BACKGROUND The mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain.OBJECTIVE To investigate the association of mechanical power with mortality in ICU patients without ARDS.DESIGN This was an individual patient data analysis that uses the data of three multicentre randomised trials.SETTING This study was performed in academic and nonacademic ICUs in the Netherlands.PATIENTS One thousand nine hundred and sixty-two invasively ventilated patients without ARDS were included in this analysis. The median [IQR] age was 67 [57 to 75] years, 706 (36%) were women.MAIN OUTCOME MEASURES The primary outcome was the all-cause mortality at day 28. Secondary outcomes were the all-cause mortality at day 90, and length of stay in ICU and hospital.RESULTS At day 28, 644 patients (33%) had died. Hazard ratios for mortality at day 28 were higher with an increasing MP, even when stratified for its individual components (driving pressure (P < 0.001), tidal volume (P < 0.001), respiratory rate (P < 0.001) and maximum airway pressure (P = 0.001). Similar associations of mechanical power (MP) were found with mortality at day 90, lengths of stay in ICU and hospital. Hazard ratios for mortality at day 28 were not significantly different if patients were stratified for MP, with increasing levels of each individual component.CONCLUSION In ICU patients receiving invasive ventilation for reasons other than ARDS, MP had an independent association with mortality. This finding suggests that MP holds an added predictive value over its individual components, making MP an attractive measure to monitor and possibly target in these patients.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580.
BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS.METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS.RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality.CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model.TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.
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INTRODUCTION: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.METHODS: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.FINDINGS: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2).INTERPRETATION: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality.
