1. Intraventricular Hemorrhage
John Baier MD

2. 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

3. Incidence of IVH

4. Developmental Anatomy
Bleeds originate in the subependymal germinal matrix
Site of neuronal and glial proliferation
cerebral neuroblasts weeks
after 24 weeks cerebral astrocytes and oligodendroglia
Size decreases as fetus matures
2.5 mm at weeks
1.4 mm at 32 weeks
disappears at 36 weeks

5. Developmental Anatomy
Arterial Supply
Heubner’s artery (branch of anterior cerebral artery)
deep lateral striate arteries (middle cerebral artery)
anterior choroidal artery (internal carotid)

6. 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

7. Developmental Anatomy
Capillary Network
large irregular vessels
lined only with endothelium
gelatinous matrix
as term approaches these vessels develop adventia

8. Why is this region prone to bleeding ?

9. 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

10. 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

11. Fluctuating cerebral blood flow
Fluctuations of CBF
ventilation
out of synchrony
PDA
hypercarbia
hypovolemia
high FiO2
restlessness
improved by neuromuscular blockade

12. Increase in cerebral blood flow
intact cerebral autoregulation in term infants
pressure passive cerebral autoregulation in sick preterm infants

13. Increased arterial BP occurs in
Hypercarbia
Stimulation
Tracheal suctioning
Pneumothorax
Rapid volume expansion
Exchange Transfusion
Ligation of PDA
Seizure
Drugs
mydriatics

14. Increased Cerebral Venous Pressure
Caused by
asphyxia
labor and delivery
respiratory
pneumothorax
high PIP
tracheal suction
respiratory mechanics

15. 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

16. 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

17. 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

18. Extravascular Factors
Deficient vascular support
Increased fibrinolytic activity
Postnatal decrease tissue pressure

19. 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

20. 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

21. Pathogenesis of Intraparenchymal Hemorrhage
Terminal vein passes through germinal matrix
Increased pressure from germinal matrix hemorrhage obstructs venous flow
venous infarction

22. Timing of IVH
Postnatal Day % infants with IVH

23. Clinical features of IVH
3 clinical presentations
catastrophic
saltatory
silent

24. 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

25. 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

26. 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

27. Clinical features of IVH
Clinically silent
symptoms may not be detected on routine exam
50% of cases of IVH
unexplained fall in hematocrit

28. Clinical Staging of IVH
Papile
I bleeding confined to subependyma
II intraventricular bleed without dilation
III intraventricular bleed with dilation
IV parenchymal bleed

29. Clinical Staging of IVH
I bleeding confined to subependyma
II intraventricular bleed without dilation
III intraventricular bleed with dilation
Periventricular Intraparenchymal Echodensity (IPE)

30. Outcome of IVH Acute seizures acute hydrocephalus
intracranial hypertension
death

31. Outcome of IVH Long Term neurologic impairment
motor
sensory
developmental impairment
cognitive
related to sensory deficits
hydrocephalus

32. Neurologic Impairment in IVH
Incidence of impairment related to degree of IVH
Incidence of
Severity Neurological sequelae
Mild %
Moderate %
Severe %
Severe + IPE %

33. Neurologic Impairment in IVH
Outcome is also related to extent of IPE
Outcome Extensive IPE Localized IPE
Mortality % 37 %
Major Motor abn 100 % 80 %
IQ < % 53 %
“Normal” %

34. Motor Problems in IVH
Periventricular lesion affects fibres from both upper and lower extremities
Spastic hemiparesis (unilateral)
Spastic quadraparesis (bilateral)

35. 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

36. Pathogenesis of Brain Injury in IVH
Arterial vasospasm with focal brain ischemia
Hydrocephalus

37. Hydrocephalus
Progressive ventricular dilation secondary to alteration in CSF dynamics
Distinguish from ventriculomegaly with normal CSF dynamics
atrophy “hydrocephalus ex evacuo”
PVL
IPE

38. Pathophysiology of Hydrocephalus
most are communicating
chronic obliterative arachnoiditis (most common)
obstruction of aqueduct by blood, clot and debris (infrequent)

39. Clinical Aspects of Hydrocephalus
onset 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

40. Management of Hydrocephalus
Medical
acetazolamide with or with out furosemide
serial lumbar punctures
serial ventricular punctures
Surgical
ventriculostomy
Rickham reservoir
VP or subgaleal shunt

41. Prevention of Hydrocephalus
Intraventricular injection of tPA may reduce the incidence of hydrocephalus
only a single small pilot study

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. Prevention of IVH Neonatal Correction of abnormal coagulation
unclear data
Phenobarbital
Indomethacin
Ethamsylate
Vitamin E

49. Prevention of IVH Phenobarbital not currently used
largest controlled study showed worse outcome in treated infants

50. 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

51. Prevention of IVH Ethamsylate (not available in US)
inhibits prostaglandin synthesis distal to cyclo-oxygenase
inhibits prostacyclin predominately
does not affect cerebral blood flow
polymerization of hyaluronic acid in basement membranes
promotes platelet adhesiveness
placental transfer
??? antenatal use

52. Summary
IVH remains a significant problem in the NICU despite recent improvements in care
Pathogenesis include anatomical susceptibility and pathologic changes in CBF
Incidence varies with gestational age
Prognosis depends on clinical stage
Current therapies are unsatisfactory and prevention remains the best way to reduce the incidence and impact of IVH