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

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

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

Meta analysis 2006

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)

TOBY

Results Outcome Cooled Non Cooled P value RR( 95% CI) Combined death and severe disability 74/163 (45%) 86/162 (53%) 0.17 0.86 (0.68-1.07) Death 42/163 (26%) 44/162 (27%) 0.78 0.95 (0.66-1.36) Survival without neurological abnormality 71/163 (44%) 44/162 (28%) 0.003 1.57 (1.16-2.12) Cerebral palsy 33/120 (28%) 48/117 (41%) 0.03 0.67 (0.47-0.96) MDI (>85) (BSID 2) 81/115 (70%) 60/110 (55%) 0.01 1.29 (1.05-1.59)

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

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

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

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

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

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

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.

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)

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

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.

Further reading TOBY trial full version http://www.nejm.org/doi/full/10.1056/NEJMoa0900854#t=articleResults Azzopardi.D et al.Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009;361:1349-58.