1. Selective Head Cooling for Acute Hypoxic Ischemic Encephalopathy
Caroline O. Chua, MD
Chief, Neonatal Fellow
Regional NICU
Maria Fareri Children’s Hospital at
Westchester Medical Center
Lance A. Parton, MD
Associate Director
Regional NICU
Maria Fareri Children’s Hospital at
Westchester Medical Center 1

2. Hypoxic Ischemic Encephalopathy
One of the leading causes of severe long-term neurologic deficits in infants and children (cerebral palsy)
Incidence of 2-3 per 1,000 term live births
Etiologies: abruptio (25%), uterine rupture, prepartum hemorrhage, dystocia, prolapsed cord, placental insufficiency, twins, extramural deliveries
Mortality is 15-20%
>25% of survivors have permanent disabilities

3. HYPOXIA - ISCHEMIA Anaerobic Glycolysis ATP Adenosine Lactate
Glutamate
Hypothermia
NMDA Receptor
NMDA
receptor blocker
Hypoxanthine
Intracellular Ca+
Ca+ channel blocker
Xanthine
oxidase
inhibitors
Activates NOS
Activates Lipases
Activates proteases
Activates nuclease
Cyclooxygenase
inhibitors
Xanthine NO O2
Free Fatty Acids
Disruption of
cytoskeleton
Damage to DNA
Superoxide
radicals O2
Free Radicals
Free radical
scavengers
Free Radicals
Free Radicals
NEURONAL CELL DEATH

4. Potential Therapeutic Window
Foundation Fact
The ability to identify infants at highest risk for progressing to HIE is critical
Hypoxia
Ischemia
Injury
No Injury
Primary
Energy
Failure
Resolve
Secondary
Energy
Failure
Resolve
Injury
Latent phase
Potential Therapeutic Window

5. Hypothermic Treatment of HIE
2 phases to injury
Initial insult at birth
Secondary failure starts within 6-24 hours of birth
Therapeutic window of 6 hours

6. Head Cooling: How It Works
Reduces cellular metabolic demands, delaying depolarization
Reduces release of excitatory amino acids (e.g. glutamate) and free radicals
Reduces intracellular reactions of excitatory amino acids
Reduces release of pro-inflammatory cytokines, microglial activation, and neutrophil recruitment.
Suppression of apoptotic biochemical pathways (e.g. caspase activity).

7. Selective Head Cooling
Technique
Head is fitted with cooling cap
Body is warmed with radiant warmer
Advantages
Brain is cooler than the rest of the body
Fewer side effects

8. Cool-Cap Trial
Randomized, controlled, masked, multi-center (25), international trial (n=234)
Protocol:
Standard of care or rectal temp of 34 to 35C for 72 hours using cool cap
Passively rewarmed for 4 h (at ~0.5C/h)
Primary end point: death or severe neurodevelopmental disability at 18 months
Confirmed Cool-Cap System is Effective & Safe
Gluckman et al. Lancet. 2005; 365:

9. Cool-Cap Trial Findings – Efficacy
Statistically significant treatment effect for moderately abnormal aEEG (p = 0.04)
Moderate encephalopathy: 1 out of 6 is shifted from unfavorable to favorable outcome
Severe encephalopathy: no effect on death and severe disability
Gluckman et al. Lancet. 2005; 365:

10. Cool-Cap Trial Findings – Safety
No statistical difference in 18 mos
33% (36/108) cooled vs. 38% (42/110) control
No difference in rates of any Serious Adverse Events
Scalp edema in some – resolved quickly
Conclusion – Cooling is safe when the Cool-Cap clinical trial protocol is followed
Gluckman et al. Lancet. 2005; 365:

11. Predictive Calculations of Efficacy for Hypothermia to treat Neonatal HIE Perlman and Shah, 2008
15-18 babies are born daily in the U.S. with moderate to severe HIE
10-12, of the above, die or develop moderate to severe disability
Hypothermia to all babies would prevent 3 from death or moderate to severe disability without any significant adverse effects

12. Selecting Infants for Treatment Indications For Use
The Olympic Cool-Cap System is indicated for use in full-term infants with clinical evidence of moderate to severe hypoxic-ischemic encephalopathy (HIE)
as defined by criteria A, B and C
The Cool-Cap System provides selective head cooling with mild systemic hypothermia to prevent or reduce the severity of neurological injury associated with HIE
* Cool as early as possible and within 6 hours of birth

13. Criteria A
Infant at ≥ 36w gestational age and at least one of the following
Apgar score ≤ 5 at 10 min
Continued need for resuscitation, including endotracheal or mask ventilation, at 10 min after birth
Acidosis defined as either umbilical cord pH or any arterial pH <7.00 within 60 min of birth
Base deficit ≥ 16 mmol/L in umbilical cord blood sample or any blood sample within 60 min of birth (arterial or venous blood)

14. Criteria B
Infant with moderate to severe encephalopathy consisting of altered state of consciousness (as shown by lethargy, stupor, or coma) and at least one of the following
Hypotonia
Abnormal reflexes, including oculomotor or pupillary abnormalities
Absent or weak suck
Clinical seizures

15. Criteria C
Infant has an amplitude-integrated encephalogram / cerebral function monitor (aEEG/CFM) recording of at least 20 minutes duration that shows either moderately/severely abnormal aEEG background activity or seizures
* Use Olympic CFM 6000

16. Contraindications Imperforate anus
Evidence of head trauma or skull fracture causing major intracranial hemorrhage
Birth weight < 1,800g

17. Practical Tips for NBN/NICUs Transferring Newborns for Cooling
Educate staff, especially “off-hours” personnel to recognize eligibility for cooling
Provide cardiorespiratory stability
Avoid hyperthermia
Turn off radiant warmer
Maintain Rectal Temperature:  C
IV Glucose, ASAP

18. Practical Tips for NBN/NICUs Transferring Newborns for Cooling
Cord Gas/ ABG/ VBG; birth weight and head circumference
Use double lumen UV lines (preferably)
Initiate transport
Call WMC-Transport team ASAP
866 - WMC PEDS or 866 –
Don’t wait for lines, images, labs
Discuss cooling but make no promises regarding: use of cooling and outcome

19. Possible Brain Insult At Birth?
Call (24/7):
(866) WMC-PEDS
MFCH is the only NICU in the Hudson Valley
Employing the Head-Cooling Cool Cap®
for patients who may have Perinatal Asphyxia
Cool Cap ® in Place
Cool Cap® Monitor 19

20. Maria Fareri Children’s Hospital
E C M O
Extra
Corporeal
Membrane
Oxygenation
Call (24/7):
(866) WMC-PEDS or
(866)
Newborn
Infant
Child
Young Adult 20

21. Extra Corporeal Membrane Oxygenation
Heart-Lung Bypass
Consider for the Following Conditions:
Neonatal
Pediatric
Congenital Diaphragmatic Hernia
Meconium Aspiration Syndrome
Persistent Pulmonary Hypertension
Respiratory Distress Syndrome
Pneumonia
Sepsis
Congenital Heart Disease
Sepsis
Pneumonia/Respiratory Failure
Trauma
Smoke Inhalation
Near Drowning
ECMO
Team
Pediatric Surgery
Cardiovascular Surgery
Pediatric Intensivists
Neonatal Intensivists
Pediatric Cardiology
Maternal-Fetal Medicine
Pediatric Pulmonary
ECMO Nurses
Perfusion Team 21

22. Possible Brain Insult At Birth?
Call (24/7):
(866) WMC-PEDS or
(866)
A.S.A.P.
Cool within 6 hours of birth 22