Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID-19: treatment modalities, clinical response, and outcomes.

BACKGROUND: Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. METHODS: Multicentre, retrospective cohort study conducted in France. RESULTS: From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57-72) years, 37 (29-48), and 5 (3-8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1-5.5) days with a median dosage of 10 (7-13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). CONCLUSIONS: Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.

Impact of global warming on weight in patients with heart failure during the 2019 heatwave in France.

Heatwaves affect human health and should be more and more frequent because of global warming and could lead to increase mortality in general population, especially regarding cardiovascular mortality. During the summer 2019, Europe experienced a strong episode of heatwave. Telemonitoring of patients with heart failure (HF) provide an elegant tool to monitor closely the weights, and we assumed to be able to assess our hypothesis through a nationwide telemonitoring system. Here, we hypothesize that (i) there will be a change in patients' weight during the heatwave and (ii) that the telemonitoring would enable us to follow these changes. The change in weight would be a surrogate for clinical worsening (with or without decompensated HF). Briefly, 1420 patients with a median age of 73.0 years and mean weight of 78.1 kg have been included in this analysis. The relationship between temperature and weight is very strong (P < 10-7 ). The magnitude of the effect seems clinically relevant with a variation of 1.5 kg during a short period. This could expose patients to increased symptoms, HF decompensations, and poor outcomes. These results suggest a new way to implement weight telemonitoring in HF. This suggests also a direct impact of global warming on Human health, with acute episodes that are expected to occur more often, threatening patients with chronic diseases, especially patients with heart failure. In clinical practice, this urges to take into consideration the episodes of extreme heatwave and suggest that we have already useful tools including telemonitoring available in frail patients.

Benefits of Interventional Telemonitoring on Survival and Unplanned Hospitalization in Patients With Chronic Heart Failure.

Aims: To assess the effect of interventional specialized telemonitoring (ITM) compared to standard telemonitoring (STM) and standard of care (SC) on preventing all causes of death, cardiovascular mortality and unplanned hospitalization in heart failure (HF) patients. Methods: We compared outcomes in three groups of HF patients followed by different modalities: SC, STM and ITM. The telemonitoring was performed by the specialized HF-cardiology staff at Toulouse University Hospital. All patients were followed with the same manner including daily weight monitoring using on-line scales, self-monitoring and reporting symptoms via a device. The difference between groups was in the management of the received alerts. In STM-group, patients were contacted by a member of telemedical center and the main responsibility for patient's therapy was taken by their primary care physicians while in the ITM-group, a cardiologist intervenes immediately in case of alerts for diuretic dose adjustment or escalation therapy or programmed hospitalization if necessary. Outcomes were compared between the three study groups and Kaplan-Meier analysis was performed. Results: Four hundred fourteen HF-patients derived from two French cohorts (OSICAT and ETAPES) were included in this study and subsequently enrolled in the following three groups: ITM-group (n = 220), STM-group (n = 99), and SC-group (n = 95). During the mean follow-up period of 341 days, there were significantly fewer primary endpoints like unplanned hospitalization (13.6 vs. 34.3 vs. 36.8%, p < 0.05), all-causes of death (4.5 vs. 20.2 vs. 16.8%, p < 0.05) and cardiovascular mortality (3.2 vs. 15.2 vs. 8.4%, p < 0.05) in the ITM-group. The multivariable logistic regression revealed a significant negative association between the ITM and unplanned hospitalization [OR = 0.303 95% CI (0.165-0.555), p < 0.001) and all-causes of death [OR = 0.255 95% CI (0.103-0.628), p = 0.003], respectively. Kaplan Meier and log rank test showed significant difference in median event-free survival in favor of ITM-group. Conclusions: In the ITM follow-up HF group, delivered by a cardiology team, the rate of unplanned hospitalization and all-causes of death are lower than SC or STM.

New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.

BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. METHODS: This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3 populations with a low rate of rebound effect. Gradual withdrawal of NO combined with pulmonary vasodilators are current practices in this population. The use of last-generation NO devices allowed good compliance with recommendations.

A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease.

OBJECTIVE: To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease. DESIGN: Multicenter, prospective, randomized, controlled trial. SETTING: Seven intensive care units. PATIENTS: A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea, Paco2> 45 mm Hg and two among the following factors: pH <7.35, Paco2 <50 mm Hg, respiratory rate >25/min. INTERVENTIONS: Noninvasive ventilation randomly applied with or without helium (inspired oxygen fraction 0.35) via a face mask. MEASUREMENTS AND MAIN RESULTS: Duration and complications of NIV and mechanical ventilation, endotracheal intubation, discharge from intensive care unit and hospital, mortality at day 28, adverse and serious adverse events were recorded. Follow-up lasted until 28 days since enrollment. Intubation rate did not significantly differ between groups (24.5% vs. 30.4% with or without helium, p = .35). No difference was observed in terms of improvement of arterial blood gases, dyspnea, and respiratory rate between groups. Duration of noninvasive ventilation, length of stay, 28-day mortality, complications and adverse events were similar, although serious adverse events tended to be lower with helium (10.8% vs. 19.6%, p = .08). CONCLUSIONS: Despite small trends favoring helium, this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease.