Transcript Regional QA Meeting May 11, 2005

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
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
HYPOXIA - ISCHEMIA
Anaerobic Glycolysis
ATP
Adenosine
Lactate
Glutamate
NMDA Receptor
NMDA
receptor blocker
Hypothermia
Hypoxanthine
Xanthine
oxidase
inhibitors
Intracellular Ca+ Ca+ channel blocker
Activates Lipases
Xanthine
O2
Free Radicals
Cyclooxygenase
inhibitors
Free Fatty Acids
NO
Superoxide
radicals
O2
Free Radicals
Activates NOS
Free radical
scavengers
NEURONAL CELL DEATH
Free Radicals
Activates proteases
Activates nuclease
Disruption of
cytoskeleton
Damage to DNA
Foundation Fact

The ability to identify infants at highest risk for
progressing to HIE is critical
Hypoxia
Ischemia
Primary
Energy
Failure
Injury
No Injury
Resolve
Resolve
Secondary
Energy
Failure
Latent phase
Potential Therapeutic Window
Injury
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
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).
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
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; 365:663-670
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; 365:663-670
Cool-Cap Trial Findings – Safety

No statistical difference in mortality @ 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; 365:663-670
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 15-18 babies would prevent 3
from death or moderate to severe disability
without any significant adverse effects
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
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)
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
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
Contraindications

Imperforate anus

Evidence of head trauma or skull fracture
causing major intracranial hemorrhage

Birth weight < 1,800g
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: 34 - 35 C

IV Glucose, ASAP
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 – 468 - 6962
 Don’t wait for lines, images, labs

Discuss cooling but make no promises regarding: use of
cooling and outcome
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® Monitor
Cool Cap ® in Place
Maria Fareri Children’s Hospital
E C M O
Extra
Newborn
Infant
Child
Young Adult
Corporeal
Membrane
Oxygenation
Call (24/7):
(866) WMC-PEDS
or
(866) 468-6962
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
Pediatric Surgery
Neonatal Intensivists
ECMO
Team
Congenital Heart Disease
Sepsis
Pneumonia/Respiratory Failure
Trauma
Smoke Inhalation
Near Drowning
Cardiovascular Surgery
Pediatric Intensivists
Pediatric Cardiology
Maternal-Fetal Medicine
ECMO Nurses
Pediatric Pulmonary
Perfusion Team
Call (24/7):
(866) WMC-PEDS
or
(866) 468-6962
A.S.A.P.
Cool within 6 hours of birth