High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-Related Acute Respiratory Distress Syndrome: A Multicenter, Randomized Open-Label Clinical Trial.

OBJECTIVE: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. DESIGN: Multicenter, randomized, open-label, clinical trial. PARTICIPANTS: Consecutive patients with confirmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina. INTERVENTION: 16 mg of dexamethasone intravenously daily for five days followed by 8 mg of dexamethasone daily for five days or 6 mg of dexamethasone intravenously daily for 10 days. MAIN OUTCOME AND MEASURES: The primary outcome was ventilator-free days during the first 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the first 28 days. RESULTS: Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms. CONCLUSIONS: Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator.

High-Flow Oxygen Therapy Application in Chronic Obstructive Pulmonary Disease Patients With Acute Hypercapnic Respiratory Failure: A Multicenter Study.

OBJECTIVES: To evaluate the effect of high-flow oxygen implementation on the respiratory rate as a first-line ventilation support in chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. DESIGN: Multicenter, prospective, analytic observational case series study. SETTING: Five ICUs in Argentina, between August 2018 and September 2019. PATIENTS: Patients greater than or equal to 18 years old with moderate to very severe chronic obstructive pulmonary disease, who had been admitted to the ICU with a diagnosis of hypercapnic acute respiratory failure, were entered in the study. INTERVENTIONS: High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation. MEASUREMENTS AND MAIN RESULTS: Forty patients were studied, 62.5% severe chronic obstructive pulmonary disease. After the first hour of high-flow nasal cannula implementation, there was a significant decrease of respiratory rate compared with baseline values, with a 27% decline (29 vs 21 breaths/min; p < 0.001). Furthermore, a significant reduction of Paco2 (57 vs 52 mm Hg [7.6 vs 6.9 kPa]; p < 0.001) was observed. The high-flow nasal cannula application failed in 18% patients. In this group, the respiratory rate, pH, and Paco2 showed no significant change during the first hour in these patients. CONCLUSIONS: High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation was an effective tool for reducing respiratory rate in these chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Early determination and subsequent monitoring of clinical and blood gas parameters may help predict the outcome.

Prevalence of Reverse Triggering in Early ARDS: Results From a Multicenter Observational Study.

BACKGROUND: The prevalence of reverse triggering (RT) in the early phase of ARDS is unknown. RESEARCH QUESTION: During early ARDS, what is the proportion of patients affected by RT, what are its potential predictors, and what is its association with clinical outcomes? STUDY DESIGN AND METHODS: This was prospective, multicenter, and observational study. Patients who met the Berlin definition of ARDS with less than 72 h of mechanical ventilation and had not been paralyzed with neuromuscular blockers were screened. A 30-min recording of respiratory signals was obtained from the patients as soon as they were enrolled, and the number of breaths with RT were counted. RESULTS: One hundred patients were included. ARDS was mild to moderate in 92% of them. The recordings were obtained after a median of 1 day (interquartile range, 1-2 days) of ventilation. Fifty patients had RT, and most of these events (97%) were not associated with breath stacking. Detecting RT was associated with lower tidal volume (Vt) and less opiate infusion. The presence of RT was not associated with time to discontinuation of mechanical ventilation (subdistribution hazard ratio, 1.03; 95% CI, 0.6-1.77), but it possibly was associated with a reduced hospital mortality (hazard ratio, 0.65; 95% CI, 0.57-0.73). INTERPRETATION: Fifty percent of patients receiving assist-control ventilation for mild or moderate ARDS, sedated and nonparalyzed, demonstrate RT without breath stacking on the first day of mechanical ventilation. RT may be associated with low VTS and opiate doses. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02732041; URL: www.clinicaltrials.gov.

Automatic detection of reverse-triggering related asynchronies during mechanical ventilation in ARDS patients using flow and pressure signals.

Asynchrony due to reverse-triggering (RT) may appear in ARDS patients. The objective of this study is to validate an algorithm developed to detect these alterations in patient-ventilator interaction. We developed an algorithm that uses flow and airway pressure signals to classify breaths as normal, RT with or without breath stacking (BS) and patient initiated double-triggering (DT). The diagnostic performance of the algorithm was validated using two datasets of breaths, that are classified as stated above. The first dataset classification was based on visual inspection of esophageal pressure (Pes) signal from 699 breaths recorded from 11 ARDS patients. The other classification was obtained by vote of a group of 7 experts (2 physicians and 5 respiratory therapists, who were trained in ICU), who evaluated 1881 breaths gathered from recordings from 99 subjects. Experts used airway pressure and flow signals for breaths classification. The RT with or without BS represented 19% and 37% of breaths in Pes dataset while their frequency in the expert's dataset were 3% and 12%, respectively. The DT was very infrequent in both datasets. Algorithm classification accuracy was 0.92 (95% CI 0.89-0.94, P < 0.001) and 0.96 (95% CI 0.95-0.97, P < 0.001), in comparison with Pes and experts' opinion. Kappa statistics were 0.86 and 0.84, respectively. The algorithm precision, sensitivity and specificity for individual asynchronies were excellent. The algorithm yields an excellent accuracy for detecting clinically relevant asynchronies related to RT.

Prone position in patients with acute respiratory distress syndrome. / Decúbito prono en pacientes con síndrome de distrés respiratorio agudo.

Acute respiratory distress syndrome occupies a great deal of attention in intensive care units. Despite ample knowledge of the physiopathology of this syndrome, the focus in intensive care units consists mostly of life-supporting treatment and avoidance of the side effects of invasive treatments. Although great advances in mechanical ventilation have occurred in the past 20 years, with a significant impact on mortality, the incidence continues to be high. Patients with acute respiratory distress syndrome, especially the most severe cases, often present with refractory hypoxemia due to shunt, which can require additional treatments beyond mechanical ventilation, among which is mechanical ventilation in the prone position. This method, first recommended to improve oxygenation in 1974, can be easily implemented in any intensive care unit with trained personnel. Prone position has extremely robust bibliographic support. Various randomized clinical studies have demonstrated the effect of prone decubitus on the oxygenation of patients with acute respiratory distress syndrome measured in terms of the PaO2/FiO2 ratio, including its effects on increasing patient survival. The members of the Respiratory Therapists Committee of the Sociedad Argentina de Terapia Intensiva performed a narrative review with the objective of discovering the available evidence related to the implementation of prone position, changes produced in the respiratory system due to the application of this maneuver, and its impact on mortality. Finally, guidelines are suggested for decision-making.

Decúbito prono en pacientes con síndrome de distrés respiratorio agudo / Prone position in patients with acute respiratory distress syndrome

RESUMEN El síndrome de distrés respiratorio agudo ocupa gran atención en la unidad de cuidados intensivos. A pesar del amplio conocimiento alcanzado sobre la fisiopatología de éste síndrome, el enfoque en la unidad de cuidados intensivos consiste, en gran parte, en un tratamiento de soporte vital y en evitar los efectos secundarios de las terapéuticas invasivas. Si bien, durante los últimos 20 años, se generaron grandes avances en ventilación mecánica con un impacto importante sobre la mortalidad, ésta continúa siendo elevada. Una característica de los pacientes con síndrome de distrés respiratorio agudo, sobre todo los más severos, es la presencia de hipoxemia refractaria debido a la existencia de shunt, pudiendo requerir tratamientos adicionales a la ventilación mecánica, entre ellos la ventilación mecánica en decúbito prono. Este método, recomendado para mejorar la oxigenación por primera vez en 1974, puede ser implementado fácilmente en cualquier unidad de cuidados intensivos con personal entrenado. El decúbito prono tiene un sustento bibliográfico sumamente robusto. Varios ensayos clínicos randomizados han demostrado el efecto del decúbito prono sobre la oxigenación en pacientes con síndrome de distrés respiratorio agudo medida a través de la relación PaO2/FiO2 e incluso su impacto en el aumento de la sobrevida de estos pacientes. Los integrantes del Comité de Kinesiología Intensivista de la Sociedad Argentina de Terapia Intensiva realizaron una revisión narrativa con el objetivo de exponer la evidencia disponible en relación a la implementación del decúbito prono, los cambios producidos en el sistema respiratorio por la aplicación de la maniobra y su impacto sobre la mortalidad. Por último, se sugerirán lineamientos para la toma de decisiones.

ABSTRACT Acute respiratory distress syndrome occupies a great deal of attention in intensive care units. Despite ample knowledge of the physiopathology of this syndrome, the focus in intensive care units consists mostly of life-supporting treatment and avoidance of the side effects of invasive treatments. Although great advances in mechanical ventilation have occurred in the past 20 years, with a significant impact on mortality, the incidence continues to be high. Patients with acute respiratory distress syndrome, especially the most severe cases, often present with refractory hypoxemia due to shunt, which can require additional treatments beyond mechanical ventilation, among which is mechanical ventilation in the prone position. This method, first recommended to improve oxygenation in 1974, can be easily implemented in any intensive care unit with trained personnel. Prone position has extremely robust bibliographic support. Various randomized clinical studies have demonstrated the effect of prone decubitus on the oxygenation of patients with acute respiratory distress syndrome measured in terms of the PaO2/FiO2 ratio, including its effects on increasing patient survival. The members of the Respiratory Therapists Committee of the Sociedad Argentina de Terapia Intensiva performed a narrative review with the objective of discovering the available evidence related to the implementation of prone position, changes produced in the respiratory system due to the application of this maneuver, and its impact on mortality. Finally, guidelines are suggested for decision-making.

Gas exchange and lung mechanics in patients with acute respiratory distress syndrome: comparison of three different strategies of positive end expiratory pressure selection.

PURPOSE: The purpose of the study was to compare gas exchange and lung mechanics between different strategies to select positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). METHODS: In 20 consecutive ARDS patients, 3 PEEP selection strategies were evaluated. One strategy was based on oxygenation using the ARDS network PEEP/fraction of inspired oxygen (Fio2) table; and two were based on lung mechanics, either PEEP titrated to reach a plateau pressure of 28 to 30 cm H2O as in the ExPress trial or best respiratory compliance method during a derecruitment maneuver. Gas exchange, airway pressures, stress index (SI), and end-expiratory transpulmonary pressure (P(tpe)) and end-inspiratory transpulmonary pressure (P(tpi)) values were assessed. Data are expressed as median (interquartile range [IQR]). RESULTS: Lower total PEEP levels were observed with the use of the PEEP/Fio2 table (8.7 [6-10] cm H2O); intermediate PEEP levels, with the Best Compliance approach (13.0 [10.2-13.8] cm H2O); and higher PEEP levels, with the ExPress strategy (16.5 [15.0-18.5] cm H2O) (P < .01). Pao2/Fio2 ratio was lower with the PEEP/Fio2 table. Oxygenation with Best Compliance approach and ExPress strategy was not different with lower plateau pressure in the former (23 [20-25] vs 30 [29-30] cm H2O; P < .01). Paco2 was slightly higher with the ExPress method than the others 2 strategies. Negative P(tpe) was observed in 35% of the patients with the PEEP/Fio2 table, in 15% applying the Best Compliance, and in only 1 case with the ExPress method. Higher SI and P(tpi), with lower lung compliance, were obtained with ExPress strategy. CONCLUSIONS: Using a best respiratory compliance approach resulted in better oxygenation levels without risk of overdistension according to SI and P(tpi), achieving a mild risk of lung collapse according to P(tpe).

Transpulmonary pressure and gas exchange during decremental PEEP titration in pulmonary ARDS patients.

BACKGROUND: Selection of the PEEP associated with the best compliance of the respiratory system during decremental PEEP titration can be used for the treatment of patients suffering from ARDS. We describe changes in transpulmonary pressure (Ptp) and gas exchange during a decremental PEEP titration maneuver in subjects with pulmonary ARDS. METHODS: Eleven subjects with early ARDS were included. After a recruitment maneuver they were ventilated in volume-controlled ventilation and PEEP was decreased from 30 to 0 cm H2O by steps of 3 cm H2O. Static airway pressure (Paw), esophageal pressure (Pes), Ptp (Paw - Pes), the ratio of dead space to tidal volume (VD/VT), and PaO2 were recorded at each step. RESULTS: A linear correlation was found between Paw and Ptp. Expiratory Ptp became negative in all subjects when PEEP decreased below 8.9 ± 5.2 cm H2O. VD/VT was 0.67 ± 0.06 with 30 cm H2O of PEEP, and decreased 15.4 ± 8.5% during the maneuver, when PEEP and expiratory Ptp were 10.6 ± 4.1 cm H2O and 1.2 ± 2.8 cm H2O, respectively. VD/VT was significantly higher during ventilation at high (> 18 cm H2O), compared to low, inspiratory Ptp values (P < .001). PaO2 decreased when expiratory Ptp became negative (P < .001). CONCLUSIONS: During decremental PEEP titration we sequentially observed high inspiratory Ptp that stressed lung tissue and increased VD/VT, and negative Ptp, indicating high risk of alveolar collapse, explaining worse oxygenation. PEEP selection based on Ptp and VD/VT in ARDS may help to avoid these situations.

Muscle weakness in septic patients requiring mechanical ventilation: protective effect of transcutaneous neuromuscular electrical stimulation.

PURPOSE: The aim of this study was to evaluate the effect of transcutaneous neuromuscular electrical stimulation (NMES) on muscle strength in septic patients requiring mechanical ventilation (MV). METHODS: Sixteen septic patients requiring MV and having 1 or more organ failure other than respiratory dysfunction were enrolled within 48 hours from admission to the intensive care unit. Neuromuscular electrical stimulation was administered twice a day on brachial biceps and vastus medialis (quadriceps) of 1 side of the body until MV withdrawal. Blinded investigators measured arm and thigh circumferences, biceps thickness by ultrasonography, and muscle strength after awakening with Medical Research Council scale. RESULTS: Two patients died before strength evaluation and were excluded from the analysis. Neuromuscular electrical stimulation was applied for 13 days (interquartile range, 7-30 days). Biceps (P = .005) and quadriceps (P = .034) strengths were significantly higher on the stimulated side at the last day of NMES. Improvement was mainly observed in more severe and weaker patients. Circumference of the nonstimulated arm decreased at the last day of NMES (P = .015), whereas no other significant differences in limb circumferences or biceps thickness were observed. CONCLUSION: Neuromuscular electrical stimulation was associated with an increase in strength of the stimulated muscle in septic patients requiring MV. Neuromuscular electrical stimulation may be useful to prevent muscle weakness in this population.