Dr F. Nakwa

Chris Hani Baragwanath Academic Hospital and

the University of the Witwatersrand

Overview What is known?

- studies

- outcomes at 18 months and 6-7 years

What is new?

- adjuvant therapies with hypothermia

Where are we now?

- Chris Hani Baragwanath experience

8 randomised trials were included

638 term infants with moderate to severe encephalopathy and evidence of intrapartum asphyxia

Hypothermia resulted in statistically significant and clinically important reduction in the combined outcome of mortality and major neurodevelopmental disability to 18 months of age

NNT =7

Borderline increase in the need for inotropic support and significant increase in thrombocytopaenia

Cochrane review

Adverse effects in hypothermia

Death and neurodevelopmentaloutcomes

Long term Outcomes (6-7 years) NICHD – death or disability was decreased (41% vs 60% P=0.03)

- survivors – IQ < 70 ( 27% vs 33%) and CP in 17% vs 29% (P=NS)

Toby – 52% hypothermia patients vs 39% control groupchildren survived with an IQ>85 (RR>1.31, P=0.04)

- number of children that died were 29% vs 30% - 45% vs 28 % survived without neurological abnormalities (RR 1.61, CI - 1.15-2.22)- a decrease in the rate of CP and moderate to severe disability

CoolCap – status at 18 months was associated with status at 6-7 years (p<0.001)

- CP diagnosed at 18 months was highly associated with WeeFim mobility scores at 7-8 years

Asphyxiated babies would not qualify for ventilation

Some studies include

Passive cooling/accidental cooling

Gel packs

Servocontrolled cooling fan

use of water bottles

These studies demonstrate that a cost effective feasible method of cooling can be achieved

Efficacy still needs to be demonstrated

Cooling in resource poor settings

AEDS – Phenobarbital, Topiramate and Levetiracetam Xenon N-acetylcysteine (NAC) EPO Melatonin Cannabinoids Pomegranate juice Trapidil Morphine Allopurinol VEGF/HIF Magnesium sulphate

Synergistic therapies with hypothermia

Chris Hani Baragwanath Experience

Where are we now?

RESULTS

Demographics Mean (SD)

n=98

Mom’s Age (years) 24.3 (5.6)

Parity 1 (0-4)*

Mode Of Delivery - NVD- Caesarian Section

56 (57)27 (28)

HIV positive 18 (18)

* Median (IQ Ranges)

98 patients were cooled

Demographics of infants that were cooled

Demographics Mean (SD)

n=98

Gestational Age (wks) 39.1 (1.5)

Birth weight (g) 3182.7 (440.8)

Gender - Males- Females

55 (56) 43 (44)

98 patients were cooled

Criteria Number (%)

Sentinel event 48 (49)

Apgars <5 at 10 min 25 (26)

Resuscitation at 10 min 59(60)

Ph <7.0Base Deficit >16 mmol/l

65 (66)81 (83)

Encephalopathy - HIE 1- HIE 2- HIE 3

2 (2)81 (83)15 (15)

aEEG pattern

Continuous normal voltage

Discontinuous normal voltage

Burst Suppression

Continuous Low Voltage

Flat Trace

58

4 (7)

26 (45)

10 (17)

16 (28)

2 (3)

Number of patients who fulfilled criteria for cooling

Platelet and Coagulation Abnormalities During Cooling

Characteristic Mean (SD)

Platelets before hypothermia (X109/l)- <150 X109/l (n=85)

220.4 (172.7)19 (22)*

Platelets during cooling (X109/l) - <150 X 109/l (n=54)

167.8 (69.9)22 (41)*

INR- >1.5 IU/l (n=35)

1.6 (1.3)3 (9)*

Ventilated during hypothermia 7 (7)*

*n(%)

Outcomes

Number (%)

Died 15 (15)

Griffiths Score at 12- 18 months (n=20)- <85- 85-100- >100

5 (25)12 (60)3 (15)

Conclusion

Therapeutic Hypothermia is feasible within a South African setting outside of an NICU setting.

Resources remain a major factor in managing these patients according to the protocol

Long-term follow-up is important to fully assess the effectiveness of induced hypothermia

Exciting times for neuroprotection

Questions as to

When is the optimal time and at what dosage to administer some of the synergistic therapies?

Need to consider risk / benefit ratio?

Cost may be prohibitive!

Consider effects long term ?

In Summary

Thank you