ScreeningandIdenti-icationofNewbornsEligible
forTherapeuticHypothermia
KrisaVanMeurs,M.D.
RosemarieHessProfessorofNeonataland
DevelopmentalMedicine
MedicalDirector,NeuroNICU
SoniaBonifacio,M.D.
AssociateProfessorNeonataland
DevelopmentalMedicine
AssociateMedicalDirector,NeuroNICU
August15,2016
Causesofneonatalmortality
Congenital
7%
Other
7%
Asphyxia
23%
Sepsis/
pneumonia
26%
Tetanus
7%
Diarrhea
3%
Preterm
27%
LawnJE,etal.IntlJEpidemiol(2006)
IncidenceandoutcomeofHIE
§  Incidencerangesfrom1to8per1,000birthsdependingon
definiZonused
§  Moderateencephalopathyisassociatedwith10%riskofdeath
and30%riskofdisability
§  Severeencephalopathyisassociatedwith60%riskofdeath
andmostsurvivorswillbedisabled
Kurinczuk JJ et al., Early Human Dev (2010)
Tin TW et al., Eur J Paediatr Neurol (2009)
MechanismofbraininjuryduringHIE
Hypoxia-Ischemia
Recovery
PrimaryEnergy
Failure
BrainInjury
LatentPeriod
ThetherapeuZcwindowis~6hours,theduraZon
ofthelatentphasebetweenprimaryandsecondary
energyfailure.
SecondaryEnergy
Failure
BrainInjury
Hypothermia probably impacts many of these pathways
Drury P, Bennet L, Gunn AJ Mechanisms of hypothermic neuroprotection.
Semin Fetal Neo Med 2010.
Coolingtrials
Trial(PublicaCondate)
N
GA
(wks)
Mode
Transport
Cooling
Tempgoal
&site
Eicher(2005)
65
≥35
Wholebody
Yes
CoolCap(2005)
234
≥36
SelecZvehead
No
Shankaran(2005)
208
≥36
Wholebody
No
TOBY(2009)
325
≥36
Wholebody
Yes
Neo.nEURO(2010)
125
≥36
Wholebody
No
Zhou(2010)
194
≥37
SelecZvehead
No
34°±0.2
nasopharyngeal
ICE(2011)
221
≥35
Wholebody
Yes
33-34°C
rectal
33°±0.5
rectal
34-35°C
rectal
33.5°C
esophageal
33.5°C
rectal
33-34°C
rectal
Meta-analysisofhypothermiaRCTs
Conclusion: Hypothermiaimprovessurvivalandneurodevelopmentinnewborns
withmoderatetosevereHIE.RiskraZois0.76withconfidence
interval0.69-0.84.Numberneedtotreat=7.
TaginMAetal.,ArchPediatrAdolescMed(2012)
RecommendationsforuseofHypothermia
Hypothermiaat<6hoursdecreasesmortalityandseveredisabilitywith
minimalsideeffectsandwithoutincreasingdisability
§  SevereHIElesslikelybenefit
§  Nodifferenceinoutcomebetweenheadandbodycooling
PeliowskiA,etal.PaediatrChildHealth(2012)
AAPCommiheeonFetusandNewborn.Pediatrics(2014)
TherapeuZchypothermiaisaneffecZvetherapy,treatedinfantsshould
meettrialentrycriteria,andeducaZonofreferringhospitalsregarding
idenZficaZonofhypothermiacandidatesiscriZcal.
NewbornswithmoderatetosevereHIEshouldbeofferedhypothermia
§  Treatmentshouldbeconsistentwithtrialprotocols.
PerlmanJM,etal.Circula:on(2010)ILCORstatement
Birth&
0&(&10&mins&
10&(&60&mins&
60&(&120&mins&
CPQCCToolKitScreeningCriteria
≥36$weeks$
≤6$hours$
Apgar$≤6$$
at$10$min$$
History$of$acute$
perinatal$event$
! 
! 
! 
! 
Con?nued$PPV$$
at$10$min$or$CPR$$
Cord$blood$gas$$
pH$≤7.15$or$BE$≤J10$
Request$cord$blood$gas$
Obtain$blood$gas$at$≤1$hour$of$age$
Perform$targeted$neurologic$exam$using$chart$below$
Observe$for$seizures$
Call$LPCH$APending$Neonatologist$
$at$(650)$723J7342$to$discuss$the$need$
for$transfer$and$cooling$
download \Toolkit @ www.cpqcc.org
NICHDNeonatalNetwork
Eligibilitycriteriafortherapeutichypothermia
Twostepprocessforinfants≥36weeksand≤6hoursofage
Ifbloodgasisavailable
Ifbloodgasisnotavailable,
Infantshouldhave:
Infantshouldhavehistoryofacute
perinataleventand
§  Cordorfirstpostnatalbloodgas
within1hourwithpH≤7.0
or
§  Basedeficitoncordgasorfirst
postnatalbloodgaswithin1hour
at≥16mEq/L
orpH7.01-7.15
orBasedeficit10-15.9mEq/L
§  Apgarscore≤5at10minutes
or
§  ConZnuedneedforvenZlaZonat
10minutes
ShankaranS,etal.NEJM(2005)
ShankaranSetal.,NEnglJMed(2005)
Themodi-iedSarnatexam
•  Sixcategories(levelofconsciousness,
spontaneousacZvity,posture,tone,primiZve
reflexes,andautonomicsystem)
•  Tobeeligibleforhypothermia:
–  3of6categorieshavetobecodedaseither
moderateorsevereencephalopathy
MODIFIEDSARNATEXAM
CATEGORY
MODERATE HIE
SEVERE HIE
1. Level of consciousness
2 = Lethargic
3 = Stupor/coma
2. Spontaneous Activity
2 = Decreased activity
3 = No activity
3. Posture
2 = Distal flexion, complete extension
3 = Decerebrate
4. Tone
2a = Hypotonia (focal or general)
3a = Flaccid
5. Primitive Reflexes
Suck
Moro
2 = Weak or has bite
2 = Incomplete
3 = Absent
3 = Absent
2 = Constricted
2 = Bradycardia
2 = Periodic breathing
3 = Deviation/dilated/ or
nonreactive to light
3 = Variable HR
3a = on vent with
spontaneous respirations
3b = on vent without
spontaneous breaths
6. Autonomic System
Pupils
Heart Rate
Respiration
Sarnat&Sarnat-1976
•  21paZentsevaluatedevery12-24hoursdailyfor6
days,theneveryotherdayZlldischarge
•  Follow-upat3,6,9,12months(only2seenat1year
ofage)
•  StageofencephalopathyisNOTstaZc
•  EvoluZonoverfirsthourstodays
•  Stage1à2à3
•  Serialexamsareimportantifonthefence
•  Onceyoumeetcriteriayoudonotreassesswith
thoughtofrecoveryandnotcoolingthepaZent
Neurologicexamsafterbirth
Challengingassessments
•  Transienteffectsofdelivery,anesthesia,analgesia
•  ExaminaZonfindingsmayimproveorgetworse
SeverityandZmingofhypoxia-ischemia
Compensatoryhemodynamicchanges
EndogenousCNSprotecZvemechanisms
•  AssociatedcondiZons:Respiratorydistress
•  Simultaneousmixofneurologicalfindings
Componentsofnone/mild,moderateorsevere
encephalopathy
Spontaneousactivity
•  EvaluateSpontaneousacZvity
–  Code1ifinfantisacZve
–  Code2ifacZvityisdecreased
–  Code3ifnoacZvity
Ifinfantissedatedclinicaljudgmenthastobeused
todecidewhethertheexaminaZonisreliable.
Paralysiswillprecludeameaningfulexam
Thetransportteamandclinicalteamshouldbe
awareofneedforthisexamwithoutsedaZon
Posture
•  Observeinfantinawakestate;assesslower
extremity
–  Code1ifinfantismovingaroundanddoesnot
maintainoneposture,shouldhaveflexionoflower
extremityathipand/orknees
–  Code2ifstrongdistalflexion,completeextensionor
“frog-legged”posiZon
–  Code3ifdecerebratewithorwithoutsZmulaZon
Levelofconsciousness
–  Code1ifinfantarousestowakefulness,responds
appropriatelyandpromptlytoexternalsZmuli,or
appearshyperalertorinconsolable/irritable
–  Code2iflethargic:delayedbutcompleteresponseto
externalsZmuli(startwithmildsZmulifirstthen
proceedtomorenoxioussZmuli)
–  Code3ifstupor/coma:infantisnotarousableandis
non-responsivetoexternalsZmuli;mayhavea
delayedbutincompleteresponsetosZmuli
LOC:maybethedecidingfactortoassignHIEstage
Tone
•  Responsetopassivemovement:assesslowerextremity
–  Code1ifthereisnormalresistance
–  Code2:
–  2aifhypotonicorfloppyeitherfocalorgeneralized
–  Code3:
–  3aifflaccid(likearagdoll)
EvaluateextremiZes,trunkandnecktoneandmakeclinicaljudgment
oftonebasedontoneintheseareas.IfresponsesdifferinmulZple
areas,basecodeonthelowerextremity
Ifvaryingtone,codethepredominantstate
PrimitiveRe-lexes
SuckandMoro
Suck
-Code1iftheinfantvigorouslysucksthe
examinersfingerortheendotrachealtube
– Code2ifsuckisweakorifinfantbites
– Code3ifsuckisabsent
Moro
–  Code1ifMoroisnormalwithextensionoflimbs
followedbyflexionwithsZmulus(gentlyraising
andloweringthehead)
–  Code2ifincomplete
–  Code3ifabsent
Ifneonatehasfractureofclavicleorbrachialplexusinjury,
evaluateotherextremity
Morohastobedonebygentlyraisingandloweringthehead
wheninfantisintubated
AutonomicSystem
Pupils,HeartRateandRespiraZon
ANS–Pupils
– Code1ifnormalinsizeandreacZvetolight
– Code2ifconstrictedandreacZngtolight
– Code3ifskewdeviaZonofeyes,pupilsare
dilatedornon-reacZvetolight
•  Ifpupilsasymmetric,assign3
Pupilsaredifficulttoassessinthenewborninfantwith
edemaofeyelids---youwillneedtogentlyseparate
theeyelidswhileasecondpersonshineslight
ANS–Heartrate
•  HR
–  Code1if>100perminconsistentlyortachycardia
–  Code2ifbradycardia(<100/min)withonly
occasionalincreasesto>120/min
–  Code3ifheartrateisnotconstantandvaries
widelybetween<100and>120
Heartrateshouldbeevaluatedbasedon
documentedrateoverthepreviousmin/hrs
DonotcodeheartrateifcoolinghasbeeniniZated
ANS-Respiration
–  Code1ifbreathingspontaneously
–  Code2ifperiodicbreathing
–  Code3ifapneaorrequiringvenZlatorsupport:
3a,ifspontaneousbreathsabovethevenZlator
3b,ifnospontaneousbreathsabovethevent
Anintubatedinfantwithspontaneousbreathswould
sZllbecodedas3asitcannotbeascertainedifthe
spontaneousbreathscansustainrespiraZonwithout
venZlatorsupport
EpicSarnatdotphrase
TABLE 2.
Classification of the Neurologic Examination Findings
CATEGORY
NORMAL
STAGE 1 (MILD)
Level of consciousness
0 ¼ Alert, responsive to
external stimuli (statedependent, eg, postfeeds)
Spontaneous activity
STAGE 2 (MODERATE)
STAGE 3 (SEVERE)
1 ¼ Hyper-alert, apparent
awareness, responds
to minimal stimuli
2 ¼ Lethargic
3 ¼ Stupor/coma
0 ¼ Changes position
when quiet
1 ¼ Normal or decreased
2 ¼ Decreased
3 ¼ None
Posture
0 ¼ Predominately flexed
when quiet
1 ¼ Mild flexion of distal joints
(fingers, wrist usually)
2 ¼ Distal flexion,
complete extension
3 ¼ Decerebrate
Tone
0 ¼ Strong flexor tone in
all extremities
1 ¼ Normal or slightly ([)
2a ¼ Hypotonia
(focal or general)
2b ¼ Hypertonia
3a ¼ Flaccid
3b ¼ Rigid
Primitive reflexes
Suck
0 ¼ Strong, easily elicited
1 ¼ Weak or Incomplete
2 ¼ Weak or
incomplete
and/or bite
3 ¼ Absent
Moro
0 ¼ Complete
1 ¼ Intact, low threshold
to elicit
2 ¼ Incomplete
3 ¼ Absent
Pupils
0 ¼ Normal, reactive
1 ¼ Mydriasis
2 ¼ Myosis
3 ¼ Variable/
nonreactive to light
HR
0 ¼ 100–160 bpm
1 ¼ Tachycardia
2 ¼ Bradycardia
3 ¼ Variable HR
Respirations
0 ¼ Regular respirations
1 ¼ Hyperventilation
2 ¼ Periodic breathing
3 ¼ Apnea or
requires ventilation
Automatic system
bpm¼beats per minute; HR¼heart rate.
oxygen concentration should be weaned as soon as the heart
rate recovers. In addition, aggressive recognition and man-
care and longitudinal follow-up. Knowledge gaps were
recognized with lack of adequately powered randomized
wustho!
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The Neurologic Exam for Neonates
with Suspected Encephalopathy
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Encephalopathy is defined by the presence of one or more signs in at least three of the following six
categories:
level of consciousness
spontaneous activity
posture
tone
primitive reflexes
autonomic nervous system
When findings are mixed, the extent of encephalopathy is determined by which category describes the
majority of signs. If signs were equally distributed, categorize based on the level of consciousness.
Importantpointers
§  IfauerDRresuscitaZon,theSarnatexamshowsevidenceof
moderateorsevereencephalopathy(abnormaliZesin≥3
categories),thenewbornshouldbecooledaslongasthereare
noexclusionsandtheotherlaboratory/historicalcriteriaare
met.
§  ImprovementorchangesintheSarnatexamoverZmearethe
normandshouldnotbeinterpretedasnegaZngtheoverallrisk
ofHIEandadverseneurodevelopmentaloutcome.
§  Newbornswithlaboratoryorhistoricaldatamakingthem
potenZallyeligiblewithaniniZalSarnatexamthatisnormalor
mildmustbeexaminedhourlyforchangesintheSarnatexam.