Pressure control plus spontaneous ventilation versus volume assist-control ventilation in acute respiratory distress syndrome. A randomised clinical trial.

PURPOSE: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS). METHODS: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO2/FiO2 < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60. RESULTS: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups. CONCLUSIONS: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels.

Modes of administration of nitric oxide devices and ventilators flow-by impact the delivery of pre-determined concentrations.

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. CONCLUSION: 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.

Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).

Is COVID-19 different from other causes of acute respiratory distress syndrome?

Coronavirus disease 2019 (COVID-19) pneumonia can lead to acute hypoxemic respiratory failure. When mechanical ventilation is needed, almost all patients with COVID-19 pneumonia meet the criteria for acute respiratory distress syndrome (ARDS). The question of the specificities of COVID-19-associated ARDS compared to other causes of ARDS is of utmost importance, as it may justify changes in ventilatory strategies. This review aims to describe the pathophysiology of COVID-19-associated ARDS and discusses whether specific ventilatory strategies are required in these patients.

Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome.

BACKGROUND: A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (CRS), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS. METHODS: Gas exchanges, CRS and hemodynamics were assessed at 2 levels of PEEP (15 cmH2O and 5 cmH2O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients. RESULTS: The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55-0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31-0.48]). The PaO2/FiO2 ratio at PEEP 15 cmH2O was higher compared to PEEP 5 cmH2O only in highly recruitable patients (173 [139-236] vs 135 [89-167] mmHg; p < 0.01). Neither PaO2/FiO2 or CRS measured at PEEP 15 cmH2O or at PEEP 5 cmH2O nor changes in PaO2/FiO2 or CRS in response to PEEP changes allowed to identify highly or poorly recruitable patients. CONCLUSION: In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.