Detrimental effects of standard medical therapy in congenital diaphragmatic hernia

Abstract

Objective: To evaluate the impact of a nonstandard ventilation strategy on survival in congenital diaphragmatic hernia (CDH).

Background: Despite recent advances, including nitric oxide, CDH remains an unsolved problem with a mortality rate of 35% to 50%. Hyperventilation and alkalization remain common therapies.

Methods: In 1992, the authors prospectively abandoned hyperventilation and alkalization. Patients are lightly sedated and ventilated with the lowest pressure providing adequate chest movement, and the rate is set to patient comfort. Nitric oxide and extracorporeal membrane oxygenation (ECMO) are reserved for life-threatening instability. Surgical repair is delayed 1 to 5 days. Sixty consecutive patients are compared with 29 previous patients treated with hyperventilation and alkalization, 13 before and 16 after the availability of ECMO.

Results: Overall, 47 of 60 patients (78%) in study era 3 survived compared with 2 of 13 (15%) in the hyperventilation era and 7 of 16 (44%) in the hyperventilation/ECMO era (p < 0.0001). The disease severity and the incidence of associated anomalies did not differ between groups. To compare management strategies, patients who had treatment withheld because of lethal associated conditions were then removed from analysis. Peak inspiratory pressure and arterial pH were lower (p < 0.0001) and Paco2 was higher (p < 0.05) in era 3 than in the previous eras. The rate of pneumothorax (1.9%) decreased (p < 0.0001). In era 3, survival was 47 of 53 (89%) treated patients, and 23 of 25 inborn patients with isolated CDH survived (92%).

Conclusions: Nonstandard ventilatory support of patients with CDH has led to significantly improved survival rates. This study sets a survival benchmark and strongly suggests the negative effects of hyperventilation and alkalization.

Figures

Figure 1. Life-table analysis of survival rate, all patients included, displayed over the first 180 days. Difference in the survival rate across eras is highly significant (p

Figure 2. PIP over the first 120 hours of life, expressed as mean ± SEM at 12-hour intervals. Significantly higher peak ventilation pressures were delivered during eras 1 and 2 compared with era 3. The differences between peak ventilation pressure varied significantly across eras, and the difference increased over time (time*era effect, p = 0.00001).

Figure 3. PaCO2 over the first 120 hours of life, expressed as mean ± SEM at 12-hour intervals. The effort to hyperventilate in eras 1 and 2 created nearly identical decrements in arterial PCO2 over time, which were difficult to sustain beyond 96 hours. PaCO2 means were statistically different at all time points except 12 and 108 hours. This difference across eras was maintained across time as well (time*era effect, p < 0.05).

Figure 4. Arterial pH over the first 120 hours of life, expressed as mean ± SEM at 12-hour intervals. Alkalosis was achieved rapidly and maintained in eras 1 and 2. No attempt to alkalinize was made in era 3. Arterial pH was significantly different across the eras at all time points except 12 hours. This effect was maintained across eras and increased over time (time*era effect, p = 0.0003).