thesis
Congenital posterolateral diaphragmatic hernia : pathophysiological studies and clinical picture
- Publication date
- 19 May 1993
- Publisher
- Congenital diaphragmatic hernias are classified according to the location of the
defect: posterolateral hernia with or without a sac (Bochdalek-type), parasternal
hernia through the foramen of Morgagni, central hernia, and diaphragmatic
eventration. The so-called hiatal hernia has a different pathophysiology and a
different clinical presentation. Posterolateral defects account for 85% of congenital
diaphragmatic herniasY Left-sided posterolateral defects occur eight times more
frequently than right-sided defects in the neonatal period. Bilateral defects are rare
and estimated at 3 to 5%.3
Children at the highest risk of dying are they who are symptomatic in the
delivery room or within six hours after birth.' The mortality rate reported in this
group ranges from 40 to 50%." Conversely, those who do not develop respiratory
failure in the first 24 hours of life have an almost 100% chance of survival.
In contrast to other major congenital anomalies the mortality due to congenital
posterolateral diaphragmatic hernia remains high despite improvements in neonatal
intensive care and pediatric surgery.'~ The main reason is that pulmonary
hypoplasia and pulmonary hypertension form the pathophysiological basis for the
clinical picture of respiratory distress and right-to-left shunting that frustrates so
many clinicians responsible for newborns with a diaphragmatic defect.
This thesis presents the research into clinical aspects of congenital posterolateral
diaphragmatic hernia related to pulmonary hypoplasia and pulmonary hypertension;
the pathophysiological background of these disorders was studied in an animal
model. The clinical studies were all carried out in the Pediatric Surgical Intensive
Care Unit of the Sophia Children's Hospital. The animal model was developed by
TenBrinck and coworkers in the Laboratory of Experimental Surgery of the Erasmus
University in Rotterdam.' In this model congenital diaphragmatic hernia is induced
in fetal rats by means of administering a single dose of Nitrofen (2,4-dichlorophenylp-
nitrophenyl ether) on the lOth day of gestation. The model interferes with lung
development in an early stage, thus providing the opportunity to study several
aspects of lung development in relation to both ventilatory capacity and pulmonary
vascular reactivity.
The results of the conducted studies, as they have been reported and discussed
in papers either published or accepted by international journals, form the core of
this thesis. These papers are preceded by a review of the literature focussed on
historical aspects, clinical picture and normal and abnormal lung development. They
are followed by a concluding chapter in which changing concepts concerning
pathogenesis and treatment are discussed