Introduction

What can we learn from the historical perspective of management of congenital diaphragmatic hernia?

The rapid death of a newborn infant in 1752 led George McCauley (along with his associate John Hunter) to perform an autopsy wherein they identified the intestines, spleen and part of the pancreas in the thorax. They reported their findings in the Philosophical Transactions of the Royal College of Physicians (1754), an early and accurate account of the natural history and gross anatomy of a congenital diaphragmatic hernia (CDH). Interestingly, the autopsy shows a right sided CDH.

Right-Sided Congenital Diaphragmtic Hernia

Photograph of the original drawing of a right sided CDH from McCauley and Hunter’s manuscript.

Autopsy Specimen

Photograph of the autopsy specimen performed by McCauley and Hunter. Preserved at the University of Glasgow in Scotland.

Although diaphragmatic herniation was a previously described entity, most accounts were traumatic in origin. In the early nineteenth century, Cooper, a British surgeon, described the hypoplastic left lung associated with a congenital posterolateral diaphragmatic defect noting it was "no larger than a small nutmeg".

A sixteenth century pathologist named Giovanni Battista Morgagni described a variety of diaphragmatic defects noted via postmortem examination which had allowed the herniation of intra-abdominal contents into the thorax. Though he noted defects of many sizes in varied locations, including both traumatic and congenital among fetal through adult patients, the congenital anteriomedial defect bears his name today.

Vincent Alexander Bochdalek was a nineteenth century anatomist and pathologist whose dedication to the study of anatomy, and specifically diaphragmatic defects, culminated in an 1848 report of observations about the origin of congenital diaphragmatic rupture. He noted previous authors had identified the diaphragmatic defect, but his personal description came from several specimens where he noted a posterior triangular diaphragmatic gap. Bochdalek considered the hernia a result of stretching of a membranous defect without muscle (indicative of a hernia with a sac) and he correctly noted that left sided defects were more common than right. Though subsequent anatomists have questioned his anatomic and embryologic descriptions, his contribution to the understanding of diaphragmatic herniation was extensive. He even predicted the eventual success of surgical repair and described a potential operative approach via a subcostal incision [1][2]. For his early description of the posterior diaphragmatic opening, and out of reverence for his tireless effort and perseverance in elucidating the development and anatomy of the posterior portion of the diaphragm, a congenital posterolateral diaphragmatic hernia is now known as Bochdalek hernia.

The late nineteenth and early twentieth centuries saw the compilation and detailed anatomic description of many cases of diaphragmatic herniation. Henry Bowditch, a Boston physician, described both traumatic and congenital diaphragmatic ruptures/hernias, compiling 88 cases from the literature including 26 congenital hernias [3]. Carl Hedblom, a surgeon from Madison, Wisconsin, collected 375 diaphragmatic hernias of varied types including 44 congenital hernias [4]. In this comprehensive report, he classifies hernias, including congenital, acquired, traumatic, and unknown and describes varied types of operation although there were no operations in the newborn. Mortality among the 44 infants with congenital hernias was 75%.

The era of surgical intervention, as envisioned by Bochdalek, began following the emergence of anesthesia (Morton, 1846). Early surgical failures in the late nineteenth century were followed by the first known successful repairs of a CDH in a nine year old (Heidenhain, 1905) and in a newborn (Johnson, 1931). In 1940, Ladd and Gross reported their case series of sixteen children with pleuroperitoneal canal (foramen of Bochdalek) defects [5]. They stated that a nonoperative approach was futile and that “surgical therapy is the proper treatment” for CDH patients. Their operative management included phrenic nerve paralysis, an abdominal approach via a vertical paramedian or subcostal incision, reduction of the abdominal viscera, primary diaphragmatic repair and meticulous postoperative care. They advocated for operation within 48 hours noting that “the policy of waiting… is apparently responsible for the loss of a great many lives that may have been saved by timely operation.” Mortality among these highly selected cases was 44%.

Additional medical innovation advanced the overall care of CDH patients. The advent and emergence of mechanical ventilation (1950s), neonatal critical care refinement (1960 to the present) and extracorporeal membrane oxygenation (ECMO) (Gibbon, 1954, and Bartlett, 1975) were all critical advances that remain cornerstones of current management. Finally, preoperative stabilization and pressure limited ventilation further ushered in modern management [6].

Contemporary management includes prenatal diagnosis with monitoring (possibly intervention within the setting of a clinical trial), pre- and post-natal risk stratification, postnatal stabilization including pressure limited conventional and high frequency ventilation, extracorporeal life support (ECLS), surgical diaphragmatic reconstruction and long-term multidisciplinary care. This approach results in a current overall mortality of less than 30%.

How do the pathophysiologic aspects of pulmonary hypoplasia, pulmonary hypertension, and ventricular dysfunction interact in the patient with congenital diaphragmatic hernia?

Sometime between the fourth and eighth weeks of gestation, during the embryonic period of pulmonary development, an insult of unknown origin leads to incomplete diaphragmatic and abnormal pulmonary development resulting in a CDH. Pathophysiologic progression through the process of pulmonary development, including pseudoglandular, canalicular, saccular, and early alveolar periods leads to pulmonary hypoplasia. Pulmonary hypoplasia is generally defined as an underdevelopment of the airways (bronchi and bronchioles) and elements of gas exchange (acini and alveoli). It is more specifically, or morphometrically, identified by a decrease in lung weight, number of bronchioles, overall bronchiole cross sectional area, radial alveolar count, and overall alveolar volume [7][8]. In addition, pulmonary functionality is compromised by thickened alveolar membranes and increased interstitial tissue.

Simultaneously, pulmonary vascularization fails to progress appropriately, resulting in pulmonary hypertension. Pulmonary hypertension is generally defined by pathophysiologic pulmonary vascularization and vascular responses, leading to increased pulmonary vascular resistance with progressive vascular and cardiac consequences. This process is marked by decreases in overall vascularity, prominent vascular remodeling, including increased muscularization and medial and adventitial thickness, and abnormal vasoreactivity including exaggerated contraction and impaired relaxation [9].

In the immediate postnatal environment, the lungs become responsible for oxygenation and pulmonary blood flow increases dramatically. Elevated pulmonary vascular resistance increases the workload of the right ventricle beyond the usual physiologic demand. In some patients, left ventricular dysfunction further exacerbates challenges with peripheral perfusion and offloading the pulmonary vasculature. This has been shown to be strongly associated with outcomes.

A 2018 analysis of data from the CDHSG registry showed that 39% of CDH patients will have early right, left, or biventricular dysfunction. Theoretical factors which may contribute to ventricular dysfunction include mechanical compression, decreased fetal pulmonary blood flow, and/or systemic hypoxia and acidosis. Early left ventricular dysfunction further exacerbates underlying PH and may also contribute to early progression toward right heart failure. Despite the interplay between ventricular dysfunction and PH, early ventricular dysfunction was an independent determinant of severity of disease and clinical outcome [10].

The cardiac consequence of ventricular dysfunction layered on top of pulmonary dysfunction can lead to progressive distention of the right ventricle, ongoing systolic/diastolic ventricular dysfunction, and, ultimately, ventricular muscle remodeling and progressive cardiopulmonary failure.

see also Congenital Diaphragmatic Hernia Repair

Content in this topic is referenced in SCORE Congenital Diaphragmatic Hernia overviewLung Physiology, Pathophysiology, Ventilators, and Pneumonia overview