Hypoxic ischaemic encephalopathy - NeoResus · 2017-12-08 · Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy Refer to online version, destroy

Hypoxic-ischaemic encephalopathy

Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy

Document title: Hypoxic-ischaemic encephalopathy

Publication date: May 2010

Document number: MN10.11-V4-R15

Replaces document: MN10.11-V3-R15

Author: Queensland Maternity and Neonatal Clinical Guidelines Program

Audience: Health professionals in Queensland public and private maternity services

Exclusions: All subsets of neonatal encephalopathy except hypoxic-ischaemic encephalopathy

Review date: May 2015

Endorsed by: Statewide Maternity and Neonatal Clinical Network QH Patient Safety and Quality Executive Committee

Contact: Queensland Maternity and Neonatal Clinical Guidelines Program Email: [email protected] URL: www.health.qld.gov.au/qcg

Disclaimer These guidelines have been prepared to promote and facilitate standardisation and consistency of practice, using a multidisciplinary approach. Information in this guideline is current at time of publication. Queensland Health does not accept liability to any person for loss or damage incurred as a result of reliance upon the material contained in this guideline. Clinical material offered in this guideline does not replace or remove clinical judgement or the professional care and duty necessary for each specific patient case. Clinical care carried out in accordance with this guideline should be provided within the context of locally available resources and expertise. This Guideline does not address all elements of standard practice and assumes that individual clinicians are responsible to:

• Discuss care with consumers in an environment that is culturally appropriate and which enables respectful confidential discussion. This includes the use of interpreter services where necessary

• Advise consumers of their choice and ensure informed consent is obtained • Provide care within scope of practice, meet all legislative requirements and maintain

standards of professional conduct • Apply standard precautions and additional precautions as necessary, when delivering care • Document all care in accordance with mandatory and local requirements

This work is licensed under a Creative Commons Attribution Non-Commercial No Derivatives 2.5 Australia licence. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/2.5/au/

© State of Queensland (Queensland Health) 2010

In essence you are free to copy and communicate the work in its current form for non-commercial purposes, as long as you attribute the authors and abide by the licence terms. You may not alter or adapt the work in any way.

For permissions beyond the scope of this licence contact: Intellectual Property Officer, Queensland Health, GPO Box 48, Brisbane Qld 4001, email [email protected] , phone (07) 3234 1479. For further information contact Queensland Maternity and Neonatal Clinical Guidelines Program, RBWH Post Office, Herston Qld 4029, email [email protected] phone (07) 3131 6777.

Refer to online version, destroy printed copies after use Page 2 of 25

http://creativecommons.org/licenses/by-nc-nd/2.5/au/�

mailto:[email protected]

http://www.health.qld.gov.au/qcg





Abbreviations

ABG Arterial blood gas

aEEG Amplitude integrated electroencephalogram

ACA Anterior cerebral artery

ADH Antidiuretic hormone

BGL Blood glucose level

CNS Central nervous system

DIC Disseminated intravascular coagulopathy

ECG Electrocardiogram

ECHO Echocardiography

EEG Electroencephalogram

FBC Full blood count

FFP Fresh frozen plasma

HIE Hypoxic-ischaemic encephalopathy

HMD Hyaline membrane disease

IM Intramuscular

ISC Infant servo control

IV Intravenous

MCA Middle cerebral artery

mmHg Millimetres of mercury

MRI Magnetic resonance imaging

MRS Magnetic resonance spectroscopy

NEC Necrotising enterocolitis

NNST Neonatal screening test

pCO2 Partial pressure of carbon dioxide

pH Partial pressure of hydrogen ions

PLIC Posterior limb of the internal capsule

pO2 Partial pressure of oxygen

PPHN Persistent pulmonary hypertension of the newborn

PPV Positive predictive value

RCT Randomised controlled trial

RSQ Retrieval Services Queensland

VBG Venous blood gas



Table of Contents

1 Introduction.....................................................................................................................................7 2 Differential diagnosis ......................................................................................................................7

2.1 Criteria for the diagnosis of HIE.............................................................................................8 2.2 HIE Staging............................................................................................................................8

3 Management...................................................................................................................................8 3.1 Resuscitation .........................................................................................................................8 3.2 Inter hospital transfer .............................................................................................................9 3.3 Cardiorespiratory ...................................................................................................................9

3.3.1 Respiratory.........................................................................................................................9 3.3.2 Cardiac...............................................................................................................................9

3.4 Infection ...............................................................................................................................11 3.5 Fluid, electrolyte and acid base ...........................................................................................12

3.5.1 Hypoglycaemia ................................................................................................................12 3.5.2 Acidosis............................................................................................................................12 3.5.3 Volume.............................................................................................................................12

3.6 Temperature ........................................................................................................................12 3.6.1 Criteria for cooling............................................................................................................13 3.6.2 Babies excluded from cooling..........................................................................................13 3.6.3 Babies born outside a Level 3 neonatal unit....................................................................13

3.7 Neurologic............................................................................................................................14 3.7.1 Neuroimaging ..................................................................................................................14 3.7.2 Electrophysiology.............................................................................................................14 3.7.3 Seizures ...........................................................................................................................14

3.7.3.1 Management .........................................................................................................15 3.7.4 Physiotherapy and speech pathology..............................................................................15

3.8 Impaired synthetic liver function/consumptive coagulopathy ..............................................15 3.9 Gastrointestinal....................................................................................................................16 3.10 Other investigations .............................................................................................................16

4 Prognosis......................................................................................................................................17 References ..........................................................................................................................................18 Appendix A: Sarnat and Sarnat staging system..................................................................................21 Appendix B: HIE staging......................................................................................................................22 Appendix C: Management of therapeutic hypothermia .......................................................................23 Acknowledgements..............................................................................................................................25 List of Tables

Table 1. Inotropic therapy.................................................................................................................... 10 Table 2. Antibiotic therapy ................................................................................................................... 11 Table 3. Prognosis............................................................................................................................... 17



Check List A: Criteria for therapeutic hypothermia

Term or near term (greater than or equal to (≥) 35 weeks) baby with a perinatal event and acidosis. Call RSQ on 1300 799 127 to discuss the need for transfer and therapeutic hypothermia with a Level 3 Neonatologist

1. Baby must meet all of the following criteria:

Greater than or equal to (≥) 35 weeks Birth weight greater than or equal to (≥) 1800 g Able to begin cooling before 6 hours of age No severe congenital anomaly Not moribund and with plans for full care

AND 2. Baby must meet either of the following criteria:

Blood gas (cord, arterial blood gas (ABG), venous blood gas (VBG)) within 60 minutes of birth with: pH less than or equal to (≤) 7.00 and base deficit greater than or equal to (≥) 12 mmol/L

OR if no blood gas is available, BOTH OF: 10 minute Apgar less than or equal to (≤) 5 or assisted ventilation required at birth and

continued for greater than or equal to (≥) 10 minutes Acute perinatal event (eg. ruptured uterus, placental abruption, cord prolapse, amniotic

fluid embolism, fetal exsanguination from vasa praevia, fetal maternal haemorrhage or severe fetal bradycardia)

AND 3. Baby must meet either of the following:

Seizures (witnessed by medical or nursing staff) OR: Early onset encephalopathy determined by the baby exhibiting a minimum of one

symptom in at least 3 categories as documented below

Category Moderate encephalopathy Severe encephalopathy

Level of consciousness

Lethargic Stupor or coma

Spontaneous activity

Decreased activity No activity

Posture Distal flexion, complete extension

Decerebrate

Tone Hypotonia (focal or general)

Flaccid

Primitive reflexes Weak suck or Incomplete Moro

Absent suck or Moro

Autonomic system Constricted pupils, bradycardia or periodic/irregular breathing

Deviated/dilated/non-reactive pupils, variable heart rate or apnoea

Adapted from: Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan ER, et al. Whole-body hypothermia for neonates with hypoxic -ischaemic encephalopathy. N Engl J Med 2005:353(15);1574-84. Jacobs SE, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database of Systematic Reviews 2007, Issue 4, Art. No.:CD003311. DO1: 10.1002/14651858.CD003311.pub2.



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 Advice to parent(s)

Resuscitation • 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

Incidence • 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

Consequences • 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

Prognosis • 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

Treatment • 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

What does the treatment entail

• Your baby will receive cooling therapy in addition to standard intensive care support

• Your baby’s temperature will be slowly lowered and kept between 33 to 34°C 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 baby’s 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 37°C



1 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

2 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.



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].

3 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 baby’s 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 baby’s 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



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.



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 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

IV infusion17,19 Prepare a fresh infusion every 24 hours17,19

Monitor heart rate and intra-arterial blood pressure17 May cause tachycardia and arrhythmias and increase pulmonary artery pressure17 Use in conjunction with Phenytoin may cause severe hypotension19 More effective than Dobutamine for treating hypotension20

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

IV infusion17,19 Prepare a fresh infusion every 24 hours17,19

Monitor heart rate and intra-arterial blood pressure17 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



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 OR

50 mg/kg/dose 12 hourly17,19

IV – slow push IM17,19

Increase the dosage interval if there is renal failure19

Benzylpenicillin 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

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

AND Gentamicin

Greater than or equal to 3.3 mg/L17 Do not give further doses. Measure level

in 24 hours17



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 – 34.0°C7,8,26



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 ½ hour, commence

continuous skin temperature monitoring if able. Maintain the temperature between 33.0 – 34.0°C 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.



3.7 Neurologic

3.7.1 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)



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

Prechtl’s Method on Qualitative Assessment of General Movements43 is a tool that may be used to assess the baby’s 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



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



4 Prognosis Table 3. Prognosis

Test Timing Outcome

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

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

Sarnat and Sarnat4

Early onset neonatal encephalopathy is the best single predictor of long-term outcome2 Quick recovery is associated with a better outcome44 Stage 3 HIE – poor neurologic outcome (death or severe disability

in almost all cases)45

Seizures Early onset of seizures34

May predict a poorer neurodevelopmental outcome, independent of the severity of hypoxic-ischaemic brain injury34

Dubowitz/ Prechtl43

May assist with outcome prediction43

Clin

ical

Time to spontaneous respiration

Greater than 30 minutes46 Overall risk of death or severe handicap 72%46

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 isoelectric) - 95%46

Moderate abnormality (slow wave activity) - 64%46

Mild or no abnormality 3.5%46

EEG First few days of life after HIE47

Persistence of EEG abnormalities at 1 month of age is associated with a higher risk of neurologic sequelae47

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 value of aEEG monitoring in asphyxiated babies50 Normalisation of initially abnormal background patterns (burst suppression, continuos low voltage, flat trace) by50: • 6 hours of age is predictive of good outcomes – positive

predictive value (PPV) 91%49 • 24 hours of age is less predictive of good outcome – PPV

61%49 • severely abnormal patterns persisting beyond 24 hours are

predictive of adverse neurological outcomes50 • adverse outcome is x 19 more likely when abnormal

background pattern (burst suppression or worse) occurs between 24 – 36 hours50

• onset of sleep wake cycling within 36 hours of birth, is predictive of good neurodevelopmental outcome – PPV 92.1%51

Background is affected by several medications and must be considered when interpreting the aEEG trace52

Elec

trop

hysi

olog

y

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

Rad

iolo

gy 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%



References 1. ACOG, Executive Summary. Neonatal encephalopathy and cerebral palsy: Defining the pathogenesis and physiology. 2003 [Available from: http://www.acog.org/from_home/Misc/neonatalEncephalopathy.cfm?printerfriendly=yes

2. Low JA. Intrapartum fetal asphyxia: definition, diagnosis, and classification. Am J Obstet Gynecol. 1997; 176(5):957-9.

3. Bax M, Nelson KB. Birth asphyxia: a statement. World Federation of Neurology Group. Dev Med Child Neurol. 1993; 35(11):1022-4.

4. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976; 33(10):696-705.

5. MacLennan Alistair. A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement. BMJ. 1999; 319:1054-9.

6. Azzopardi D, Brocklehurst P, Edwards D, Halliday H, Levene M, Thoresen M, et al. The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr. 2008; 8:17.

7. Gluckman P, Wyatt J, Azzopardi D, Ballard R, Edwards A, Ferriero D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005; 365(9460):663-70.

8. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005; 353(15):1574-84.

9. Shankaran S, Pappas A, Laptook AR, McDonald SA, Ehrenkranz RA, Tyson JE, et al. Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy. Pediatrics. 2008; 122(4):e791-8.

10. Australian Resuscitation Council. Neonatal Guidelines [updated February 2006. Available from: www.resus.org.au/

11. Lynn A, Beeby P. Cord and placenta arterial gas analysis: the accuracy of delayed sampling. Arch Dis Child Fetal Neonatal Ed. 2007; 92(4):F281-5.

12. Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed. 2005; 90(1):F49-52.

13. Bada HS, Korones SB, Perry EH, Arheart KL, Ray JD, Pourcyrous M, et al. Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage. J Pediatr. 1990; 117:607-14.

14. Miall-Allen VM, de Vries LS, Whitelaw AG. Mean arterial blood pressure and neonatal cerebral lesions. Arch Dis Child. 1987; 62(10):1068-9.

15. Kattwinkel J, editor. Textbook of Neonatal Resuscitation. 5th ed. Chicago: American Academy of Paediatrics and American Heart Association; 2006.

16. Kluckow M, Evans N. Relationship between blood pressure and cardiac output in preterm infants requiring mechanical ventilation. J Pediatr. 1996; 129:506-12.

17. Young T, Mangum B. Neofax. A manual of drugs used in neonatal care. 21 ed. Montvale: Thompson Reuters; 2008.

18. Davies MW, Cartwright D. Common drugs and infusions. In: Davies MW, Cartwright D, Inglis G, editors. Pocket notes on neonatology 2ed. Marrickville: Churchill Livingstone; 2008.

19. Hey E. Neonatal Formulary. Drug use in pregnancy and the first year of life. 5 ed. Massachusetts: Blackwell Publishing Ltd; 2007.

20. Osborn D, Evans N, Kluckow M. Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow. J Pediatr. 2002; 140(2):183-91.

http://www.acog.org/from_home/Misc/neonatalEncephalopathy.cfm?printerfriendly=yes

http://www.resus.org.au/



21. Burridge N, editor. SHPA. Australian Injectable Drug Handbook. 4 ed: Health communication Network; 2008.

22. Shann F. Drug doses. 14 ed. Parkville: Intensive Care Unit, Royal Children's Hospital; 2008.

23. Beveridge CJ, Wilkinson AR. Sodium bicarbonate infusion during resuscitation of infants at birth. Cochrane Database Syst Rev. 2006; (1):CD004864.

24. Perlman J. Intervention strategies for neonatal hypoxic-ischaemic cerebral injury. Clinical Therapeutics. 2006; 28(9):1353-65.

25. Kecskes Z, Healy G, Jensen A. Fluid restriction for term infants with hypoxic-ischaemic encephalopathy following perinatal asphyxia. Cochrane Database Syst Rev. 2005; (3):CD004337.

26. Jacobs S, Hunt R, Tarnow-Mordi W, Inder T, Davis P. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2007; (4):CD003311.

27. Zanelli S, Stanley D, Kaufman D. Hypoxic-ischaemic encephalopathy. eMedicine. 2008 [Available from: http://emedicine.medscape.com/article/973501-overview

28. Laptook A, Tyson J, Shankaran S, McDonald S, Ehrenkranz R, Fanaroff A, et al. Elevated temperature after hypoxic-ischemic encephalopathy: risk factor for adverse outcomes. Pediatrics. 2008; 122(3):491-9.

29. Ilves P, Talvik R, Talvik T. Changes in Doppler ultrasonography in asphyxiated term infants with hypoxic-ischaemic encephalopathy. Acta Paediatrica. 1998; 87(6):680-4.

30. Ment LR, Bada HS, Barnes P, Grant PE, Hirtz D, Papile LA, et al. Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2002; 58(12):1726-38.

31. Srinivasan L, Rutherford MA. MRI of the newborn brain. Paediatrics and Child Health. 2008; 18(4):183-95.

32. Toet MC, Hellstrom-Westas L, Groenendaal F, Eken P, de Vries LS. Amplitude integrated EEG 3 and 6 hours after birth in full term neonates with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 1999; 81(1):F19-23.

33. Spitzmiller RE, Phillips T, Meinzen-Derr J, Hoath SB. Amplitude-integrated EEG is useful in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischemic encephalopathy: a meta-analysis. J Child Neurol. 2007; 22(9):1069-78.

34. Glass HC, Glidden D, Jeremy RJ, Barkovich AJ, Ferriero DM, Miller SP. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury. J Pediatr. 2009; 155(3):318-23.

35. Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2008; 93(3):F187-91.

36. Malone A, Ryan C, Boylan G, Connolly S. Ability of medical staff to accurately distinguish neonatal seizures from non-seizure movements. Irish Journal of Medical Science. 2005; 14(2e3).

37. Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999; 341(7):485-9.

38. Silverstein F, Jensen F, Inder T, Hellstrom-Westas L, Hirtz D, Ferriero DM. Improving the treatment of neonatal seizures: National Institute of Neurological Disorders and Stroke Workshop Report. Pediatr. 2008; 153(1):12-15e1.

39. Queensland Maternity and Neonatal Clinical Guidelines Program. Neonatal seizures. Guideline No. MN10.23-V1-R16. Queensland Health. 2010.

40. Rennie JM, Boylan GB. Neonatal seizures and their treatment. Curr Opin Neurol. 2003; 16:177-81.

41. Hellstrom WL, Blennow G, Lindroth M, Rosen I, Svenningsen NW. Low risk of seizure recurrence after early withdrawal of antiepileptic treatment in the neonatal period. Arch Dis Child Fetal Neonatal Ed. 1995; 72:F97-101.

42. Evans D, Levene M. Neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 1998; 78(1):F70-5.

http://emedicine.medscape.com/article/973501-overview



43. Prechtl HF, Ferrari F, Cioni G. Predictive value of general movements in asphyxiated full term infants. Early Hum Dev. 1993; 35(2):91-120.

44. Carli G, Reiger I, Evans N. One-year neurodevelopmental outcome after moderate newborn hypoxic ischaemic encephalopathy. J Paediatr Child Health. 2004; 40(4):217-20.

45. Murray DM, Boylan GB, Ryan CA, Connolly S. Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years. Pediatrics. 2009.

46. Perlman JM, Risser R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers? Pediatrics. 1996; 97(4):456-62.

47. Mariani E, Scelsa B, Pogliani L, Introvini P, Lista G. Prognostic value of electroencephalograms in asphyxiated newborns treated with hypothermia. Pediatr Neurol. 2008; 39(5):317-24.

48. Azzopardi D, Guarino I, Brayshaw C, Cowan F, Price-Williams D, Edwards AD, et al. Prediction of neurological outcome after birth asphyxia from early continuous two-channel electroencephalography. Early Hum Dev. 1999; 55(2):113-23.

49. van Rooij LG, Toet MC, Osredkar D, van Huffelen AC, Groenendaal F, de Vries LS. Recovery of amplitude integrated electroencephalographic background patterns within 24 hours of perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed. 2005; 90(3):F245-51.

50. ter Horst HJ, Sommer C, Bergman KA, Fock JM, van Weerden TW, Bos AF. Prognostic significance of amplitude-integrated EEG during the first 72 hours after birth in severely asphyxiated neonates. Pediatr Res. 2004; 55(6):1026-33.

51. Osredkar D, Toet MC, van Rooij LG, van Huffelen AC, Groenendaal F, de Vries LS. Sleep-wake cycling on amplitude-integrated electroencephalography in term newborns with hypoxic-ischemic encephalopathy. Pediatrics. 2005; 115(2):327-32.

52. Hellstrom-Westas L, Rosen I. Continuous brain-function monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med. 2006; 11(6):503-11.

53. Jyoti R, O'Neil R, Hurrion E. Predicting outcome in term neonates with hypoxic-ischaemic encephalopathy using simplified MR criteria. Pediatr Radiol. 2006; 36(1):38-42.

54. Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics. 1998; 102(4 Pt 1):885-92.

55. Thoresen M, Whitelaw A. Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics. 2000; 106(1 Pt 1):92-9.

56. Azzopardi D, Robertson NJ, Cowan FM, Rutherford MA, Rampling M, Edwards AD. Pilot study of treatment with whole body hypothermia for neonatal encephalopathy. Pediatrics. 2000; 106:684-94.

57. Gilman JT, Gal P, Duchowny MS, Weaver RL, Ransom JL. Rapid sequential phenobarbital treatment of neonatal seizures. Pediatrics. 1989; 83:674-8.

58. Fary R, Smith R, editors. RWH Neonatal Pharmacopoeia. 2 ed. Melbourne: Pharmacy Dept, Royal Women's Hospital Melbourne; 2005.



Appendix A: Sarnat and Sarnat staging system The staging system proposed by Sarnat and Sarnat in 19764 is often useful in classifying the degree of encephalopathy. Stages 1, 2, and 3 correlate with the descriptions of mild, moderate, and severe encephalopathy described in Appendix B: HIE staging.

Stage 1 Stage 2 Stage 3

Level of consciousness Hyperalert Lethargic or obtunded Stuporous

Neuromuscular control

Muscle tone Normal Mild hypotonia Flaccid

Posture Mild distal flexion Strong distal flexion Intermittent decerebration

Stretch reflexes Overactive Overactive Decreased or absent

Segmental myoclonus Present Present Absent

Complex reflexes

Suck Weak Weak or absent Absent

Moro Strong, low threshold

Weak, incomplete, high threshold Absent

Oculo vestibular Normal Overactive Weak or absent

Tonic neck Slight Strong Absent

Autonomic function Generalized sympathetic

Generalized parasympathetic Both systems depressed

Pupils Mydriasis Miosis Variable, often unequal, poor light reflex

Heart rate Tachycardia Bradycardia Variable Bronchial and salivary secretions Sparse Profuse Variable

Gastrointestinal motility

Normal or decreased Increased, diarrhoea Variable

Seizures None Common, focal or multifocal

Uncommon (excluding decerebration)

Electroencephalogram findings

Normal (awake)

Early: low-voltage continuous delta and theta Later: periodic pattern (awake) Seizures: focal 1-to 1-Hz spike-and-wave

Early: periodic pattern with Isopotential phases Later: totally isopotential

Duration Less than 24 hours 2 – 14 days Hours to weeks



Appendix B: HIE staging Clinical manifestations and course vary depending on the severity of HIE27 Mild HIE (Stage 1)

• Muscle tone may be increased slightly and deep tendon reflexes may be brisk during the first few days

• Transient behavioural abnormalities, such as poor feeding, irritability, or excessive crying or sleepiness, may be observed

• By 3 - 4 days of life, the central nervous system examination findings become normal Moderate HIE (Stage 2)

• The baby is lethargic, with significant hypotonia and diminished deep tendon reflexes • The grasping, Moro, and sucking reflexes may be sluggish or absent • The baby may experience occasional periods of apnoea • Seizures may occur within the first 24 hours of life • Full recovery within 1 - 2 weeks is possible and is associated with a better long-term

outcome • An initial period of well-being or mild HIE may be followed by sudden deterioration,

suggesting ongoing brain cell dysfunction, injury, and death; during this period, seizure intensity might increase

Severe HIE (Stage 3)

• Stupor or coma is typical. The baby may not respond to any physical stimulus • Breathing may be irregular, and the baby often requires ventilatory support • Generalized hypotonia and depressed deep tendon reflexes are common • Neonatal reflexes (e.g. sucking, swallowing, grasping, Moro) are absent • Disturbances of ocular motion, such as a skewed deviation of the eyes, nystagmus, bobbing,

and loss of "doll's eye" (i.e. conjugate) movements may be revealed by cranial nerve examination

• Pupils may be dilated, fixed, or poorly reactive to light • Seizures occur early and often and may be initially resistant to conventional treatments. The

seizures are usually generalized, and their frequency may increase during the 24 - 48 hours after onset, correlating with the phase of reperfusion injury. As the injury progresses, seizures subside and the EEG becomes isoelectric or shows a burst suppression pattern. At that time, wakefulness may deteriorate further, and the fontanelle may bulge, suggesting increasing cerebral oedema

• Irregularities of heart rate and blood pressure are common during the period of reperfusion injury, as is death from cardiorespiratory failure

Babies who survive HIE

• The level of alertness improves by days 4 - 5 of life • Hypotonia and feeding difficulties may persist, requiring tube feeding for weeks to months

Multiorgan dysfunction Multiorgan systems involvement is a hallmark of HIE. Organ systems involved following a hypoxic-ischaemic event include the following:

• Heart (43 – 78%). May present as reduced myocardial contractility, severe hypotension, passive cardiac dilatation and tricuspid regurgitation

• Lungs (71 – 86%). Babies may have severe pulmonary hypotension requiring assisted ventilation

• Renal (46 – 72%). Failure presents as oliguria and during recovery as high output tubular failure leading to significant water and electrolyte imbalances

• Liver (80 – 85%). Elevated liver function tests, hyperammonemia, and coagulopathy can be seen. This may suggest possible gastrointestinal dysfunction. Poor peristalsis and delayed gastric emptying are common, necrotising enterocolitis is rare. Intestinal injuries may not be apparent in the first few days of life or until feeds are initiated

• Haematologic (32 – 54%). Disturbances include increased nucleated red blood cells, neutropenia, or neutrophilia, thrombocytopenia and coagulopathy. Severely depressed respiratory and cardiac function and signs of brainstem compression suggest a life threatening rupture of the vein of Galen (i.e. great cerebral vein) with a haematoma in the posterior cranial fossa



Appendix C: Management of therapeutic hypothermia Care system:

• Nurse baby on an open cot that has a radiant warmer. Venous and arterial catheters should be inserted

Monitoring: Monitoring throughout the cooling and rewarming period should include:

• continuous invasive blood pressure monitoring • continuous oxygen saturation • continuous respiratory monitoring • continuous electrocardiograph (ECG) • documented hourly observations including:

o oxygen saturation o heart rate and blood pressure o respiration rate o urine output

• daily investigations (and more frequently if abnormal): o blood gases, electrolytes, glucose and lactate (may all be obtained from the blood gas

sample) o full blood count including platelets (which may be sampled from an arterial line)

• continuous amplitude integrated electroencephalography (aEEG) commenced as soon as possible, if available. This is prognostic and may assist in guiding therapy (treatment of significant electrical seizures may lessen excitotoxic damage)

Cooling: Cooling should be started (within 6 hours of birth) after the baby has been assessed and stabilised and then continued for 72 hours:

• Measure core temperature continuously (for both passive and active cooling) by a thermistor inserted very gently (using appropriate lubricants ) 5 cm into the rectum and taped to the thigh

• Lower core temperature to between 33.0 - 34.0 °C7,8,26 • Achieve cooling primarily by exposing the baby to the ambient air temperature which

includes: o turning the radiant warmer off o nursing the baby naked with no:

nappy or wraps sheepskin or water bag occlusive wrap

o cool packs may be applied as needed: cool packs (covered with a cotton/other appropriate cover) around 10 °C (taken

from the fridge, NEVER the freezer) may be applied to the back of the neck and head, and across the torso

• Active cooling should be: o reduced when the rectal temperature falls below 34.5 °C, by removing one/some/all

cool packs o stopped when the rectal temperature falls below 34.0 °C, by removing all cool packs

• If the temperature falls below 33.0 °C, manually adjust the heater output on the radiant warmer to maintain the target rectal temperature greater than or equal to 33.0 °C

• If the baby is ventilated maintain the humidifier temperature at the temperature recommended by the manufacturer

Sedation/pain relief If the baby shows any signs of distress (they tend to shiver a lot), consider:

• Morphine or Midazolam (if ventilated) • Paracetamol (give per rectum, the presence of the rectal thermistor does not inhibit

administration)



Consider ceasing cooling if there is: • persistent hypoxaemia in 100% oxygen • life threatening coagulopathy • an arrhythmia requiring medical treatment (not sinus bradycardia)

Feeding: No enteral feeds are to be given during cooling Rewarming: After 72 hours, re-warming should occur at a rate not exceeding 0.5 °C every 2 hours:

• This may be achieved by nursing the baby on Infant Servo Control (ISC) mode. The lowest setting that can be achieved on ISC is 34.5 °C, therefore manual heater increases will need to be carefully managed until ISC settings can be used

• Increase the desired set temperature by 0.1 °C every 20 minutes. This will leave a further 20 minutes within that 2 hour period before needing to resume increasing the set temperature

• The target rectal temperature is 37 °C • Babies will take up to 12 hours to rewarm • Rectal probe measurements may cease after the baby has reached the target rectal

temperature and maintained this temperature with stability for 6 hours • Prevent rebound hyperthermia which is detrimental. Use of a specific rewarming chart

documenting exact time periods and increments required, may assist in ensuring that the baby is rewarmed accurately and safely

Cooling risks: Complications of therapeutic hypothermia are infrequent and symptoms may also be related to the effects of the original asphyxial insult on all systems.

• There have been no serious adverse effects reported54-56 • Adverse effects which are transient and reversible with warming include26:

o sinus bradycardia o hypotension requiring inotropic treatment o increased oxygen requirement o thrombocytopaenia

Follow up:

• Consider a magnetic resonance imaging (MRI) brain scan at approximately one week of age

• If the baby dies the value of an autopsy should be discussed with parent(s) • All babies with grade 2 to 3 HIE, and all babies who have received therapeutic

hypothermia as treatment for HIE, should be enrolled in a long term neurodevelopmental assessment program



Acknowledgements The Maternity and Neonatal Clinical Guidelines Program gratefully acknowledge the contribution of Queensland clinicians and other stakeholders who participated throughout the guideline development process particularly:

Working Party Clinical Lead

Dr Lucy Cooke, Mater Health Services, Brisbane

Working Party Members

Dr Gary Alcock, Neonatologist, The Townsville Hospital Glen Alexander, Clinical Nurse Consultant, Logan Hospital Ms Tanya Beaumont, Acting Clinical Network Coordinator, Central Maternity and Neonatal Network Ms Maxine Ballinger, Midwife, Rockhampton Dr David Cartwright, Neonatologist, Royal Brisbane and Women’s Hospital Greg Coulson, Neonatal Nurse Practitioner, Mackay Base Hospital Ms Megan Davidson, Midwifery Unit Manager, Mt Isa Hospital Dr Mark Davies, Neonatologist, Royal Brisbane and Women’s Hospital Dr Glenn Gardener, Director MFM, Mater Health Services, Brisbane Dr John Gavranich, Director of Paediatrics, Ipswich Dr Glenn Harte, Paediatrician, Pindara Private Hospital Ms Karen Hose, Clinical Nurse Consultant, Royal Brisbane and Women’s Hospital Dr Derek Jackson, Clinical Nurse, Gold Coast Dr Pieter Koorts, Neonatologist, Royal Brisbane and Women’s Hospital Dr David Knight, Director Neonatology, Mater Health Services, Brisbane Ms Naid Lumsden, Statewide Maternity and Neonatal Clinical Network Coordinator Ms Naoni Ngenda, Physiotherapist, Royal Brisbane and Women’s Hospital Ms Michelle Doidge, Centre for Healthcare Related Infection Surveillance and Prevention (CHRISP), Brisbane Dr Peter Schmidt, Neonatologist, Gold Coast Hospital Andrew Shearman, Neonatal Critical Care Scientist, Mater Health Services, Brisbane Ms Jacqueline Smith, Neonatal Nurse Practitioner, The Townsville Hospital Ms Mary Tredinnick, Pharmacist, Royal Brisbane and Women’s Hospital Professor David Tudehope, Neonatologist, Mater Health Services, Brisbane Dr Tim Warnock, Consultant Paediatrician Child &Youth Health, Far North Queensland Dr Judy Williams, Paediatrician, Bundaberg

Program Team

Associate Professor Rebecca Kimble, Director, Queensland Maternity and Neonatal Clinical Guidelines Program Ms Joan Kennedy, Principal Program Officer, Queensland Maternity and Neonatal Clinical Guidelines Program Ms Jacinta Lee, Program Officer, Queensland Maternity and Neonatal Clinical Guidelines Program Mrs Catherine van den Berg, Program Officer, Queensland Maternity and Neonatal Clinical Guidelines Program Steering Committee, Queensland Maternity and Neonatal Clinical Guidelines Program

Documents

Hypoxic ischaemic encephalopathy - NeoResus · 2017-12-08 · Queensland Maternity and Neonatal Clinical Guideline: Hypoxic-ischaemic encephalopathy Refer to online version, destroy