Hypoxic Ischaemic Encephalopathy Including Total Body Cooling - Guideline for the Management of

Last review: 28/06/2018  
Next review: 28/06/2021  
Clinical Guideline
ID: 1188 
Supported by: Yorkshire and Humber Neonatal operational Delivery Network.
Approved By:  
Copyright© Leeds Teaching Hospitals NHS Trust 2018  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Management of Hypoxic Ischaemic Encephalopathy (Including Total Body Cooling)

NOTE: This guideline is adapted from the Network HIE/Cooling Guideline. 

Summary of Guideline

AT DELIVERY Adequate resuscitation

Take arterial and venous umbilical cord gases and document in baby’s notes
If encephalopathy suspected and >36wks gestation, commence passive cooling by switching off the overhead warmer. Continue to monitor temperature if being passively cooled and avoid overcooling.

Check if fits criteria for cooling. Likely to incur most benefit if applied early (certainly less than 4-6 hours based on current evidence). Note neurological status can change during first few hours therefore reassessment is recommended as the baby may subsequently “meet” the cooling criteria.
 If indicated passive cooling should be started as soon as possible (see section 5). Consider switching off resuscitaire heater during resuscitation and switch off the overhead or incubator heater on the unit. Insert rectal probe and commence continuous rectal temperature monitoring. Aim to keep temperature between 33 and 34°C if possible and avoid hyperthermia and severe hypothermia (<32ºC). Document rectal temperatures every 30 minutes.

Cooling should be offered to all babies who
Achieve at least 1 criteria A as well as B

Criteria A

Infants ≥ 36/40 with at least one of

  • Apgar ≤ 5 @ 10 mins after birth
  • Continued need for assisted ventilation @ 10 mins after birth
  • pH<7.00 within 60 mins of birth (umb/ arterial/ capillary)
  • Base deficit ≥ 16 in umb/cap/venous/ art blood sample within 60 mins of birth

Criteria B

  • Seizures
  • Moderate to severe encephalopathy i.e. altered state of consciousness (lethargy/stupor/coma)  
  • Abnormal tone
    (focal/ hypotonia / flaccid)

NB. In some cases babies outside these criteria (i.e. >35 weeks) should be considered for cooling if these definitions are otherwise met. If an infant is cooled outside these criteria an early cranial ultrasound scan to exclude intracranial haemorrhage is recommended.

Consider artificial ventilation to maintain oxygenation
Maintain PaO2 6-10 kPa, PaCO2 5-7 kPa
Morphine sedation is routinely considered in infants who are offered therapeutic hypothermia but may need to be discontinued in order to enable assessment of severity of encephalopathy. Avoid paralysis unless essential for effective ventilation.

Obtain central vascular access (UVC/UAC).
Collect samples for FBC, U&Es, Ca, Mg, LFTs, group & save, cultures & clotting
If MAP <40mmHg consider the following:

  • 10ml/kg 0.9% Saline bolus

If BP remains low:
5-10 microgram/kg/min dopamine and/or 5-10 microgram/kg/min dobutamine. These can be titrated up to a maximum 20 microgram/kg/min.
Avoid bicarbonate and fluid boluses unless infant has signs of hypovolaemia (in which case consider blood product replacement).

Perform a neurological assessment on admission and repeat over first 24 hours
See section on Assessment of Encephalopathy

1st line: Phenobarbital 20mg/kg over 20 minutes. Further dose of 10 mg/kg can be used 1-2 hours later.
Consult local guidance for further management of seizures

Start antibiotics after taking cultures if clinically indicated. However if using gentamicin, do pre dose level and wait for result before giving second dose.

Fluid restrict at 40ml/kg/day and monitor blood sugars. May need higher concentration of dextrose if hypoglycaemia is a problem.

Senior member of medical team should aim to speak to family as soon as possible to explain level of concerns mentioning risk of death & disability.
Parent info leaflets available - see below.

If it is considered that the baby may require transfer or advice is needed discuss with LGI consultant and call Embrace as early as possible for discussion (08451472472)


  • To ensure that babies with suspected hypoxic ischaemic encephalopathy (HIE) are appropriately assessed and managed clinically.
  • To ensure therapeutic hypothermia is considered and initiated appropriately
  • To ensure that cooling is managed in a safe and timely manner
  • To outline the care pathway for the care of infants with HIE

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Cooling (therapeutic hypothermia) is an effective therapy for the treatment of newborn encephalopathy. Active cooling should only be conducted in centres that regularly cool infants and have the appropriate equipment and monitoring. Passive cooling should be initiated as soon as possible after delivery and can occur in the hospital of birth, using these guidelines.

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Cooling should be offered to all babies who achieve at least 1 criteria A as well as B (see above).
Cooling should be started as soon as possible with an aim to achieve the therapeutic target temperature within 6 hours of birth. Passive cooling should be started as soon as possible. Consider switching off resuscitaire heater during resuscitation and switch off overhead or incubator heaters once on the neonatal unit. For some infants, the need for cooling may become clear after a few hours and therefore neurological status should be reassessed frequently, however initiating cooling beyond 12 hours of age is not to be recommended.

Confirm severity of encephalopathy with cerebral function monitoring before cooling if possible, but do not delay cooling for cerebral function monitoring. Normal initial cerebral function monitoring indicates a high probability of normal outcome. In this case cooling is unlikely to be beneficial, and if treatment has been commenced the neonatal consultant may consider discontinuing.

Special cases:
*Infants 34-35 weeks
For infants 34-35 weeks that otherwise fit the criteria for therapeutic hypothermia, decisions need to be made on a case by case basis depending on the clinical history.
There is no evidence of any therapeutic benefit from cooling for these babies (due to lack of studies) however there are increasing reports of lack of harm, although these are observational studies. Recent reviews have suggested cooling these babies in some situations may be appropriate. Any decision to cool these babies should be made with a consultant in conjunction with the parents.

Postnatal Ward Collapse
Again observational studies and case series have been reported for infants cooled after postnatal ward collapse. Data extrapolated from adult literature in addition to the current perinatal data gives a good theoretical basis for benefit for these infants however there have been no randomised controlled trials. These infants would be best discussed on a case by case basis with consultant. Of note, all these case series and reviews suggest significant intracranial haemorrhage should be a contraindication to therapeutic hypothermia in view of the potential impairment in coagulation that cooling may worsen.

Criteria for defining moderate and severe encephalopathy:


Moderate Encephalopathy

Severe Encephalopathy

Level of consciousness

Reduced response to stimulation

Absent response to stimulation

Spontaneous activity

Decreased activity

No activity


Distal flexion, complete extension



Hypotonia (focal or general)











Heart rate




Periodic breathing


Passive Cooling Guideline

  • Stop active warming by turning off the heater:
  • Monitor and measure the rectal temperature every 15 minutes. A rectal probe should be used in all babies that are being cooled.
  • Commence continuous skin temperature monitoring if able.
  • Maintain the rectal temperature between 33.0 – 34.0°C by passive cooling only (heater off).
  • Ensure a low reading thermometer is used.
  • Turn the heater on if the rectal temperature is less than 33.5 °C and continue to closely monitor the rectal temperature.

Do not delay passive cooling to await the arrival of the transport/retrieval team.

Risks and Precautions
Ensure low reading thermometer is used to check axilla temperatures- some will have a lower limit with leads to false readings.
Do not allow the temperature to fall below 33°C
Active cooling with the use of a fan, or using cool bags of fluids can cause overcooling. These methods should only be used with rectal monitoring.
Ice packs must not be used to reduce the infant’s temperature as they can result in severe hypothermia

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Daily investigations (and more frequently if abnormal):

  • blood gases, electrolytes, glucose and lactate (may all be obtained from the blood gas sample)
  • 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)

Cranial USS @ 48-72 hours - specify time of birth on request. If concerns about large intracranial heamorrhage, early USS may be warranted.

Consider formal EEG

MRI - 5-10 days on discussion with neuroradiologist.

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Treatment / Management

Further Supportive Care
The main principle of the management of these infants is to maintain normal homeostasis
Good documentation is essential. There is a section on Badger that must be completed as well as documented in the notes.

At delivery
Adequate resuscitation, as per the Newborn Life Support guidelines. Take arterial and venous umbilical cord gases and document in baby’s notes. If encephalopathy suspected, switch off overhead heater.

Postnatal collapses -Consider other diagnoses, such as sepsis and metabolic disorders.

Ongoing care

  • Consider artificial ventilation to maintain oxygenation.
  • Maintain O2 6-10 kPa, CO2 5-7 kPa.
  • Try to avoid iatrogenic hypocarbia. Some babies spontaneously hyperventilate and this cannot easily be prevented, but consider ventilation and sedation if extreme and persistent.
  • Morphine may be used as sedation acutely, but may require to be discontinued later to allow adequate assessment of the baby’s neurological status, especially if considering withdrawal of intensive care.
  • Avoid paralysis unless essential for effective ventilation.

Cardiovascular system

  • Consider central vascular access both venous and arterial.
  • Collect samples for FBC (including the nucleated red cell count) CRP, U&Es, Ca, Mg, LFTs, group & save, cultures & clotting.
  • In term infants the mean pressure should be > 40mmHg (see blood pressure guidelines)
  • If MAP <40mmHg consider the following:
    • 10mL/kg 0.9% Saline bolus
    • Further 0.9% saline bolus or blood product replacement only if evidence of hypovolemia e.g. Feto-maternal haemorrhage.
    • Only use bicarbonate boluses if prolonged acidosis is causing compromise- the acidosis is usually due to anaerobic metabolism during the hypoxic ischaemic insult and will usually correct without intervention
    • If BP remains low there may be depressed myocardial function and large volumes of colloid or crystalloid may be harmful causing worsening hypotension and increasing risk of cerebral oedema.
  • Follow hypotension guideline and consider doing echo and ECG.

Fluids & Metabolic

  • Start 10% dextrose at 40 mL/kg/day, but review carefully in the light of progress at least 3 times in the first 24 hours. Maintain normoglycaemia – increasing glucose concentration rather than volume will avoid fluid overload.
  • Monitor and treat hypocalcaemia (due to transient hypoparathyroidism and sick cell syndrome) and hypomagnesaemia.
  • Some babies may develop hyponatraemia secondary to SIADH. This should usually be managed with fluid restriction. Additional sodium should only be considered if severe (d/w consultant)
  • Check the lactate soon after admission, but remember the acidosis is usually metabolic due to anaerobic metabolism and will usually correct without volume or bicarbonate.
  • Check LFTs and consider full metabolic screen including cardiac and muscle isoenzymes.
  • Monitor the urine output and have a low threshold for catheterisation.
  • Test the urine for blood and protein.
  • If urine output is poor treat as renal failure with fluid restriction, but remember that prolonged fluid restriction may exacerbate or even cause renal failure.

CNS & Seizures

  • Use CFM early, if available, to establish severity of encephalopathy. It may also be used to monitor seizures. See 'Use of CFM (Cerebral Function Monitoring) electrodes' standard operating procedure.
  • Perform a neurological examination and document the clinical stage of encephalopathy
  • Consider requesting a formal EEG.
  • For seizures; Phenobarbitol 20mg/kg over 20 minutes as first line, a further dose of 10mg/kg can be given 1-2 hours later if seizures still present and then follow local seizure guideline.
  • Opisthotonic and tonic generalised seizures after profound asphyxia may have no EEG correlates and may not benefit from anticonvulsants. Prolonged and unresponsive seizure must be discussed with the consultant.
  • Morphine sedation for comfort during therapeutic hypothermia. Consider low doses if not ventilated


  • Early imaging is relatively insensitive at finding abnormalities. Early ultrasound may be useful to exclude anatomical abnormalities. Ultrasound with dopplers should be done at 48-72hours after birth.
  • MRI may be useful (timing as per local guidance)


  • Start antibiotics after taking cultures if clinically indicated.
  • If using gentamicin, consider the need for early pre dose gentamicin levels and awaiting result because of acute renal injury.


  • Consider minimal enteral feeding (trophic) until re-warmed 6
  • Ensure mouthcare using EBM as available.

Feed intolerance is common as gut circulation may have been compromised, this may increase the risk for necrotising enterocolitis (NEC) 7:

  • Breast milk is preferable
  • Feeds should be introduced gradually

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:
    • oxygen saturation
    • heart rate and blood pressure
    • respiration rate
    • urine output


Senior member of medical team should aim to speak to family as soon as possible to explain level of concerns mentioning risk of death & disability. Discuss use of CFM and cooling if appropriate.
Information leaflets are available from Bliss and the NPEU

Parental advice regarding therapeutic hypothermia


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


This can result in brain damage from direct injury and also from ongoing changes that begin around six hours after the injury


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 by one fifth and reduces the risk of severe long-term disability by one third.

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.
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

Infants who may require transfer for cooling/intensive care should be referred as early as possible to enable the team to mobilise quickly. These infants will require:

  • Full documentation (Badger)
  • X rays
  • 2 points of iv access
  • Labelled maternal blood sample for cross match

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Record: 1188

To provide guidance on the management of hypoxic-ischaemic encephalopathy, including the use of total body cooling, and to facilitate collection of data for the UK TOBY Cooling Register.

Clinical condition:

Hypoxic-Ischaemic Encephalopathy

Target patient group: Term and near term newborn infants
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Adapted from:

Evidence base

References and Evidence levels:

  1. Yorkshire and Humber Neonatal Operational Delivery network HIE Guideline 2015.
  2. NICE Interventional Procedure Guidance 347. Therapeutic Hypothermia with intracorporeal temperature monitoring for hypoxic Perinatal brain injury. May 2010
  3. Smit E, Liu X. Cooling neonates who do not fulfil the standard cooling criteria-short and long-term outcomes. Acta Paediatrica 2014, 104; 138-145
  4. Thoresen M. Who should we cool after perinatal asphyxia? Seminars in Fetal and Neonatal Medicine.2015; 20:66-71
  5. Saliba E. Should we extend the indications for therapeutic hypothermia? Acta Paediatrica 2014 104: 114
  6. Austin T, Shanmugalingam S, Clarke P. To cool or not to cool? Hypothermia treatment outside trial criteria. Arch Dis Child Fetal Neonatal Ed 2013, 98; F451-453
  7. Balamurugan Thyagarajan. Minimal enteral nutrition during neonatal hypothermia treatment for perinatal hypoxic-ischaemic encephalopathy is safe and feasible. Acta Paediatrica 2015 Feb;104(2):146-51
  8. Zanelli S, Stanley D, Kaufman D. Hypoxic-ischaemic encephalopathy. eMedicine. 2008 [Available from: http://emedicine.medscape.com/article/973501-overview
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Murray DM, Boylan GB, Ryan CA, Connolly S. Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years. Pediatrics. 2009.
  14. 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.
  15. Predictive value of the amplitude integrated EEG in infants with hypoxic ischaemic encephalopathy:data from a randomised trial of therapeutic hypothermia. Azzopardi D, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F80–F82.
  16. Thorensen M. Effect of hypothermia on amplitude integrated Electroencephalogram in Infants with Asphyxia Paediatrics 2010 126: e130
  17. 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
  18. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86(6):329-38
  19. Gluckman PD, Wyatt JS, Azzopardi D et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365(9460):663-670.
  20. Shankaran S, Laptook AR, Ehrenkranz RA et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353(15):1574-1584.
  21. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy CochraneDatabase of SystematicReviews 2013, Issue 1.Art.No.:CD003311.DOI: 10.1002/14651858.CD003311.pub3
  22. Azzopardi D, Strohm B, Edwards AD et al. Moderate hypothermia to treat perinatal asphyxia encephalopathy. N Engl J Med 2009; 361:1349-58.
  23. British Association of Perinatal Medicine. Position Statement on Therapeutic Cooling for Neonatal Encephalopathy. July 2010
  24. Abbot R. Laptook, Seetha Shankaran, Namasivayam Ambalavanan et al. Prediction of Early Childhood Outcome of Term Infants using Apgar Scores at 10 Minutes following Hypoxic-Ischemic Encephalopathy. Pediatrics. Dec 2009; 124(6): 1619.

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