1. Hypothermia Therapy for Hypoxic
Ischemic Encephalopathy
By Ben Savage

2. Objectives
 What is Hypoxic Ischemic Encephalopathy
 Stages Of HIE
 Antepartum Risk factors
 Effects of HIE
 Hypothermia Therapy
 Methods
 Evidence
 The Future

3. What is Hypoxic Ischemic
Encephalopathy (HIE)
 Condition that can occur in newborn
 Is caused by hypoperfusion and therefore
hypoxia in the brain (Menezes et al, 2006)
 Lack of oxygen leads to damage to the cell
and free radical formation (Shalak et al, 2004)
 Cell function is restored but cerebral energy
failure recurs after 6-48 hrs (Shalak et al, 2004)

4. What is Hypoxic Ischemic
Encephalopathy (HIE)
 Mitochondrial dysfunction, apoptosis and
cytotoxic oedema cause this delayed damage
(Shalak et al, 2004)
 The most active cells in the brain are the
most affected. In term babies this is in the
grey matter (Triulzi et al 2006)
 It is associated with a high level of morbidity
and mortality.

5. Progression of illness (GUNN, 2007)

6. Stages Of HIE (Anon(a), 2009)

7. Antepartum Risk factors (Menezes et al, 2006)
 Maternal diabetes
 Pregnancy-induced hypertension
 IUGR
 Maternal hypotension/shock
 Severe bleeding
 Placental insufficiency
 Cord prolapse
 Abruptio placentae
 Dystocia

8. Effects of HIE
 Neurodevelopment problems and
disability
 Cerebral palsy
 Seizures
 Death

9. Hypothermia Therapy

10. (Anon (b), 2009)

11. Hypothermia (Shalak et al, 2004)
 The hypothermia treatment is targeted at
reducing the damage caused by the second
stage
 It reduces energy requirements and therefore
the levels of free radicals
 Preserves antioxidants
 Inhibits apoptosis

12. Entry Criteria (Azzopardi et al, 2009)
 36wks or greater gestation, age >6hrs
 Any of:
 APGAR 10mins 5 or less
 Continued need for resuscitation 10mins
 Within 60mins birth acidosis,
 pH <7.00/ base deficit >16mmol/L
 Moderate to severe encephalopathy
 Abnormal background activity of at least 30mins or seizures on
aEEG
 Exclusion if there is a major congenital abnormality that requires
immediate surgical correction

13. Methods
 To cool the babies there
are two options
 Cool Cap – the only part of
the body actively cooled is
the head
 Total body cooling

14. Method (Azzopardi et al 2009)
 Treatment needs to begin before 6 hours
after birth, before the 2nd
stage is entered
 Baby is rapidly cooled to 33-34°C and
continuously monitored
 They are kept cooled for 72 hours
 Gradually re-warmed at no rate greater than
0.5°C per hour, to a maximum of 37±0.2°C

15. Evidence Base
 There have been several trials and a
cochrane review looking at the
effectiveness of treatment.
 The cochrane review looked at various
outcomes. One of these was the
difference between the two cooling
methods. (Jacobs et al 2007)

17. (Jacobs et al 2007)

18. Cochrane Review (Jacobs et al 2007)
 This review showed:
 Selective head cooling has no statistically significant effect
on mortality or severe disability
 Whole body cooling causes a statistically significant
reduction in mortality and severe disability.
 Hypothermia therapy reduces mortality and major disability

19. TOBY trial 2009 (Azzopardi et al, 2009)
 Multi centre RCT.
 325 infants randomised to intensive care with
cooling or intensive care alone
 Babies cooled to 33-34 °C for 72hrs then
slowly re-warmed

20. TOBY trial 2009 (Azzopardi et al, 2009)

21. TOBY trial 2009 (Azzopardi et al, 2009)
 Conclusion:
 No significantly reduction in the combined
rate of death or severe disability
 Improved neurological outcomes in
survivors

22. Summary
 HIE is a serious condition that can have
implications for the survival and development
of the child
 Hypothermia therapy used to reduce effect of
2nd
phase cell damage
 Treatment using total body cooling is most
effective

23. The Future
 Is this method cost effective
 TOBY study current looking at this.
 National guidelines, only currently
consultation document
 NICE (2010)
 Whether this would be suitable for perterm or
surgical babies

24. Reflection
 Why I picked this topic
 What have I learnt

25. References
 Anon(a) http://inicq.org/enicq/help/Appendix_E/Modified_SARNAT_Stage_Prior_ to_Cooling.htm, 10/11/09
 Anon (b) http://img.medscape.com/pi/emed/ckb/pediatrics_cardiac/1331339-1331345-973501-1484988.jpg
10/11/09
 Denis V. Azzopardi et al, Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy, New
England Journal of Medicine October, 2009, 361;14
 ALISTAIR JAN GUNN & PETER D. GLUCKMAN, Head Cooling for Neonatal Encephalopathy: The State of
the ArtCLINICAL OBSTETRICS AND GYNECOLOGY, Volume 50, Number 3, 636–651, 2007
 Jacobs SE et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database of
Systematic Reviews 2007, Issue 4. Art. No.: CD003311. DOI: 10.1002/14651858.CD003311.pub2.
 Marcio Sotero de Menezes et al http://emedicine.medscape.com/article/1183351-overview April 2006
 Lina Shalak et al, Hypoxic–ischemic brain injury in the term infant-current concepts, Early Human
Development 80 (2004) 125– 141
 Triulzi et al, Patterns of damage in the mature neonatal brain Pediatric Radiology [0301-0449] Triulzi
yr:2006 vol:36 iss:7 pg:608 -620

26. Thank you for listening
Any Questions