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Therapeutic hypothermia forhypoxic-ischaemic
encephalopathy (HIE)
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Moderate or severe HIE
Complicates 1/1000 term live births:
Mortality: >25%
Major neurological sequelae: >25%
Cognitive impairments at school-age, evenwithout neuromotor deficitsAssociated behavioral and educational difficulties
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Basic sciences
Neuronal death occurs in 2 phases
Severe insult Immediate neuronal death cellular hypoxia
and primary energy failure
Delayed neuronal death occurs at least 6
hours later; allows a therapeutic window
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Basic sciences
Secondary phase accounts for a major
proportion of cell loss
Pathology hyperemia, cytotoxic oedema,mitochondrial failure, accumulation of
cytotoxins, apoptosis, nitric oxide synthesis,
free radical damage
Clinically encephalopathy, increased
seizures activity
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Mechanism of protection by
hypothermia
Survival of cells otherwise destined to die
through apoptosis
Reduced metabolic rate Reduced release of excitatory amino acids
(glutamate, dopamine)
Lower production of nitric oxide and free
radicals
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Methods of cooling newborns
Selective head cooling with mild systemic
hypothermia
Rationale: cool brain more than body Newborn brain produces 70% of total body heat
Minimized adverse effects of systemic cooling
Whole body hypothermia
Rationale: reduce systemic temperature to achievedeep brain cooling Core body temperature and deep brain temperature are similar
Mathematic modeling supports this
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Potential adverse effects of cooling
Heart
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Randomized control trial included
Term or near term newborns
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RCTs intervention
Therapeutic hypothermia (whole body or
selective head cooling)
Or no cooling (standard care)Active (device) and/or passive cooling
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RCTs outcome
Primary Death or long term (>18 months) major
neurodevelopmental disability Secondary
Death, neurodevelopmental disability, CP,neuromotor delay, intellectual impairment,
blindness, deafnessAdverse effects of cooling: CVS, FBC,
coagulation, hypoglycemia, renal, cultureproven sepsis
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Large published RCTs
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Large published RCTs
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Systemic reviews and meta-
analyses
7 reviews published
Cochrane review cooling of newborns with
HIE updated July 2007 Updated to include 12 RCTs and 1504 term
newborns with moderate or severe HIE 7 trials of whole body cooling 5 trials of selective head cooling
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Cochrane review summary
When used with strict protocols in tertiary NICUs,
therapeutic hypothermia is beneficial in to near-
term newborns with moderate or severe HIE Cooling reduces mortality and major disability
The benefits of cooling on survival and
neurodevelopment outweigh the short term adverse
effects (sinus bradycardia, thrombocytopenia) Whole body and selective head cooling both effective
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Delivery room resuscitationDelivery room resuscitation
Initiate resuscitation targeted oxygen concentration (21-30%)Initiate resuscitation targeted oxygen concentration (21-30%) Set pulse oximeter pre-ductal immediately after birth.Set pulse oximeter pre-ductal immediately after birth.
Keep SpO2 (90-93%) avoiding hyperoxemia.Keep SpO2 (90-93%) avoiding hyperoxemia.
Avoid hyperventilationAvoid hyperventilation
Set rectal probe for temperature and disconnect radiant heaterSet rectal probe for temperature and disconnect radiant heaterafter resuscitation is accomplished.after resuscitation is accomplished.
Keep rectal temperature between 33.5-34.0C.Keep rectal temperature between 33.5-34.0C.
Perform cord blood gases and repeat as needed in the first 60Perform cord blood gases and repeat as needed in the first 60
min.min. Never correct acid-base status with IVSBNever correct acid-base status with IVSB
Evaluate neurologic status using clinical signs (tone,Evaluate neurologic status using clinical signs (tone,
response, heart rate, breathing) and use aEEG if possible.response, heart rate, breathing) and use aEEG if possible.
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PRENATAL ALERT!
POSTNATAL ASSESSMENT
RESUSCITATION
CALL NEONATAL
TRANSPORT
DISCONNETC RADIANT
HEATERMONITOR
T, GLYCEMIA,
BG, ions,
Ca++, Mg++
AVOID!Hypoglycemia
Hypocalcemia
Hypomagnesemia
Hyperoxia
Hypocapnia
KEEP
TEMPERATURE
DURING TRANSPORT
INICIATE PROTOCOL
IN REFERRAL CENTER
AVOID!
Hypoglycemia
Hypocalcemia
Hypomagnesemia
Hyperoxia
Hypocapnia
Neurologic evaluation
aEEG
MRI
ULTRASOUND
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