Holistic Approach to ChildrenHolistic Approach to Children

ith Ch i L Diwith Chronic Lung Disease

Suchada Sritippayawan, MD.

Div. Pulmonology & Crit Care

Wanida Pao-in, MD.

Div. Pulmonology & Crit Care gy

Dept. Pediatrics,

Faculty of Medicine

gy

Dept. Pediatrics,

Faculty of Medicine

Chulalongkorn UniversityThammasart University

Case illustration

• Triplet, GA 25 weeks

• Triplet A (male) 635 g, triplet B (female) 720 g, triplet C (female) 605 gtriplet C (female) 605 g

• APGAR: A-2,7, B-1,7, C-1,7• Surfactant, on mechanical ventilator,

antibiotics since birthantibiotics since birth• Triplet B died at DOL 2 because of pulmonary

hemorrhage

Case illustration

Triplet C• BW 605 g, HC 21 cm, Ht 30, APGAR 1,7• Ventilator support: conventional mode• Ventilator support: conventional mode

Initial setting: Conventional mode PIP 15 cmH2O, PEEP 4 cmH2O, IMV rate 60/min, T 0 34 sec FiO 0 8TI 0.34 sec, FiO2 0.8

Case illustration

• Antibiotics, antifungal• Dopamine to maintain BP

PRC furosemide• PRC, furosemide• Monitor fluid, electrolytes • Indomethacin for PDA closure• PPN • Enteral feeding: start at DOL 3, full feed at te a eed g sta t at O 3, u eed at

DOL 13

Chest x-ray at DOL 1

Triplet C at DOL 28

• BW 670 g• Ventilator support: PIP 19 cmH2O, PEEP 4

cmH O IMV rate 70/min T 0 34 sec FiO 0 8cmH2O, IMV rate 70/min, TI 0.34 sec, FiO2 0.8 • PE: active, PR 130, RR 79, BP 50/28, BT 36.7

Heart: normal S1S2, no murmur, no hyperactive precordiumhyperactive precordiumLung: subcostal retraction, occ. coarse crepitations and wheezing Others: unremarkableOthers: unremarkable

Triplet C at DOL 28

Labs • CBG: pH 7.23, PCO2 70, PO2 43, HCO3 28

BUN 25 Cr 1 5• BUN 25, Cr 1.5• Eye exam: no ROP• U/S: no IVH

Chest x-ray at DOL 28

Problem lists

• Premie 25 weeks• Ventilator dependent since birth• PDA (S/P close with indomethacin)• PDA (S/P close with indomethacin)• Bacterial / fungal infection• Renal insufficiency

Poor weight gain• Poor weight gain

Questions

Q1: Does this patient have CLD?Q2: What are respiratory problems and their

pathophysiology?pathophysiology?Q3: How can we treat respiratory problems?Q4: What are other comorbids and their

pathophysiology?pathophysiology?Q5: How can we treat these comorbids?Q6: Is there any long term sequelae and

how to follow up?how to follow up?

Problem lists

• Premie (GA 25 weeks)• Ventilator dependent since birth• PDA (S/P close with indomethacin)PDA (S/P close with indomethacin)• Bacterial / fungal infection • Renal insufficiency• Poor weight gain• Poor weight gain

Respiratory problems

• Premie (GA 25 weeks)• Ventilator dependent

at DOL 28at DOL 28• CBG: CBG: pH 7.23,

PCO2 70, PO2 43, HCO3 28C f• CXR: Bilateral hyperinflation, radiolucent areas plus strands of radiodensity ad o uce t a eas p us st a ds o ad ode s ty

Q1: Does this patient

have CLD?

What is chronic lung disease?

• Bronchopulmonary

dysplasia

P l d MV• Prolonged MV use

• Chronic aspirationChronic aspiration

• Chronic infection

• BronchiectasisChronic ILD• Chronic ILD

• Asthma, etc.,

Chronic lung disease

AJRCCM 2003;168:356-96

Definition of BPD

Old definition (Bancalari’s criteria)• MV at least 3 days in neonate plus• Oxygen dependent at DOL 28 plus• Oxygen dependent at DOL 28 plus• Radiologic changes

Clin Pediatr (Phila) 2002;41:77-85

Definition of BPD

Old definition (Bancalari’s criteria)• Radiologic changes

- RDS (D1-3)RDS (D1 3)- Opacification of both lungs (D4-10) - Small rounded areas of radiolucency in both lungs (D10-20)both lungs (D10 20)

- Enlarged radiolucent areas + strands of radiodensity

Clin Pediatr (Phila)2002;41:77-85

Definition of BPD

New definition (NIH consensus)• Time point of assessment

GA < 32 wk : 36 wk PMA or D/C homeGA < 32 wk : 36 wk PMA or D/C homeGA > 32 wk : > 28 d but < 56 d of postnatal age or D/C home

• Treatment with oxygen > 21% for at least 28Treatment with oxygen 21% for at least 28 days plus

Clin Pediatr (Phila)2002;41:77-85

Definition of BPD

New definition (NIH consensus)• Severity of BPD

Mild BPDMild BPDGA < 32 wk : Breathing RA at 36 wk PMA or D/C homeGA > 32 wk : Breathing RA at 56 d of postnatalGA 32 wk : Breathing RA at 56 d of postnatal age or D/C home

Clin Pediatr (Phila)2002;41:77-85

Definition of BPD

New definition (NIH consensus)• Severity of BPD

Moderate BPDModerate BPDGA < 32 wk : Need FiO2 ≥ 0.3 and/or positive pressure at 36 wk PMA or D/C homeGA > 32 wk : Need FiO2 ≥ 0.3 and/or positiveGA 32 wk : Need FiO2 ≥ 0.3 and/or positive pressure at 56 d of postnatal age or D/C home

Clin Pediatr (Phila) 2002;41:77-85

Definition of BPD

New definition (NIH consensus)• Lung parenchymal disease plus• Clinical features of respiratory distress plusClinical features of respiratory distress plus• Not acute event

Clin Pediatr (Phila) 2002;41:77-85

Q2: What are respiratory problems

d h i h h i l ?and their pathophysiology?

Pulmonary system

Abnormal lung Abnormal AbnormalAbnormal lung parenchyma &

chest wall

Abnormal airway

Abnormal cardiorespiratory

control duringchest wall control during sleep

Other bid

Abnormal gas

comorbids

gexchange and lung

function during gawake and sleep

Chronic lung disease: BPD

• Age at the onset

• Types and severity of

respiratory insults

• DurationSeverity of

BPDDuration

• Body responseBPD

• Treatment

• Genetics

Pediatr Respir Rev 2003;4:28-39.

Pulmonary system

Abnormal lung Abnormal AbnormalAbnormal lung parenchyma &

chest wall

Abnormal airway

Abnormal cardiorespiratory

control duringchest wall control during sleep

Other bid

Abnormal gas

comorbids

gexchange and lung

function during gawake and sleep

Pathogenesis of CLD• Oxygen free radical

↓ ti id tAcute lung injury • Ventilator-induced

PDA l l d• ↓ antioxidant

enzymes system Recruitment of

• PDA, vol. overload

• Infections

inflammatory cells

• Age at the onset

• Types, severity,

Acute inflammatory reactions

yp y

duration of

respiratory insults

Resolved Persistent inflammation

respiratory insults

• Body response

• Treatment

No CLDLung destruction & damage

• Treatment

• Genetics

No CLDCLD

Pathogenesis of BPD

N Engl J Med 2007; 357:1946-55

Old BPD vs. New BPD

Old BPD New BPD

• Alternating atelectasis

with hyperinflation

• Less regional heterogeneity

of lung diseasewith hyperinflation

• Severe airway epithelial

of lung disease

• Rare airway epithelial

lesions

• Marked airway smooth

lesions

• Mild airway smoothMarked airway smooth

muscle hyperplasia

y

muscle thickening

• Extensive diffuse fibroproliferation

• Rare fibroproliferative changes

Lancet 2006;367:1421-31

p

Old BPD vs. New BPD

Old BPD New BPD

• Hypertensive remodeling

of pulmonary arteries

• Fewer arteries but

dysmorphicof pulmonary arteries

• Decreased alveolarisation

dysmorphic

• Fewer, larger and and surface area simplified alveoli

Lancet 2006;367:1421-31

Pulmonary system

Abnormal lung Abnormal AbnormalAbnormal lung parenchyma &

chest wall

Abnormal airway

Abnormal cardiorespiratory

control duringchest wall control during sleep

Other bid

Abnormal gas

comorbids

gexchange and lung

function during gawake and sleep

Airway abnormalities in CLD

• Prolonged intubation, PPV

• Cyanotic spell

• Inappropriate intubation,

suctioning Cyanotic spell

• Wheezing not respond

g• Concomitant infections

Central & upper airway obstruction

to bronchodilator

• Recurrent atelectasis

• Lobar emphysema• Glottic and subglottic stenosis

• Tracheobronchial stenosis • Failed extubation• Ventilator dependent

Tracheobronchial stenosis

• Granuloma formation

AJRCCM 2003;168:356-96

• Tracheobronchomalacia

Abnormal lung function in CLD

CLD

Abnormal Abnormal lungAbnormal Other co-morbid

airway Abnormal lung parenchyma chest wall

mechanics

Other co morbid

• RAD

• GER• etc.

Ob t ti d f t• Hypoxemia • Obstructive defect

• Restrictive defect

• Hypoxemia

• Hypercarbia Can persist • Diffusion defect• BHR

until adult• O2 dependent

• BHR• MV dependent

Pulmonary system

Abnormal lung Abnormal AbnormalAbnormal lung parenchyma &

chest wall

Abnormal airway

Abnormal cardiorespiratory

control duringchest wall control during sleep

Other bid

Abnormal gas

comorbids

gexchange and lung

function during gawake and sleep

Cardiorespiratory control during sleep in CLDsleep in CLD

CLD

Abnormal Abnormal lung AbnormalOther co-morbid

airway Abnormal lung mechanics

Abnormal chest wall mechanics

• RAD• GERGER

Sleep-related hypoxemia, hypercarbia

Abnormal hypoxic ventilatory and arousal

• Poor RV function

response during sleep

AJRCCM 2003;168:356-96

Poor RV function• Abnormal autonomic control of HR

Q3: How can we treat

respiratory problems?p y p

Management of Respiratory ProblemRespiratory Problem

Ventilatory strategiesVentilatory strategies

After Birth

• Early initiation of nasal CPAP

After Birth

Early initiation of nasal CPAP• Nasal intermittent positive pressure

ventilation (NIPPV)ventilation (NIPPV)• Patient-triggered ventilation (SIMV, assist-

control, and pressure support ventilation)control, and pressure support ventilation)• High-frequency ventilation (HFV)• Volume targeted ventilation:• Volume targeted ventilation:• Permissive hypercapnia

P i i h i• Permissive hypoxemia

Ventilatory strategies

Established CLD

• Minimizing ventilatory support (e.g. nCPAP, NIPPV whenever possible)

• Tolerating higher PaCO (55-60 mm Hg• Tolerating higher PaCO2 (55-60 mm Hg provided pH >7.25)

• Target SpO2 : 89-94%• If on IMV: consider using PTV• If on IMV: consider using PTV • Oxygen therapy to maintain SpO2 > 92-93%

Other strategiesg

• Methylxanthines• Steroids: considered in infants after 10-14Steroids: considered in infants after 10 14

days of age• Diuretics for features of pulmonary edema • Bronchodilators for bronchospasmBronchodilators for bronchospasm • Sedation and muscle relaxation for ‘BPD

spells’

Wheezing in CLDI

• Airway hyperresponsiveness• Airway inflammation

A t i l d f t b l tti t i• Anatomical defect: subglottic stenosis, airway malacia

• Interstitial edemaH t f il• Heart failure

• Aspiration syndromep y• Infection

Q4: What are other comorbidsQ4: What are other comorbids

and their pathophysiology?and their pathophysiology?

Chronic lung diseases

Multidisciplinary (Holistic)(Holistic)

approach and follow-up isfollow-up is

required

AJRCCM 2003;168:356-96

Comorbids in CLD

Abnormal CVS in CLD

• PHT, Cor pulmonale

• LVH, LVF

• Systemic HT

• ↑systemic-to-pulmonary collateral circulation• ↑systemic-to-pulmonary collateral circulation

Lancet 2006; 367:1421-31

AJRCCM 2003;168:356-96

Pathophysiology of PHT in CLD• Hypoxemia

H bi ↓ Al l• Premie

• Hypercarbia

• MetabolicPulmonary

vasoconstriction↓ Alveolar

development• Hypoxemia

• HYperoxiaacidosis

Vascular remodeling

• Intrauterineinfection

↓ Pulmonary vascular Endothelial

ll i j developmentcell injury

I ti lIntimal proliferation

Pulmonary hypertension RHF

Lancet 2006; 367:1421-31

AJRCCM 2003;168:356-96

Pathophysiology of HT & LVH in CLD• Hypoxemia

H bi ↑ R i ↑ N ti• Hypercarbia

• Metabolic

↑ Renin-angiotensin

activity

↑ WOB↑ Negative intrathoracic pressure

acidosis

↑↓ ↑ LV afterload↓ Pulmonary endothelial

function

↑ PVR

SystemicLVH↓ Clearance of

norepinephrine Systemic HT

norepinephrine

AJRCCM 2003;168:356-96

Pathophysiology of GER in CLD

• ↑ intrathoracic –ve

pressure

• Low, flat diaphragmLow, flat diaphragm

Abnormal KUB function in CLD

↑ PVR Prolonged loop diuretic use

• Hypoxia

↑ RAP

diuretic use• Hypotension

• Nephrotoxic

• ↑ ANP

• Hypercalciuria

• Nephrocalcinosis

pdrug

• ↑ Vasopressin

p

• Hyperphosphaturia

↓ M K

• ↑ water retention

• ↓ Mg, K

• Metabolic alkalosisTubular injury

• ↓ Na

Clin Pediatr 2002; 41:77-85.

Other comorbids in CLD

• ↑REE

• ↓ intake

• Drugs

• Other comorbids

Q5: How can we treat

these comorbids?

Management of Oth C bidOther Comorbids

Management of ComorbidsManagement of Comorbids

• PHT

• GERDOxygen GERD

• KUB

Calcium channel blockersProstacyclin Phosphodiesterase inhibitor: sildenafil• KUB

N t iti

Phosphodiesterase inhibitor: sildenafil Endothelin receptor antagonists: bosentan

• Nutrition

GERDGERD

• Feeding• Drugs: - prokineticsDrugs: prokinetics• - H2-receptor antagonists• - proton-pump inhibitors

• FundoplicationFundoplication

nutritionnutrition

– Calorie intake to 120 to 150 Kcal/kg/d– Breast milk fortified with HMF– Fat supplementation (e.g. MCT oil) – Multivitamin to meet RDA Multivitamin to meet RDA

Q6: Is there any long term

sequelae and how to seque ae a d o to

follow up?follow up?

Abnormal lung function in CLD

CLD

Abnormal Abnormal lungAbnormal Other co-morbid

airway Abnormal lung parenchyma chest wall

mechanics

Other co morbid

• RAD

• GER• etc.

Ob t ti d f tH i • Obstructive defect

• Restrictive defect

• Hypoxemia

• Hypercarbia Can persist • Diffusion defect• BHR

• Exerciseintolerance

until adult

• BHRintolerance

Long term sequelae

Management of Long Term SequelaeLong Term Sequelae

Management of Long Term SequelaeManagement of Long Term Sequelae

• Respiratory system• Infection prevention• Infection prevention• Neurologic/developmentalg p• Hearing/vision• Growth• Other

Triplet C at DOL 1 - 4.5 months

• NSS neb, chest PT• On nasal CPAP at age 2 months• Seretide® Ventolin® MDI at age 2 months• Seretide®, Ventolin® MDI at age 2 months

(2 weeks) • O2box/cannula at age 2.5 months (36 wk PMA)

Discharge at age 4 5 mo (corrected age 1 mo)• Discharge at age 4.5 mo (corrected age 1 mo)– BW 2,700 g, HC 35 cm, length 48 cm – Home med: MTV, FeSO4

Triplet C at DOL 9 months

Age 9 mo (corrected age 6 mo)• 5.6 kg, HC 39.5 cm, length 61 cm

• spastic diplegia • DENVER II: PS 6 mo FM 4 mo L 4 mo• DENVER II: PS 6 mo, FM 4 mo, L 4 mo,

GM 6 mo