Tracheal Ligation and Corticosteroids in Congenital Diaphragmatic Hernia: For Better for Worse?

Abstract

C ongenital diaphragmatic hernia (CDH) continues to frustrate clinicians for several reasons: it is not possible to predict accurately the extent of pulmonary hypoplasia in the individual fetus and the postnatal response to treatment modalities such as inhalational nitric oxide (NO) is variable. Moreover, the use of extra corporeal membrane oxygenation (ECMO) carries a high morbidity and sometimes profound long-term sequelae.Analysis of the literature reveals a myriad of treatment modalities proposed as "solutions" for the problem pulmonary hypoplasia in CDH. They range from termination of pregnancy following prenatal ultrasound to gentle handling of the lung postnatally to diminish iatrogenic damage of the fragile hypoplastic lungs (1). The fetal sheep model of CDH opened the way to fetal intervention and endoscopic fetoscopic procedures (FETENDO) such as tracheal ligation/occlusion in the human (2-7). Others have studied the basic mechanisms of pulmonary growth in a drug-induced CDH model (the Nitrofen rodent model) with or without the evaluation of additional treatment modalities such as corticosteroids and/or TSH releasing hormone (TRH) (8 -14).The supposed "lung growth" resulting from tracheal ligation is not founded on clean concepts of underlying mechanisms, although a variety of factors has been suggested (15-17).Intriguing are recent observations from different laboratories of the negative effects of tracheal ligation, in fetal sheep, on type II cell differentiation, as nicely evaluated by Kay et al. in this issue (18). The question of whether we will end up with a combined approach of tracheal ligation/occlusion and maternal betamethasone therapy to rescue type II cell differentiation as optimal treatment of CDH in humans is therefore still open.We have to bear in mind that the experiments described in the paper of Kay et al. were not conducted in a CDH model. As a consequence, we can only assume that the response will be the same in the hypoplastic lungs of CDH. However, no research data are available to support this assumption. Other questions are unanswered too, because the authors only assessed certain structural features of Type II cell density and markers of mRNA for two surfactant proteins. Whether steroids do more than up-regulate mRNA for the surfactant proteins or enhance function remains controversial. The study by Kay et al. involved no physiologic assessment of lung function, gas exchange or the development of pulmonary hypertension.Before we apply the results of the experimental approach of Kay et al. in a clinical setting, we have to analyze the arguments for the use of corticosteroids to enhance lung development in prenatally diagnosed CDH, because the few reports on the use of corticosteroids in human CDH consist of personal communications, individual case reports, and anecdotal small series. However prenatal steroids are used to enhance lung development in premature infants.

Hernia diafragmática congénita. Experiencia en el Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 1999-2009

“…Aún no se ha definido si el uso de corticosteroides es benéfico en los pacientes con HDC diagnosticada prenatalmente; su uso se ha basado en la posible deficiencia de surfactante en estos pacientes (19)(20)(21).…”

The History of Congenital Diaphragmatic Hernia from 1850s to the Present

“…But this drive for accelerated growth was found to have negative effects on type II cells, 33 which has prompted some investigators to study whether antenatal steroids could reverse these adverse effects of tracheal occlusion on lung maturation. 34,35 The preoperative care now reflects the fact that the pulmonary hypoplasia and pulmonary hypertension caused by CDH represent a physiologic emergency, not a surgical one. The optimal timing of surgery for delayed repair, the most currently adopted approach, is unknown.…”