Effects of inhaled nitric oxide on haemodynamics and gas exchange in children after having undergone cardiac surgery utilising cardiopulmonary bypass.

INTRODUCTION: For CHD patients undergoing corrective surgery utilising cardiopulmonary bypass, post-operative inhaled nitric oxide has been administered to alleviate pulmonary hypertension. We performed a systematic review and meta-analyses to determine the effect of inhaled nitric oxide on haemodynamics, gas exchange, and hospitalisation characteristics in children immediately after cardiopulmonary bypass. MATERIALS AND METHODS: A systematic review of the literature was performed to identify full-text manuscripts in English. PubMed, EMBASE, and the Cochrane databases were queried. Once manuscripts were identified for inclusion, a list of all the endpoints in each manuscript was created. Endpoints with data present from two or more studies were then kept for pooled analyses. All endpoints included were continuous variables and so mean and standard deviation were utilised as the effect data for comparison. RESULTS: A total of eight studies were deemed appropriate for inclusion. There were significant differences with decreases in mean pulmonary artery pressure of -6.82 mmHg, left atrial pressure of -1.16 mmHg, arteriovenous oxygen difference of -1.63, arterial carbon dioxide concentration of -2.41 mmHg, mechanical ventilation duration of -8.56 hours, and length of cardiac ICU stay duration of -0.91 days. All significant variables achieved p < 0.001. CONCLUSION: Inhaled nitric oxide in children immediately after cardiopulmonary bypass decreases mean pulmonary artery pressure significantly and decreases the arterial carbon dioxide concentration significantly without significantly altering other haemodynamic parameters. This results in a statistically shorter duration of mechanical ventilation and cardiac ICU length of stay without altering overall hospital length of stay.

Postoperative Inhaled Nitric Oxide Does Not Decrease Length of Stay in Pediatric Cardiac Surgery Admissions.

Pulmonary hypertension is one of the most challenging complications in congenital heart surgery. The purpose of this study was to characterize inhaled nitric oxide administration in children with and without pulmonary hypertension who underwent congenital heart surgery and to describe the effect of nitric oxide administration on admission outcomes. This is a cross-sectional study utilizing data from the Pediatric Health Information System (PHIS) and PHIS + databases from 2004 to 2015. Pediatric patients with a congenital heart disease diagnosis were included and divided into groups with pulmonary hypertension that received and not received inhaled nitric oxide and patients without diagnosis of pulmonary hypertension who received and did not receive inhaled nitric oxide. For all admissions, the following were captured: age of admission, gender, year of admission, length of stay, billed charges, inpatient mortality, the presence of specific congenital malformations of the heart, specific cardiac surgeries, and comorbidities. Comparisons between groups were completed using a Mann-Whitney-U test and Fisher's exact test. Outcomes evaluation was completed using univariate and regression analyses. A total of 40,194 pediatric cardiac surgical admissions without pulmonary hypertension were identified. Of these, 726 (1.8%) received inhaled nitric oxide. Regression analyses demonstrated that inhaled nitric oxide was independently associated with increased length of stay, billed charges, and inpatient mortality. A total of 1678 pediatric cardiac surgical admissions with pulmonary hypertension were identified. Of these, 195 (11.6%) received inhaled nitric oxide. Regression analyses demonstrated that inhaled nitric oxide was independently associated with a significant increase in length of stay and billed charges. There was no statistically significant association between inhaled nitric oxide and decrease mortality. Administration of inhaled nitric oxide after pediatric cardiac surgery increases length of stay and billed charges while not providing improved inpatient mortality. In fact, administration of inhaled nitric oxide was associated with increased mortality in those without pulmonary hypertension while not impacting mortality in any way in those with pulmonary hypertension.

Modulation of pulmonary cytochrome P4501A1 expression by hyperoxia and inhaled nitric oxide in the newborn rat: implications for lung injury.

Inhaled nitric oxide (iNO), with supplemental oxygen, is used in the treatment of hypoxic respiratory failure of the newborn. In this study, we tested the hypothesis that exposure of newborn rats to iNO, hyperoxia, or iNO + hyperoxia would modulate the expression of pulmonary cytochrome P450 (CYP)1A1 in relation to acute lung injury. Newborn Fischer 344 rats were maintained in room air, or exposed to iNO, hyperoxia (>95%), or iNO (20 or 40 ppm) + hyperoxia for up to 168 h, and lung injury parameters and CYP1A1 expression were studied. Animals given iNO (40 ppm) + hyperoxia were more susceptible to lung injury than those exposed to hyperoxia or iNO alone. On the other hand, animals exposed to iNO (20 ppm) + hyperoxia did not elicit lung damage. Pulmonary CYP1A1 protein and mRNA expression were induced by hyperoxia, iNO (20 or 40 ppm), or iNO (20 ppm) + hyperoxia for up to 168 h, compared with air-breathing controls. In animals given iNO (40 ppm) + hyperoxia, pulmonary CYP1A1 was enhanced at 48 h, followed by down-regulation at later time points. Immunohistochemistry experiments showed localization of CYP1A1 in the pulmonary epithelial and endothelial cells. In conclusion, because previous studies have shown beneficial effects of CYP1A1 induction in hyperoxic lung injury, our current observations showing maintenance of pulmonary CYP1A1 induction by iNO (20 ppm) + hyperoxia through the 168-h period support the hypothesis that this phenomenon may contribute to the protective effects of iNO against hyperoxic injury.