Inhaled nitric oxide and related therapies

Abstract

Children with congenital heart defects are at risk for perioperative pulmonary hypertension if they require corrective or palliative surgery in the first week of life or if they have defects associated with significant pulmonary overcirculation. In addition, children undergoing cavopulmonary connections for single ventricle lesions require low pulmonary vascular resistance for surgical success. Treatment of perioperative pulmonary hypertension with inhaled nitric oxide has become standard therapy in many centers. Related drugs that increase nitric oxide synthesis, including arginine and citrulline, have also been studied in the perioperative period. In this article, previous clinical trials of inhaled nitric oxide, intravenous arginine, and intravenous and oral citrulline in children with perioperative pulmonary hypertension or elevated pulmonary vascular resistance after a cavopulmonary connection are reviewed. In addition, recommendations are presented for each agent on the clinical use in the perioperative setting including clinical indications, assessment of clinical effect, and length of therapy.

Figure 1

Russel et al noted a significant decrease in pulmonary artery pressure compared to baseline in patients who received inhaled nitric oxide at 80 ppm compared to placebo during the 20 minute postoperative study period.

Figure 2

Nitric oxide weaning protocol utilized at Vanderbilt Children’s Hospital. If inhaled nitric oxide is initiated, then attempts to wean the nitric oxide are made to achieve the lowest therapeutic dose using changes in oxygenation or mean arterial pressure as outcomes. Further attempts at weaning are made every 12 hours until the nitric oxide can safely be discontinued.

Figure 3

The hepatic urea cycle is primarily known for processing of nitrogen waste but it is also the major source of the amino acids arginine and citrulline- key intermediates in nitric oxide synthesis.