Role of admission gas exchange measurement in predicting congenital diaphragmatic hernia survival in the era of gentle ventilation

Background/Purpose

Neonates with significant congenital diaphragmatic hernia (CDH) require cardiopulmonary support. Management has been characterized by progressive abandonment of hyperventilation. Ability to prognosticate outcomes using measures of ventilation and oxygenation with gentle ventilation remains unclear. We sought to determine whether assessment of gas exchange at the time of NICU admission is predictive of survival in this current era.

Methods

Neonates with CDH admitted to a Children’s Hospital from 1995 to 2006 were evaluated for demographics, blood gas (ABG) measurements and ventilator settings for the first 48 hours, and discharge outcome.

Results

One-hundred-and-nineteen CDH patients were admitted, 88 (74%) survived. Mean admission ABG pCO₂ was higher in infants who died compared to survivors (86 ± 48 versus 49 ± 20, p ≤ 0.001); positive predictive value (PPV) for mortality of pCO₂ ≥ 80 mmHg was 0.71. Mean first hour preductal oxygen saturation (preductalO₂Sat) was lower in infants who died compared to survivors (81 ± 17 versus 97 ± 5, p < 0.001); PPV for mortality of preductalO₂Sat < 85% was 0.82. Eleven patients met both pCO₂ and preductalO₂Sat criteria, and 10 (91%) died, PPV of 0.92. Within hours of admission, pCO₂ and preductalO₂Sat differences between survivors and nonsurvivors lost significance.

Conclusion

Admission pCO₂ and preductalO₂Sat may be useful in predicting survival in neonatal CDH. The differential in gas exchange between survivors and nonsurvivors loses significance with contemporary neonatal care.     

Ductus venosus closure results in transient portal hypertension—Is this the silent trigger for necrotizing enterocolitis?

Introduction

The etiology of necrotizing enterocolitis (NEC) remains elusive and no definite trigger has been identified. There are no studies to date examining the potential role of closure of the ductus venosus (DV), its effect on increasing portal venous pressure (PVP) and its association to mesenteric venous ischemia in the development of NEC. Our aim was to develop an animal model to examine this physiology.

Methods

Fifteen near-term lambs were used. The DV was occluded in experimental animals by a balloon tip catheter, while the sham controls underwent catheterization without DV occlusion. Vital signs and PVP were monitored for 4 h, followed by intestinal biopsy.

Results

The experimental group (n = 5) demonstrated a significant increase in PVP following DV occlusion (11.87 mm Hg [95% CI: 11.40–12.34]), compared to controls (8.95 mm Hg [95% CI: 8.34–9.56]) (F = 12.16, p = 0.001). Histology of the terminal ileum showed vacuolar degeneration, indicative of reversible cellular damage in the experimental group.

Conclusions

We demonstrate that DV closure in the neonatal lamb leads to transient portal hypertension which is associated with cellular damage and inflammatory changes of the intestinal mucosa. Additional studies will be necessary to determine if the transient portal hypertension following DV closure leads to clinically apparent intestinal ischemia and NEC.     

Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest

BACKGROUND: Glucocorticoids during cardiopulmonary bypass benefit pediatric patients undergoing repair of congenital heart defects and are routine therapy, but underlying mechanisms have not been fully examined. The hypothesis was that glucocorticoids could improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Crossbred piglets (5 to 7 kg) were cooled with cardiopulmonary bypass, followed by 120-min deep hypothermic circulatory arrest. Animals were then warmed to 38 degrees C, removed from bypass, and maintained for 120 min. Methylprednisolone (60 mg/kg) was administered in the cardiopulmonary bypass pump prime (intraoperative glucocorticoids) or 6 hours before bypass (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; preoperative and intraoperative glucocorticoids). Controls (no glucocorticoids) received saline. RESULTS: Pulmonary vascular resistance in controls increased from a baseline of 152 +/- 40 to 364 +/- 29 dynes. s/cm(5) at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 +/- 55 dynes. s/cm(5) at 2 hours of recovery, p < 0.001). However, animals receiving pre and intraoperative glucocorticoids had no increase in pulmonary vascular resistance (155 +/- 54 dynes. s/cm(5)). Plasma endothelin-1 in controls increased from 1.3 +/- 0.2 at baseline to 9.9 +/- 2.0 pg/mL at 2 hours recovery (p < 0.01), whereas glucocorticoid-treated animals had lower endothelin-1 levels (4.5 +/- 2.1 pg/ml, preoperative and intraoperative glucocorticoids; 4.9 +/- 1.7 pg/mL, intraoperative glucocorticoids) at the end of recovery (p < 0.05). Intracellular adhesion molecule-1 in lung tissue was lower in animals receiving pre and intraoperative glucocorticoids (p < 0.05). Myeloperoxidase activity was elevated in control lungs at 2 hours of recovery compared with glucocorticoid-treated groups (p < 0.05). Inhibitor kappaBalpha, the inhibitor of nuclear factor-kappaB, was higher in lungs of animals receiving glucocorticoids compared with controls (p < 0.05). CONCLUSIONS: Glucocorticoids prevented pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest, which was associated with reduced plasma endothelin-1. Glucocorticoids also reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity. Inhibition of nuclear factor-kappaB, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.