The biological role and future therapeutic uses of nitric oxide in extracorporeal membrane oxygenation, a narrative review.

BACKGROUND: Nitric oxide (NO) is a gas naturally produced by the human body that plays an important physiological role. Specifically, it binds guanylyl cyclase to induce smooth muscle relaxation. NO's other protective functions have been well documented, particularly its protective endothelial functions, effects on decreasing pulmonary vascular resistance, antiplatelet, and anticoagulation properties. The use of nitric oxide donors as vasodilators has been known since 1876. Inhaled nitric oxide has been used as a pulmonary vasodilator and to improve ventilation perfusion matching since the 1990s. It is currently approved by the United States Food and Drug Administration for neonates with hypoxic respiratory failure, however, it is used off-label for acute respiratory distress syndrome, acute bronchiolitis, and COVID-19. PURPOSE: In this article we review the currently understood biological action and therapeutic uses of NO through nitric oxide donors such as inhaled nitric oxide. We will then explore recent studies describing use of NO in cardiopulmonary bypass and extracorporeal membrane oxygenation and speculate on NO's future uses.

The safe addition of nitric oxide to the sweep gas of the extracorporeal membrane oxygenation circuit in a pediatric cardiac intensive care unit.

Background: Nitric Oxide (NO) is a naturally occurring modulator of inflammation found in the human body. Several studies in the pediatric cardiothoracic surgery literature have demonstrated some beneficial clinical effects when NO is added to the sweep gas of the cardiopulmonary bypass circuit.Purpose: Our primary aim was to determine the safety of incorporating nitric oxide into the oxygenator sweep gas of the extracorporeal membrane oxygenation (ECMO) circuit. Secondarily, we looked at important clinical outcomes, such as survival, blood product utilization, and common complications related to ECMO.Methods: We performed a single center, retrospective review of all patients at our institution who received ECMO between January 1, 2017 and March 31, 2023. We began additing NO to the ECMO sweep gas in 2019. Results: There were no instances of clinically significant methemoglobinemia with the addition of NO to the sweep gas (0% vs 0%, p = 1). The median daily methemoglobin level was higher in those who received NO via the sweep gas when compared to those who did not (1.6 vs 1.1, p = <0.001). Conclusions: The addition of NO to the sweep gas of the ECMO circuit is safe.

Risk Factors for an Elevated Ventricular End-Diastolic Pressure Prior to the Fontan Operation.

Systemic ventricular end-diastolic pressure (SVEDP) is an important determinant of pulmonary artery pressure in those with a Fontan circulation. Predictors of an elevated SVEDP have been incompletely identified in this population. All who underwent the Fontan operation at our center between 1/2009 and 12/2013 were retrospectively identified. SVEDP at the pre-Fontan catheterization and other patient variables were extracted. We identified 61 patients. Pre-Fontan SVEDP was positively associated with systemic ventricular systolic pressure (ß = 0.4, p = 0.004), aortic systolic pressure (ß = 0.3, p = 0.007), aortic mean pressure (ß = 0.3, p = 0.02), and decreased ventricular systolic function (p = 0.03). Compared to those with pre-Fontan SVEDP ≤ 7 mmHg, patients with SVEDP > 7 mmHg had higher average ventricular systolic pressure (85.0 ± 7.5 vs. 78.7 ± 8.3 mmHg, p = 0.003), higher average descending aorta mean pressure (62.4 ± 4.9 vs. 58.6 ± 8.1 mmHg, p = 0.03), and a higher incidence of decreased ventricular systolic function (36 vs. 15%, p = 0.07). For those with a systemic right ventricle, the SVEDP decreased significantly from the pre-Stage 2 to pre-Fontan measurements (8.7 ± 2.6 vs. 7.3 ± 2.0 mmHg, p = 0.02), but not for those with a systemic left ventricle (7.8 ± 2.0 vs. 7.2 ± 1.8 mmHg, p = 0.3). At pre-Fontan catheterization, decreased ventricular systolic function and markers of systemic afterload were positively associated with the SVEDP. SVEDP decreased significantly after Stage 2 for those with a systemic right ventricle, but not for those with a systemic left ventricle; the systemic right ventricle may be particularly vulnerable to pre-Stage 2 volume loading.

Left Pulmonary Artery from the Ascending Aorta: A Case Report and Review of Published Cases.

The left pulmonary artery arising from the ascending aorta is an infrequent finding. It may be found isolated or with intracardiac anomalies. We present a new case of the left pulmonary artery arising from the ascending aorta and pool these findings with those of previously reported cases. Associated cardiac, extracardiac, and syndromic findings are discussed along with the implications of these in the evaluation and management of this condition.

Atrial fibrillation in adults with congenital heart disease following cardiac surgery in a single center: Analysis of incidence and risk factors.

OBJECTIVE: The primary aim of our work is to determine the incidence of atrial fibrillation following cardiac surgery in adults with congenital heart disease. Secondary aims include identifying risk factors predictive of developing early postoperative atrial fibrillation and morbidities associated with early postoperative atrial fibrillation. DESIGN: Retrospective analysis. SETTING: Single center, quaternary care children's hospital. PATIENTS: This review included patients at least 18 years of age with known congenital heart disease who underwent cardiac surgery requiring a median sternotomy at our congenital heart center from January 1, 2012 to December 31, 2016. INTERVENTIONS: None. OUTCOME MEASURES: The primary outcome was early postoperative atrial fibrillation. Secondary outcomes included preoperative comorbidities, preoperative echocardiographic findings, operative details, and postoperative morbidities, such length of stay, reintubation, stroke, and death. RESULTS: The incidence of early postoperative atrial fibrillation was 21%. Those who developed early postoperative atrial fibrillation were older (50 years vs 38 years, P =< .001), had a history of atrial fibrillation prior to surgery, had preoperative pulmonary hypertension, and had longer cardiopulmonary bypass times (103 minutes vs 84 minutes, P = .025) when compared to those who did not develop postoperative atrial fibrillation. Multivariate analysis identified age greater than 60, preoperative pulmonary hypertension, mitral valve intervention, and the need for postoperative inotropic support as being independent predictors of postoperative atrial fibrillation. Those who developed postoperative atrial fibrillation remained in the hospital longer (9 days vs 7 days, P =< .001). CONCLUSIONS: Atrial fibrillation is a common complication following cardiac surgery in adults with congenital heart disease. Age, preoperative comorbidities, type of surgical intervention, and the need for perioperative inotropic infusions may predict the risk of atrial fibrillation in this unique patient population.

Recurrent nonbacterial thrombotic endocarditis: A novel therapeutic approach.

We present the case of a 29-year-old male with a history of Mizuho hemolytic anemia, a rare form of unstable hemoglobinopathy, who presented with congestive heart failure secondary to recurrent valve thrombosis despite appropriate oral anticoagulation. He subsequently required mitral and aortic valve replacement. Pathologic examination revealed extensive nonbacterial thrombotic endocarditis. Due to recurrent thrombosis despite therapeutic anticoagulation, we elected to treat him with red blood cell exchange transfusions and hydroxyurea. He has remained free of symptoms for almost two years with this treatment regimen without side effects. .