Thomas G. Keens, M.D. Professor of Pediatrics, Physiology and Biophysics

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

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

“And this woman's son died in the night ...”

1 Kings 3: 19(950 B.C.)

Antoon Claeissens, The Judgment of Solomon, ~1600.

Determination of Cause of Death

Sudden Deathof an Infant

EmergencyResponders

Coroner'sInvestigation

Autopsy

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

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.

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

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

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

SIDS Autopsy Findings

• No identifiable cause of death.

• No signs of severe illness.

• No signs of significant stress.

Kinney, H.C., and B.T. Thach. N. Eng. J. Med., 361: 795-805, 2009.

SIDS

Infant Vulnerability

Development Environment

Hannah Kinney

Filiano, J.J., and H.C. Kinney. Biol. Neonate, 65: 194-197, 1994.

Kinney, H.C., and B.T. Thach. N. Eng. J. Med., 361: 795-805, 2009.

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

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

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.

SIDS

Infant Vulnerability

Development Environment

Hannah Kinney

Filiano, J.J., and H.C. Kinney. Biol. Neonate, 65: 194-197, 1994.

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

SIDS

V

DE

Known Cause of

Death

“True” SIDS

Biology Interacts

with Environment

SIDS

SIDS

V

D E

V

D E

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

AAP Policy Statement. Pediatrics, 128: 1030-1039, 2011.

SIDS

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

SIDS Risk Reduction: Curriculum for Nurses, NICHD, 2006. NIH Publication No. 06-6005.

Supine Prone

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.

SIDS InfantApnea

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.

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.

• 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?

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?

• 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?

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.

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?

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.

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.

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.

Home Apnea Bradycardia MonitorsCan Detect Central Apnea

Flow

Rib Cage

Abdomen

Time

Home Apnea Bradycardia MonitorsCan Not Detect Obstructive Apnea

Flow

Rib Cage

Abdomen

Time

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

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.

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.

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.

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.

CHIME Steering Committee, NICHDBethesda, Maryland, U.S.A. July, 1992.

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.

Neuman, M.R., et al., and CHIME. Physiol. Meas., 22: 267-286, 2001.

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.

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

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

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%)

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

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)

Rat

e of

at l

east

1 e

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4-w

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ith a

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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

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

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.

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.

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.

SIDS

Infant Vulnerability

Development Environment

Hannah Kinney

Filiano, J.J., and H.C. Kinney. Biol. Neonate, 65: 194-197, 1994.