BACKGROUND: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators\' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity.
METHODS: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer.
RESULTS: We identified three iNO-device generations based on the way they deliver NO flow: \"Continuous\", \"Sequential to inspiratory phase\" (I-Sequential) and \"Proportional to inspiratory and expiratory ventilator flow\" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations.
CONCLUSIONS: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations\' accuracy. Ventilator\'s flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested.

UNASSIGNED: Nontuberculous mycobacteria (NTM) infections have emerged as a significant clinical challenge due to their intrinsic multidrug resistance and the limited efficacy of existing treatments. These infections are becoming increasingly prevalent, with a need for new and effective therapeutic strategies.
UNASSIGNED: This review addresses several key aspects of NTM infections: i) pathogenesis and epidemiology; ii) the limitations and challenges of current treatment options; iii) emerging and alternative therapeutic strategies; iv) advanced drug delivery systems such as nanoparticles and efflux pump inhibitors; v) innovative antibacterial alternatives like antimicrobial peptides, bacteriophage therapy, and phytochemicals; and vi) other potential treatment modalities such as inhaled nitric oxide, small molecules, surgical debridement, phototherapy, and immunomodulatory therapy.
UNASSIGNED: Personalized medicine, advanced drug delivery systems, and alternative therapies hold promise for the future of NTM treatment. Early and accurate identification of NTM species, enabled by improved diagnostic methods, is critical for tailoring treatment regimens. Emerging therapies show promise against drug-resistant NTM strains, but overcoming barriers like clinical trials, regulatory hurdles, and high production costs is crucial. Continued research and innovation are essential to improve treatment efficacy and patient outcomes.

Background Congenital heart disease (CHD) is a structural deformity of the heart present at birth. Pulmonary hypertension (PH) may arise from increased blood flow to the lungs, persistent pulmonary arterial pressure elevation, or the use of cardiopulmonary bypass (CPB) during surgical repair. Inhaled nitric oxide (iNO) selectively reduces high blood pressure in the pulmonary vessels without lowering systemic blood pressure, making it useful for treating children with postoperative PH due to heart disease. However, reducing or stopping iNO can exacerbate postoperative PH and hypoxemia, necessitating long-term administration and careful tapering. This study aimed to evaluate, using machine learning (ML), factors that predict the need for long-term iNO administration after open heart surgery in CHD patients in the postoperative ICU, primarily for PH management. Methods We used an ML approach to establish an algorithm to predict \'patients with long-term use of iNO\' and validate its accuracy in 34 pediatric postoperative open heart surgery patients who survived and were discharged from the ICU at Kagoshima University Hospital between April 2016 and March 2019. All patients were started on iNO therapy upon ICU admission. Overall, 16 features reflecting patient and surgical characteristics were utilized to predict the patients who needed iNO for over 168 hours using ML analysis with AutoGluon. The dataset was randomly classified into training and test cohorts, comprising 80% and 20% of the data, respectively. In the training cohort, the ML model was constructed using the important features selected by the decrease in Gini impurity and a synthetic oversampling technique. In the testing cohort, the prediction performance of the ML model was evaluated by calculating the area under the receiver operating characteristics curve (AUC) and accuracy. Results Among 28 patients in the training cohort, five needed iNO for over 168 hours; among six patients in the testing cohort, one needed iNO for over 168 hours. CPB, aortic clamp time, in-out balance, and lactate were the four most important features for predicting the need for iNO for over 168 hours. In the training cohorts, the ML model achieved perfect classification with an AUC of 1.00. In the testing cohort, the ML model also achieved perfect classification with an AUC of 1.00 and an accuracy of 1.00. Conclusion The ML approach identified that four factors (CPB, in-out balance, aortic cross-clamp time, and lactate) are strongly associated with the need for long-term iNO administration after open heart surgery in CHD patients. By understanding the outcomes of this study, we can more effectively manage iNO administration in postoperative open heart surgery in CHD patients with PH, potentially preventing the recurrence of postoperative PH and hypoxemia, thereby contributing to safer patient management.

BACKGROUND: During resuscitation pulmonary artery pressure (PAP) increases. This reduces left ventricular filling, leading to decreased blood flow. Inhaled nitric oxide (iNO) produces selective pulmonary vasodilation. We hypothesized that iNO would lower PAP during resuscitation resulting in increased survival.
METHODS: 30 pigs (40 kg) were subjected to cardiac arrest for 9.5 min after myocardial ischemia induced by coronary artery occlusion of the left anterior descending artery and ventricular fibrillation. During resuscitation, the pigs were randomized to 40 ppm iNO or placebo. The primary outcome was return of spontaneous circulation (ROSC). Pigs achieving ROSC underwent 4-hours intensive care.
RESULTS: The ROSC rate was 9/14 (64%) in the control group and 11/16 (69%) in the iNO group (OR 1.2 95%CI [0.3;5.6], p > 0.99). There was no difference in diastolic aorta pressure/PAP ratio (mean difference -0.99 [95% CI: -2.33-0.36], p = 0.14). Mean pulmonary artery pressure was lower in the iNO group 60 and 120 min after ROSC (mean difference: -12.18 mmHg [95%CI: -16.94; -7.43] p < 0.01 and -5.43 [95%CI: -10.39; -0.46] p = 0.03). Troponin I levels in the iNO group were significantly higher 60 and 120 min after ROSC (mean difference: 266105 ng/l [95%CI: 6356; 525855] p = 0.045 and 420049 ng/l [95%CI: 136779; 703320], p = 0.004). The area at risk of the heart was 33% (SD 1) in controls and 34% (SD 1) in the iNO group. The infarct size divided by the area at risk was 55% (SD 3) in controls and 86% (SD 1) in the iNO group, p = 0.01.
CONCLUSIONS: Application of iNO did not improve the rate of ROSC or hemodynamic function but increased myocardial injury.

UNASSIGNED: Bronchopulmonary dysplasia (BPD) is the commonest adverse outcome of extremely prematurely born infants, and its incidence is increasing. Affected infants suffer chronic respiratory morbidity and are at risk of early onset of chronic obstructive pulmonary disease. It is, therefore, important that these infants are appropriately managed, with efficacious pharmacological treatments.
UNASSIGNED: Searches were made on Embase, PubMed, and the Cochrane database for (\'treatment\' or \'drug therapy/\') and (\'bronchopulmonary dysplasia\' or \'chronic lung disease\') and (\'neonatology\' or \'newborn\' or \'prematurity\' or \'baby\') between 2019 and 2024. Corticosteroids, diuretics, caffeine, anti-asthmatics, nutritional supplements, and medications treating patent ductus arteriosus and pulmonary hypertension are discussed.
UNASSIGNED: Dexamethasone is associated with adverse neurodevelopmental outcomes and impairment of adult lung function. Inhaled corticosteroids have not resulted in significant effects on BPD. Diuretics only result in short-term improvements in lung function and have side-effects. Evidence suggests it is better to wait and see than aggressively treat PDA; inhaled nitric oxide and sildenafil can improve oxygenation, but whether they improve long-term outcomes remains to be tested. Stem cells are a promising therapy, but further research is required. Appropriately designed trials are required to identify efficacious treatments for infants with BPD.

UNASSIGNED: Persistent pulmonary hypertension (PPHT) of the newborn is a disorder of circulatory transition resulting in high pulmonary vascular resistance with extrapulmonary right-to-left shunts causing hypoxemia. In this study, our aim was to evaluate the risk factors, administered treatments, and mortality of patients followed in our neonatal intensive care unit (NICU) due to PPHT over the past six years.
UNASSIGNED: Patients diagnosed with PPHT and followed in the NICU between January 2017 and November 2022 were included in the study. The sociodemographic characteristics, diagnoses that could lead to pulmonary hypertension, the presence of congenital anomalies, the duration of respiratory support treatment and hospital follow-up, treatments administered for PPHT, and mortality rates were evaluated.
UNASSIGNED: Out of 21 patients diagnosed with persistent pulmonary hypertension, 9 of them (42.9%) were male. The mean gestational age of the patients was 37.6±3.7 weeks, and their birth weight was 3006±819grams. The APGAR scores at 1 and 5 minutes were 4(2-7) and 6(3-8), respectively. Risk factors during the antenatal period included fetal distress (38.1%), oligohydramnios (23.8%), intrauterine growth restriction (23.8%), gestational diabetes (14.3%), preeclampsia (4.8%), and chorioamnionitis (4.8%). The median duration of invasive mechanical ventilation for cases requiring respiratory support was 20.1 days, while the median duration of non-invasive ventilation was 3.7 days. Patients with a diagnosis of persistent pulmonary hypertension were treated with inhaled nitric oxide (iNO) in 76.2% of cases, milrinone in 66.7% of cases, sildenafil in 52.4% of cases, and iloprost in 14.3% of cases. The length of hospital stay for patients was 38.4 days, and 9 (42.9%) patients died. The patients who died had severe PPHT along with fetal inflammatory response syndrome (FIRS), congenital heart disease, pulmonary hypoplasia, pneumothorax, hypoxic-ischemic encephalopathy (HIE), and congenital anomalies.
UNASSIGNED: Persistent pulmonary hypertension, characterized by severe hypoxemia, is a neonatal emergency that necessitates early intervention, effective treatment of the underlying cause to prevent potential short-term and long-term morbidities and mortality. Effective treatment of the underlying cause in patients diagnosed with PPHT could reduce morbidity and mortality. It is inevitable to avoid the loss of patients with major abnormalities, severe comorbidities, and unpreventable organ dysfunctions.

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This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.

Interstitial pneumonia is the most common and serious secondary lesion of dermatomyositis. In some cases, patients may develop severe acute pneumonia that can quickly progress to respiratory failure, resulting in high mortality rates. A 57-year-old woman with dermatomyositis and interstitial pulmonary fibrosis experienced severe hypoxemia due to pulmonary infection. Despite receiving various treatments after entering the intensive care unit (ICU), such as anti-infection therapy, lung recruitment, prone position ventilation, sedative and muscle relaxation, the patient\'s oxygen saturation continued to decline. Electrical impedance tomography (EIT) monitoring revealed that prone position could not improve ventilation homogeneity. However, the patient\'s ventilation/perfusion (V/Q) matching significantly improved 10 min after initiation of supine position ventilation combined with inhalation of nitric oxide (iNO). The patient\'s PaO2/FiO2 (P/F) ratio increased from 86 mmHg to 150 mmHg at 30 min post-treatment. iNO treatment continued for 2 days. Then the patient\'s condition improved and she was successfully weaned off the ventilator with rigorous monitoring and symptomatic care. The implementation of mechanical ventilation combined with iNO therapy rapidly improved V/Q matching and oxygenation in a patient with hypoxemia caused by dermatomyositis complicated with interstitial pneumonia. This approach successfully avoided the need for invasive extracorporeal membrane oxygenation (ECMO) support.

A retrospective study of 24 neonates to evaluate the feasibility and efficacy of high frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for transferring critically ill neonates to tertiary neonatal intensive care, who were transported by road ambulance was done. Efficacy was measured by clinical improvement, patient safety was assessed by comparing cardiorespiratory indicators before and after transport, and adverse events during transport. Significant oxygenation improvement was observed in neonates transported with HFOV ± iNO compared to earlier ventilator settings. Pre- and post-transport vital signs were stable, and no transport-related deaths occurred. A substantial rise in median SpO2 was seen after transfer [86 (81, 91) vs. 93 (89, 97) before transport, p <0.001]. Twelve of twenty-one newborns who received nitric oxide demonstrated significant improvement in oxygenation index (a 10% decrease from prior value). Overall survival was 70.8%, however non-transfer or inadequate respiratory treatment may have exacerbated mortality.