Neonatal Therapeutic Hypothermia: Case Report &

Discussion

Dr Julia UffindellConsultant Neonatologist

Cooling 'cure' averts infant brain damageHi-tech 'ice pack' helps to protect newborns starved of oxygen through suffocation

Cooling ‘cuts baby brain damage’

Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy

Volume 361(14):1349-1358. October 1, 2009

Case Report – highlighting use of NPEU TOBY Register criteria and guidelines for Cooling

Discussion about rationale and evidence for Therapeutic Neonatal Hypothermia

38+1 weeks gestation Birth weight 4460g (99.6th centile) Born at a hospital with level 2 NNU

Mother: 22 years, white British, unemployed Insulin dependent Diabetes Mellitus Past obstetric history: Miscarriage at 11/40 Antenatal screening serology negative Group B streptococcus on HVS this pregnancy (intrapartum

antibiotics given)

Father 32 years, white British, unemployed Parents not consanguineous

Case Report

Spontaneous vaginal delivery Shoulder dystocia – 7 mins delay between delivery of head

and body

Apgar score 0 at 1 minute

Resuscitation included inflation breaths, ventilation breaths, cardiac massage, intubation. HR > 100 at 7 mins

Apgar score 2 at 5minutes, 4 at 10 mins

Cord gas: pH 7.096, pO2 1.52, pCO2 10.74, BE -7.5

Delivery & resuscitation

Ventilated – relatively low pressures, soon stable in air

Blood cultures & started high dose broad spectrum antibiotics in view of history of GBS

Hypoglycaemia

Generalised tonic clonic seizures noted – requiring 2 X Phenobarbitone

Hypotension – requiring inotropes

Diagnosis: Presumed Hypoxic Ischaemic Encephalopathy – fulfilling criteria for Therapeutic Hypothermia

Progress on NNU

Criteria A

Infants > 36 weeks admitted to NNU with at least one of the following:

• Apgar score of < 5 at 10 mins of age

• Continued need for resuscitation, including ET or mask ventilation at 10 mins of age

• Acidosis within 60 mins of birth (defined as any occurrence of umbilical cord, arterial or capillary pH <7.00)

• Base deficit > 16 in umbilical cord or any blood sample (arterial, venous or capillary) within 60 mins of birth

Criteria B

If infant meets criteria A, assess for criteria B

• Seizures

OR

• Moderate to severe encephalopathy, consisting of:

• Altered state of consciousness (reduced or absent response to stimulation) AND

• Abnormal tone (focal or general hypotonia or flaccid) AND

• Abnormal primitive reflexes (weak or absent suck or Moro).

Cooling

1 hour of age – Passive cooling commenced

Cooling centre contacted. NTS contacted

Changed from axillary to rectal temperature monitoring

2 hours of age – rectal temp 35.1 3 hours of age – rectal temp 36.3

3 hours 40 mins – Transport team commenced active cooling using cold water gloves

7 hours of age – target rectal temp of 33-340C achieved

8 hours of age – arrived at Cooling Centre – active cooling using cooling mattress commenced

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Temperature chart for Registered cooled baby

Recorded rectal temperatures for baby 2087

Target Low

Target High

Ventilated on low pressures in air

No further seizures

Blood and CSF cultures negative

CFM trace on day 1 – moderately abnormal- no seizure activity

CFM normalised on day 2

Cranial ultrasound scan on day 1 – cerebral oedema

Progress at Cooling centre

Day 2 - Hypotension resolved

Day 3 - Extubated – self ventilating in air

Cooling continued for 72 hours then slow rewarming (0.50C per hour)

Day 4 – weak gag reflex present – started NG feeds

Day 5 – gag reflex improved – started breast feeds

Day 7 – full sucking feeds achieved - MRI scan normal

Day 8 – discharged home

Subsequent progress

Hypoxic Ischaemic Encephalopathy (H.I.E.) 1 – 3 per 1000 live full term births

15-20% die in the postnatal period

25% of survivors - severe & permanent neuropsychological sequelae, including mental retardation, visual dysfunction, increased hyperactivity, cerebral palsy & epilepsy.

Outcomes are devastating & permanent - major burden for the patient, family & society.

Urgent need to identify & develop therapeutic strategies to reduce brain injury in newborns with H.I.E

Neuropathology of H.I.E.

Hypoxia and/or ischaemia

Inadequate glucose & oxygen supply

Primary energy failure = Primary neuronal death

Reperfusion - Cytotoxic mechanisms

Further oxidative stress damage = Delayed neuronal death

Therapeutic Hypothermia

1hour 6 hours 5

days

11

CytotoxicMechanisms

Hypothermia

Delayed Neuronal

Death

Primary Death

Hypoxia-Ischaemia Asphyxia

How is hypothermia neuroprotective?

Decreases metabolic need

Maintains ATP, inhibits secondary energy failure

Stops or reduces many damaging processes

Reduced inflammatory responses

Seizures during hypothermia may be less damaging than during normothermia

TOBY Trial

Randomised to Intensive Care alone or Intensive care plus Total body cooling to 33-340C for 72 hours then slow rewarming by 0.50C per hour

Continuous rectal temperature monitoring

Primary outcome: Combined death & severe neurodevelopmental disability at 18 months

Secondary outcomes

TOBY Trial results

Outcome Hypothermia (%)

Normothermia (%) P value

Primary outcome:Combined death & severe neurodisability

45 53

(Note: predicted 70)

0.17

Secondary outcomes (significant)

Survival without neurologic abnormality

44 28 0.003

Cerebral palsy 28 41 0.03

•Improvements in other neurological outcomes in cooled group were not significant

•Adverse events were mostly minor and not associated with cooling

MRI scan results

TOBY trial: 131 scans from 325 infants available

MRI performed at 7-10 days

PPV = 84% non-cooled PPV = 86% for cooled

MRI is valid as a predictor after hypothermia treatment

Basal ganglia–thalamus pattern +/- cortical injury

Abnormal signal intensity within posterior limb of internal capsule (PLIC) predicts abnormal motor outcome Sensitivity = 0.9 Specificity = 1.0 (Rutherford et al Pediatrics 1998)

MRI after H.I.E.

de Vries L S , Jongmans M J Arch Dis Child Fetal Neonatal Ed 2010;95:F220-F224

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