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Intraventricular Hemorrhage. John Baier MD. Incidence of IVH. Late 1970’s- 80’s 39-49% Late 1980’s < 34 weeks 19% <1501 g 16% Still large problem 1.24% of 4 million births are < 1500 g 7400 infants per year sustain IVH. Incidence of IVH. Developmental Anatomy.
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Intraventricular Hemorrhage John Baier MD
Incidence of IVH • Late 1970’s- 80’s 39-49% • Late 1980’s • < 34 weeks 19% • <1501 g 16% • Still large problem • 1.24% of 4 million births are < 1500 g • 7400 infants per year sustain IVH
Developmental Anatomy • Bleeds originate in the subependymal germinal matrix • Site of neuronal and glial proliferation • cerebral neuroblasts 10-24 weeks • after 24 weeks cerebral astrocytes and oligodendroglia • Size decreases as fetus matures • 2.5 mm at 23-24 weeks • 1.4 mm at 32 weeks • disappears at 36 weeks
Developmental Anatomy • Arterial Supply • Heubner’s artery (branch of anterior cerebral artery) • deep lateral striate arteries (middle cerebral artery) • anterior choroidal artery (internal carotid)
Developmental Anatomy • Venous drainage • medullary veins • choroidal vein • thalamostriate vein • enters the terminal vein at head of caudate • veins change direction at internal cerebral vein making a U turn
Developmental Anatomy • Capillary Network • large irregular vessels • lined only with endothelium • gelatinous matrix • as term approaches these vessels develop adventia
Pathogenesis of IVH • Fluctuating cerebral blood flow • Increase in cerebral blood flow • Increase in cerebral venous pressure • Decrease in cerebral blood flow and reperfusion injury • Platelet and coagulation defect • Vascular factors
Fluctuating cerebral blood flow • Normal • even arterial pressure wave • peak to peak systolic < 10% difference • cerebral blood flow parallels arterial wave • Fluctuating • systolic and diastolic pressure vary beat to beat • cerebral blood flow parallels arterial wave
Fluctuating cerebral blood flow • Fluctuations of CBF • ventilation • out of synchrony • PDA • hypercarbia • hypovolemia • high FiO2 • restlessness • improved by neuromuscular blockade
Increase in cerebral blood flow • intact cerebral autoregulation in term infants • pressure passive cerebral autoregulation in sick preterm infants
Increased arterial BP occurs in • Hypercarbia • Stimulation • Tracheal suctioning • Pneumothorax • Rapid volume expansion • Exchange Transfusion • Ligation of PDA • Seizure • Drugs • mydriatics
Increased Cerebral Venous Pressure • Caused by • asphyxia • labor and delivery • respiratory • pneumothorax • high PIP • tracheal suction • respiratory mechanics
Decreases in Cerebral Blood Flow • Caused by asphyxia or hemorrhage • may be the required precedent for IVH • may be caused by less obvious factors • taking temperature • chest auscultation • suctioning • Ischemic changes in germinal matrix • free radical production • can be reduced by superoxide dismutase in animal models
Platelets and coagulation • Uncertain role in IVH • Platelet-capillary function • 40% of VLBW infants have platelets < 100,000 • IVH rate is greater in thrombocytopenic infants • increased PGI may interfere with platelet function • Coagulation • common in VLBW infants • FFP may decrease IVH without changing coagulation
Vascular Factors • Tenuous capillary integrity • Remodeling capillary bed • Deficient vascular lining • absent muscle and collagen • Large vascular and luminal area • Vulnerability of matrix capillaries • Vascular border zone • Between striate and thalamic arteries • High metabolic activity
Extravascular Factors • Deficient vascular support • Increased fibrinolytic activity • Postnatal decrease tissue pressure
Changes in CBF with Asphyxia • Initially hypotension with decreased CBF • ischemia to germinal matrix • generation of free radicals • injury of endothelia • Resuscitation (PPV,Bicarbonate,volume etc) • loss of cerebral autoregulation • hypercarbia • Increase in blood pressure and CBF • Fluctuation of CBF
Ventilated Premature Infant with RDS Decreases in CBF Fluctuating CBF Increases in CBF Increases in cerebral venous pressure Endothelial injury (+/- prior decrease in CBF) Vulnerable germinal matrix capillaries Capillary rupture Extravascular: fibronolytic activity Intravascular: platelet/capillary and/or coagulation disturbances INTRAVENTRICULAR HEMORRHAGE
Pathogenesis of Intraparenchymal Hemorrhage • Terminal vein passes through germinal matrix • Increased pressure from germinal matrix hemorrhage obstructs venous flow • venous infarction
Timing of IVH Postnatal Day % infants with IVH 1 50 2 25 3 15 4+ 10
Clinical features of IVH • 3 clinical presentations • catastrophic • saltatory • silent
Clinical features of IVH • Catastrophic Syndrome (least common) • evolution over minutes to hours • Stupor or coma • arrhythmias, hypoventilation and apnea • Generalized seizures and “Decerebrate posturing” • Fixed Pupils, eyes fixed to vestibular stimulation • Flaccid quadriparesis
Clinical features of IVH • Catastrophic syndrome • falling hematocrit • bulging anterior fontanelle • hypotension and bradycardia • temperature changes • SIADH and very rarely DI • Outcome generally poor because of associated large intraparenchymal bleeds
Clinical features of IVH • Saltatory • more subtle • alteration in level of consciousness • change in movement (decrease) • hypotonia • minor changes in eye movements • decreased popliteal angle • outcome more favorable • depends of degree of underlying IVH
Clinical features of IVH • Clinically silent • symptoms may not be detected on routine exam • 50% of cases of IVH • unexplained fall in hematocrit
Clinical Staging of IVH • Papile • I bleeding confined to subependyma • II intraventricular bleed without dilation • III intraventricular bleed with dilation • IV parenchymal bleed
Clinical Staging of IVH • I bleeding confined to subependyma • II intraventricular bleed without dilation • III intraventricular bleed with dilation • Periventricular Intraparenchymal Echodensity (IPE)
Outcome of IVH • Acute • seizures • acute hydrocephalus • intracranial hypertension • death
Outcome of IVH • Long Term • neurologic impairment • motor • sensory • developmental impairment • cognitive • related to sensory deficits • hydrocephalus
Neurologic Impairment in IVH • Incidence of impairment related to degree of IVH Incidence of Severity Neurological sequelae Mild 5% Moderate 15 % Severe 35 % Severe + IPE 90 %
Neurologic Impairment in IVH • Outcome is also related to extent of IPE Outcome Extensive IPE Localized IPE Mortality 81 % 37 % Major Motor abn 100 % 80 % IQ < 80 85 % 53 % “Normal” 0 10 %
Motor Problems in IVH • Periventricular lesion affects fibres from both upper and lower extremities • Spastic hemiparesis (unilateral) • Spastic quadraparesis (bilateral)
Pathogenesis of Brain Injury in IVH • Preceding hypoxic-ischemic injury • PVL • pontine hemorrhage • Destruction of glial precursors in germinal matrix • effects on mylenation • cerebral organization • Destruction of periventricular white matter • infarction • intraventricular blood • potassium • glutamate • vasoactive compounds
Pathogenesis of Brain Injury in IVH • Arterial vasospasm with focal brain ischemia • Hydrocephalus
Hydrocephalus • Progressive ventricular dilation secondary to alteration in CSF dynamics • Distinguish from ventriculomegaly with normal CSF dynamics • atrophy “hydrocephalus ex evacuo” • PVL • IPE
Pathophysiology of Hydrocephalus • most are communicating • chronic obliterative arachnoiditis (most common) • obstruction of aqueduct by blood, clot and debris (infrequent)
Clinical Aspects of Hydrocephalus • onset 1 - 3 weeks after IVH • rapidity of progression relates to degree of IVH • Head growth and signs of increased ICP follow ventricular dilation • days to weeks • Posterior horn dilate earlier and greater than anterior horns
Management of Hydrocephalus • Medical • acetazolamide with or with out furosemide • serial lumbar punctures • serial ventricular punctures • Surgical • ventriculostomy • Rickham reservoir • VP or subgaleal shunt
Prevention of Hydrocephalus • Intraventricular injection of tPA may reduce the incidence of hydrocephalus • only a single small pilot study
Prevention of IVH • Antenatal and Perinatal • PREVENTION OF PREMATURE BIRTHS • Maternal Transfer to high risk facility • Maternal Phenobarbital • Maternal Vitamin K • Maternal Steroids • Management of Labor and Delivery • breech delivery or prolonged labor • ? CS
Prevention of IVH • Maternal Phenobarbital • controversial (now largely abandoned) • treated infants were more ill • lower BP required increased fluids • may decrease incidence of severe IVH • may increase need for ventilation at birth • may increase RDS
Prevention of IVH • Maternal Vitamin K • vitamin K administered 4 hours prior to delivery • vitamin K administered to all infants at birth • PT normal in treated (67% normal in controls) • IVH was not related to PT • incidence of IVH was decreased in two studies
Prevention of IVH • Antenatal glucocorticoids • currently in favor • significant reduction in IVH • reduction in degree not incidence of HMD • may relate to brain maturation • glucocorticoids mature other organ systems • gut and respiratory tract
Prevention of IVH • Neonatal • Resuscitation must be prompt and adequate • avoid hypercarbia and hypoxemia • Avoid rapid infusion of volume expanders and hypertonic solutions • Correction of fluctuation in cerebral blood flow velocity • paralysis • however not easy to identify which infants have this fluctuation
Prevention of IVH • Neonatal • Prevention and treatment of hemodynamic aberrations • apnea • acute hypercarbia (CO2) > 60 mm Hg • pneumothorax • suctioning • rapid transfusions • inotrope use • exchange transfusions
Prevention of IVH • Neonatal • Correction of abnormal coagulation • unclear data • Phenobarbital • Indomethacin • Ethamsylate • Vitamin E
Prevention of IVH • Phenobarbital • not currently used • largest controlled study showed worse outcome in treated infants
Prevention of IVH • Indomethacin • effect first noted in studies to prevent symptomatic PDA • decreases baseline cerebral blood flow • attenuates cerebral hyperemia in asphyxia • may be deleterious if hypotension occurs • decreased oxidized cytochrome oxidase • decreased cerebral intracellular oxidation • inhibits free radical formation • may accelerate maturation of germinal matrix