Neonatal Respiratory Distress Syndrome (NRDS)
Tongji Hospital
Neonatal Respiratory Distress Syndrome (NRDS)
or,Hyaline Membrane Disease (HMD)
? Most common cause of respiratory failure in the first days
? Occurring in 1~2% of newborn infants (GA 26~28w,50%,
30~31w,less than 20~25%)
? Mortality ~50% at 20 yrs ago,Survive 80~90% now
? High risk,IDM,GA<37w,multi preg.,C-section,asphyxia,
cold stress,history of prior affected,male or white infants
? Low risk,chronic or pregnancy-associated hypertension,
maternal opiate addiction,PROM,antenatal corticosteroid
Lung Development
?Embryonic Lung Development
?Fetal Lung Development
(Pseudoglandular,Canalicular,Terminal Saccular)
?Postnatal Lung Development
Embryonic Lung Development
primitive lung
main bronchi
lobar bronchi
segmental bronchi
Fetal Lung Development
Pseudoglandular Stage ~ 7th – 16th week
Primitive bronchial tree
Terminal bronchioles
Fetal Lung Development
Canalicular Stage ~ 16th – 24th week
Terminal Saccular Stage ~ 24th – 36th week
Respiratory bronchioles Transitory saccules and ducts
Postnatal Lung Development
Postnatal Development ~ birth – 8 year
Alveolar period
Secondary alveolar septa Alveolar ducts and alveoli
Surfactant
?start synthesis in 20~24w
?increase in 28~32w
?meet demands after 35w
?double in alveolar within 24h
?adult level after 3~7d
?half-life 12~24h
?renew in 24~48,>90% reuse
Surfactant Composition
? Phospholipid 90% (neutral 5%)
saturated 50％
unsaturated 35％
? Protein 10％ (albumin 5%)
SP-A,30~35kDa,18 ologomer,hydrophilic
D,43kDa,12 oligomer
SP-B,8kDa,dimer,hydrophobic
C,4kDa,dimer
Function of Pulmonary Surfactant
? Decrease alveolar surface tension,reduce respiratory work
? Maintain alveoli inflation and functional residual capacity
? Accelerate lung fluid absorption,reduce alveolar effusion
? Pathogen Opsonization,alveolar macrophage activation
Effects,improve oxygenation,
ameliorate ventilation/perfusion
anti-inflammation
Fluid surface tension
Pressure (P) = 2xsurface tension(?)radius (r)
Etiology and Pathophysilogy
?Surfactant lowers the surface tension of
alveolar membrane
?Pulmonary immaturity results in surfactant
deficiency
?Alveoli collapse at the end of expiration
leads to respiratory failure
?Surfactant deficiency can arise after
asphyxia/shock and acidosis
Pathology
atelectasis,pulmonary edema,vascular congestion,hemorrhage,
generalized capillary leak and mucosal necrosis leads to the
small air filled terminal airways,the respiratory bronchioles
and alveolar ducts,being surrounded by collapsed alveoli filled
with debris in a near uniform distribution (hyaline membranes)
Pathophysiology
? Lack of alveolar surfactant in the lungs of infants
Avery and Mead,Am J Dis Child 1959
? progressive atelectasis
? loss of functional residual capacity (FRC)
? alteration of ventilation-perfusion ratio
? Weak respiratory muscles and compliant chest wall
? impair alveolar ventilation
? Diminished oxygenation,cyanosis and acidosis
? increased pulmonary vascular resistance (PVR)
? right-to-left shunting through ductus arteriousus
? intrapulmanary ventilation-perfusion mismatch
Clinical Presentation
? Present at birth or within several hours after birth:
? tachypnea
? grunting
? retractions
? cyanosis with increasing oxygen requirements
? Physical findings:
? rales
? poor air exchange
? use of accessory muscles of breathing
? nasal flaring
? abnormal patterns of respiration with apnea
Radiographic Changes of RDS
a bell shaped thorax with diffuse and symmetrical,ground glass”
infiltrates,air bronchograms and decreased lung volume
or severe bilateral opacity characterized by the term of,white out”
Laboratory Findings
? Respiratory and metabolic acidosis
? Phospholipid (PL)/ Sphingomyelin (S) <2:1;
or Phosphatidyl glycerol (PG) negative
? Shaking Test
? Add 1 mL of 95% alcohol to 1 mL of gastric
fluid,shake for 15 seconds,watch for foam
formation
Diagnosis and Differential Diagnosis
?,Wet lung” or transient respiratory distress
? Amniotic fluid or meconium aspiration syndrome
? Group B hemolytic Streptococcus pneumonia
? Diaphragmatic hernia
Treatment
? Careful assessment and resuscitation
? Adequate ventilation,oxygenation,circulation and
temperature must be assured
? Surfactant replacement therapy (natural/synthetic)
? Ventilatory management (CPAP,IPPV,PEEP)
? Acid-base and electrolyte homeostasis
? Closure of patent ductus arteriousus (PDA)
? Supportive treatment
? Antibiotic
Respiratory Management
? Continuous Positive Airway Pressure (CPAP)
Indication,when FiO2>0.6,PaO2<50mmHg or TcSO2<85%
Pressure,4~10cm H2O,flow 5L/min,32° C,humidity 100%
? Conventional Mechanical Ventilation (CMV)
Indication,PaO2<50mmHg or TcSO2<85% with CPAP (8cm);
PCO2>70mmHg; or frequent apnea
Complication,PAL (pulmonary air leak)
BPD (bronchopulmonary dysplasia; or CLD)
RLF (retrolental fibroplasia)
VAP (ventilator-associated pneumonia)
Application of Pulmonary Surfactant
Intratracheal instillation,50~200mg/kg,6~12h interval
? Neonatal Respiratory Distress Syndrome (NRDS)
? meconium aspiration syndrome (MAS)
? Pneumonic Respiratory failure
? Acute lung injury,ARDS
? Respiratory failure after open-chest surgery or lung
transplantation
Prevention
? Careful maternal care and fetal monitoring
? Avoidance of asphyxia and infection at birth
? Maternal glucocorticoids (betamethasone,12mgX2,im,
24h apart,dexamethasone,6mgX4,im,6h apart)
? Preventive use of surfactant
The most effective way to prevent RDS is to
prevent preterm delivery,If preterm delivery is
inevitable,attempts to,mature the fetus” are
reasonable.
Tongji Hospital
Neonatal Respiratory Distress Syndrome (NRDS)
or,Hyaline Membrane Disease (HMD)
? Most common cause of respiratory failure in the first days
? Occurring in 1~2% of newborn infants (GA 26~28w,50%,
30~31w,less than 20~25%)
? Mortality ~50% at 20 yrs ago,Survive 80~90% now
? High risk,IDM,GA<37w,multi preg.,C-section,asphyxia,
cold stress,history of prior affected,male or white infants
? Low risk,chronic or pregnancy-associated hypertension,
maternal opiate addiction,PROM,antenatal corticosteroid
Lung Development
?Embryonic Lung Development
?Fetal Lung Development
(Pseudoglandular,Canalicular,Terminal Saccular)
?Postnatal Lung Development
Embryonic Lung Development
primitive lung
main bronchi
lobar bronchi
segmental bronchi
Fetal Lung Development
Pseudoglandular Stage ~ 7th – 16th week
Primitive bronchial tree
Terminal bronchioles
Fetal Lung Development
Canalicular Stage ~ 16th – 24th week
Terminal Saccular Stage ~ 24th – 36th week
Respiratory bronchioles Transitory saccules and ducts
Postnatal Lung Development
Postnatal Development ~ birth – 8 year
Alveolar period
Secondary alveolar septa Alveolar ducts and alveoli
Surfactant
?start synthesis in 20~24w
?increase in 28~32w
?meet demands after 35w
?double in alveolar within 24h
?adult level after 3~7d
?half-life 12~24h
?renew in 24~48,>90% reuse
Surfactant Composition
? Phospholipid 90% (neutral 5%)
saturated 50％
unsaturated 35％
? Protein 10％ (albumin 5%)
SP-A,30~35kDa,18 ologomer,hydrophilic
D,43kDa,12 oligomer
SP-B,8kDa,dimer,hydrophobic
C,4kDa,dimer
Function of Pulmonary Surfactant
? Decrease alveolar surface tension,reduce respiratory work
? Maintain alveoli inflation and functional residual capacity
? Accelerate lung fluid absorption,reduce alveolar effusion
? Pathogen Opsonization,alveolar macrophage activation
Effects,improve oxygenation,
ameliorate ventilation/perfusion
anti-inflammation
Fluid surface tension
Pressure (P) = 2xsurface tension(?)radius (r)
Etiology and Pathophysilogy
?Surfactant lowers the surface tension of
alveolar membrane
?Pulmonary immaturity results in surfactant
deficiency
?Alveoli collapse at the end of expiration
leads to respiratory failure
?Surfactant deficiency can arise after
asphyxia/shock and acidosis
Pathology
atelectasis,pulmonary edema,vascular congestion,hemorrhage,
generalized capillary leak and mucosal necrosis leads to the
small air filled terminal airways,the respiratory bronchioles
and alveolar ducts,being surrounded by collapsed alveoli filled
with debris in a near uniform distribution (hyaline membranes)
Pathophysiology
? Lack of alveolar surfactant in the lungs of infants
Avery and Mead,Am J Dis Child 1959
? progressive atelectasis
? loss of functional residual capacity (FRC)
? alteration of ventilation-perfusion ratio
? Weak respiratory muscles and compliant chest wall
? impair alveolar ventilation
? Diminished oxygenation,cyanosis and acidosis
? increased pulmonary vascular resistance (PVR)
? right-to-left shunting through ductus arteriousus
? intrapulmanary ventilation-perfusion mismatch
Clinical Presentation
? Present at birth or within several hours after birth:
? tachypnea
? grunting
? retractions
? cyanosis with increasing oxygen requirements
? Physical findings:
? rales
? poor air exchange
? use of accessory muscles of breathing
? nasal flaring
? abnormal patterns of respiration with apnea
Radiographic Changes of RDS
a bell shaped thorax with diffuse and symmetrical,ground glass”
infiltrates,air bronchograms and decreased lung volume
or severe bilateral opacity characterized by the term of,white out”
Laboratory Findings
? Respiratory and metabolic acidosis
? Phospholipid (PL)/ Sphingomyelin (S) <2:1;
or Phosphatidyl glycerol (PG) negative
? Shaking Test
? Add 1 mL of 95% alcohol to 1 mL of gastric
fluid,shake for 15 seconds,watch for foam
formation
Diagnosis and Differential Diagnosis
?,Wet lung” or transient respiratory distress
? Amniotic fluid or meconium aspiration syndrome
? Group B hemolytic Streptococcus pneumonia
? Diaphragmatic hernia
Treatment
? Careful assessment and resuscitation
? Adequate ventilation,oxygenation,circulation and
temperature must be assured
? Surfactant replacement therapy (natural/synthetic)
? Ventilatory management (CPAP,IPPV,PEEP)
? Acid-base and electrolyte homeostasis
? Closure of patent ductus arteriousus (PDA)
? Supportive treatment
? Antibiotic
Respiratory Management
? Continuous Positive Airway Pressure (CPAP)
Indication,when FiO2>0.6,PaO2<50mmHg or TcSO2<85%
Pressure,4~10cm H2O,flow 5L/min,32° C,humidity 100%
? Conventional Mechanical Ventilation (CMV)
Indication,PaO2<50mmHg or TcSO2<85% with CPAP (8cm);
PCO2>70mmHg; or frequent apnea
Complication,PAL (pulmonary air leak)
BPD (bronchopulmonary dysplasia; or CLD)
RLF (retrolental fibroplasia)
VAP (ventilator-associated pneumonia)
Application of Pulmonary Surfactant
Intratracheal instillation,50~200mg/kg,6~12h interval
? Neonatal Respiratory Distress Syndrome (NRDS)
? meconium aspiration syndrome (MAS)
? Pneumonic Respiratory failure
? Acute lung injury,ARDS
? Respiratory failure after open-chest surgery or lung
transplantation
Prevention
? Careful maternal care and fetal monitoring
? Avoidance of asphyxia and infection at birth
? Maternal glucocorticoids (betamethasone,12mgX2,im,
24h apart,dexamethasone,6mgX4,im,6h apart)
? Preventive use of surfactant
The most effective way to prevent RDS is to
prevent preterm delivery,If preterm delivery is
inevitable,attempts to,mature the fetus” are
reasonable.
