The following points are useful when making a diagnosis of HIE: 

• History of a sentinel event, e.g. abruption or uterine rupture
• History of foetal/intrapartum distress or acidosis 
• Low Apgar scores and/or delayed onset of respiration requiring resuscitation 
• Symptoms or signs of encephalopathy
  
  • characteristic feature of many cases of HIE is an evolving encephalopathy – babies get worse and then get better 
• Signs of multi-organ involvement usually occurs in association with a moderate to severe encephalopathy 
• Exclusion of other likely causes of encephalopathy 

Treatment criteria

• Babies ≥36 weeks’ gestation, meeting criteria A, B and C aged ≤6 hr 
• Babies 35⁺⁰–35⁺⁶ weeks’ gestation but meeting criteria A, B and C aged ≤6 hr, discuss with cooling centre, as may be suitable for treatment
  
  • there is limited evidence of benefit of TH in babies <35 weeks’ gestation and some evidence of an increased risk of complications 
• If in doubt about the suitability of any baby for cooling, discuss with cooling centre

Criterion A

At least ONE of the following:

• Apgar score ≤5 at 10 min after birth 
• Continued need for resuscitation, including endotracheal or mask ventilation at 10 min after birth (does not include those receiving PEEP or CPAP alone) 
• Acidosis within 60 min of birth (defined as umbilical cord, arterial or capillary pH <7.0) 
• Base deficit ≥16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 min of birth

Criterion B

• Moderate-to-severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:
  
  • hypotonia
  • abnormal reflexes including oculomotor or pupillary abnormalities
  • absent or weak suck
  • clinical seizures

Criterion C

• Babies meeting Criteria A and B should be assessed for at least 30 min of amplitude integrated EEG 
• There must be one of the following:
  
  • normal background (upper margin >10 µV and lower margin >5 µV) with some seizure activity 
  • moderately abnormal activity (upper margin >10 µV and lower margin <5 µV)
  • suppressed activity (upper margin <10 µV and lower margin <5 µV)
  • continuous seizure activity

Neurological assessment – repeat and document at regular intervals as babies go through pathway of care

Consent

• Discuss cooling treatment with parents as soon as practically possible. It is not necessary to wait for informed consent before starting cooling
• Document discussions in baby’s notes

In addition

• Request cord gases (if not already obtained)
• Request midwives save placenta for histological examination

Passive cooling

• As soon as decision made for cooling, referring unit to telephone cooling centre and to begin passive cooling
  
  • document this time as ‛age when passive cooling commenced’
  • document baby’s temperature at this time
  • begin passive cooling by switching off overhead heater and active heating in a transport incubator
• Nurse baby in an open Babytherm^® cot with heater switched off
• If baby nursed in an incubator, open portholes
• Nurse baby naked apart from a nappy

Continuous rectal temperature monitoring

• Insert a rectal probe to 6 cm and commence continuous rectal temperature monitoring
• Target rectal temperature 33–34°C

• Once baby accepted by a cooling centre, contact neonatal transport team to arrange transport of baby and complete cooling proforma
• Use servo controlled total body cooling mattress (if available) before arrival of neonatal transport team. Use fans or gloves filled with cold water only if continuous rectal temperature monitoring is in place and cooling mattress is not available

Passive cooling

• Use referral form from: https://networks.pcc-cic.org.uk/nhs-networks/west-midlands-neonatal-operational-delivery/neonatal-guidelines-2022-2024-1/supporting-links-for-guidelines-2022-2024
• Ensure baby’s temperature does not fall below 33ºC. Document every 15 min 
• Follow Passive cooling protocol flowchart
• Care continues in referring unit with advice from cooling centre as required
• If not already intubated at delivery [most babies will need to be intubated for transfer (see Intubation guideline)] discuss with receiving consultant and newborn transfer service
• If possible, insert umbilical arterial and venous catheters and monitor arterial blood pressure (see Umbilical artery catheter: insertion and removal and Umbilical venous catheter: insertion and removal guidelines). Check position of lines on X-ray
• Aim to maintain arterial PaCO₂ of 6–8 kPa
• Document neurology before commencing sedation or anticonvulsants, including size and reactivity of pupils
• Sedate baby using morphine at an infusion rate of 20 microgram/kg/hr. Aim for heart rate of 100 bpm. Faster rates may be a sign of distress, in which case increase sedation
• Maintain mean arterial blood pressure at >45 mmHg (see Hypotension guideline)
• Restrict total fluids to 40 mL/kg/day initially
• Keep glucose within normal range – use higher glucose concentration infusion if necessary (see Hypoglycaemia guideline)
• Take blood for blood culture, FBC, arterial blood gas, lactate, electrolytes, urea and creatinine, calcium, magnesium, prothrombin time, APTT, glucose and LFT
• Babies ≥37 weeks’ gestation with severe brain injury diagnosed in the first 7 days of life meet the Healthcare Safety
• Investigation Branch criteria for a maternity investigation if baby was:
  
  • actively cooled
  • diagnosed with Grade III HIE
  • had reduced central tone, was comatose and had seizures of any kind
  • notify obstetric team before transfer if baby meets above criteria 

Continue with management below if baby not transferred to cooling centre, or in cooling centre without local guideline for active cooling. NOTE that some of the target values are different to those recommended if a baby is being actively cooled 

Oxygen

• Avoid hypoxaemia. Maintain PaO₂ 10–12 kPa and SpO₂ >94% 
• Episodes of hypoxaemia (possibly associated with convulsions) are an indication for IPPV 

Carbon dioxide

• Maintain PaCO₂ 5.0–7.0 kPa 
• Hypoventilation leading to hypercapnia (>7.0 kPa) is an indication for IPPV
• Hyperventilation is contraindicated but, if baby spontaneously hyperventilating, mechanical ventilation, with/without paralysis, may be necessary to control PaCO₂ 

Circulatory support

• Maintain mean arterial blood pressure at ≥45 mmHg (see Hypotension guideline) 
• If cardiac output poor (e.g. poor perfusion: blood pressure is a poor predictor of cardiac output) use inotropes 
• Avoid volume replacement unless evidence of hypovolaemia

Fluid balance and renal function

• Start fluids at 40 mL/kg/day (see Intravenous fluid therapy guideline)
• Observe for SIADH and avoid severe hyponatremia (suggested by hypo-osmolar serum with low serum sodium, associated with an inappropriately high urine sodium and osmolality) 
• Further fluid restriction if serum sodium falls and weight gain/failure to lose weight 
• If in renal failure, follow Renal failure guideline
• Observe for accumulation of nephrotoxic drugs

Acidosis

• Will normally correct itself once adequate respiratory and circulatory support provided (correction occasionally required during initial resuscitation)
• Sodium bicarbonate correction is rarely required post resuscitation and it is better to allow spontaneous correction

Glucose

• Regular blood glucose monitoring 
• Target >2.6 mmol/L 
• Fluid restriction may require use of higher concentrations of glucose to maintain satisfactory blood glucose 
• Avoid hyperglycaemia (>8 mmol/L)

Calcium

• Asphyxiated babies are at increased risk of hypocalcaemia
• Treat with calcium gluconate when serum corrected calcium <1.7 mmol/L or if ionized calcium <0.8 (see Hypocalcaemia guideline)
• Maintain serum magnesium (>1 mmol/L) 

Seizures

• In muscle-relaxed baby, abrupt changes in blood pressure, SpO₂ and heart rate can indicate seizures
• Consider treating seizures confirmed with aEEG, particularly if associated with physiological disturbance, prolonged (>3 min) or frequent (>3/hr) (see Seizures guideline)

• While seizures are common in HIE, unremitting seizure activity should lead to urgent consideration of other causes of epileptic encephalopathy, including consideration of a trial of pyridoxine 

Gastrointestinal system

• Give buccal colostrum unless maternal breast milk contraindicated (see Nutrition and enteral feeding guideline)
• If no ongoing organ dysfunction or poor perfusion, offer trophic breast milk 
• Term babies who suffer a severe asphyxial insult are at risk of developing NEC [see Necrotising enterocolitis (NEC) guideline]

Sedation

• Assess for pain and distress and treat with opiate medication (evidence that distress increases brain injury in neonatal encephalopathy)
• Use analgesia for procedures likely to cause pain and distress (see Pain assessment and management guideline)

Rewarming

• Monitor for hypotension, apnoea and seizures, including continuing aEEG
• Can be delayed or slowed if seizures emerge
• After rewarming maintain normothermia using paracetamol and environmental measures if required 

Cranial ultrasound

• Within 12 hr to rule out other causes of encephalopathy
• Generalised increase in echogenicity, indistinct sulci and narrow ventricles
• After aged 2–3 days, increased echogenicity of thalami and parenchymal echodensities 
• After 1 week, parenchymal cysts, ventriculomegaly and cortical atrophy may develop
• Cerebral Doppler used early, but does not affect management
  
  • relative increase of end-diastolic blood flow velocity compared to peak systolic blood flow velocity (Resistive Index <0.55) in anterior cerebral artery predicts poor outcome (repeat after 24 hr)

MRI

• Between days 5–15 of life (preferably day 5–7)

• Risk of long-term problems increases with the degree of encephalopathy
• Normal EEG during first 3 days has good prognosis
• Overall risk of death or significant handicap is negligible for mild HIE, 26% for moderate and almost 100% for severe HIE
• Prolonged encephalopathy (e.g. moderate HIE lasting >6 days) also associated with poor outcome
• Persistent oliguria is associated with poor outcome in 90% 
• Prognostic factors indicative of worse outcome: 
  
  • prolonged duration of ventilation
  • prolonged need for anticonvulsants 
  • time taken to establish oral feeding 
  • lack of normal background activity on EEG
  • areas of altered signal in thalamus, basal ganglia and posterior limb of the internal capsule
• Discuss prognosis with parents before discharge from NICU, document and relay to referring unit

• When prognosis very poor, discuss withdrawing intensive care support and palliative care
• Very poor prognostic factors include:
  
  • need for prolonged resuscitation at birth
  • evidence of severe asphyxia
  • multi-organ failure
  • intractable seizures
  • coma
  • very abnormal cranial ultrasound scan and/or MRI
  • persistent burst suppression pattern on cerebral function monitoring and/or EEG
• If baby physiologically stable during TH delay consideration of reorientation of care for 48 hr to allow for any recovery before discussions
• Decision to withdraw care requires discussion with parents, and other nursing and medical staff. Such decisions are frequently reached by baby’s consultant after a series of discussions
• It helps if the same staff speak to parents on each occasion
• The best interests of the child are paramount
• Record a summary of discussion in notes

• Arrange clinic follow-up in 4–6 weeks for babies discharged
• Arrange hearing screen (see Hearing and screening guideline)
• All babies who have been cooled need a standardised neurodevelopmental assessment at aged 2 yr

Offer parents information on HIE, available from: https://www.bliss.org.uk/parents/about-your-baby/medical-conditions/hypoxic-ischaemic-encephalopathy-hie