Impact of junctional ectopic tachycardia on postoperative morbidity following repair of congenital heart defects.

OBJECTIVE: To determine the incidence of postoperative junctional ectopic tachycardia (JET), we reviewed 343 consecutive patients undergoing surgery between 1997 and 1999. The impact of this arrhythmia on in-hospital morbidity and our protocol for treatment were assessed. METHODS: We reviewed the postoperative course of patients undergoing surgery for ventricular septal defect (VSD; n=161), tetralogy of Fallot (TOF; n=114), atrioventricular septal defect (AVSD; n=58) and common arterial trunk (n=10). All patients with JET received treatment, in a stepwise manner, beginning with surface cooling, continuous intravenous amiodarone, and/or atrial pacing if the haemodynamics proved unstable. A linear regression model assessed the effect of these treatments upon hours of mechanical ventilation, and stay on the cardiac intensive care unit (CICU). RESULTS: Overall mortality was 2.9% (n=10), with three of these patients having JET and TOF. JET occurred in 37 patients (10.8%), most frequently after TOF repair (21.9%), followed by AVSD (10.3%), VSD (3.7%), and with no occurrence after repair of common arterial trunk. Mean ventilation time increased from 83 to 187 h amongst patients without and with JET patients (P<0.0001). Accordingly, CICU stay increased from 107 to 210 h when JET occurred (P<0.0001). Surface cooling was associated with a prolongation of ventilation and CICU stay, by 74 and 81 h, respectively (P<0.02; P<0.02). Amiodarone prolonged ventilation and CICU stay, respectively, by 274 and 275 h (P<0.05; P<0.06). CONCLUSIONS: Postoperative JET adds considerably to morbidity after congenital cardiac surgery, and is particularly frequent after TOF repair. Aggressive treatment with cooling and/or amiodarone is mandatory, but correlates with increased mechanical ventilation time and CICU stay. Better understanding of the mechanism underlying JET is required to achieve prevention, faster arrhythmic conversion, and reduction of associated in-hospital morbidity.

Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide (iNO) is a potential therapeutic agent for the management of acute respiratory distress syndrome (ARDS). Concerns remain, however, regarding the potential toxicity from iNO and/or its oxidative derivatives and methaemoglobinaemia. AIMS: To determine the risk of toxicity from iNO, which includes worsening of lung injury, a prospective study evaluating the acute effects of three concentrations of iNO on gas exchange and haemodynamics in 12 children with ARDS was performed in a tertiary paediatric intensive care unit. INTERVENTION: iNO was administered for one hour at three concentrations (1, 10, and 20 parts per million (ppm)) in a random order of possible dosing schedules to avoid dose accumulation bias. Arterial blood gas, methaemoglobin concentrations, and haemodynamic parameters were obtained at baseline before commencement of iNO, at the end of each study hour, and after iNO was discontinued. Nitric oxide and nitrogen dioxide concentrations were continuously monitored during the study. RESULTS: iNO significantly improved the oxygenation ratio (Pao2/Fio2) from a mean (SEM) baseline of 11.9 (1.7) kPa to 20 (3.9) kPa, 24 (4.5) kPa, and 21.6 (3.9) kPa at 1, 10, and 20 ppm iNO, respectively. There was no significant difference in the improvement in oxygenation achieved between the three concentrations. Correspondingly, there was a significant improvement in oxygenation index (pre-iNO 28.3 (5) v post-iNO 18 (3) (1 ppm), 15 (3) (10 ppm), 16 (3) (20 ppm)). No toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO administration. CONCLUSION: The results show that a low concentration of iNO (1 ppm) is as effective as higher concentrations (10 and 20 ppm) in improving oxygenation in children with ARDS and may be important in minimising toxicity during iNO use.

Inhaled nitric oxide during emergency neonatal transportation.

Inhaled nitric oxide is currently being investigated as a selective pulmonary vasodilator for neonates with persistent pulmonary hypertension. The use of continuous inhaled nitric oxide during emergency transportation of three critically III neonates with meconium aspiration and pulmonary hypertension is described. The successful application of this technique may allow safer transportation of neonates who require high level intensive care including ongoing nitric oxide, high frequency ventilation and/or extracorporeal life support. Regionally based nitric oxide-equipped retrieval teams may relieve the pressure on smaller neonatal intensive care units to provide inhaled nitric oxide therapy and allow centralization of nitric oxide resources, thus facilitating development of expertise and the completion of meaningful research programs with substantial recruitment.

Pharmacological control of pulmonary blood flow with inhaled nitric oxide after the fenestrated Fontan operation.

BACKGROUND: A transient increase in pulmonary vascular resistance can result in hemodynamic compromise after a Fontan operation. An interatrial fenestration is designed to maintain cardiac output in these circumstances but may result in severe hypoxemia and a vicious circle due to hypoxemia induced pulmonary vasoconstriction. Our aim was to determine whether inhaled nitric oxide (iNO), a selective pulmonary vasodilator, could be used to reduce pulmonary vascular resistance in desaturated patients (SaO2 < or = 85%) after a fenestrated Fontan operation. METHODS AND RESULTS: Responses to iNO (20 ppm for 15 min) were assessed in 10 consecutive children with SaO2 < or = 85% and compared with 5 with SaO2 > 85% after a fenestrated Fontan operation. Exposure to iNO resulted in a significant increase in SaO2 (from 64 +/- 5% to 82 +/- 2%, P < .01) and reduction in transpulmonary gradient (TPG) (from 12.2 +/- 1 [SEM] to 9.6 +/- 1.1, P < .01) in patients with baseline SaO2 < or = 85%. Baseline saturation was a predictor of response to iNO, with a greater response in those with lower saturations (r = -.86, P < .01). In contrast, no significant effects were noted in PaO2 or TPG (from 122 +/- 46 mm Hg and 8 +/- 1.8 to 123 +/- 43 mm Hg and 7 +/- 1.2, respectively) in patients with baseline SaO2 > 85%. CONCLUSIONS: iNO improved both oxygenation and TPG in desaturated patients after the fenestrated Fontan operation, possibly by counteracting hypoxemia-induced pulmonary vasoconstriction. A trial of iNO should be considered in clinically unstable desaturated patients after the fenestrated Fontan operation.

Low-dose inhaled nitric oxide for neonates with pulmonary hypertension.

OBJECTIVE: Inhaled nitric oxide (iNO) has been shown to cause selective pulmonary vasodilatation and improve ventilation-perfusion matching and may be an important therapeutic option for the treatment of persistent pulmonary hypertension of the newborn (PPHN). We report our experience on the use of iNO in neonates with severe PPHN. METHODOLOGY: Inhaled NO was administered to 10 infants with PPHN and persistent hypoxaemia (meconium aspiration syndrome, n = 9; pneumonia, n = 1) after failure of conventional therapy to improve oxygenation. With the exception of one infant, iNO was commenced at 10 ppm. RESULTS: After 30 min exposure to iNO, the arterial oxygen tension (PaO2) rose from a median of 49 mmHg (6.5 kPa) [range 12-82 mmHg (1.6-10.9 kPa)] to 75 mmHg (10 kPa) [range 17-450 mmHg (2.3-60 kPa)] (P = 0.005), while the median oxygenation index fell (pre-iNO of 37 vs post-iNO 20) (P = 0.005) and median systemic arterial pressure rose (pre-iNO 46.5 mmHg (6.2 kPa) [range 32-63 mmHg (4.3 to 8.4 kPa vs post-iNO 54.5 mmHg (7.3 kPa) [range 36-74 kPa]) P = 0.005). All infants subsequently continued to receive iNO with the duration of exposure to iNO ranging from 12 to 168 h (median duration 100 h). Three infants died despite showing an initial beneficial response to iNO. The mean duration of intubation for survivors was 11.9 +/- 2.6 days. Methaemoglobinaemia and toxic levels of nitrogen dioxide were not seen during iNO administration. Of the seven survivors, 12 month follow up in two infants and 4 month follow up in four infants showed age-appropriate neurodevelopmental skills, with one infant having very mild hearing loss. CONCLUSIONS: Inhaled NO reduces the oxygenation index by improving the PaO2 and decreasing ventilation pressures, and appears to be clinically useful in severely hypoxaemic infants with PPHN refractory to conventional treatment.

Very-low-dose inhaled nitric oxide: a selective pulmonary vasodilator after operations for congenital heart disease.

Inhaled low-dose nitric oxide (2, 10, 20 ppm), together with high inspired oxygen concentration (0.80), was administered after corrective operations 13 times to 10 infants (median age 6 months) who were at risk of postoperative pulmonary hypertension because of their congenital heart disease and left-to-right shunt. Inhaled nitric oxide, even in a very low dose (2 ppm), caused selective pulmonary vasodilatation. The pulmonary/systemic artery pressure ratio was a predictor of the response to nitric oxide, with a greater response being seen in those with a high ratio (> or = 0.50). In children with a high pulmonary/systemic pressure ratio, the mean pulmonary vascular resistance index fell by 37% to 42%, accompanied by only a 10% fall in the systemic vascular resistance index but a 14% to 16% rise in mean cardiac index. No toxicity was seen in any subject. This exciting new therapy may prove to be an important adjunct in the management of postoperative pulmonary hypertension in the child with congenital heart disease.

Guidelines for the safe administration of inhaled nitric oxide.

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator, potentially useful in the treatment of pulmonary hypertension and ventilation-perfusion mismatch. High doses of inhaled NO and its oxidative product nitrogen dioxide (NO2) may cause acute lung injury. Using a standard infant ventilator, ventilator circuit and test lung, an administration and monitoring strategy has been defined for inhaled NO and these observations validated in eight ventilated infants. In 90% oxygen, doses of inhaled NO > or = 80 parts per million may result in toxic NO2 concentrations.

Inhaled nitric oxide for pulmonary hypertension after repair of exomphalos.

Inhaled nitric oxide was used successfully to treat a newborn infant with severe pulmonary hypertension complicating repair of congenital exomphalos. The infant had failed conventional treatment and extracorporeal membrane oxygenation was unsuitable because of the risk of bleeding from the recent laparotomy. Extended treatment with inhaled nitric oxide appears safe and may offer an alternative to mechanical life support in severe cases of neonatal pulmonary hypertension.

Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.