Lung Volume, Pulmonary Vasculature, and Factors Affecting Survival in Congenital Diaphragmatic Hernia

Abstract

Objectives. There is a wide variation in published mortality from congenital diaphragmatic hernia (CDH). The prevailing opinion is that this variation is related directly to the degree of pulmonary hypoplasia. Our aim was to test the hypothesis that other factors are important for outcome.

The specific objectives of this study were: 1) to quantitate the degree of lung hypoplasia and pulmonary arterial wall thickness in infants eligible for, and treated with, extracorporeal membrane oxygenation (ECMO), using postmortem analysis of lung DNA, wet lung weight, lung volume, and vessel morphometrics; 2) to correlate the degree of lung hypoplasia and vascular changes with functional tests of oxygenation and estimated right ventricular systolic pressures (RVSP); 3) to determine the minimum lung volume necessary for survival; and 4) to determine contributory clinical factors as potential causes of death in ECMO-treated infants with CDH.

Methodology. We retrospectively analyzed all 90 infants with CDH admitted consecutively over a 9-year period to a children's hospital with an ECMO program. Infants were categorized as lived or died, with or without ECMO. Indication for ECMO was an evolving process; however, in general, it was the therapy of last resort for pulmonary insufficiency. Clinically, the single best oxygenation index before ECMO or CDH repair while on conventional ventilation, and serial echocardiograms before, during, and after ECMO, were obtained. Twelve of 14 infants dying with ECMO and 6 of 12 without ECMO had postmortem examinations. Lung volume, DNA content, wet weights, and arterial wall thickness at the level of alveolar ducts were measured in both lungs. Postmortem morphometric findings were correlated with in vivo tests of cardiopulmonary function and contributory clinical factors in mortality.

Results. Sixty-three percent of all infants with CDH and 61% of ECMO-treated infants lived. All infants with CDH requiring ECMO had elevated RVSP/systolic systemic blood pressure ratios before ECMO (0.98 ± 0.24). Eighty-eight percent of ECMO-treated infants with CDH decreased this ratio to <0.5 within 14 days, regardless of lung size. However, infants dying with normal ratios still had increased arterial wall thickness and muscle in both lungs. In infants whose lung volume, DNA, and weight were >45% of values predicted for age-matched controls, the oxygenation index ranged from 4 to 29, significantly less than that in infants with values <45% of predicted values (range, 25 to 133). We speculate that eight infants with lung volumes >45% of that for controls died from potentially preventable surgical and medical complications.

Conclusion. A minimum lung volume of 45% of the value predicted from age-matched controls is required for survival in ECMO-treated infants. The RVSP/systolic systemic blood pressure ratio can be reduced with ECMO to <0.5 in the majority of infants, even with lung volumes inadequate for survival. We speculate that 9% of infants with adequate lung volume were potentially survivable, but died of medical and surgical complications.