Hypothermia Therapy for Hypoxic Ischemic Encephalopathy

By Ben Savage

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

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)

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.

Progression of illness (GUNN, 2007)

Stages Of HIE (Anon(a), 2009)

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

Effects of HIE Neurodevelopment problems and

disability Cerebral palsy

Seizures

Death

Hypothermia Therapy

(Anon (b), 2009)

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

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

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

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

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)

(Jacobs et al 2007)

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

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

TOBY trial 2009 (Azzopardi et al, 2009)

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

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

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

Reflection Why I picked this topic

What have I learnt

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

Thank you for listeningAny Questions