Nitric Oxide Inhalation Research Articles

How to Heal a Broken Heart with Time and a Hybrid Mechanical Circulatory Support Armada

<h3>Introduction</h3> Continuous flow VADs are used as left ventricular assist devices (LVAD) with an off-label option as right ventricular assist device (RVAD). The Berlin Heart® EXCOR is a paracorporeal, pulsatile ventricular assist device (VAD) used for right-, left- or biventricular support. While inotropes are is the first-line treatment in patients in acute cardiogenic shock, mechanical circulatory support (MCS) in that setting has evolved and different devices are available. <h3>Case Report</h3> A 59-year-old male patient was admitted in 06/2020 for inferior pericardiectomy due to hemodynamic instability after right ventricular (RV) lead dislocation with pericardial effusion. He presented severely impaired biventricular function with indication for Impella® 5.5 implantation. With further RV deterioration, a temporary RVAD with a ProtekDuo®canula + CentriMag^TM pump was implanted. The patient was weaned from nitric oxide (NO) inhalation and extubated on the first postoperative day (POD). However, he developed hyperbilirubinemia with Bilirubin > 13 mg/dl under full t-RVAD support and continuous inotrope therapy, with acute-on-chronic renal failure leading to anuria. High urgent listing for transplantation (HTX) was not an option in this clinical situation. The patient gave consent to biventricular assist device (BIVAD) implantation. On POD 19 after pericardiectomy, a HeartMate 3^TM LVAD in a hybrid combination with a Berlin Heart® Excor RVAD was successfully implanted. He was weaned from NO and extubated within 24 hours. On POD 3 after BIVAD, a right ventricular chamber upgrade to a 80ml chamber was performed. After 4 weeks on BIVAD support, the patient developed a haemothorax with need for surgical revision due to overanticoagulation. Thereafter, he slowly recovered and could be discharged from ICU to the normal care ward after 92 days. He has been free from dialysis since 11/2020 and was discharged home with a Berlin Heart®Excor mobile in 12/2020. Active listing for HTX was granted in 06/2021, one year after first admission. The patient is now stable in NYHA 3 with BIVAD support at home. <h3>Summary</h3> Treatment options in biventricular failure are limited. In countries with long waiting list time, hybrid BIVAD support with a continuous flow LVAD and a pulsatile paracorporeal RVAD is feasible and allows successful discharge. Further research is needed to evaluate this clinical approach.

Right-sided heart reperfusion ("Berlin bridge technique") for right ventricle support during left ventricular assist device (LVAD) implantation.

Right-sided heart reperfusion ("Berlin bridge technique") for right ventricle support during left ventricular assist device (LVAD) implantation.

Nitric Oxide Inhalation Therapy Attenuates Postoperative Hypoxemia in Obese Patients with Acute Type A Aortic Dissection.

Objective To investigate the differences between inhaled nitric oxide (iNO) treatment and conventional therapy in the treatment of postoperative hypoxemia in obese patients with acute type A aortic dissection (ATAAD). Methods ATAAD patients diagnosed and treated with emergency surgery in our hospital from June 2017 to December 2019 were retrospectively analyzed. Patients with postoperative hypoxemia were divided into the iNO group and control group. Propensity score matching was used to analyze clinical characteristics and results of the two groups. Results A total of 218 ATAAD patients with BMI ≥ 25 were treated with surgery. Among them, 115 patients developed refractory hypoxemia (64 in the control group and 51 in the iNO group). Patients in the iNO group had significantly shorter invasive mechanical ventilation time, intensive care unit (ICU) stay, and hospital stay. After 6 h of iNO treatment, the PaO2/FiO2 ratio in the iNO group increased significantly, and this ratio was higher than that in the control group at 6, 12, 24, 48, and 72 h after treatment. Conclusion Low-dose iNO could improve oxygenation and shorten mechanical ventilation and ICU stay in patients with hypoxemia after ATAAD surgery, but without significant side effects or increase in postoperative mortality or morbidity. These findings provide a basis for a randomized multicenter controlled trial to assess the efficacy of iNO in the treatment of hypoxemia after ATAAD surgery.

Procalcitonin is associated with postnatal respiratory condition severity in preterm neonate.

Postnatal respiratory failure is common in preterm neonates and is difficult to distinguish from early-onset neonatal bacterial infection by clinical symptoms. Similar to C-reactive protein (CRP), procalcitonin (PCT) is used as a marker of bacterial infection. Recently, it has been reported that the serum PCT levels increase because of respiratory failure immediately after birth. However, there is insufficient information concerning the relationship between biological inflammation markers, such as PCT and CRP, and postnatal respiratory condition severity. Preterm neonates were classified according to the received respiratory management as follows: nonrespiratory support (NRS), respiratory support (RS), surfactant administration therapy (STA), and STA with nitric oxide inhalation therapy (NO). The median serum PCT and CRP levels at 12-36 h postnatally were compared among the four groups. Additionally, the median serum PCT and CRP levels in the STA group were compared by STA timing and STA number. The PCT levels for the NRS, RS, STA, and NO groups were 1.04, 6.46, 12.93, and 86.79 μg/L, respectively; the CRP levels were 0.40, 0.80, 1.10, and 16.40 mg/L, respectively. The PCT levels were significantly lower among neonates receiving STA in the birth subgroup (4.82 μg/L) than among those receiving STA in the admission subgroup (14.71 μg/L). The PCT levels were significantly higher among the STA multiple-dose subgroup (24.87 μg/L) than among the STA single-dose subgroup (12.47 μg/L). No significant differences in the CRP levels were observed. The serum PCT levels in preterm neonates were associated with postnatal respiratory condition severity.

Right Ventricular Function in Acute Respiratory Distress Syndrome: Impact on Outcome, Respiratory Strategy and Use of Veno-Venous Extracorporeal Membrane Oxygenation.

Acute respiratory distress syndrome (ARDS) is characterized by protein-rich alveolar edema, reduced lung compliance and severe hypoxemia. Despite some evidence of improvements in mortality over recent decades, ARDS remains a major public health problem with 30% 28-day mortality in recent cohorts. Pulmonary vascular dysfunction is one of the pivot points of the pathophysiology of ARDS, resulting in a certain degree of pulmonary hypertension, higher levels of which are associated with morbidity and mortality. Pulmonary hypertension develops as a result of endothelial dysfunction, pulmonary vascular occlusion, increased vascular tone, extrinsic vessel occlusion, and vascular remodeling. This increase in right ventricular (RV) afterload causes uncoupling between the pulmonary circulation and RV function. Without any contractile reserve, the right ventricle has no adaptive reserve mechanism other than dilatation, which is responsible for left ventricular compression, leading to circulatory failure and worsening of oxygen delivery. This state, also called severe acute cor pulmonale (ACP), is responsible for excess mortality. Strategies designed to protect the pulmonary circulation and the right ventricle in ARDS should be the cornerstones of the care and support of patients with the severest disease, in order to improve prognosis, pending stronger evidence. Acute cor pulmonale is associated with higher driving pressure (≥18 cmH2O), hypercapnia (PaCO2 ≥ 48 mmHg), and hypoxemia (PaO2/FiO2 < 150 mmHg). RV protection should focus on these three preventable factors identified in the last decade. Prone positioning, the setting of positive end-expiratory pressure, and inhaled nitric oxide (INO) can also unload the right ventricle, restore better coupling between the right ventricle and the pulmonary circulation, and correct circulatory failure. When all these strategies are insufficient, extracorporeal membrane oxygenation (ECMO), which improves decarboxylation and oxygenation and enables ultra-protective ventilation by decreasing driving pressure, should be discussed in seeking better control of RV afterload. This review reports the pathophysiology of pulmonary hypertension in ARDS, describes right heart function, and proposes an RV protective approach, ranging from ventilatory settings and prone positioning to INO and selection of patients potentially eligible for veno-venous extracorporeal membrane oxygenation (VV ECMO).

Evaluation of the clinical efficacy of inhaled nitric oxide synthesized from natural air in conditions of thoracic surgical intervention on the lung tissue

Introduction. Despite the significant development of an-esthetic procedures in the XX–XXI centuries the problem of optimal one-lung ventilation (OLV) of comorbid pa-tients isn’t resolved. Occasionally, there would be a situa-tion when the resectable patient is functionally inoperable or has high risk of intra- and postoperative complications. This article provides one possible solution of this problem. Purpose of the study. To analyze the use of inhaled nitric oxide (INO) on the dependent lung in order to increase the oxygenation index in the clinical practice of thoracic surgery. Materials and research methods. This is a prospec-tive study of the influence of INO on oxyge nation during thoracic operations on the organs of the respiratory sys-tem. The study participants were divided into 2 groups, each comprised of 10 individuals. Group A received INO intraoperatively as part of a combined multicomponent general anesthesia; group B received standard combined multicomponent general anesthesia. All patients under-went analysis of the gas composition of arterial blood at 2 control points: the 1st one was 10 minutes after the be-ginning of OLV; the 2nd — 40 minutes after INO entered the respiratory circuit (immediately after receiving the result of the 1st control point). Research results. In the INO group an increasing of oxygenation index was observed in 8 out of 10 cases (p=0.022). In the control group an increasing of oxygenation index occured in 2 cases out of 10 (p=0.037). Conclusions. Based on the available data a positive cor-relation was found between the raise of oxygenation in-dex and the use of INO in conditions of ALV for thoracic interventions. It could potentially help to increase the number of operable patients, reduce operative risks and intraoperative time for the borderline operability group.

Evaluation of the effect of nitric oxide inhalation in the patients with chronic thromboembolic pulmonary hypertension or pulmonary disease during balloon pulmonary angioplasty.

Balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary disease (CTEPD) is performed worldwide. High mean pulmonary arterial pressure (mPAP) during BPA is associated with aggravation of procedure‐related complications. Inhaled nitric oxide (NO) acts as a pulmonary vasodilator in CTEPH patients. The aim of this retrospective observational study was to evaluate the effects of inhaled NO in CTEPH/CTEPD patients during BPA. We assessed hemodynamic changes and the frequency of procedure‐related complications with or without NO inhalation. We performed 338 consecutive BPA in 72 CTEPH/CTEPD patients between April 2016 and November 2020. Since December 2019, all 16 patients (72‐BPA sessions) inhaled NO during the procedure as a routine. Inhaled NO significantly reduced mPAP from 31.3 ± 8.5 to 27.2 ± 6.8 mmHg (p < 0.001) without lowering systemic blood pressure (systolic: 139.9 ± 19.9 vs. 135.3 ± 21.8 mmHg; p = 0.247, diastolic: 82.8 ± 13.0 vs. 79.0 ± 9.3 mmHg; p = 0.085, before vs. after NO inhalation, respectively). Procedure‐related complications were observed in 46 sessions (13.6%). The incidence of hemoptysis was significantly higher in the NO group than in the non‐NO group (20.8% vs. 10.9%; p = 0.031). In contrast, all fatal complications (death and use of positive pressure ventilation) occurred in the non‐NO group, but the difference was not statistically significant (0 sessions [0.0%] vs. 7 sessions [2.6%], p = 0.353). Inhaled NO acts as a selective pulmonary vasodilator in CTEPH/CTEPD patients during the BPA procedure.

Nitric oxide inhalation for the newborn in Japan

Nitric oxide inhalation for the newborn in Japan

Abstract 11986: A Safety Study of Intermittent versus Continuous Inhaled NO Therapy in Spontaneously Breathing COVID-19 Patients: A Randomized Controlled Trial

Introduction: Nitric oxide (NO) inhalation (iNO) therapy has been approved as a salvage therapy in patients with acute respiratory distress syndrome. However, the optimal patterns of therapeutic administration and iNO efficacy in COVID-19 patients with hypoxemia have not been studied so far. Hypothesis: A combination of high-concentration intermittent iNO treatment with continuous low-concentration NO gas supplementation between therapeutic high-dose iNO sessions may be a safe approach in COVID-19 patients with hypoxemia compared with the high-dose spike therapy alone. Methods: A single-center randomized controlled trial examined the safety of administration of intermittent high-dose iNO therapy versus the intermittent therapy in the presence of continuous low-dose iNO in spontaneously breathing COVID-19 patients (www.clinicaltrials.gov #NCT04476992). The study comprised adult patients tested positive for the COVID-19 by RT-PCR, who required oxygen and was admitted to the respiratory hospital. After attrition, a total of 20 patients were enrolled and randomized to the group of intermittent high-dose iNO treatment combined with continuous low-dose NO supplementation (group 1) or the group of intermittent high-dose iNO treatment(group 2). Control group (group 3) comprised retrospective patients who received conventional treatment for COVID-19 in hospital. Results: Administration of intermittent high-dose iNO therapy combined with continuous low-dose NO supplementation significantly improved physiological interactions in the heart-lung blood circulation system and was not associated with the extrapulmonary organ dysfunction. Safety parameters are presented in Table 1. Conclusions: High-dose intermittent iNO therapy combined with continuous low-dose NO gas supplementation may be considered a safe adjuvant modality of treatment for COVID-19 in spontaneously breathing hypoxemic patients.

Left atrial myxoma resection through right mini-thoracotomy in a patient with retrosternal gastric tube.

We report a case with a retrosternal gastric tube after oesophagectomy, who required left atrial myxoma resection, pulmonary vein isolation and left atrial appendage closure. A right mini-thoracotomy approach was adopted to avoid neo-oesophagus injury, and nitric oxide inhalation was useful to facilitate one-lung ventilation while dissecting the pleural adhesion.

Systematic Evaluation of Early Inhalation of Nitric Oxide for Prevention and Treatment of Bronchopulmonary Dysplasia in Premature Infants

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, which seriously affects the quality of life of premature infants and may even lead to death of premature infants. At present, there is no unified opinion on the prevention and treatment of BPD, and the mechanism of its occurrence and development is not completely clear in clinical practice. Therefore, finding a better way to prevent and treat BPD is one of the hot spots in clinical practice. The safety of nitric oxide in premature infants with BPD is a focus of clinical attention, but its systematic evaluation has not been reported. In this study, meta-analysis method was used to analysis. The results demonstrated that there were no obvious differences in the incidence, survival, BPD-free survival, and mortality between the inhaled nitric oxide group (iNO group) and the placebo group. The common complications such as toxemia, necrotizing enterocolitis, and visual impairment between the iNO group and the placebo group were not obvious. This suggests that the use of NO to prevent BPD in premature infants has no obvious effect.

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity.

Inhaled nitric oxide (INO) is used to treat hypoxic respiratory failure without clear evidence of benefit. Future trials to evaluate its use will be designed based on an understanding of the populations in which this therapy is provided and with outcomes based on patient characteristics, for example, a history of premature birth. This was a multi-center prospective observational study that evaluated subjects in the pediatric ICU who were treated with INO for a respiratory indication, excluding those treated in the neonatal ICU or treated for birth-related disease. We used logistic regression to evaluate characteristics associated with mortality and duration of mechanical ventilation. Specifically, we compared subjects born early preterm (<32 weeks post-conceptual age), late preterm (32-37 weeks post-conceptual age), and full term. A total of 163 children (median age [interquartile range], 1.8 [0.7-6.0] y) were included, 41 (25.2%) had a history of preterm birth (18 born early preterm and 23 born late preterm). INO was initiated for less-severe lung disease in the early preterm versus late preterm versus full-term subjects (median mean airway pressures, 16 vs 19 vs 19 cm H2O; P = .03), although the oxygenation index and oxygenation saturation index did not differ. The early preterm subjects had more ventilator-free days (median, 18.0, 7.0, 4.5 d; P = .02) and lower 28-d mortality (0, 26.1, 32.0%; P = .007). Lower respiratory tract disease, but not a history of prematurity, was independently associated with lower mortality. INO was used differently in early preterm subjects. Clinical trials that evaluate INO use should have standardized oxygenation deficit thresholds for initiation of therapy and should consider stratifying by early preterm status.

High-Dose Nitric Oxide From Pressurized Cylinders and Nitric Oxide Produced by an Electric Generator From Air.

High-dose (≥ 80 ppm) inhaled nitric oxide (INO) has antimicrobial effects. We designed a trial to test the preventive effects of high-dose NO on coronavirus disease 2019 (COVID-19) in health care providers working with patients with COVID-19. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for health care professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using 2 different NO sources, namely pressurized nitrogen/NO cylinders (INO) and electric NO (eNO) generators. NO gas was inhaled at 160 ppm in air for 15 min twice daily, before and after each work shift, over 14 d by health care providers (NCT04312243). During NO administration, vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO2) concentration. Twelve healthy health care professionals received a collective total of 185 administrations of high-dose NO (160 ppm) for 15 min twice daily. One-hundred and seventy-one doses were delivered by INO and 14 doses by eNO. During NO administration, SpMet increased similarly in both groups (P = .82). Methemoglobin decreased in all subjects at 5 min after discontinuing NO administration. Inhaled NO2 concentrations remained between 0.70 ppm (0.63-0.79) and 0.75 ppm (0.67-0.83) in the INO group and between 0.74 ppm (0.68-0.78) and 0.88 ppm (0.70-0.93) in the eNO group. During NO administration, peripheral oxygen saturation and heart rate did not change. No adverse events occurred. This pilot study testing high-dose INO (160 ppm) for 15 min twice daily using eNO seems feasible and similarly safe when compared with INO.

Role of Sildenafil in Management of Pediatric Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) has high mortality and multiple therapeutic strategies have been used to improve the outcome. Inhaled nitric oxide (INO), a pulmonary vasodilator, is used to improve oxygenation. This study was conducted to determine the role of sildenafil, an oral vasodilator, to improve oxygenation and mortality in pediatric ARDS (PARDS). The prevalence of pulmonary hypertension in PARDS was studied as well. Inclusion criteria included children (1-18 years) with ARDS requiring invasive ventilation admitted to the pediatric intensive care unit of a teaching hospital in Northern India over a 1-year period of time. Thirty-five patients met the inclusion criteria. Pulmonary arterial pressure (PAP) was determined by echocardiogram. Patients with persistent hypoxemia were started on oral sildenafil. The majority of patients (77%) had a primary pulmonary etiology of PARDS. Elevated PAP (>25 mm Hg) was detected in 54.3% patients at admission. Sildenafil was given to 20 patients who had severe and persistent hypoxemia. Oxygenation improved in most patients after the first dose with statistically significant improvement in PaO 2 /FiO 2 ratios at both 12 and 24 hours following initiation of therapeutic dosing of sildenafil. Improvement in oxygenation occurred irrespective of initial PAP. Outcomes included a total of 57.1% patients discharged, 28.6% discharged against medical advice (DAMA), and a 14.3% mortality rate. Mortality was related to the severity of PARDS and not the use of sildenafil. This is the first study to determine the effect of sildenafil in PARDS. Sildenafil led to improvement in oxygenation in nearly all the cases without affecting mortality. Due to unavailability of INO in most centers of developing countries, sildenafil may be considered as an inexpensive alternative in cases of persistent hypoxemia in PARDS. We recommend additional randomized controlled trials to confirm the effect of sildenafil in PARDS as determined in this study.

Prenatal evaluation of functional pulmonary hypoplasia via fetal magnetic resonance imaging.

The purpose of this study was to retrospectively examine the use of lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images to predict functional pulmonary hypoplasia. The subjects of this study were pregnant women who underwent magnetic resonance imaging (MRI). Patients who required nitric oxide inhalation and those who died from respiratory disorders were classified as having functional pulmonary hypoplasia (FPH). All other cases were presented as the control group. We retrospectively analyzed MRI and perinatal data. LLSIR was defined as the ratio of lung signal intensity to liver signal intensity. We examined the relationship between LLSIR and gestational age, compared the LLSIRs in the two groups, and calculated the best cut-off value of the LLSIR to predict FPH. One hundred and ninety-one patients were eligible for this study, and 12 cases were classified as having FPH. In the control group, LLSIR increased with age (r=0.383, p < 0.001). We used the observed/expected LLSIR (o/e LLSIR), which was the ratio of obtained LLSIR to expected LLSIR calculated by the regression line to correct the effect of gestational age. In the FHP group, o/e LLSIR was significantly lower than in the control group (p < 0.001). A receiver operating characteristic curve analysis showed that cases with o/e LLSIR above 0.85 were less likely to cause FPH. Low o/e LLSIR might reflect the histological characteristics of hypoplastic lung structures. O/e LLSIR seems to be a useful MRI parameter for screening FPH.

Assessment of nitric oxide (NO) potential to mitigate COVID-19 severity.

Novel coronavirus disease by SARS-CoV-2 virus (also known as COVID-19) has emerged as major health concern worldwide. While, there is no specific drugs for treating this infection till date, SARS-CoV-2 had spread to most countries around the globe. Nitric oxide (NO) gas serves as an important signaling molecule having vasodilatory effects as well as anti-microbial properties. Previous studies from the 2004 SARS-CoV infection demonstrated that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication cycle and is an effective supportive measure for treating infection in patients with pulmonary complications. NO gas inhalation is being suggested as potential therapy for managing severe acute respiratory distress syndrome in COVID-19 patients. In view of COVID-19 pandemic, several clinical trials are underway to examine the effects of NO inhalation on infected patients. Previously published reports on beneficial effects of endogenous NO and NO inhalation therapy were thoroughly searched to assess the potential of NO therapy for treating COVID-19 patients. Present report summarized the therapeutic importance of NO to reverse pulmonary hypertension, restore normal endothelial activity and produce anti-thrombotic effects. In addition to this, NO also reduces viral infection by inhibiting its replication and entry into the host cell. In absence of vaccine and effective treatment strategies, we suggest that NO inhalation therapy and NO releasing foods/compounds could be considered as an alternative measure to combat COVID-19 infection.

Inhaled Nitric Oxide Delivery Systems for Mechanically Ventilated and Nonintubated Patients: A Review.

Nitric oxide (NO) is a biologically active molecule approved for the treatment of pulmonary hypertension in newborn patients. Commercially available NO delivery systems use pressurized cylinders as the source of NO and a sensor to control the concentrations of NO and nitrogen dioxide (NO2) delivered. Cylinder-based delivery systems are safe and widely used around the world, but they are bulky, expensive, and reliant on a robust supply chain. In the past few years, novel NO generators and delivery systems have been developed to overcome these limitations. Electric NO generators produce NO from ambient air using high-voltage electrical discharge to ionize air, which leads to the formation of NO, NO2, and ozone (O3). A scavenging system is incorporated to reduce the concentration of the toxic byproducts generated in this type of system. NO can also be generated by the reduction of NO2 by ascorbic acid or released from liquid solutions or solid nanoparticles. The development of easy-to-use, safe, and portable NO delivery systems may enable the delivery of NO in the out-patient setting or at home. Furthermore, non-cylinder-based NO generators reduce the cost of NO production and storage and may therefore make NO delivery feasible in low-resource settings. Here we review commercially available systems that can generate and administer inhalable NO.

Inhaled nitric oxide improves pulmonary hypertension and organ functions after adult heart valve surgeries.

Pulmonary hypertension during cardiac surgery is associated with increased morbidity and mortality. Inhaled nitric oxide serves as a selective pulmonary vasodilator and has other potential extrapulmonary protective roles. Its effects on pulmonary hypertension and organ functions after adult valve surgeries were evaluated. From April 2017 to March 2000, 30 patients received inhaled nitric oxide therapy for pulmonary hypertension during weaning from cardiopulmonary bypass in valvular surgery (iNO group). The group was compared with a control group of 65 patients who developed pulmonary hypertension during weaning from cardiopulmonary bypass in valvular surgery and received conventional therapy from April 2014 to March 2017. Intraoperative hemodynamic changes and postoperative Sequential Organ Failure Assessment (SOFA) score were evaluated. The inhalation of nitric oxide lowered the pulmonary-to-systemic pressure ratio (Pp/Ps) (p < 0.0001) in the iNO group, and this ratio after the inhalation was significantly lower than that in the control group (p = 0.015). Moreover, norepinephrine requirement was lower in the iNO group than in the control group (p = 0.0060). The SOFA total scores, respiratory scores, coagulation scores, and the increase of renal scores within postoperative 2 days were lower in the iNO group than in the control group (p < 0.0001, p = 0.0002, p = 0.0013, and p = 0.037). Inhaled nitric oxide therapy ameliorated pulmonary hypertension and improved postoperative respiratory, coagulation, and renal functions in adult valve surgeries.

Clinical Outcomes of Critically Ill Patients Using Inhaled Nitric Oxide (iNO) during Intrahospital Transport.

Critically ill patients with severe hypoxemia are often treated in the intensive care unit (ICU) with inhaled nitric oxide (iNO). These patients are at higher risk when they require intrahospital transportation. In this study, we collected clinical and laboratory data from 221 patients who were hospitalized in the general ICU and treated with iNO at Soroka Medical Center, Israel, between January 2010 and December 2019. We retrospectively compared the 65 patients who received iNO during intrahospital transportation to the 156 patients who received iNO without transportation. Among critically ill patients who were transported while being administered iNO, only one patient had an adverse event (atrial fibrillation) on transport. We found that maximal iNO dosage during ICU stay, duration of mechanical ventilation, and percent of vasopressor support were the only independent risk factors for ICU mortality in both study groups. No difference in primary outcome of ICU mortality rate was found between the critically ill patients treated with iNO during intrahospital transportation and those who were treated with iNO but not transported during the ICU stay. We anticipate that this study will advise clinical decision-making in the ICU, especially when treating patients who are administered iNO.

Disposable Nitric Oxide Generator Based on a Structurally Deformed Nitrite-Type Layered Double Hydroxide.

The inhalation of nitric oxide (NO), which acts as a selective vasodilator of pulmonary blood vessels, is an established medical treatment. However, its wide adoption has been limited by the lack of a convenient delivery technique of this unstable gas. Here we report that a solid mixture of FeIISO4·7H2O and a layered double hydroxide (LDH) containing nitrite (NO2-) in the interlayer spaces (NLDH) stably generates NO at a therapeutic level (∼40 ppm over 12 h from freshly mixed solids; ∼80 ppm for 5-10 h from premixed solids) under air flow (0.25 L min-1) if the NLDH has been prepared by using a reconstruction method. Mg/Al-type LDH was calcined at 550 °C to remove interlayer CO32- and then treated with NaNO2 in water to reconstruct the NLDH. This one-pot, organic solvent-free process can be performed at large scales and is suitable for mass production. Humid air promotes anion exchange between NO2- and SO42- in the solid mixture, resulting in persistent interactions of NO2- and Fe2+, generating NO. In contrast to the previously reported NLDH prepared using an anion-exchange method, the reconstructed NLDH exhibits stable and persistent generation of NO because of partial deformation of the layered structures (e.g., particle aggregation, reduced crystallinity, and enhanced basicity). Degradation of the solid mixture is suppressed under dry conditions, so that a portable cartridge column that is readily available as an NO source for emergency situations can be prepared. This work demonstrates that the interlayer nanospace of LDH serves as a reaction mediator for excellent controllability of solid-state reactions. This inexpensive and disposable NO generator will facilitate NO inhalation therapy in developing countries and nonhospital locations.