Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease. The effects of inhaled nitric oxide on postoperative pulmonary hypertension in infants and children undergoing surgical repair of congenital heart disease. Randomized controlled study of inhaled nitric oxide after operation for congenital heart disease. Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study.
Pulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO.
                Alkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery.
                Critical care unit of a tertiary care pediatric hospital.
                Prospective, randomized, crossover design.
                Twelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease.
                Patients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect.
                Cardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR.
                Inhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period. The role of inhaled nitric oxide in the immediate post-bypass period after surgical repair of congenital heart disease is uncertain. In a controlled, randomized, double-blind study, we tested the hypothesis that inhaled nitric oxide (NO) would reduce pulmonary hypertension immediately after surgical repair of congenital heart disease in 40 patients with preoperative evidence of pulmonary hypertension (mean pulmonary arterial pressure [MPAP] exceeding 50% of mean systemic arterial pressure [MSAP]). Patients were then followed in the intensive care unit (ICU) to document the incidence of severe pulmonary hypertension. Of the patients, 36% (n = 13) emerged from bypass with MPAP > 50% MSAP. In these patients, inhaled NO reduced MPAP by 19% (P = 0.008) versus an increase of 9% in the placebo group. No effect on MPAP was observed in patients emerging from bypass without pulmonary hypertension (n = 23). Inhaled NO was required five times in the ICU, always in the patients who had emerged from cardiopulmonary bypass with pulmonary hypertension (5 of 13 [38%] versus 0 of 23). We conclude that, in infants and children undergoing congenital heart surgery, inhaled NO selectively reduces MPAP in patients who emerge from cardiopulmonary bypass with pulmonary hypertension and has no effect on those who emerge without it. Implications: In a randomized double-blind study, inhaled nitric oxide selectively reduced pulmonary artery pressures in pediatric patients who developed pulmonary hypertension (high blood pressure in the lungs) immediately after cardiopulmonary bypass and surgical repair. Inhaled nitric oxide selectively decreases pulmonary vascular resistance. This study was performed to determine whether inhaled nitric oxide decreases the incidence of pulmonary hypertensive crises after corrective procedures for congenital heart disease.
                Patients with a systolic pulmonary arterial pressure of 50% or more of the systolic systemic arterial pressure during the early postoperative period were randomized to receive 20 parts per million inhaled nitric oxide (n = 20) or conventional therapy alone (n = 20). Acute hemodynamic and blood gas measurements were performed at the onset of therapy. The efficacy of sustained therapy was determined by comparing the number of patients in each group who experienced a pulmonary hypertensive crisis.
                In comparison to controls, there were no significant differences in the baseline and 1-hour measurements of patients who were treated with nitric oxide. Four patients in the control group and 3 patients in the nitric oxide group experienced a pulmonary hypertensive crisis.
                Nitric oxide did not substantially improve pulmonary hemodynamics and gas exchange immediately after operation for congenital heart disease. Nitric oxide also failed to significantly decrease the incidence of pulmonary hypertensive crises. Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. We did a randomised double-blind study to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk.
                We enrolled 124 infants (64 male, 60 female; median age 3 months [IQR 1-5]), 76% with large ventricular or atrioventricular septal defects, who had high pulmonary flow, pressure, or both, and were undergoing corrective surgery for congenital heart disease. They were randomly assigned continuous low-dose inhaled nitric oxide (n=63) or placebo (n=61) from surgery until just before extubation. We measured the numbers of PHTC, time on study gas, and hours spent in intensive care. Analysis was done by intention to treat.
                Compared with placebo, infants receiving inhaled nitric oxide had fewer PHTC (median four [IQR 0-12] vs seven [1-19]; relative risk, unadjusted 0.66, p<0.001, adjusted for dispersion 0.65, p=0.045) and shorter times until criteria for extubation were met (80 [38-121] vs 112 h [63-164], p=0.019). Time taken to wean infants off study gas was 35% longer in the nitric oxide group than in the placebo group (p=0.19), but the total time on the study gas was still 30 h shorter for the nitric oxide group (87 [43-125] vs 117 h [67-168], p=0.023). No important toxic effects arose.
                In infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course, with no toxic effects.
We observed no differences with the use of iNO in the outcomes reviewed. No data were available for several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions given concerns regarding methodologic quality, sample size, and heterogeneity.