1. Hypoxic Ischemic Encephalopathy Current trends in management
Dr.Arun Ramachandran
Consultant Neonatologist
Singleton Hospital

2. Impact of HIE
Perinatal asphyxia causes moderate to severe encephalopathy in 2/1000 births (may cause 30% of CP)
Significant cost to family and society
Significant medico legal implications

3. Pathophysiology of hypoxia
Primary cerebral energy failure ( upto 6 hrs)
Secondary cerebral energy failure ( 6-72hrs)
- free radicals, ↑Ca, inflammation
Total body Cooling
- ↓ cerebral oedema, ICP
- ↓ apoptosis

4. Meta analysis 2006

5. TOBY trial Babies > 36 weeks Criteria A Criteria B
APGAR ≤ 5 at 10 min Resuscitation needed at 10 min
pH < 7 within first 1 hr - Base deficit > 16 mmol/L in 1 hour
Criteria B
Mod/severe encephalopathy ( altered consciousness +)
Hypotonia Abnormal reflexes - Seizures - Poor suck
Criteria C - Abnormal CFM ( minimum 30 min)

6. TOBY

7. Results Outcome Cooled Non Cooled P value RR( 95% CI)
Combined death and severe disability
74/163 (45%)
86/162 (53%)
0.17
( )
Death
42/163 (26%)
44/162
(27%)
0.78
0.95
( )
Survival without neurological abnormality
71/163 (44%)
44/162 (28%)
0.003
1.57
( )
Cerebral palsy
33/120 (28%)
48/117 (41%)
0.03
( )
MDI (>85)
(BSID 2)
81/115
(70%)
60/110
(55%)
0.01
1.29
( )

8. aEEG Vs EEG EEG - Difficult to record and interpret in NICU
- Large amount of data.
aEEG
- Single EEG lead ( 3 wires - 2 active and 1 noise suppression. Biparietal / bifrontal)
- Monitor global electro cortical activity
- Filtering ( < 2Hz and > 15Hz)
- Compressed and slow, show trends

9. Normal Sleep/wake cycling Upper margin >10 mV
Lower margin > 5 mV
Limited variability in EEG

10. Moderately abnormal No sleep wake cycle Upper margin >10
Lower margin <5
Increased variability in EEG

11. Severely abnormal No sleep/wake cycle Upper margin < 10
Greatly reduced variability in EEG
Note low voltage bursts on EEG

12. Complications with cooling
Impaired coagulation
Thrombocytopenia
Subcutaneous fat necrosis
Hypercalcemia
PPHN
Hypotention
Rhythm anomalies

13. Poor prognostic factors in HIE
Prolonged asphyxia
Sarnat stage 3
Early and difficult to control seizures
Persistently absent reflexes
Persistently abnormal CFM
Burst suppression activity in EEG
Basal ganglia changes in MRI

14. T1 weighted image in a 5 day old term baby with HIE showing basal ganglia changes (arrowheads) and occipital changes ( white arrows). Black arrows show internal capsule.

15. Prognostication using aEEG
Good correlation noted between CFM trace improving in 24 hours and better clinical outcome.
When abnormal physical exam is combined with abnormal aEEG the negative predictive value for CP is 92% and positive predictive value is 85%.
Paediatrics (2003) 111 (351-57)

16. New agents to combine with cooling to enhance neuroprotection
Xenon
Melatonin
Allopurinol
Erythropoietin
N-acetyl cysteine

17. Summary
Total body cooling is now standard of care in term or near term ( >36 weeks) babies exposed to perinatal asphyxia provided they fit the criteria.
Babies with moderate HIE will benefit significantly.
Newer agents likely to further improve outcomes.

18. Further reading TOBY trial full version
Azzopardi.D et al.Moderate hypothermia to treat perinatal asphyxial encephalopathy N Engl J Med 2009;361: