Hypoxic-ischaemic encephalopathy

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Document title:

Hypoxic-ischaemic encephalopathy

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Check List B: Parental advice regarding therapeutic hypothermia

Suggested information that clinicians may wish to use when discussing aspects of HIE and
therapeutic hypothermia with parent(s).

Criteria
Resuscitation
Incidence
Consequences

Prognosis
Treatment

What does the

treatment entail

Advice to parent(s)
Your baby needed significant resuscitation at birth to help him/her
breathe. He/she appears to have suffered from the effects of lack of
oxygen and blood supply to the brain
About I in 1000 newborn babies suffer from the effects of reduced blood
flow or oxygen supply to their brain around the time of birth
This can result in brain damage from direct injury and also from ongoing
changes that begin around six hours after the injury
These secondary changes are known to increase the amount of brain
injury that occurs
Approximately 30 to 60% of those babies who survive after this degree of
damage to their brain may develop long-term disabilities. These
disabilities include cerebral palsy and severe learning difficulties
In the past there were no treatments to reduce the severity of brain injury
in these newborn babies
Recent research has shown that cooling these babies reduces the
secondary brain injury, increases the chances of survival and reduces the
severity of possible long-term disability
Your baby will receive cooling therapy in addition to standard intensive
care support
Your babys temperature will be slowly lowered and kept between 33 to
34C for 72 hours. Cooling will be achieved by exposing your baby to the
ambient air temperature and with the use of cool gel packs if required
Your babys temperature and other vital signs will be closely monitored
throughout the process. If your baby shows any signs of discomfort during
cooling he/she will be prescribed medication to reduce this
After 72 hours of cooling, your baby will be gradually rewarmed to a
temperature of 37C

Refer to online version, destroy printed copies after use

Page 6 of 25

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Introduction

Neonatal encephalopathy and its subset of hypoxic-ischaemic encephalopathy (HIE) are defined
clinically on the basis of a constellation of findings to include a combination of abnormal1:
consciousness
tone and reflexes
feeding
respiration
seizures
Encephalopathy can result from a myriad of conditions and may or may not result in permanent
neurologic impairment1:
Approximately 70% of neonatal encephalopathy is secondary to events arising before the
onset of labour1
Neonatal encephalopathy attributable to intrapartum hypoxia, in the absence of any other
preconceptional or antepartum abnormalities, is approximately 1.6 per 10,0001
The pathway from an intrapartum hypoxic-ischaemic injury to subsequent permanent neurologic
impairment must progress through neonatal encephalopathy. 1
Perinatal asphyxia can be defined as a condition of impaired blood gas exchange leading to
progressive hypoxaemia and hypercapnia with a significant metabolic acidosis evidenced by an
umbilical artery base deficit greater than 12 mmol/L at birth.2
Classification of the severity of intrapartum fetal asphyxia can be determined by the short term
outcome which is expressed by:
neonatal encephalopathy and
other newborn organ system complications2
It is recommended that the terms perinatal asphyxia, birth asphyxia and HIE not be used until or
unless there is some available evidence specific to the asphyxial origin for the neurological illness in
the baby.3

Differential diagnosis

The differential diagnosis of neonatal encephalopathy includes1:

HIE
infection
prenatal stroke
intracranial haemorrhage
congenital brain malformations
inborn errors of metabolism
genetic syndromes
HIE is the term used to describe babies who have the spectrum of clinical findings described by
Sarnat and Sarnat4 AND convincing evidence of antepartum or intrapartum hypoxia (criteria as
outlined by the International Cerebral Palsy Taskforce).5
This guideline will focus on the management of HIE and not the other causes of neonatal
encephalopathy.

Refer to online version, destroy printed copies after use

Page 7 of 25

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

2.1

Criteria for the diagnosis of HIE

Essential criteria for the diagnosis of HIE in the neonatal period includes5:
evidence of metabolic acidosis (pH less than 7.00, base deficit greater than or equal to 12
mmol/L in fetal, cord or early neonatal blood samples)
early onset encephalopathy (fitting the Sarnat and Sarnat criteria)4 in babies born at 34 or
more weeks gestation [refer to Appendix A: Sarnat and Sarnat staging system and
Appendix B: HIE staging]
Criteria that collectively suggest an intrapartum timing (within close proximity to labour and delivery
e.g. 0 48 hours) but are not specific to asphyxial insults include5:
sentinel hypoxic event occurring immediately before or during labour (e.g. ruptured
uterus, placental abruption, cord prolapse, amniotic fluid embolism, fetal exsanguination
from vasa praevia or fetal maternal haemorrhage)5
sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the
presence of persistent, late or variable decelerations, usually after a hypoxic sentinel
event when the pattern was previously normal
Apgar scores of 0 3 for longer than 5 minutes
early evidence of multi system involvement (within 72 hours of birth)
early imaging study showing evidence of acute non focal cerebral abnormality

2.2

HIE Staging

[refer to Appendix A: Sarnat and Sarnat staging system and Appendix B: HIE staging]
HIE is classified in stages,4 which if applied consistently provide useful information about magnitude
of injury and prognosis. Babies with:
Stage 1 HIE usually require minimal support and the neurological examination is normal
by Day 3 4
Stage 2 to 3 will be significantly more unwell and the level of support required will depend
upon organ compromise
Assessment of HIE staging should be undertaken as soon as possible after the baby is stabilised so
that therapeutic interventions that will require transfer to a Level 3 neonatal unit can be coordinated
[refer to Check List A: Criteria for therapeutic hypothermia].

Management

Clinical management is primarily supportive and is dependent on the extent of organ compromise.
High level evidence6-9 supports the use of therapeutic hypothermia for the treatment of moderate to
severe cases of HIE [refer to section 3.6].
Each babys management should be individualised, with close monitoring of cardiorespiratory status
and early identification and treatment of multi-organ system complications where appropriate.

3.1

Resuscitation

Appropriate and timely resuscitation is required to prevent hypoxia, hypercarbia and acidosis. This
may prevent or reduce the clinical severity of HIE [refer to Guideline: Neonatal resuscitation].
Cord blood gases should be measured if possible in every resuscitated newborn baby as the most
objective way to assess the babys condition just before birth10:
Collect umbilical cord arterial blood gases from a clamped cord as soon as possible after
delivery (preferably before 30 minutes, arterial pH and base excess become unstable in a
clamped cord at room temperature after 30 minutes)11
Blood samples taken for acid base status remain stable in a plastic syringe for up to 30
minutes before analysis11

Refer to online version, destroy printed copies after use

Page 8 of 25

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Check List B: Parental advice regarding therapeutic hypothermia

Suggested information that clinicians may wish to use when discussing aspects of HIE and
therapeutic hypothermia with parent(s).

Criteria
Resuscitation
Incidence
Consequences

Prognosis
Treatment

What does the

treatment entail

Advice to parent(s)
Your baby needed significant resuscitation at birth to help him/her
breathe. He/she appears to have suffered from the effects of lack of
oxygen and blood supply to the brain
About I in 1000 newborn babies suffer from the effects of reduced blood
flow or oxygen supply to their brain around the time of birth
This can result in brain damage from direct injury and also from ongoing
changes that begin around six hours after the injury
These secondary changes are known to increase the amount of brain
injury that occurs
Approximately 30 to 60% of those babies who survive after this degree of
damage to their brain may develop long-term disabilities. These
disabilities include cerebral palsy and severe learning difficulties
In the past there were no treatments to reduce the severity of brain injury
in these newborn babies
Recent research has shown that cooling these babies reduces the
secondary brain injury, increases the chances of survival and reduces the
severity of possible long-term disability
Your baby will receive cooling therapy in addition to standard intensive
care support
Your babys temperature will be slowly lowered and kept between 33 to
34C for 72 hours. Cooling will be achieved by exposing your baby to the
ambient air temperature and with the use of cool gel packs if required
Your babys temperature and other vital signs will be closely monitored
throughout the process. If your baby shows any signs of discomfort during
cooling he/she will be prescribed medication to reduce this
After 72 hours of cooling, your baby will be gradually rewarmed to a
temperature of 37C

Refer to online version, destroy printed copies after use

Page 6 of 25

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Introduction

Neonatal encephalopathy and its subset of hypoxic-ischaemic encephalopathy (HIE) are defined
clinically on the basis of a constellation of findings to include a combination of abnormal1:
consciousness
tone and reflexes
feeding
respiration
seizures
Encephalopathy can result from a myriad of conditions and may or may not result in permanent
neurologic impairment1:
Approximately 70% of neonatal encephalopathy is secondary to events arising before the
onset of labour1
Neonatal encephalopathy attributable to intrapartum hypoxia, in the absence of any other
preconceptional or antepartum abnormalities, is approximately 1.6 per 10,0001
The pathway from an intrapartum hypoxic-ischaemic injury to subsequent permanent neurologic
impairment must progress through neonatal encephalopathy. 1
Perinatal asphyxia can be defined as a condition of impaired blood gas exchange leading to
progressive hypoxaemia and hypercapnia with a significant metabolic acidosis evidenced by an
umbilical artery base deficit greater than 12 mmol/L at birth.2
Classification of the severity of intrapartum fetal asphyxia can be determined by the short term
outcome which is expressed by:
neonatal encephalopathy and
other newborn organ system complications2
It is recommended that the terms perinatal asphyxia, birth asphyxia and HIE not be used until or
unless there is some available evidence specific to the asphyxial origin for the neurological illness in
the baby.3

Differential diagnosis

The differential diagnosis of neonatal encephalopathy includes1:

HIE
infection
prenatal stroke
intracranial haemorrhage
congenital brain malformations
inborn errors of metabolism
genetic syndromes
HIE is the term used to describe babies who have the spectrum of clinical findings described by
Sarnat and Sarnat4 AND convincing evidence of antepartum or intrapartum hypoxia (criteria as
outlined by the International Cerebral Palsy Taskforce).5
This guideline will focus on the management of HIE and not the other causes of neonatal
encephalopathy.

Refer to online version, destroy printed copies after use

Page 7 of 25

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

2.1

Criteria for the diagnosis of HIE

Essential criteria for the diagnosis of HIE in the neonatal period includes5:
evidence of metabolic acidosis (pH less than 7.00, base deficit greater than or equal to 12
mmol/L in fetal, cord or early neonatal blood samples)
early onset encephalopathy (fitting the Sarnat and Sarnat criteria)4 in babies born at 34 or
more weeks gestation [refer to Appendix A: Sarnat and Sarnat staging system and
Appendix B: HIE staging]
Criteria that collectively suggest an intrapartum timing (within close proximity to labour and delivery
e.g. 0 48 hours) but are not specific to asphyxial insults include5:
sentinel hypoxic event occurring immediately before or during labour (e.g. ruptured
uterus, placental abruption, cord prolapse, amniotic fluid embolism, fetal exsanguination
from vasa praevia or fetal maternal haemorrhage)5
sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the
presence of persistent, late or variable decelerations, usually after a hypoxic sentinel
event when the pattern was previously normal
Apgar scores of 0 3 for longer than 5 minutes
early evidence of multi system involvement (within 72 hours of birth)
early imaging study showing evidence of acute non focal cerebral abnormality

2.2

HIE Staging

[refer to Appendix A: Sarnat and Sarnat staging system and Appendix B: HIE staging]
HIE is classified in stages,4 which if applied consistently provide useful information about magnitude
of injury and prognosis. Babies with:
Stage 1 HIE usually require minimal support and the neurological examination is normal
by Day 3 4
Stage 2 to 3 will be significantly more unwell and the level of support required will depend
upon organ compromise
Assessment of HIE staging should be undertaken as soon as possible after the baby is stabilised so
that therapeutic interventions that will require transfer to a Level 3 neonatal unit can be coordinated
[refer to Check List A: Criteria for therapeutic hypothermia].

Management

Clinical management is primarily supportive and is dependent on the extent of organ compromise.
High level evidence6-9 supports the use of therapeutic hypothermia for the treatment of moderate to
severe cases of HIE [refer to section 3.6].
Each babys management should be individualised, with close monitoring of cardiorespiratory status
and early identification and treatment of multi-organ system complications where appropriate.

3.1

Resuscitation

Appropriate and timely resuscitation is required to prevent hypoxia, hypercarbia and acidosis. This
may prevent or reduce the clinical severity of HIE [refer to Guideline: Neonatal resuscitation].
Cord blood gases should be measured if possible in every resuscitated newborn baby as the most
objective way to assess the babys condition just before birth10:
Collect umbilical cord arterial blood gases from a clamped cord as soon as possible after
delivery (preferably before 30 minutes, arterial pH and base excess become unstable in a
clamped cord at room temperature after 30 minutes)11
Blood samples taken for acid base status remain stable in a plastic syringe for up to 30
minutes before analysis11

Refer to online version, destroy printed copies after use

Page 8 of 25

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.2

Inter hospital transfer

Any baby with moderate to severe HIE must be considered for transfer to a Level 3 neonatal unit for
therapeutic hypothermia or the possibility thereof. Other babies that may need transfer include those
with moderate to severe encephalopathy requiring:
ventilation
inotropic support
any diagnostic tests unavailable at a Level 1 or 2 neonatal unit
Early consultation with a Level 3 Neonatologist is recommended. Management and transfer
discussions can be facilitated by calling Retrieval Services Queensland (RSQ) on 1300 799 127.

3.3

Cardiorespiratory

3.3.1 Respiratory
Monitor for hypoxia, acidosis and hypercarbia. Respiratory distress may have multiple causes
including:
acidosis
meconium aspiration
sepsis
persistent pulmonary hypertension of the newborn (PPHN)
hyaline membrane disease (HMD)
Babies with respiratory depression should be intubated and ventilated particularly if:
there is severe encephalopathy
there is severe acidosis
the baby is having frequent seizures
the baby requires large or frequent doses of anticonvulsant medication
Avoid hyperoxaemia and hypocarbia (severe hyperoxaemia with PaO2 greater than 200 mmHg
and hypocarbia with pCO2 less than 20 mmHg are associated with poor outcome).12
Any concerns regarding respiratory status should be discussed with a Level 3 Neonatologist.
3.3.2 Cardiac
Hypotension (mean arterial blood pressure of less than 35 - 40 mmHg)7 has been associated with
poor outcomes.13,14 Loss of cerebral autoregulation makes hypertension equally hazardous. Acute
tubular necrosis or the presence of inappropriate antidiuretic hormone (ADH) secretion, affect fluid
output, increasing the risk of fluid overload.15
Blood pressure is used in neonatology as a marker for systemic perfusion, however it is a poor
predictor of low cardiac output16 and should not be the only criterion by which systemic perfusion is
monitored.

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Assessment should include:

assessment of peripheral perfusion
establishment of whether hypotension is symptomatic of another problem including:
o hypovolaemia or blood loss
o sepsis
o high mean airway pressure on mechanical ventilation
the need for intravenous crystalloid boluses (10 mL/kg of 0.9% Sodium Chloride) if:
o perfusion is poor (capillary refill greater than 3 seconds)
o blood gas lactate is not improving
o mean blood pressure is less than 35 - 40 mmHg7
the need for echocardiography (ECHO) which may identify hypovolaemia, poor
myocardial contractility and low flow states and should be considered in ventilated babies
after a significant hypoxic-ischaemic insult
If hypotension persists or low flow states are identified on ECHO consider inotropic therapy including:
Dopamine or Dobutamine [refer to Table 1. Inotropic therapy]
o Inotropes should preferably be administered via an appropriately positioned catheter in
a central vein (e.g. umbilical venous catheter positioned above the ductus venosus).17
A dedicated intravenous line is preferred. Never give inotropes into an arterial
line.18
Table 1. Inotropic therapy

Drug

Dose

Route

Comment

Dopamine

10 micrograms/kg/minute18

IV infusion17,19

Monitor heart rate and intra-arterial

blood pressure17

Prepare a
fresh infusion
every 24
hours17,19

May cause tachycardia and

arrhythmias and increase
pulmonary artery pressure17

Infusion:
(Dilute 30 mg/kg of Dopamine
up to a total of 50 mL with 5%
or 10% Glucose or 0.9%
Sodium Chloride.17 This gives
a Dopamine solution of 600
micrograms/kg/mL. If run at 1
mL/hr this will deliver 10
micrograms/kg/min)18

Dobutamine

10 micrograms/kg/minute18,19
Infusion:
(Dilute 30 mg/kg of
Dobutamine up to a total of
50 mL with 5% or 10%
Glucose or 0.9% Sodium
Chloride.17 This gives a
Dobutamine solution of 600
micrograms/kg/mL. If run at 1
mL/hr this will deliver 10
micrograms/kg/min)18

Use in conjunction with Phenytoin

may cause severe hypotension19
More effective than Dobutamine for
treating hypotension20
IV infusion17,19

Monitor heart rate and intra-arterial

blood pressure17

Prepare a
fresh infusion
every 24
hours17,19

May cause hypotension if baby is

hypovolaemic17
May cause significant respiratory
depression if injected rapidly of if
high dose infusion is used
Tachycardia may occur and
increase pulmonary blood pressure
leading to pulmonary oedema19
Do not mix with Sodium
Bicarbonate19,21
More effective than Dopamine for
treating low cardiac output20

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.4

Infection

Perinatal infection may co-exist with HIE. All babies should have:
a full blood count (FBC)
blood cultures
intravenous antibiotics (Penicillin (Benzylpenicillin, Ampicillin or Amoxicillin)) and
Gentamicin) as soon as possible after birth [refer to Table 2. Antibiotic therapy]
Administer antibiotics in accordance with local/hospital guidelines. In the absence of such
guidelines use the dosage regimen below.
Table 2. Antibiotic therapy

Drug

Dose

Route

Comment

Ampicillin

50 mg/kg/dose
12 hourly17,19

IV slow push
IM17,19

Increase the dosage interval if

there is renal failure19

60 mg/kg/dose
12 hourly19,22

IV - slow push
IM19

Halve the dose and double the

dose interval if there is renal
failure19

Babies greater than 32

weeks gestation
5 mg/kg 24 hourly19

IV slow push
(infusion over 30
minutes is not
necessary)19
IM19

Trough level prior to 3rd dose in

babies less than a week old and in
babies with poor renal function19

OR
Benzylpenicillin

AND
Gentamicin

CAUTION
Caution must be exercised in the administration of second and subsequent doses
of aminoglycosides (Gentamicin) to babies who are oliguric. Wait for a trough
level result prior to 2nd dose
Trough level

Comment

Less than or equal to 1 mg/L17,19

Therapeutic17,19

1.1 2.3 mg/L17

Extend the dosage interval by 12 hours17

2.4 3.2 mg/Ls17

Extend the dosage interval by 24 hours17

Greater than or equal to 3.3 mg/L17

Do not give further doses. Measure level

in 24 hours17

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.5

Fluid, electrolyte and acid base

3.5.1 Hypoglycaemia
Perform an early blood glucose level and correct hypoglycaemia. Babies with Stage 2 to 3 HIE will
require intravenous glucose administration [refer to Guideline: Neonatal hypoglycaemia: assessment
and blood glucose level (BGL) monitoring].
3.5.2 Acidosis
Perform early arterial blood gas and correct:
respiratory acidosis (hypercarbia and acidosis) with appropriate ventilatory support
it is possible to correct persistent severe metabolic acidosis in a baby who is appropriately
ventilated with intravenous Sodium Bicarbonate given at a rate of no more than 0.5
mmol/kg per minute.19 Do not give Sodium Bicarbonate to a baby who is not effectively
ventilating (either spontaneously or mechanically) as it causes hypercarbia and worsens
respiratory acidosis. There is no convincing evidence that administration of Sodium
Bicarbonate produces long term benefits in this situation.23
3.5.3 Volume
Many restrict maintenance fluids15,24 to 40 50 mL/kg/day until a urine output equal to 1 mL/kg/hr has
been established. Fluid restriction is recommended in standard textbooks to avoid fluid overload and
cerebral oedema, however no RCTs address the use of fluid restriction following perinatal asphyxia.
There is concern that fluid restriction may cause dehydration and hypotension decreasing cerebral
perfusion and causing further brain damage.25 Monitor serum sodium trends to gauge whether more
or less fluids are needed.
Administer intravenous 10% Glucose in the first 24 hours. Once renal function is stable,
sodium and potassium additives can be commenced if required
If the baby has oliguria/anuria consider:
o urinary catheterisation especially if there is a palpable bladder and/or baby is not
voiding spontaneously
o Dopamine (4 microgram/kg/minute or less)18 if not already receiving inotropic therapy
o withholding second or subsequent dose of aminoglycoside (Gentamicin) antibiotics if
prescribed. Be guided by serum aminoglycoside levels if considering further doses
Assess the fluid balance regularly and check urea, electrolytes and creatinine (there is a
risk of fluid overload and hyperkalaemia)

3.6

Temperature

Therapeutic hypothermia (cooling) following a hypoxic-ischaemic insult can benefit certain babies
and is now considered standard care.26
For cooling to provide benefit:
it must be commenced within 6 hours of birth before secondary reperfusion injury begins27
it must be discussed with a Level 3 Neonatologist as soon as HIE is suspected to facilitate
commencement of cooling within the critical period [refer to Check list A: Criteria for
therapeutic hypothermia]
hyperthermia should be avoided2,15,28
rectal temperature should be maintained at 33.0 34.0C7,8,26

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.6.1 Criteria for cooling

Current evidence and consensus professional opinion supports therapeutic hypothermia (cooling) to
be used for the following babies:
greater than or equal to 35 weeks gestational age AND
greater than or equal to 1800 g
with evidence of moderate to severe encephalopathy [refer to Appendix A: Sarnat and
Sarnat staging system and Appendix B: HIE staging] AND
with evidence of intrapartum hypoxia indicated by at least two of the following:
o Apgar score of less than or equal to 5 at 10 minutes
o needing mechanical ventilation or ongoing resuscitation at 10 minutes of age
o cord, arterial or venous blood gas with pH of less than or equal to 7.00 and base
deficit of greater than or equal to 12 mmol/L within 60 minutes of birth
3.6.2 Babies excluded from cooling
Babies that were excluded from RCTs for therapeutic hypothermia included babies:
less than 35 weeks gestation6,7,26
with a birth weight less than 1800 grams7,26
where cooling could not be started within 6 hours of birth6,7,26
with major congenital abnormalities6,7,26 including:
o suspected neuromuscular disorders
o suspected significant chromosomal abnormalities
o life threatening abnormalities of the cardiovascular or respiratory systems
so severely affected that there was little hope for normal outcome7,26 i.e. moribund or in
extremis (e.g. very low blood pressure or severe acidosis unresponsive to treatment)
There is no evidence of any therapeutic benefit from cooling for these babies and cooling is still
considered experimental (i.e. not standard care). Any decision to cool these babies should be made
by a Level 3 Neonatologist after discussion where possible with the parent(s).
3.6.3 Babies born outside a Level 3 neonatal unit
All babies who require cooling should be referred to a level 3 neonatal unit as early as possible.
Where cooling is advised the referring unit should:
stop active warming by turning off the heater:
o monitor and measure the axillary or rectal temperature every hour, commence
continuous skin temperature monitoring if able. Maintain the temperature between
33.0 34.0C by passive cooling only (heater off)
turn the heater on if the axillary or rectal temperature is less than 33.5 C and continue to
closely monitor the axillary/rectal temperature
Do not delay passive cooling to await the arrival of the transport/retrieval team. Active cooling will
only be started once the retrieval team arrives at the referring unit.

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.7
3.7.1

Neurologic
Neuroimaging
Cranial ultrasound:
o With middle cerebral artery (MCA) and anterior cerebral artery (ACA) Doppler should
be considered in the first 48 hours. Although not sensitive, any persistent changes in
the basal ganglia or abnormal cerebral artery Doppler are specific for poor neuromotor
outcome.29 There is a lack of evidence from RCTs regarding the value of these tests in
a baby undergoing therapeutic hypothermia
Magnetic resonance imaging (MRI):
o Should be considered in babies with moderate to severe neonatal encephalopathy and
performed at approximately one week of age.30 Neonates who develop signs of HIE
following an acute sentinel event (e.g. placental abruption) sustain bilateral and
usually symmetrical lesions within the basal ganglia and thalami, and exhibit an
abnormal appearance in the posterior limb of the internal capsule (PLIC). Abnormality
seen in the PLIC is a an excellent predictor of abnormal outcome31
o Earlier MRI may be considered in order to make decisions about the withdrawal of
intensive care in the severely unwell baby

3.7.2

Electrophysiology
A formal EEG should be considered in the presence of moderate and severe
encephalopathy or seizures
amplitude-integrated electroencephalogram (aEEG) may be considered. It enables
extended monitoring of cerebral electrical activity, seizure detection and outcome
prediction32,33

3.7.3

Seizures
HIE is the most common cause of early onset neonatal seizures.24 Approximately 30% of
babies with HIE have seizures which usually occur in the first 24 hours after birth and may
be difficult to control. The early onset of seizures may predict a poorer
neurodevelopmental outcome independent of the severity of hypoxic-ischaemic brain
injury34
Electrolyte abnormalities and multi system complications may coexist. Localised
ischaemic events may result in focal clonic seizures. It is important to exclude other
causes of seizures which include:
o intracranial haemorrhage (approximately 15%)
o neonatal stroke
o intracranial infections
o metabolic abnormalities
o central nervous system malformations
o drug withdrawal
o hypoglycaemia (always check the BGL of all babies who present with seizures)

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.7.3.1 Management
30-90% of seizures are subclinical and up to 50% of clinical seizures may not be
detected35,36
66% of electrographic seizures do not have overt clinical signs35
Anticonvulsants may not treat electroencephalographic seizures even if effective for
clinical seizure activity35,37
Seizures should be treated to reduce the risk of additional injury, however little consensus
exists regarding the optimal treatment protocol.38 Ensure that ventilation and
cardiovascular status are stable and monitored before giving anticonvulsant therapy
Anticonvulsant therapy should be given intravenously to achieve a rapid onset of action
and predictable blood levels [refer to Guideline: Neonatal seizures39]. Recommended
anticonvulsant therapy includes40:
o Phenobarbitone (first line treatment)
o Phenytoin
o Midazolam
o Clonazepam
Refer to Guideline: Neonatal seizures for anticonvulsant therapy administration
information
Drug levels are important when maintenance doses of these drugs are used. Slow elimination rates
secondary to hepatic and/or renal injury may lead to drug accumulation.
Duration of drug therapy depends on the likelihood of seizure recurrence:
following HIE there is a low risk of seizure recurrence after early withdrawal of
anticonvulsant in the neonatal period41
anticonvulsant treatment may be withdrawn once seizures are controlled and the
neurological examination is normal42
babies with prolonged or difficult seizures and those with abnormality on EEG may benefit
from continuing anticonvulsant treatment, however there is a lack of evidence from RCTs
to address duration of treatment
3.7.4 Physiotherapy and speech pathology
Neurological examination of the baby, including assessment of tone, movement, and oromotor
responses (cough, gag, suck and swallow), are valuable in order to track progress and can assist in
the decision to:
commence oral feeding
provide parents and staff with handling and positioning strategies
Prechtls Method on Qualitative Assessment of General Movements43 is a tool that may be used to
assess the babys neurological status to help determine appropriate early neurodevelopmental
intervention.

3.8

Impaired synthetic liver function/consumptive coagulopathy

Disseminated intravascular coagulopathy (DIC) is a significant risk after hypoxic injury to the liver.27
Liver function tests (LFTs) should be monitored regularly.
If there is evidence of bleeding or petechiae, perform platelet level and coagulation profile. Consider:
fresh frozen plasma (FFP) and
a second dose of Vitamin K

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

3.9

Gastrointestinal

Do not feed during therapeutic hypothermia and only recommence feeds after rewarming.
Commence feeding after assessment of the severity of asphyxia and associated system
complications including:
whether the baby is being cooled
respiratory distress
encephalopathy
hypotension
renal impairment
Feed intolerance is common as gut circulation may have been compromised, this may increase the
risk for necrotising enterocolitis (NEC)27:
Breast milk is preferable
Feeds should be introduced gradually

3.10 Other investigations

Calcium, magnesium, glucose
Serum lactate
To exclude other causes of neonatal encephalopathy consider:
C-reactive protein
Lumbar puncture
Liver function tests
Coagulation profile
Serum for chromosome analysis, ammonia, amino acids
Urine for amino and organic acids, ketones, reducing substances
Early newborn screening test (NNST) if metabolic/genetic disorders suspected. Repeat
the NNST when it would normally have been collected

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Prognosis

Clinical

Table 3. Prognosis

Test

Timing

Outcome

Sarnat and
Sarnat4

Early onset neonatal

encephalopathy is the
best single predictor of
long-term outcome2

Severity of the acute encephalopathy predicts the overall risk of

death and severe handicap45
Stage 1 HIE normal neurologic outcome in greater than 90% of
cases45

Quick recovery is
associated with a better
outcome44
Seizures

34

Early onset of seizures

Stage 2 HIE incidence of poor outcomes ranges from 30 - 60%45

Stage 3 HIE poor neurologic outcome (death or severe disability
45
in almost all cases)
May predict a poorer neurodevelopmental outcome, independent of
the severity of hypoxic-ischaemic brain injury34
May assist with outcome prediction43

Dubowitz/
Prechtl43
Time to
spontaneous
respiration

Greater than 30 minutes46

Overall risk of death or severe handicap 72%46

EEG

First few days of life after

HIE47

Background EEG abnormalities, detected in the first few days of life

after HIE can provide prognostic information even in babies treated
with hypothermia47
Grade of abnormality predicts the rate of death or severe
handicap46
Severe abnormality (burst suppression, low voltage or
46
isoelectric) - 95%
Moderate abnormality (slow wave activity) - 64%46
Mild or no abnormality 3.5%46
Persistence of EEG abnormalities at 1 month of age is
associated with a higher risk of neurologic sequelae47

Electrophysiology

aEEG

aEEG at an early age

(within several hours after
birth) can differentiate
between babies with later
severe neurologic deficits
and babies with mild
deficits or normal
outcomes48-50

The course of aEEG background activity adds to the prognostic

50
value of aEEG monitoring in asphyxiated babies
Normalisation of initially abnormal background patterns (burst
suppression, continuos low voltage, flat trace) by50:
6 hours of age is predictive of good outcomes positive
49
predictive value (PPV) 91%
24 hours of age is less pred ictive of good outcome PPV
49
61%
severely abnormal patterns persisting beyond 24 hours are
50
predictive of adverse neurological outcomes
adverse outcome is x 19 more likely when abnormal
background pattern (burst suppression or worse) occurs
50
between 24 36 hours
onset of sleep wake cycling within 36 hours of birth, is
predictive of good neurodevelopmental outcome PPV
92.1%51

Radiology

Background is affected by several medications and must be

considered when interpreting the aEEG trace52
Cerebral
artery
Doppler

12 +/- 2 hours29

Severe increase in mean cerebral blood flow velocity post hypoxia,

is predictive of Stage 3 HIE with poor neurologic outcome (death or
severe disability) in 100%29

MRI/magnetic
resonance
spectroscopy
(MRS)

7 10 days of age53

Both sensitive and specific for outcome prediction53

Grade 1 changes normal outcome 100%
Grade 3 changes death or severe disability 100%

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Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

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