Elevated preoperative serum asymmetrical dimethylarginine (ADMA) is associated with poor outcomes after pediatric cardiac surgery

Abstract

Asymmetrical dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is elevated in vascular pathologies such as hypertension and chronic kidney disease. Children undergoing cardiac surgery are at high risk of poor hemodynamic and renal outcomes secondary to cardiopulmonary bypass (CPB). This study tested the hypothesis that elevated preoperative ADMA levels are associated with overall worse clinical outcomes after pediatric CPB. This was a prospective, observational study of 100 patients aged from 2 weeks to 18 years who underwent cardiac surgery involving CPB. Serum ADMA levels were obtained preoperatively and on postoperative days zero through four. Clinical outcomes measured included acute kidney injury (AKI) by pRIFLE criteria, low cardiac output syndrome (LCOS), length of mechanical ventilation, hospital and ICU length of stay, unplanned reoperation, and mortality. The 29 patients with an elevated preoperative ADMA were more likely to have prolonged mechanical ventilation, increased ICU and hospital length of stay, unplanned reoperation, and LCOS than those with a normal preoperative level. ADMA levels inversely correlated with estimated glomerular filtration rate (eGFR), but did not differ between patients with and without AKI after CPB. Preoperative ADMA levels correlated with hospital length of stay (r(s) = 0.289), ICU length of stay (r(s) = 0.308), and length of mechanical ventilation (r(s) = 0.402); [all p < 0.05]. ADMA levels before surgery had good predictive power for prolonged mechanical ventilation (AUC-ROC 0.809; 95 % CI 0.704, 0.914; p < 0.001). Patients with elevated ADMA before surgery were more likely to have prolonged mechanical ventilation, develop LCOS, require an extended length of stay, and require reoperation. ADMA levels inversely correlated with eGFR, but did not predict AKI. Preoperative serum ADMA appears to identify pediatric cardiac surgery patients at risk of poor postoperative outcomes following CPB.