Case (1)

A male infant, 3400 g, GA 37 wks

Mother: 24 y/o, G1P1A0, A+
Uncomplicated hospital nursery
LOGO Breast-feeding
34 hours: T.bili 7.5 mg/dL
Present: R2 鄭伯良 40 hours: Discharge
Instructor: VS 陳健伸 2 days later: PED office: marked
N Engl J Med 2008;358:920-8. jaundice.

Case (2) The Clinical Problem

3020 g, is 11% below birth weight 60% Jaundice in 1st week
T.bili 19.5 mg/dL ; D.bili 0.6 mg/dL The neonatal liver cannot clear
CBC / blood smear: normal. bilirubin rapidly enough from the blood
type A Rh-positive blood. Potentially toxic to the CNS
Consult a neonatologist regarding the Bilirubin encephalopathy
need for phototherapy. kernicterus,
devastating, permanent
neurodevelopmental handicaps.
US: 5~40 / 1000 term or late-term
receive phototherapy

Normal Bilirubin Metabolism and Bilirubin Metabolism

during Phototherapy Risk
Gilbert’
Gilbert’s syndrome
2 isomers
Monoglucuronides + diglucuronide Breast-feeding
MRP2 Poor caloric intake associated with
breast-feeding difficulties

Increase in the enterohepatic

circulation of bilirubin!

yellow photoisomers + colorless oxidation products

 Mechanism of Phototherapy Important Factors in the Efficacy of Phototherapy
Mechanism unknown
Photoisomerization > photodegradation

less lipophilic

The rate of formation of bilirubin photoproducts

is highly dependent on the intensity and
wavelengths of the light used.

Important factors Clinical evidence

Spectrum RCTs since1960s ~ 1990s
Wavelength Ethnics…prevent any trial
Distance Effective alternative –
Irradiance Exchange transfusion
once common procedures in the NICU,
Skin area exposed are now rare
O’Shea TM’s Studies
Intensive phototherapy: ● PT withheld: 36% exchange
auxiliary light source below the infant ● PT used: 2% exchange
William Beaumont Hospital: 2425 infants-
No exchange!
Discuss later

Clinical Use Guidelines for intensive phototherapy in hospitalized

infants born at a gestational age of 35 weeks or more
Guideline: American Academy of
Pediatrics in 2004.
American Academy of Pediatrics
Subcommittee on Hyperbilirubinemia.
Management of hyperbilirubinemia in the
newborn infant 35 or more weeks of
gestation.
Pediatrics 2004;114:297-316.

Standard phototherapy for total serum bilirubin levels that are 2~3 mg/dL lower
than the range for which intensive phototherapy is recommended
Risk factors of PT Guideline Efficacy depends on Irradiance
Risk factors: Unit: μW/cm2/nm
Isoimmune hemolytic disease Distance: 20 cm above the infant
G6PD Conventional:
Asphyxia 8~10 μW/cm2/nm in 430-to-490-nm
Lethargy band
Temperature instability Special blue fluorescent lamps:
Sepsis 30 ~ 40 μW/cm2/nm
Acidosis
Intensive phototherapy: >30 μW/cm2/nm
Albumin level < 3.0 g/dL

Some: routine in infants <1000 g Figure.3

Dosage in phototherapy Others

No single standardized method! Distance
Guideline- Radiometer, measured Skin area exposed
below the center of the lights As larger as possible
Special blue fluorescent lamps Unnecessary to remove the diaper
Light-emitting diode (LED) Aluminum foil or white cloth placed the
Filtered halogen lights either side

Eyes’ protection: eye patches

Decline in bilirubin Discontinune?

Skin concentration↑，PT efficacy ↑ No firm standards
Birth hospitalization: below the level at which phototherapy
lower level, lower rate was initiated
 Rebound? Expense
Risk: < $1,000 US (2002 dollars)
GA < 37 weeks Home phototherapy- less efficient
Hemolytic diseases special blue or LED lights
s/p PT at birth hospitalized

Recheck 24 hours after discharge

Adverse effects (1) Adverse effects (2)

Rare
Bronze baby syndrome,
skin, serum, and urine develop a dark,
grayish-brown discoloration
only in infants with cholestasis
Unknown mechanism
Rare purpuric and bullous eruptions
Erythematous rash
Congenital porphyria + concomitant
use of photosensitizing drugs =
contraindication!
Severe blistering and agitation
Thermal- Conventional phototherapy
LEDS – no studies
IV – not required

Adverse effects (3) Areas of Uncertainty

A single study: increase the number of
atypical melanocytic nevi at school
age
Swedish study: PT associated with
type1 DM / Asthma
Other study: bilirubin as antioxidant
Lower it could have undesirable
consequences
Exchange transfusions: rare
PT Mechanism: Reduce circulating
levels of bilirubin by accelerating its
elimination
Possible toxicity of photoisomers?
The precise contributions of the
different photochemical pathways to
the elimination of bilirubin during
phototherapy are also unknown.
 Case (1)
A male infant, 3400 g, GA 37 wks
Mother: 24 y/o, G1P1A0, A+
Uncomplicated hospital nursery
Breast-feeding
34 hours: T.bili 7.5 mg/dL
40 hours: Discharge
RETURN TO THE VIGNETTE 2 days later: PED office: marked
jaundice.

Case (2)
3020 g, is 11% below birth weight
T.bili 19.5 mg/dL ; D.bili 0.6 mg/dL
CBC / blood smear: normal.
type A Rh-positive blood.
Consult a neonatologist regarding the
need for phototherapy.

Hospital admission and intensive

phototherapy Intensive phototherapy:
> 30 μW/cm2/nm
blue spectrum delivered to the maximum
surface area
Expect: 30 to 40% decrease in 24
hours
Discontinue: T.bil 13~14 mg/dL THANKS FOR YOUR ATTENTION!
11% BW loss: IV fluids, breast-fed
 Case (1)
A male infant, 3400 g, GA 37 wks
Mother: 24 y/o, G1P1A0, A+
Uncomplicated hospital nursery
LOGO Breast-feeding
34 hours: T.bili 7.5 mg/dL
Present: R2 鄭伯良 40 hours: Discharge
Instructor: VS 陳健伸
N Engl J Med 2008;358:920-8.
2 days later: PED office: marked
97/05/06 jaundice.

Case (2) The Clinical Problem

3020 g, is 11% below birth weight 60% Jaundice in 1st week
T.bili 19.5 mg/dL ; D.bili 0.6 mg/dL The neonatal liver cannot clear
CBC / blood smear: normal. bilirubin rapidly enough from the blood
type A Rh-positive blood. Potentially toxic to the CNS
Consult a neonatologist regarding the Bilirubin encephalopathy
need for phototherapy. kernicterus,
devastating, permanent
neurodevelopmental handicaps.
US: 5~40 / 1000 term or late-term
receive phototherapy

Normal Bilirubin Metabolism and Bilirubin Metabolism

during Phototherapy Risk
Gilbert’
Gilbert’s syndrome
2 isomers
Monoglucuronides + diglucuronide Breast-feeding
MRP2 Poor caloric intake associated with
breast-feeding difficulties

Increase in the enterohepatic

circulation of bilirubin!

yellow photoisomers + colorless oxidation products

 Mechanism of Phototherapy Important Factors in the Efficacy of Phototherapy
Mechanism unknown
Photoisomerization > photodegradation

less lipophilic

The rate of formation of bilirubin photoproducts

is highly dependent on the intensity and
wavelengths of the light used.

Important factors Clinical evidence

Spectrum RCTs since1960s ~ 1990s
Wavelength Ethnics…prevent any trial
Distance Effective alternative –
Irradiance Exchange transfusion
once common procedures in the NICU,
Skin area exposed are now rare
O’Shea TM’s Studies
Intensive phototherapy: ● PT withheld: 36% exchange
auxiliary light source below the infant ● PT used: 2% exchange
William Beaumont Hospital: 2425 infants-
No exchange!
Discuss later

Clinical Use Guidelines for intensive phototherapy in hospitalized

infants born at a gestational age of 35 weeks or more
Guideline: American Academy of
Pediatrics in 2004.
American Academy of Pediatrics
Subcommittee on Hyperbilirubinemia.
Management of hyperbilirubinemia in the
newborn infant 35 or more weeks of
gestation.
Pediatrics 2004;114:297-316.

Standard phototherapy for total serum bilirubin levels that are 2~3 mg/dL lower
than the range for which intensive phototherapy is recommended
Risk factors of PT Guideline Efficacy depends on Irradiance
Risk factors: Unit: μW/cm2/nm
Isoimmune hemolytic disease Distance: 20 cm above the infant
G6PD Conventional:
Asphyxia 8~10 μW/cm2/nm in 430-to-490-nm
Lethargy band
Temperature instability Special blue fluorescent lamps:
Sepsis 30 ~ 40 μW/cm2/nm
Acidosis
Intensive phototherapy: >30 μW/cm2/nm
Albumin level < 3.0 g/dL

Some: routine in infants <1000 g Figure.3

Dosage in phototherapy Others

No single standardized method! Distance
Guideline- Radiometer, measured Skin area exposed
below the center of the lights As larger as possible
Special blue fluorescent lamps Unnecessary to remove the diaper
Light-emitting diode (LED) Aluminum foil or white cloth placed the
Filtered halogen lights either side

Eyes’ protection: eye patches

Decline in bilirubin Discontinune?

Skin concentration↑，PT efficacy ↑ No firm standards
Birth hospitalization: below the level at which phototherapy
lower level, lower rate was initiated
 Rebound? Expense
Risk: < $1,000 US (2002 dollars)
GA < 37 weeks Home phototherapy- less efficient
Hemolytic diseases special blue or LED lights
s/p PT at birth hospitalized

Recheck 24 hours after discharge

Adverse effects (1) Adverse effects (2)

Rare
Bronze baby syndrome,
skin, serum, and urine develop a dark,
grayish-brown discoloration
only in infants with cholestasis
Unknown mechanism
Rare purpuric and bullous eruptions
Erythematous rash
Congenital porphyria + concomitant
use of photosensitizing drugs =
contraindication!
Severe blistering and agitation
Thermal- Conventional phototherapy
LEDS – no studies
IV – not required

Adverse effects (3) Areas of Uncertainty

A single study: increase the number of
atypical melanocytic nevi at school
age
Swedish study: PT associated with
type1 DM / Asthma
Other study: bilirubin as antioxidant
Lower it could have undesirable
consequences
Exchange transfusions: rare
PT Mechanism: Reduce circulating
levels of bilirubin by accelerating its
elimination
Possible toxicity of photoisomers?
The precise contributions of the
different photochemical pathways to
the elimination of bilirubin during
phototherapy are also unknown.
 Case (1)
A male infant, 3400 g, GA 37 wks
Mother: 24 y/o, G1P1A0, A+
Uncomplicated hospital nursery
Breast-feeding
34 hours: T.bili 7.5 mg/dL
40 hours: Discharge
RETURN TO THE VIGNETTE 2 days later: PED office: marked
jaundice.

Case (2)
3020 g, is 11% below birth weight
T.bili 19.5 mg/dL ; D.bili 0.6 mg/dL
CBC / blood smear: normal.
type A Rh-positive blood.
Consult a neonatologist regarding the
need for phototherapy.

Hospital admission and intensive

phototherapy Intensive phototherapy:
> 30 μW/cm2/nm
blue spectrum delivered to the maximum
surface area
Expect: 30 to 40% decrease in 24
hours
Discontinue: T.bil 13~14 mg/dL THANKS FOR YOUR ATTENTION!
11% BW loss: IV fluids, breast-fed
 Outline

Croup
‹ The clinical problem
¾ Classification
¾ Epidemiologic
‹ Strategies and Evidence
¾ Evaluation
Journal：NEJM 2008; 358: 384-391 ¾ Treatment
Speaker： 劉 劭 穎 (R0) ‹ Areas of Uncertainty
‹ Guidelines
Supervisor: 陳 建 伸 (V.S)
‹ Conclusions
Date : 5/6/2008

Introduction The clinical problem

‹ Case ‹ The clinical problem
¾ previously healthy 2 y/o girl 1. Classification
¾ 11 pm 2. Epidemiologic
¾ 2 hours later at ER
¾ barking cough and inspiratory stridor
¾ T/P/R- 36.1C/ 151/ 20
¾ SpO2- 94%
¾ mild sternal retractions without cyanosis

‹ How to evaluate and treat?

1) Classification
‹ a number of respiratory illness
¾ characterized by inspiratory stridor, barking
cough and hoarseness
¾ due to obstruction of larynx
 2) Epidemiologic
‹ Croup (laryngotracheitis and spasmodic
croup)
¾ < 6 y/o
¾ peak: 7~36 months
¾ boys: girls- 1.5:1
• 14 year; hospitalized; Ontario and Canada;
1988~2002

Strategies and Evidence 1) Differential diagnosis

‹ Evaluation ‹ Epiglottitis
1. Differential diagnosis
2. Assessment of severity ‹ foreign body
‹ Treatment
1. Acute laryngotracheitis and Spasmodic ‹ angioneurotic edema
croup
2. Laryngotracheobronchitis and
Laryngotracheobronchopneumonitis ‹ LTB and LTBP

‹ Epiglottitis ‹ foreign body & angioneurotic edema

¾ absence of barking cough ¾ suddenly
• Barking seal or sea lion ¾ no fever
¾ sitting posture with chin pushed forward ¾ no other signs of infection
¾ reluctance or refusal to lie down
¾ lat. Neck XR will confirm but rarely necessary
‹ LTB and LTBP ‹ Lab is rarely useful for routine croup
¾ Signs of lower airway involvement ‹ clinical suggest LTB or LTBP
• crackles, air trapping, wheezing, pneumonia on ¾ WBC/DC
XR
¾ CXR(PA & lat)
¾ bacterial cause should be suspect
¾ neck XR
• also in laryngotracheitis
– when s/s persist or worsen despite treatment with
¾ intubation is commonly required
steroid and epinephrine • Tracheal bac. culture at this time
¾ lat. Neck XR ¾ direct identification of influenza virus
• soft densities indicating purulent exudate within • nasal wash or tracheal secretions
the trachea • as well in severe laryngotracheitis
• antiviral therapy guide

2) Assessment of severity Treatment

‹ Acute laryngotracheitis and Spasmodic
croup
1. Humidified air
2. Corticosteroid
3. Epinephrine
4. Other treatment

‹ LTB and LTBP

1) Humidified air 2) Corticosteroid

‹ one recent trial ‹ now routinely recommended
¾ comparing of high humidity(100%), low(40%),
blow-by humidity ‹ In a laryngotracheitis model
¾ no significant differences in the croup-score ¾ reduce the degree of inflammation & cell
¾ Other two small trials had similar results damage
¾ none included untreated control group ¾ though increased viral load, shedding
‹ recent Cochrane Collabortion review duration was not prolonged
¾ from three other studies
¾ no evidence improvement in mild to
moderate croup
‹ Meta-analyses of randomized trials
¾ significant improvement as compared to
controls
¾ lower scores at 6 hrs
¾ decrease in return visits, time spent in
hospital
‹ might predispose to infectious
complications
¾ not powered to asses these risks
¾ but complications would be expected to be
rare with standard therapy(single dose)
‹ Subsequent trials
¾ racemic epinephrine by nebulization alone
as effective by intermittent positive-pressure
breathing
‹ Later trials
¾ nebulized L-epinephrine diluted in 5 ml of
saline at a ration of 1:1000
¾ as effective as racemic epinephrine
‹ Trials for drugs, dosages and routes
¾ most
• dexamethasone (0.6 mg/kg PO or IM)
• nebulized budesonide (2mg in 4ml water)
¾No directly compared the outcomes of single
dose therapy with 2 day treatment
3) Epinephrine
‹ Early controlled trials
¾ 2.25% racemic epinephrine(0.5ml in 2.5 ml of
saline) by intermittent positive-pressure
breathing
¾ significant reduced score
¾ though benefit last less than 2 hours
‹ In severe croup
¾ repeated treatment often decreased the need
for intubation
 4) Other treatment
‹ Moderate or severe croup and hypoxia ‹ Antibiotics
(ambient air; <92%)
¾ when suspect 2nd bacterial infection
¾ should receive O2

‹ Sever croup by influenza A B

‹ Antitussive and decongestant agents ¾ neuraminidase inhibitors should be
¾ not been studied considered
¾ not indicated ¾ though no data for the efficacy

‹ Influenza immunization
¾ is now routinely recommended

LTB and LTBP Area of uncertainty

‹ ABX after appropriate culture
¾ against
• Staphylococcus aureus
• Streptococcus pneumoniae
• Haemophilus influenza
• Moraxella catarrhaalis
‹ Efforts to warranted to improve the use of
corticosteroids
¾ viral, bacterial and fungal complications
¾ occurred in children who had received
multiple doses

‹ Most require
¾ mechanical airway
¾ ICU care

Guidelines

For Croup
‹ not recommed additional corticosteroid
doses in who do not have a response
¾ lack data for efficacy
¾ potential risks associated with long term
therapy
¾ should be evaluated in ER or admitted
¾ further test may useful
• CXR- for LTB or LTBP
• rapid influenza test
For LTB and LTBP
‹ When we suggest LTB or LTBP
¾ WBC increased
¾ low WBC with increasing band forms
¾ CXR
• pneumonia
• soft densities within the trachea
Conclusions
‹ Case
¾ previously healthy 2 y/o girl
¾ barking cough and inspiratory stridor
¾ T/P/R- 36.1C/ 20/ 151
¾ SpO2- 94%
¾ mild sternal retractions without cyanosis
⇒ single dose of oral dexamethasone
(0.6 mg/kg)
‹ with severe symptoms
¾ should receive nebulized epinephrine
• 0.5 ml of 2.25% racemic epinephrine in 4.5 ml of
N/S
• L-epinephrine diluted in 5 ml N/S at a ratio of
1:1000
¾ may need to repeat many times
• Prevent the need for intubation
‹ Outpatient
¾ observe for at least 2 hours
‹ Treat with Abx
¾ Vancomycin and cefotaxime
‹ most need intubation
‹ Severe croup caused by influenza viruses
¾ neuramidase inhibitors is appropriate