Endothelial Dysfunction in Children after Cardiopulmonary Bypass

Objectives Cardiopulmonary bypass (CPB) is required for surgical repair of congenital heart defects; however, CBP causes an inflammatory response which profoundly impacts post‐operative management. CBP‐induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, changes in biomarkers, and the presence of capillary leak. However, peripheral vascular endothelial dysfunction has never been quantified in children. We used laser Doppler perfusion monitoring (LDPM) coupled with iontophoresis of vasoactive compounds to assess endothelial function in cutaneous arterioles in infants undergoing CPB. Study Design Enrollment criteria included age less than 1 year and a congenital heart lesion requiring use of CPB. Timing of assessment of endothelial function included pre‐operatively, 2–4 hours and 24 hours after CPB. Trans‐cutaneous iontophoresis of acetylcholine (ACh, endothelium‐dependent vasodilator) was used to trigger increases in local perfusion and LDPM signals were quantified as peak perfusion and area under the curve (AUC). Sodium nitroprusside (NP) provided an endothelium independent control vasodilator. With each assessment of endothelial function, estimates of extracellular water were obtained using bioelectrical impedance analysis. Clinical markers of the severity of postoperative illness were obtained through chart review. Peak serum lactate, total colloid and crystalloid replacement volume, urine output, and peak vasoactive inotrope score will be correlated with the degree of endothelial impairment. Means and standard error of the mean were calculated for peak perfusion and AUC to determine if there was significant change between pre and post‐CPB values. Results 15 patients have completed the study protocol. Comparing pre‐bypass LDPM responses to ACh with initial (2–4 hour) post‐bypass measurements, we observed a significant decrease in both the peak perfusion values (75.6 ± 10.7 vs. 32.3 ± 7.7 perfusion units (PU), p < 0.05) as well as the AUC (19,417 ± 3286 vs. 6980 ± 2197 PU, p < 0.05). The percent change from baseline responses to ACh at 2–4 hours post‐CPB was −56% ± 8.8% for peak values and −61% ± 11% for AUC. Responses to ACh 24 hours after CBP remained impaired, but this effect was not statistically significant. In contrast, responses to NP were not significantly altered at 2–4 or 24 hours post‐CPB. Analysis of LDPM correlation to biochemical and clinical outcomes is ongoing. Conclusion Profound cutaneous vasomotor endothelial dysfunction is present in infants 2–4 hours after separating from CPB. This effect may persist for at least 24 hours. The clinical significance of this finding remains to be determined. Support or Funding Information Dr. Fred Lamb's Laboratory at Vanderbilt Children's Hospital