NWNODN Cooling Guideline Page 1

Title:

NWNODN Hypoxic Ischaemic Encephalopathy (HIE) Guideline

Reference Number GL-ODN-03

Main Author (s) Emma Kyte

Target Audience NWNODN clinicians ConnectNW/Cot Bureau

Ratified by: NOPG

Date Ratified: 02/07/19

Review Date: 01/07/22

Version: FINAL

Document status: Circulated at locality NSGs February& March 2019

Document History:

Date Version Author Notes

30/7/19

V14 EK Front page amended by CN to use standard template. Review date extended. All guidelines to be reviewed every 3 years unless rational for earlier review.

The North West Neonatal Network (NWNODN) consists of 3 locality neonatal networks, Cheshire and Merseyside (CM) Lancashire and South Cumbria (LSC) and Greater Manchester (GM). This document has

agreed by locality Clinical Effective Groups (CEG) and can be adapted for local use.

This guideline has been developed and adapted based on previous Cooling guidelines that have been in place across the NWNODN. We would like to acknowledge all the previous work that has been undertaken and thank everyone for their collaborative working in allowing this document to be

developed.

We would like to extend particular thanks to the NWNODN Cooling specialist interest group, NOPG, Connect NW, Dr Kaleem Musa (AHCH) & the East of England Neonatal Network.

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NWNODN Hypoxic Ischaemic Encephalopathy (HIE) Guideline

Table of Contents

Section Title Page number

1 Hypoxic Ischaemic Encephalopathy (HIE) 4

2 Treatment of Hypoxic Ischaemic Encephalopathy (HIE) 4

3 Network Recommendations 4

4 Gestational Age for Cooling 5

5 Cooling referral pathway 5

6 Criteria for Cooling - table A 6

7 Cases for consideration 7

8 Diagnosing HIE 7

9 When Cooling is not appropriate 8

10 When to cool 8

11 Centres where Cooling should take place 9

12 Passive Cooling 9

13 Active Cooling 10

14 Cerebro Functioning Monitoring (CFM) 10

15 Supportive Management 10

16 Parent Communication 12

17 Neuroimaging 12

18 Early termination of Cooling 13

19 Follow up 13

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References 14

Appendices:

Appendix 1 - Passive cooling guide adapted from TOBY handbook

16

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NWNODN Guideline for the management of Hypoxic Ischemic

Encephalopathy (HIE)

This clinical guideline has been developed to ensure appropriate evidence based standards of care are achieved across the whole North West Neonatal Operational Delivery Network (NWNODN). Currently across the NWNODN all NICUs provide active cooling alongside a number Local Neonatal Units (LNUs). The LNUs providing active cooling initiate and manage the Cooling treatment until the transport service Connect North-West, are able to transfer the infant to an appropriate NICU for on-going management and care. 1. Hypoxic Ischaemic Encephalopathy (HIE) Hypoxic perinatal brain injury is caused by a decrease in the amount of oxygen supplied to an infant’s brain close to the time of birth or early neonatal period. It can result in stillbirth or neonatal death. Infants who survive may develop hypoxic-ischaemic encephalopathy (HIE) which can lead to severe lifelong disability or death. Hypoxic perinatal brain injury may be associated with multi-organ failure affecting the heart, lungs, liver and kidneys in some infants. 2. Treatment of HIE - Therapeutic hypothermia

Therapeutic hypothermia also referred to as ‘Cooling’ is a treatment that aims to cool the brain to several degrees below the baseline temperature, usually between 33°C and 34°C, with the intention of preventing continued neuronal loss that occurs in the days after brain injury. Treatment is started as soon as possible after diagnosis, usually within 6 hours of the insult. Therapeutic hypothermia is induced by whole body cooling using a cooling mattress. A rectal thermometer is used to measure the intracorporeal temperature as a proxy for brain temperature. The rectal temperature is measured continuously throughout the Cooling treatment. Treatment is usually undertaken for 72 hours after which point the infant is slowly rewarmed, over several hours, to normal body temperature. 3. Network Recommendations:

Rectal temperature monitoring is undertaken in all babies undergoing active or passive cooling.

CFM monitoring: LNUs wishing to undertake CFM are encouraged to do so and will be supported by the NWNODN.

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Active Cooling: LNUs wishing to initiate active cooling are encouraged to do so and will be supported by the NWNODN.

BadgerNet Data: all babies who are Cooled should have the HIE data form on BadgerNet completed.

Conference Calling: Connect North West (CNW) offer the opportunity for a conference call to be set up should a case need to be discussed in more detail, for example if the referring unit is unsure if the infant meets the criteria for Cooling.

4. Gestational Age for Cooling

Therapeutic hypothermia is a standard of care for infant’s ≥36+0/40 weeks. Infants who are >34+0 - 35+6/40 GA and meet the criteria in table A can be considered for Cooling if the local clinicians feel Cooling may benefit the patient. When considering cooling patients that fall within this gestational age bracket the north-west Cot Bureau can set up a conference call to discuss patients on a case by case basis. 5. Cooling Referral Pathway

All definite and suspected cases for Cooling should be referred immediately to Connect North-West via the North-West Cot Bureau. Clinical details will be taken with the option of a conference call, if necessary, to discuss, advise and develop a management plan for each baby on a case by case basis. NW Cot Bureau/ Connect North West Telephone number: 0300 330 9299

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6. Criteria for Cooling Table A: Criteria for cooling

Criteria for initiating active cooling

Criteria Met

1 ≥ 34+0 – 35+6/40 weeks gestational age: consider cooling if criteria met

>36+0/40 weeks gestational age: Cooling is standard treatment if criteria met

2 Infant < 6 hours old or <6 hours after initial insult

3 Evidence of intrapartum hypoxic ischaemia: (one of the following criteria to be met)

● Apgar ≤ 5 at 10 minutes

● Need for resuscitation at 10 minutes after birth including face mask or ETT ventilation.

Acidosis defined as any cord/blood sample within 60mins of birth: o pH <7.00 o Base deficit (BE) ≥ 16 mmol/L o Lactate > 12

4 Evidence of encephalopathy: (one of the following criteria to be met)

● Altered state of consciousness (reduced or no response to stimulation, need for respiratory support because of diminished respiratory drive)

● Abnormal tone (focal or general hypotonia or flaccid)

● Abnormal primitive reflexes (weak or absent suck or Moro response)

● Seizures

● An abnormal aEEG recording for a continuous period of at least 30min

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Note: to meet the criteria for cooling in Table A both sections 1 & 2 need to be met, plus one criteria from section 3 and one criteria from section 4. Passive cooling should be initiated if active cooling is not immediately available. Please refer to Appendix 1 - Passive cooling guide adapted from TOBY handbook. 7. Cases for Consideration:

Infants who are ≥34+0 weeks gestation and meet the criteria in section 1, 2 & 3 in Table A, but do not initially demonstrate any features of encephalopathy can be observed on NICU or the postnatal ward, depending on clinical condition, but MUST have neurological assessment. If there is any abnormality or evidence of encephalopathy the infant must admitted promptly to NICU for further assessments.

If this evolves into more definite HIE start CFM monitoring, if available, and passive or active cooling, if available. For advice around Cooling contact Cot bureau who have the facility, if required, to set up a conference call with Connect NW to discuss and establish a management plan for each patient on a case by case basis (please refer to section 5 of this guideline ‘Cooling Referral Pathway’). Postnatal Ward Collapse: cooling can be considered for those infants who suffer a collapse requiring resuscitation on the post-natal ward. If deemed appropriate. Cooling should be initiated within 6 hours of the initial insult. If there is uncertainty around the appropriateness to Cool following a postnatal ward collapse please contact the Cot Bureau who will set up a conference call with Connect NW and an appropriate Cooling centre, allowing each patient to be discussed on a case by case basis (please refer to section 5 of this guideline ‘Cooling Referral Pathway’). Also consider other diagnoses such as sepsis, cardiac and metabolic disorders.

8. Diagnosing HIE

The following points are useful when making a diagnosis of HIE: ● History of a sentinel event such as 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. A 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

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● Exclusion of other likely causes of encephalopathy Table B: HIE - Grading of severity (adapted from Sarnat and Sarnat)

Grade 1 (mild) Grade 2 (moderate) Grade 3 (severe)

Irritable, hyper alert Lethargic Comatose

Mild hypotonia Marked abnormality of tone

Severe hypotonia

Poor sucking Tube feeding required Failure to maintain self-ventilation

No seizures Seizures Prolonged or intractable seizures

9. When cooling is not appropriate: Initiating and/or continuing Cooling treatment may not be appropriate in certain circumstances. Please call the north-west cot bureau immediately who will set up a conference call to discuss the management of the patient (please refer to section 3 of this guideline ‘Cooling Referral Pathway’). Examples of cases where Cooling may not be appropriate:

● Any conditions requiring immediate surgery – please call cot bureau to set-up a conference call to discuss the management of any surgical infant that fulfils the Cooling criteria.

● Confirmed major congenital or chromosomal abnormalities or syndromes with long term poor prognosis. Infants with suspected or confirmed Trisomy 21 should not be excluded from Cooling treatment.

● Moribund infants with severe HIE not responding to resuscitation or intensive care.

10. When to Cool Cooling (passive or active) should be started as soon as possible after resuscitation is completed. Current evidence suggests that cooling is most beneficial within three hours of the initial insult and has limited benefits when started beyond six hours (Thorsen et al, 2015). If active cooling is not available passive cooling should be initiated. 11. Centres where Cooling should take place Cooling (active or passive) can be initiated in any hospital, however all infants eligible for cooling should be transferred to a regional Neonatal Intensive care unit (NICU) fro on

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going care and treatment (NICE/BAPM). NICUs have the facilities for providing full neuro-intensive care, recording aEEG and carrying out appropriate investigations including neuroimaging (section 16). 12. Passive Cooling For all infants that fulfil the criteria for Cooling born in units that do not provide active cooling, passive cooling should be initiated and continued until the infant is transferred. Please see appendix 1 for the Passive Cooling Flow Chart (Toby Trial). The 72hrs of cooling is considered to have commenced when a rectal temperature of 33-34C has been reached and maintained. Practical Guide to Passive Cooling:

Target temperature for passive cooling should be 33-34°C (due to the risk of over cooling).

Stop active warming by turning off the heater, open port holes and keep the baby unclothed apart from a nappy. Do not use fans, gloves filled with cold water or ice packs to cool the baby – this can result in severe hypothermia and rapid cooling.

Insert rectal temperature probe and start continuous core (rectal) temperature monitoring and record every 15 minutes on the infants observation chart.

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. Some babies can rapidly cool even with passive cooling.

Please consult the transport team or nearest Cooling centre if you are unsure or experience difficulties.

Risks and Precautions

If axilla thermometers are being used ensure low reading thermometer is used to check axilla temperatures- some will have a lower limit which can potentially lead to false readings.

Every effort should be made to avoid rapid cooling as a temperature below 33°C can be detrimental.

13. Active Cooling If an infant is born in a unit which provides active cooling this should be initiated as soon after birth as possible. For infants who have initially undergone passive cooling, active

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cooling will be initiated on transfer by Connect North-west, using a servo-controlled system. Cooling equipment used across the NWNODN maybe different and for this reason please follow your unit’s Active Cooling Guideline. LNU’s wishing to undertake active cooling will be supported to do so by the NWNODN and they will be required to demonstrate a robust education and training policy to support its use. 14. Cerebral Function Monitoring (CFM) The use of CFM is not mandated and the network recognises it will not be available in all neonatal units. The NWNODN supports and encourages all neonatal units who wish to undertake Cerebral Function Monitoring as it is as a tool that can aid clinical decision making, especially in hard to define cases. Please refer to your local guidelines for use and interpretation of CFM monitoring. 15. Supportive Management Monitoring: Monitoring throughout the cooling and rewarming period should include:

Continuous invasive blood pressure monitoring

Continuous oxygen saturation monitoring

Continuous respiratory monitoring

Continuous electrocardiograph (ECG)

Documented hourly observations including: o oxygen saturation o temperature (skin & rectal) o heart rate and blood pressure o respiration rate o urine output

Respiratory Support: Ventilate if poor respiratory effort, frequent apnoea, pCO2 >60mmHg or 8kPa or severe hypoxaemia. If transferring a baby for cooling therapy intubation to secure the airway during transfer may be necessary. The aim during ventilation is to maintain a normal pH, pO2 (60 – 90mmHg or 8-12 kPa) and pCO2 (35 - 50 mmHg or 5-6.6 kPa). Avoid hyperventilation and alkalosis. Infants can be extubated whilst being cooled if their respiratory drive is sufficient.

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Cardiovascular Support: Most cooled infants will have a resting heart rate of approximately 100 bpm or less. Gain and secure central vascular access, both venous and arterial umbilical lines, ideally with a double lumen UVC. Intra-arterial access is required to continually monitor systemic blood pressure. Once cooled it becomes difficult to insert peripheral lines and capillary blood gas analysis becomes unreliable Hypotension is usually secondary to myocardial compromise from hypoxic-ischaemic damage rather than hypovolaemia. For management of hypotension please refer to local hypotension guidelines. Collect samples for FBC (including the nucleated red cell count) CRP, U&Es, Ca, Mg, LFTs, group & save, cultures & clotting. Seizure management: Please follow local seizure management guidelines. Early use of amplitude EEG (aEEG) to establish severity of encephalopathy is seen as best practice, however it is recognised not all neonatal unit have this facility. Perform a neurological examination and document the clinical stage of encephalopathy In all cases a discussion with the consultant prior to commencing anti-seizure medication should be undertaken. Cooling may affect the metabolism of several drugs, including anticonvulsants and sedatives, and toxic drug levels may occur even with normal doses. Analgesia/Sedation: Cooling therapy is potentially distressing. Stress may have adverse effects in asphyxiated infants and may influence the therapeutic effect of hypothermia. All ventilated infants receiving cooling treatment should be commenced on morphine. Non-ventilated infants who appear distressed will also require sedative therapy with either morphine or chloral hydrate. Respiratory function must be monitored in these babies. Fluid Therapy: Infants should initially be commenced on 60ml/kg/day with this being reviewed daily on the consultant ward round. Fluid balance must be assessed on at least a 12 hourly basis and adjusted according to blood glucose measurement, serum sodium levels, daily weights and urine output. Regular blood glucose monitoring (at least 4 hourly in the first 24 hours) should be performed. Anti-cerebral oedema therapy: Infants should not be treated with steroids (other than for treatment of hypotension), or mannitol. Nutrition: Asphyxiated infants are at increased risk of NEC, aspiration secondary to pharyngeal incoordination and transient milk intolerance due to reduced small intestinal motility. Minimal enteral feeds or comfort feeds using breast milk via naso/orogastric tube may be commenced in infants receiving cooling therapy. Once the infant is rewarmed enteral feeding can be cautiously introduced once the initial biochemical and metabolic disturbance are corrected, bowel sounds are present and the gastric aspirates are minimal. The decision to commence enteral feeding is made by the consultant.

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Infection: A full septic screen including LP should be considered and antibiotics commenced as meningitis may have similar presenting features and infection can be the underlying aetiological factor for HIE. Whilst there is little published evidence, CRP can be elevated in HIE without infection and must be interpreted with caution.

Coagulopathy: Disseminated intravascular coagulation can occur in HIE and therefore clotting studies must be performed on day one in all babies. If normal no further samples will be required. If abnormal treat and repeat until normalised. 16. Parent Communication This is one of the most important aspects of management. It is often difficult to give the parents an accurate prognosis early on, and this should be made clear to them. Do not give opinions on the obstetric or midwifery management, but refer the parents to their obstetrician or midwife. Parents should be spoken to by a senior member of the team as soon as possible and counselled within the first 24 hours after admission by the consultant. A clear summary of the discussion should be documented in the health care record. BLISS parent information leaflet on HIE should be offered to all parents (available for down load from the NWNODN website). 17. Neuroimaging: MRI is the modality of choice to determine the severity of neurological damage in HIE.

Most local imaging departments are equipped with suitable equipment (1.5T MRI scanner) and the scanning is usually achieved by employing “feed and wrap” method

and hence avoided GA. MRI scanners are potentially unsafe places for sick or unstable

babies. Hence careful monitoring by suitably trained staff and meticulous attention to MRI safety protocols (including the use of hearing protection) are essential. Optimal timing of cranial MR has been debated vigorously over the recent years and

there is sufficient evidence to conclude that the risks of pseudonormalisation on DWI

have been overstated and so a pragmatic approach (scan when the baby is well enough

for transfer) seems reasonable.

18. Early termination of Cooling In a few cases Cooling therapy maybe stopped prior to the 72h treatment time. The decision to terminate Cooling early must be made by a Consultant Neonatologist and

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the rationale for doing so must be clearly documented in the medical notes and discussed with the infant’s family. 19. Follow up All infants who receive cooling treatment will receive a 6-8 week clinic appointment at the responsible neonatal unit. Babies will continue to be reviewed until at least 2 years. MRI: Follow up MRI appointments should be arranged by the neonatal unit undertaking the follow up care.

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References

1. 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.

2. Allanson ER, et al (2016) Umbilical lactate as a measure of acidosis and predictor of neonatal risk:

a systematic review. Available at: https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1111/1471-0528.14306

3. Agut T, et al. Early identification of brain injury in infants with hypoxic ischemic

encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life. BMC Pediatrics. 2014; 14(1):177.

4. Azzopardi D, Strohm B, Edwards AD et al. Moderate hypothermia to treat perinatal asphyxia encephalopathy. N Engl J Med 2009; 361:1349-58.

5. Azzopardi D et al. Neurological outcomes at 18 months of age after moderate

hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and

meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363

6. 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

7. British Association of Perinatal Medicine. Position Statement on Therapeutic

Cooling for Neonatal Encephalopathy. July 2010

8. Boudes E, et al. MRI obtained during versus after hypothermia in asphyxiated newborns. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2015;100(3):F238-F42.

9. Karlsson, M et al (2010) Lactate dehydrogenase predicts hypoxic ischaemic encephalopathy in newborn infants: a preliminary study. Available at: First published: 01 July 2010 https://doi.org/10.1111/j.1651-2227.2010.01802.x

10. Lomax R, Zipitis C, Dady I (2015) Cool & Transfer – the way forward. Journal of neonatal Nursing 21, pp114-120

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11. Martinez-Biarge M, et al, Outcomes after central grey matter injury in term

perinatal hypoxic-ischaemic encephalopathy, Early Hum Dev (2010).

doi:10.1016/j.earlhumdev.2010.08.013

12. Shah DK, Wusthoff CJ, Clarke P, et al. Arch Dis Child Fetal Neonatal Ed 2014; 99:

F219–F224.

13. Shah s, Tracey M, Smyth J (2004) Postnatal lactate as an early predictor of short-

term outcome after intrapartum asphyxia. Journal of Perinatology . 2004 Jan;24(1):16-20.available at: https://www.ncbi.nlm.nih.gov/pubmed/14726932

14. Smit E, Liu X, Jary S, Cowan F, Thoresen M. (2015) Cooling neonates who do not

fulfil the standard cooling criteria–short‐and long‐term outcomes. Acta paediatrica. Feb 1;104(2):138-45.

15. Skranes JH, et al. (2015) Brain imaging in cooled encephalopathic neonates does not differ between four and 11 days after birth. Acta Paediatrica..

16. Thorensen M. Effect of hypothermia on amplitude integrated

Electroencephalogram in Infants with Asphyxia Paediatrics 2010 126: e130

17. Thoresen M. Who should we cool after perinatal asphyxia? (2015) Seminars in

Fetal and Neonatal Medicine; 20:66-71

18. UK TOBY Cooling Register Clinician’s Handbook. Version 4, May 2010

19. UK Toby Cooling Register Clinician’s handbook. V 4 May 2010.

https://www.npeu.ox.ac.uk/toby/protocol

20. TOBY study protocol. https://www.npeu.ox.ac.uk/toby/protocol

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Appendices: Appendix 1 - Passive Cooling Flow Chart (TOBY handbook

Any baby receiving passive cooling should have continuous rectal temperature monitoring where possible. If not available 15 minute axilla monitoring must be undertaken.

Target rectal temperature is 330C to 340C

Contact local cooling centre as needed for advice.