Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)-protocol for a randomized clinical trial.

BACKGROUND: It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. DESIGN AND METHODS: The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. DISCUSSION: The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation-patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible-however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. TRIAL REGISTRATION: ISRCTN ISRCTN11536318 . Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Practice of tracheostomy in patients with acute respiratory failure related to COVID-19 - Insights from the PRoVENT-COVID study.

OBJECTIVE: Invasively ventilated patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) potentially benefit from tracheostomy. The aim of this study was to determine the practice of tracheostomy during the first wave of the pandemic in 2020 in the Netherlands, to ascertain whether timing of tracheostomy had an association with outcome, and to identify factors that had an association with timing. METHODS: Secondary analysis of the 'PRactice of VENTilation in COVID-19' (PRoVENT-COVID) study, a multicenter observational study, conducted from March 1, 2020 through June 1, 2020 in 22 Dutch intensive care units (ICU) in the Netherlands. The primary endpoint was the proportion of patients receiving tracheostomy; secondary endpoints were timing of tracheostomy, duration of ventilation, length of stay in ICU and hospital, mortality, and factors associated with timing. RESULTS: Of 1023 patients, 189 patients (18.5%) received a tracheostomy at median 21 [17 to 28] days from start of ventilation. Timing was similar before and after online publication of an amendment to the Dutch national guidelines on tracheostomy focusing on COVID-19 patients (21 [17-28] vs. 21 [17-26] days). Tracheostomy performed ≤ 21 days was independently associated with shorter duration of ventilation (median 26 [21 to 32] vs. 40 [34 to 47] days) and higher mortality in ICU (22.1% vs. 10.2%), hospital (26.1% vs. 11.9%) and at day 90 (27.6% vs. 14.6%). There were no patient demographics or ventilation characteristics that had an association with timing of tracheostomy. CONCLUSIONS: Tracheostomy was performed late in COVID-19 patients during the first wave of the pandemic in the Netherlands and timing of tracheostomy possibly had an association with outcome. However, prospective studies are needed to further explore these associations. It remains unknown which factors influenced timing of tracheostomy in COVID-19 patients.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy

Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ;IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mug/m;IQR, 5.0-23.8 mug/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P = 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. Trial registration: ClinicalTrials.gov identifier: NCT04318366.

Impaired ventilation is not independently associated with 28-day mortality in coronavirus disease 2019 (COVID19) acute respiratory distress syndrome (ARDS)

INTRODUCTION Surrogates for impaired ventilation such as estimated dead-space fractions and the ventilatory ratio are independently associated with an increased risk of mortality in the acute respiratory distress syndrome (ARDS) and small case series of COVID-19 related ARDS. METHODS This study aimed to quantify the dynamics and determine the prognostic value of surrogate markers of impaired ventilation in patients with COVID-19 related ARDS. The present study is a secondary analysis of the PRactice Of VENTilation in COVID-19 patients (PROVENT-COVID) in 22 intensive care unit hospitals in the Netherlands. Surrogates of impaired ventilation such as the estimated dead space fraction (by Harris-Benedict-VD/VT HB and direct method-VD/VT DIR), ventilatory ratio (VR), and end-tidal-to-arterial PCO2 ratio (PETCO2/PaCO2) were used. RESULTS 927 consecutive patients admitted with COVID-19 related ARDS were included in this study. Surrogates of impaired ventilation were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p <0.001). As ARDS severity increased, mortality increased with successive tertiles for VD/VT HB and VD/VT DIR, and VR, and decreased with successive tertiles for PETCO2/PaCO2. Mortality over the first 28 days was higher in patients in the high group of dead space fraction by VD/VT HB (16.4% vs. 12.3%;p = 0.003), but similar in the groups considering the dead space fraction by VD/VT DIR (15.4% vs. 13.3%;p = 0.100), and VR (15.5% vs. 13.2%;p = 0.080) (Figure 2). After adjustment for a base risk model that included chronic comorbidities, ventilation and oxygenation parameters, none of the surrogates of impaired ventilation measured at the start of ventilation or the following days were significantly associated with 28-day mortality. CONCLUSION Surrogate markers for impaired ventilation are abnormal at the start of invasive ventilation in patients with COVID-19 related ARDS and worsen during consequent days. Ventilation impairment seems to be more extensive in non-survivors than in survivors, but they do not yield prognostic information when added to a baseline risk model. In the absence of bedside capnography, surrogates of impaired ventilation may serve as an important tool to assess the severity of COVID-19 related ARDS along with other variables such as oxygenation abnormalities and respiratory mechanics.