Prevention of Intraventricular Hemorrhage

in preterm infants

Andrew Whitelaw MD FRCPCH

Emeritus Professor of Neonatal Medicine

University of Bristol

Bristol, UK

Rio de Janeiro, 29th August 2014

Highly vascular germinal matrix Unstable cerebral blood flow

0

5

10

15

20

25

30

35

<750 751-1000 1001-

1250

1251-

1500

1551-

2250

Birth weight (g)

Pe

rce

nt w

ith

IV

H

Incidence of Intraventricular haemorrhage (IVH)

in premature newborn infants

Sheth RD. Trends in incidence and severity of intraventricular hemorrhage.

J Child Neurol. 1998 Jun;13(6):261-4.

Vermont-Oxford Network

Infants 500-1500g

Grade 3 or 4 IVH 6.2% in 2000-1

Grade 3 or 4 IVH 6.2% in 2008-9

Corresponds to 4,000 to 5,000 annually in US

Risk factors for IVH

Very short gestation

Male gender

Labour and vaginal delivery v elective Caesarean

Respiratory distress syndrome

Pneumothorax

Early hypothermia (marker of prolonged resuscitation)

Fluctuating blood pressure/cerebral blood flow

Early hypotension and rapid correction

Coagulopathy and thrombocytopenia

IVH in term infants is different from IVH in prematures Wu YW, et al . Intraventricular hemorrhage in term neonates

caused by sinovenous thrombosis. Ann Neurol. 2003 ;54:123-6.

29 term infants with IVH in 5 yr UCSF

Perinatal asphyxia

Congenital heart disease

ECMO

9 cerebral sinovenous thrombosis:

Presented with seizures, apnoea or temperature

3 Thrombophilia

Voutsinas L, et al.. Clin Imaging. 1991;15:273-5.

Protein C deficiency.

Kita H, et al. No To Shinkei. 1990;42:297-302.

Homocystinuria

Interventions shown to prevent IVH in randomised clinical trials

Antenatal corticosteroids Postnatal Muscle relaxation Ethamsylate Vitamin E Indomethacin Delayed cord clamping Volume targeted ventilation

Antenatal steroid and IVH

Antenatal steroid and neurodevelopmental delay

Antenatal dexamethazone is associated with more PVL than is

betamethazone

Corticosteroids target

Very short gestation

Male gender

Labour and vaginal delivery v elective Caesarean

Respiratory distress syndrome

Pneumothorax

Early hypothermia (marker of prolonged resuscitation)

Fluctuating blood pressure/cerebral blood flow

Early hypotension and rapid correction

Coagulopathy and thrombocytopenia

Indomethacin and IVH

Indomethacin and severe IVH

Indomethacin and death/disability at 1+yr

Indomethacin and specific impairments

Indomethacin reduces IVH

No reduction in disability or death

Not recommended as routine

Ethamsylate and IVH

Ethamsylate and severe IVH

Ethamsylate and disability

No reduction in disability or death.

Not recommended as routine

Vitamin E and IVH in preterm infants

Reduced IVH

IV vit E increased Sepsis

IV vit E increased parenchymal infarction

No effect on mortality

Not recommended routinely

Brion LP et al. Cochrane Library 2003.

Perlman J. Reduction in intraventricular hemorrhage by

Elimination of fluctuating blood flow velocity in preterm infants

with respiratory distress syndrome. NEJM 1985; 312: 1353-7

IVH

Panc 5/14

No Panc 10/10

Severe IVH

Panc 0/14

No Panc 7/10

Neuromuscular paralysis and IVH

Neuromuscular paralysis and IVH

• Reduction in IVH in one small trial

• Modern ventilators can synchronize with the infant’s breathing

• Uncertainty over effects of long periods of neuro-muscular paralysis

• Not recommended as routine

Delayed cord clamping (30-45 seconds): and IVH

Delayed cord clamping (30-45 sec)and severe IVH

Mercer JS et al. Seven month developmental outcomes

of very low birth weight infants enrolled in a randomized

trial of delayed versus immediate cord clamping. J

Perinitalogy 2010; 30: 11-16

Infants 24-31 weeks

Higher motor scores in male infants at 7 months

The umbilical cord should NOT be clamped EARLY

but resuscitation has to be possible while cord intact.

Fresh frozen plasma 10 ml/kg after delivery and at 24 h

without coagulopathy screening

Beverley (1985)

IVH

Plasma 7/38

No plasma 14/42

Fresh frozen plasma 10 ml/kg after abnormal coagulation

INR > 1.4 or APTT >50 sec on screening at 2 h

(infants 23-26 w).

Dani (2009)

IVH

Early screen 34.5%

No early screen 61.1%

Factor XIII infusion at 6 hr reduced IVH

from 75% to 15%

in preterm infants at high risk if IVH

Shirata A. Thrombosis Research 1990;57: 755-63

Tranexamic acid did not reduce IVH in

a randomised trial.

Hensey O. Arch Dis Child 1984; 59: 719-21.

Recombinant Factor VII did not

Prevent IVH. Veldman A.

Ped Crit Care Med 2006; 7: 34-9

Recommendations to reduce IVH based

on epidemiology and pathophysiology but not

supported by randomised trials

Carteaux P et al.

Evaluation and development of potentially

better practices for prevention of brain

hemorrhage and ischemic brain injury in very

low birth weight infants.

Pediatrics 2003; 111: e489-496.

Practices which may prevent IVH

1. Delivery in tertiary center with NICU

Direct clinical management and delivery by maternal

fetal medicine specialists

Antibiotics for preterm rupture of membranes

2. Delivery room resuscitation by neonatologists and

an experienced team

Maintain baby’s temperature at 36.0 or above

Maintain cardiorespiratory stability during surfactant

administration

Practices which may prevent IVH

1. Delivery in tertiary center with NICU

Direct clinical management and delivery by maternal

fetal medicine specialists

Antibiotics for preterm rupture of membranes

2. Delivery room resuscitation by neonatologists and

an experienced team

Maintain baby’s temperature at 36.0 or above

Maintain cardiorespiratory stability during surfactant

administration

3. Minimise pain and stress responses

Reduce environmental noise

Minimize handling

Minimize lighting

Judicious use of narcotic sedation

4. Neutral head position and elevate head

(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).

5. Avoid rapid correction of hypotension

6. Optimize respiratory management

Avoid hypocapnia/severe hypercapnia

Avoid routine chest physiotherapy

Avoid routine suctioning

7. Limit sodium bicarbonate

3. Minimise pain and stress responses

Reduce environmental noise

Minimize handling

Minimize lighting

Judicious use of narcotic sedation

4. Neutral head position and elevate head

(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).

5. Avoid rapid correction of hypotension

6. Optimize respiratory management

Avoid hypocapnia/severe hypercapnia

Avoid routine chest physiotherapy

Avoid routine suctioning

7. Limit sodium bicarbonate

3. Minimise pain and stress responses

Reduce environmental noise

Minimize handling

Minimize lighting

Judicious use of narcotic sedation

4. Neutral head position and elevate head

(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).

5. Avoid rapid correction of hypotension

6. Optimize respiratory management

Avoid hypocapnia/severe hypercapnia

Avoid routine chest physiotherapy

Avoid routine suctioning

7. Limit sodium bicarbonate

3. Minimise pain and stress responses

Reduce environmental noise

Minimize handling

Minimize lighting

Judicious use of narcotic sedation

4. Neutral head position and elevate head

(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).

5. Avoid rapid correction of hypotension

6. Optimize respiratory management

Avoid hypocapnia/severe hypercapnia

Avoid routine chest physiotherapy

Avoid routine suctioning

7. Limit sodium bicarbonate

3. Minimise pain and stress responses

Reduce environmental noise

Minimize handling

Minimize lighting

Judicious use of narcotic sedation

4. Neutral head position and elevate head

(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).

5. Avoid rapid correction of hypotension

6. Optimize respiratory management

Avoid hypocapnia/severe hypercapnia

Avoid routine chest physiotherapy

Avoid routine suctioning

7. Limit sodium bicarbonate

Take home message: Prevention of IVH

• Antenatal betamethazone 24 mg 24 hr before delivery

• Antibiotics for preterm rupture of membranes

• Delayed cord clamping

• Maintain temperature >36.0.

• Minimize pain and stress/handling/noise/light

• Judicious opiate sedation, rarely pancuronium.

• Neutral head position with head up tilt.

• Avoid rapid swings in blood pressure and CO2

• Minimize chest physio and tube suction