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Thomas G. Keens, M.D.Professor of Pediatrics, Physiology and Biophysics
Keck School of Medicine of the University of Southern CaliforniaDivision of Pediatric PulmonologyChildren’s Hospital Los Angeles
No Conflicts of Interest to Disclose
Turkish Thoracic Society15th Annual CongressSide-Antalya, Turkey
April 13, 2012
Apnea and Sudden Infant Death Syndrome
Turkish Thoracic Society
Turkish Thoracic Society
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Thank You!
Refika Hamutcu Ersu, M.D.
Division of Pediatric PulmonologyMarmara University
Istanbul, Turkey
Formerly, Postdoctoral Fellow in Pediatric Pulmonology
Children’s Hospital Los Angeles
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“And this woman's son died in the night ...”
1 Kings 3: 19(950 B.C.)
Antoon Claeissens, The Judgment of Solomon, ~1600.
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Determination of Cause of Death
Sudden Deathof an Infant
EmergencyResponders
Coroner'sInvestigation
Autopsy
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Spectrum of Infant Deaths
Known Cause of
Death
“True” SIDS
Biology Interacts
with Environment
Clear evidence of suffocation,
entrapment, etc.
Dx: Accidental
No Risk Factors.
Dx: SIDS
Some Risk Factors, but would not cause death in all infants.
Dx: Variable
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Sudden Infant Death SyndromeThe sudden unexpected death of an infant,
under one-year of age, with onset of the fatal episode apparently occurring during sleep,that remains unexplained after a thorough investigation, including performance of a
complete autopsy, and review of the circumstances of death and the clinical history.
Krous, H.F., J.B. Beckwith, R.W. Byard,T.O. Rognum, T. Bajanowski, T, Corey, E. Cutz,
R. Hanzlick, T.G. Keens, and E.A. Mitchell.
Pediatrics, 114: 234-238, 2004.
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0.0
0.5
1.0
1.5
2.0
1980 1985 1990 1995 2000 2005 2010
SID
S R
ate
per
1,00
0 L
ive
Bir
ths
CaliforniaUSA
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Infant Deaths by Age of Death California 2003
0
10
20
30
40
<1 1 2 3 4 5 6 7 8 9 10 11
Age of Death in Months
Num
ber o
f Dea
ths
by A
ge o
f Dea
th
SIDSUndeterminedAll Other
California 2002-2003 Birth & 2003 Death Statistical Master Files & SUID Database, 2003.California Department of Health Services, MCAH/OFP, September 2005.
Carrie Florez
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Infant Deaths by Race/EthnicityCalifornia 2003 SUID Data
0
20
40
60
80
100
White/Other AfricanAmerican
Asian/PacificIslander
Multiple Race Hispanic
Race/Ethnicity
Rat
e pe
r 100
,000
Rac
e/Et
hnic
Sp
ecifi
c Li
ve B
irths
SIDSUndeterminedAll Other
California 2002-2003 Birth & 2003 Death Statistical Master Files & SUID Database, 2003.California Department of Health Services, MCAH/OFP, September 2005.
Carrie Florez
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SIDS Autopsy Findings
• No identifiable cause of death.
• No signs of severe illness.
• No signs of significant stress.
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Kinney, H.C., and B.T. Thach. N. Eng. J. Med., 361: 795-805, 2009.
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SIDS
Infant Vulnerability
Development Environment
Hannah Kinney
Filiano, J.J., and H.C. Kinney. Biol. Neonate, 65: 194-197, 1994.
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Kinney, H.C., and B.T. Thach. N. Eng. J. Med., 361: 795-805, 2009.
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Paterson, D.S., et al. J. Amer. Med. Assoc., 296: 2124-2132, 2006.
5-HT1A Receptor Binding Density in theMid-Medulla from SIDS vs Control
Hannah Kinney
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Duncan, J.R., et al. J. Amer. Med. Assoc., 303: 430-437, 2010.
Hannah KinneyHannah Kinney
0
20
40
60
80
100
Raphe Obscurus PGCL
Bra
inst
em S
erot
onin
Con
cent
ratio
n (p
mol
/mg)
SIDS (n=35)Controls(n=5)Hospitalized(n=5)
P <0.05
P <0.04
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Brainstem Neurotransmitters in SIDS
Panigrahy, A., et. al. J. Neuropath. Exp. Neurol., 59: 377-384, 2000. Kinney, H.C., et al. J. Neuropath. Exp. Neurol., 60: 228-247, 2001.
Kinney, H.C., et al. J. Neuropath. Exp. Neurol., 62: 1178-1191, 2003.Paterson, D.S., et al. J. Amer. Med. Assoc., 296: 2124-2132, 2006.
Duncan, J.R., et al. J. Amer. Med. Assoc., 303: 430-437, 2010.
Professor Hannah Kinney.Neuropathologist.
Harvard Medical School.
• 5-HT abnormalities may be developmental in origin.
• SIDS victims may have abnormal neurologic control of cardiac, respiratory, and/or arousal function.
• Confirms a biological basis for SIDS.
• Supports risk reduction strategies.
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SIDS
Infant Vulnerability
Development Environment
Hannah Kinney
Filiano, J.J., and H.C. Kinney. Biol. Neonate, 65: 194-197, 1994.
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Spectrum of Infant Deaths
Known Cause of
Death
“True” SIDS
Biology Interacts
with Environment
Clear evidence of suffocation,
entrapment, etc.
Dx: Accidental
No Risk Factors.
Dx: SIDS
Some Risk Factors, but would not cause death in all infants.
Dx: Variable
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SIDS
V
DE
Known Cause of
Death
“True” SIDS
Biology Interacts
with Environment
SIDS
SIDS
V
D E
V
D E
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SIDS
V
DE
Known Cause of
Death
“True” SIDS
Biology Interacts
with Environment
SIDS
SIDS
V
D E
V
D E
Clear evidence of suffocation,
entrapment, etc.
Dx: Accidental
No Risk Factors.
Dx: SIDS
Some Risk Factors, but would not cause death in all infants.
Dx: Variable
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AAP Policy Statement. Pediatrics, 128: 1030-1039, 2011.
SIDS
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0.0
0.5
1.0
1.5
2.0
1980 1985 1990 1995 2000 2005 2010
SID
S R
ate
per
1,00
0 L
ive
Bir
ths
CaliforniaUSA
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SIDS Risk Reduction: Curriculum for Nurses, NICHD, 2006. NIH Publication No. 06-6005.
Supine Prone
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0
20
40
60
80
1990 1992 1994 1996 1998 2000 2002 2004 2006
0.5
1.0
1.5
U.S. Prone Sleeping and SIDS RatePr
one
Slee
p ing
(%)
SID
S R
ate
per
1,00
0
0
M. Willinger, et al. J. Amer. Med. Assoc., 280: 329-335, 1998.Colson, E.R., et al. Arch. Pediatr. Adolesc Med., 163: 1122-1128, 2009.
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SIDS InfantApnea
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Post-neonatal Apnea and SIDS
0
5
10
15
20
800-1499 1500-2499 >2500
Infa
nts
(%)
SIDSControls
Birthweight (gm)Total(P<0.001)
Hoffman, H.J., et al. Ann. N.Y. Acad. Sci., 533: 13-30, 1988.
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Apparent Life-Threatening Event(ALTE)
An event, which is frightening to the observer, with:
• Color change (cyanosis or pallor).
• Tone change (limpness).
• Apnea.
• Requirement for intervention.Kahn, A. Eur. J. Pediatr., 163: 108-115, 2004.
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• Attempt to identify criteria for safe discharge from ED.
• Prospective study of ALTE seen in ED over 3-years.
• Information on presentation and outcome obtained.
• 59 infants <1-year of age were studied.
• 55 were hospitalized.
Claudius, I., and T. Keens. Pediatrics, 119: 679-683, 2007.
Ilene Claudius, M.D.
Do all ALTE need to be Hospitalized?
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Critical Outcome Criteria:
• Subsequent events requiring resuscitation.
• Identified cause of ALTE requiring hospitalization.
• Diagnosis that would have put the child at risk if discharged (i.e., sepsis, child abuse).
• Development of life-threatening condition (i.e., hypoxia).
Claudius, I., and T. Keens. Pediatrics, 119: 679-683, 2007.
Ilene Claudius, M.D.
Do all ALTE need to be Hospitalized?
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• 8 infants (14%) had Critical Outcomes, and should have been hospitalized.
• 3 multiple apneas.
• 2 required treatment for infection or neurologic problem.
• 2 required PICU care.
• 1 developed hypoxia.
• All were hospitalized.Claudius, I., and T. Keens. Pediatrics, 119: 679-683, 2007.
Ilene Claudius, M.D.
Do all ALTE need to be Hospitalized?
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Do all ALTE need to be Hospitalized?• None of the remaining 51
infants had Critical Outcomes.
• 47 of these were hospitalized.
• 4 of these were not hospitalized.
• None had serious sequelae.
• These results suggest that some ALTE need not be hospitalized, but how do you predict which ones?
Claudius, I., and T. Keens. Pediatrics, 119: 679-683, 2007.
Ilene Claudius, M.D.
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Admitting all infants age <1-month and/or who had multiple ALTE included all infants who had critical outcomes.
Claudius, I., and T. Keens. Pediatrics, 119: 679-683, 2007.
Ilene Claudius, M.D.
High Risk
Low Risk
Age <1 mo and/or Multiple ALTE 8 22Age >1 mo andonly one ALTE 0 29
Do all ALTE need to be Hospitalized?
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When an ALTE Infant is Hospitalized
• Continuous cardiorespiratory monitoring and/or pulse oximetry.
• Preferably with memory capability.
• Diagnostic evaluation to identify medical cause for the ALTE.
• No cookbook diagnostic evaluation.
• Diagnostic testing should be individualized.
• 50%-70% of ALTE can be explained.
Kahn, A. Eur. J. Pediatr., 163: 108-115, 2004.
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0 10 20 30 40 50 60
Child Abuse
Accidents
Metabolic Errors
Cardiovascular
Respiratory
Neurological
Gastrointestinal
Idiopathic
%
Most Common Causes of ALTE
Kahn, A. Eur. J. Pediatr., 163: 108-115, 2004.
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Management of ALTE• When specific cause for ALTE is found, treat
the specific cause.
• Respiratory stimulants (methylxanthines) are not effective and have side effects.
• Home apnea-bradycardia monitoring is used most commonly when a specific cause can not be found.
• No universally accepted indications for home monitoring.
Kahn, A. Eur. J. Pediatr., 163: 108-115, 2004.
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Home Apnea Bradycardia MonitorsCan Detect Central Apnea
Flow
Rib Cage
Abdomen
Time
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Home Apnea Bradycardia MonitorsCan Not Detect Obstructive Apnea
Flow
Rib Cage
Abdomen
Time
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Home Apnea Bradycardia MonitorAlarm Thresholds
Age (months)
Apnea (seconds)
Low HR (bpm)
High HR (bpm)
0-1 20 80 off
1-3 20 70 off
3-12 20 60 off
>12 25 50 off
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Instructions to Monitoring ParentsInstructions to Monitoring Parents
• Monitor when sleeping and whenever Monitor when sleeping and whenever the baby is otherwise unobserved.the baby is otherwise unobserved.
• Caregivers must be trained in infant Caregivers must be trained in infant CPR and graded response to monitor CPR and graded response to monitor alarms.alarms.
• Must be able to hear the alarm (No Must be able to hear the alarm (No shower, vacuum, loud stereo if alone).shower, vacuum, loud stereo if alone).
• Trained babysitters and child care.Trained babysitters and child care.
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Graded Response to Monitor AlarmsGraded Response to Monitor Alarms
Time Action
0-20 sec Time for Monitor to Alarm.
20-30 sec Reach Infant’s Location and
Observe color, tone, breathing. Is this a real alarm?
30-40 sec Gentle stimulation
40-50 sec Vigorous stimulation
>50 sec. Cardiopulmonary resuscitation.
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Inborn Errors of -Oxidation of Fatty Acids
• Rare cause of ALTE, but more likely if:• Apneas persist --- do not resolve in 3-
months.• Severe apneas --- require resuscitation.• Family history of consanguinity, ALTE,
seizures, SIDS, or other infant deaths.
• Serum ammonia elevated in all cases.• 4% of infants with severe ALTE.
Arens, R., et al. J. Pediatr., 123: 415-418, 1993.
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When to discontinue HomeApnea-Bradycardia Monitoring
• No true alarms requiring intervention for 2-months.
• 6-weeks since the last true alarm requiring intervention.
• Testing is not helpful.Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
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CHIME Steering Committee, NICHDBethesda, Maryland, U.S.A. July, 1992.
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The CHIME Home Monitor
• Respiratory Inductance Plethysmography.• Central and Obstructive Apneas.• Electrocardiogram.• Pulse Oximeter.• Body Position.• Computer to record events and
normative data.Neuman, M.R., et al., and CHIME. Physiol. Meas., 22: 267-286, 2001.
Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
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Neuman, M.R., et al., and CHIME. Physiol. Meas., 22: 267-286, 2001.
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CHIME Study -- Event Definitions
Event Type Apnea (seconds)
Bradycardia (bpm)
Age (wks PCA)
Conventional >20
<80 for >15 s or <60 for >5 s <44
<60 for >15 s or <50 for >5 s >44
Extreme >30 <60 for >10 s <44
<50 for >10 s >44
Neuman, M.R., et al., and CHIME. Physiol. Meas., 22: 267-286, 2001. Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
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CHIME -- Conventional Events
Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
0
2,000
4,000
6,000
8,000
Conventional Events Apnea withoutBradycardia
Bradycardia withoutApnea > 20 s
Num
ber
of C
onve
ntio
nal
Eve
nts
6,958 Conventional Events in 444 of 1,079 infants (41%)
4,937(78%)
769(12%)
6,958
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Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
0
20
40
60
80
0 30 60 90 120 150 180
Perc
ent o
f inf
ants
with
at l
east
one
C
onve
ntio
nal
Eve
nt
Days from beginning of monitoring
CHIME -- Conventional EventsSymp. Preterm
Asymp. PretermSibling Term
AOI Preterm
Sibling Preterm
AOI Term
Healthy Term
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CHIME -- Extreme Events
Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
0
100
200
300
400
500
600
700
Extreme Events Apnea withoutBradycardia
Bradycardia withoutApnea > 20 s
Num
ber
of E
xtre
me
Eve
nts
653 Extreme Events in 116 of 1,079 infants (10%)
653321
(49%)144
(22%)
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Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
0%
5%
10%
15%
20%
25%
30%
35%
0 25 50 75 100 125 150Days from beginning of monitoring
Symp. Preterm
Healthy Term
ALTE Term
Sibling Term
Asymp. Preterm
ALTE PretermSibling Preterm
Perc
ent o
f inf
ants
with
at l
east
one
E
xtre
me
even
t
CHIME -- Extreme Events
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Time from One Extreme Event to the Next
Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
0%
25%
50%
75%
100%
0 20 40 60 80
Infa
nts (
%)
Number of days from prior event
Event #3 to #4 (n=35)
Event #2 to #3 (n=60)
Event #1 to #2 (n=116)
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Rat
e of
at l
east
1 e
xtre
me
even
t per
4-w
eek
peri
od(#
of i
nfan
ts w
ith a
t lea
st 1
eve
nt p
er 2
0,00
0 ho
urs o
f mon
itori
ng)
Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
0
10
20
30
40
50
60
70
30 35 40 45 50 55 60
PCA (weeks) at beginning of 4-week observation period
Symp. PretermAsymp. Preterm
ALTE PretermSibling Preterm
ALTE TermSibling Term
Healthy Term
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0
10
20
30
40
50
60
70
30 35 40 45 50 55 60
PCA (weeks) at beginning of 4-week observation period
Rat
e of
at l
east
1 e
xtre
me
even
tSIDS
Ramanathan, R., and CHIME. J. Amer. Med. Assoc., 285: 2199-2207, 2001.
Apnea
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Apnea, SIDS, andHome Monitoring
• Home monitoring should not be prescribed to prevent SIDS.
• Home monitoring may be warranted for preterm infants at risk for apnea, bradycardia, and hypoxia after hospital discharge.
• In these preterm infants, use of home monitors should be limited to 43-weeks PCA.
AAP Policy Statement. Pediatrics, 111: 914-917, 2003.
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Apnea, SIDS, andHome Monitoring
AAP Policy Statement. Pediatrics, 111: 914-917, 2003.
• Home monitoring may be warranted for some infants with a risk of sudden death, but not necessarily an increased risk of SIDS.• ALTE.
• Tracheostomy or unstable airway.
• Neurologic or metabolic abnormalities affecting respiratory control.
• Chronic lung disease requiring oxygen, CPAP, BiPAP, or home mechanical ventilation.
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Apnea, SIDS, andHome Monitoring
AAP Policy Statement. Pediatrics, 111: 914-917, 2003.
• Home monitors should be equipped with event recorders.
• Parents should be advised that home monitoring has not been proven to prevent sudden unexpected deaths in infants.
• Pediatricians should continue to promote proven practices to decrease the risk of SIDS --- Back to Sleep recommendations.
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SIDS
Infant Vulnerability
Development Environment
Hannah Kinney
Filiano, J.J., and H.C. Kinney. Biol. Neonate, 65: 194-197, 1994.
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