dr julia uffindell consultant neonatologist. cooling 'cure' averts infant brain damage...
TRANSCRIPT
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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Hours from start of cooling
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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