Selective Head Cooling for Acute Hypoxic Ischemic Encephalopathy

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Selective Head Cooling for Acute Hypoxic
Ischemic Encephalopathy
Caroline O. Chua, MD Chief, Neonatal
Fellow Regional NICU Maria Fareri Childrens
Hospital at Westchester Medical Center
Lance A. Parton, MD Associate Director Regional
NICU Maria Fareri Childrens Hospital
at Westchester Medical Center
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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
• gt25 of survivors have permanent disabilities

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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
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Foundation Fact

• The ability to identify infants at highest risk
  for progressing to HIE is critical

Hypoxia Ischemia
Injury
No Injury
Resolve
Primary Energy Failure
Secondary Energy Failure
Resolve
Injury
Latent phase
Potential Therapeutic Window
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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

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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).

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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

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Cool-Cap Trial

• Randomized, controlled, masked, multi-center
  (25), international trial (n234)
• 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 365663-670
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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 365663-670
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Cool-Cap Trial Findings Safety

• No statistical difference in mortality _at_ 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 365663-670
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Predictive Calculations of Efficacy for
Hypothermia to treat Neonatal HIEPerlman 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 15-18 babies would prevent 3
  from death or moderate to severe disability
  without any significant adverse effects

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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
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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 lt7.00 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)

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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

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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
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Contraindications

• Imperforate anus
• Evidence of head trauma or skull fracture causing
  major intracranial hemorrhage
• Birth weight lt 1,800g

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Practical Tips for NBN/NICUsTransferring
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 34 - 35? C
• IV Glucose, ASAP

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Practical Tips for NBN/NICUsTransferring
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 866 468 - 6962
• Dont wait for lines, images, labs
• Discuss cooling but make no promises regarding
  use of cooling and outcome

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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
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Maria Fareri Childrens Hospital
E C M O
Call (24/7) (866) WMC-PEDS or [phone]
Newborn Infant Child Young Adult
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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/Respirat
ory Failure Trauma Smoke Inhalation Near Drowning
ECMO Team
Cardiovascular Surgery
Pediatric Surgery
Pediatric Intensivists
Neonatal Intensivists
Pediatric Cardiology
Maternal-Fetal Medicine
Pediatric Pulmonary
Perfusion Team
ECMO Nurses
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Possible Brain Insult At Birth?
Call (24/7) (866) WMC-PEDS or [phone]
A.S.A.P. Cool within 6 hours of birth