABP) as a major mechanism of capillary rupture and hemorrhage (see appendix). First, the cerebral circulation of the sick infant was considered pressure passive.21, 22, 23, 24, 25 Second,

Periventricular White Matter Injury (WMI) Associated With PV–IVH

The etiology of the periventricular cerebral intraparenchymal lesion was unclear in the early 1980s. The earlier notion was that the intraparenchymal lesion represented an “extension” of hemorrhage from the germinal matrix or lateral ventricle into previously normal periventricular white matter. However, subsequent neuropathologic data indicated that the intraparenchymal lesions represent regions of hemorrhagic necrosis.3, 14, 15, 43 The pathogenesis of the WMI associated with hemorrhage

Perturbations on the Arterial Side

Several studies had established an association between RDS and PV–IVH by the early 1980s.46, 47 However, the mechanism(s) that linked these 2 comorbidities of prematurity were unclear. Using Doppler ultrasound, we described an association between fluctuations in CBFV and subsequent PV–IVH in preterm infants with RDS.35 Thus, in a study of preterm infants weighing < 1500 g and requiring mechanical ventilation for RDS, 21 of 23 infants (91%), with a beat-to-beat fluctuating CBFV pattern measured

Conventional Mechanical Ventilation

Mechanical ventilation can directly or indirectly affect CBF through modulating cardiac output by impeding venous return or through changes in the acid–base balance. Elevated mean airway pressure can impede venous return, which may increase central venous pressure and intracranial venous pressure as well as decrease cardiac output.71, 72, 73, 74, 75 This situation increases the risk for hypoperfusion, particularly in vulnerable regions, such as the periventricular white matter. Importantly, the

General Considerations

According to the data accumulated over the years, several factors should be considered when assessing the risk for PV–IVH, starting with the condition of the infant at delivery. The infant's condition seems to be influenced in part by the administration of antenatal glucocorticoids80, 81, 82, 83, 84 and/or the presence of histologic chorioamnionitis/fetal vasculitis.85 The single most important “intervention” shown to reduce significantly the development of PV–IVH has been a short course of

Future Directions

In recent years, WMI, often in the absence of PV–IVH, is the predominant finding observed on magnetic resonance imaging in very low birth weight infants.1, 2 Because antenatal glucocorticoids significantly reduce IVH, the target population should be those VLBW infants delivered rapidly or emergently with minimum intrapartum care. In addition, close attention to blood pressure should be a priority to avoid hypotension and/or perturbations. It is this group of infants who may derive benefit from

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