Association of early positive end-expiratory pressure settings with ventilator-free days in patients with coronavirus disease 2019 acute respiratory distress syndrome: A secondary analysis of the Practice of VENTilation in COVID-19 study

Christel M A Valk, Anissa M Tsonas, Michela Botta, Lieuwe D J Bos, Janesh Pillay, Ary Serpa Neto, Marcus J Schultz, Frederique Paulus, Writing Committee for the PRoVENT-COVID∗ Collaborative Group, Christel M A Valk, Anissa M Tsonas, Michela Botta, Lieuwe D J Bos, Janesh Pillay, Ary Serpa Neto, Marcus J Schultz, Frederique Paulus, Writing Committee for the PRoVENT-COVID∗ Collaborative Group

Abstract

Background: There is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).

Objective: To investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (VFDs).

Design: Multicentre observational study conducted from 1 March to 1 June 2020.

Setting and patients: Twenty-two ICUs in The Netherlands and 933 invasively ventilated COVID-19 ARDS patients.

Interventions: Patients were categorised retrospectively as having received invasive ventilation with higher (n=259) or lower PEEP (n=674), based on the high and low PEEP/FiO2 tables of the ARDS Network, and using ventilator settings and parameters in the first hour of invasive ventilation, and every 8 h thereafter at fixed time points during the first four calendar days. We also used propensity score matching to control for observed confounding factors that might influence outcomes.

Main outcomes and measures: The primary outcome was the number of VFDs. Secondary outcomes included distant organ failures including acute kidney injury (AKI) and use of renal replacement therapy (RRT), and mortality.

Results: In the unmatched cohort, the higher PEEP strategy had no association with the median [IQR] number of VFDs (2.0 [0.0 to 15.0] vs. 0.0 [0.0 to 16.0] days). The median (95% confidence interval) difference was 0.21 (-3.34 to 3.78) days, P = 0.905. In the matched cohort, the higher PEEP group had an association with a lower median number of VFDs (0.0 [0.0 to 14.0] vs. 6.0 [0.0 to 17.0] days) a median difference of -4.65 (-8.92 to -0.39) days, P = 0.032. The higher PEEP strategy had associations with higher incidence of AKI (in the matched cohort) and more use of RRT (in the unmatched and matched cohorts). The higher PEEP strategy had no association with mortality.

Conclusion: In COVID-19 ARDS, use of higher PEEP may be associated with a lower number of VFDs, and may increase the incidence of AKI and need for RRT.

Trial registration: Practice of VENTilation in COVID-19 is registered at ClinicalTrials.gov, NCT04346342.

Conflict of interest statement

Subdistribution hazard ratio from a clustered Fine–Gray competing risk model, with death before extubation treated as competing risk.

Hazard ratio from a (shared-frailty) Cox proportional hazard model. For the ICU and hospital length of stay analyses, all patients who died prior to discharge were assigned the maximum length of stay to account for death as a competing risk in this model. P value for Schoenfeld residuals: ICU length of stay (P = 0.420 in the unmatched cohort and P = 0.330 for the matched cohort); hospital length of stay (P = 0.830 in the unmatched cohort and P = 0.770 for the matched cohort); 7-day mortality (P = 0.380 in the unmatched cohort and P = 0.780 in the matched cohort); 28-day mortality (P = 0.260 in the unmatched cohort and P = 0.110 in the matched cohort); 90-day mortality (P = 0.100 in the unmatched cohort and P = 0.055 in the matched cohort).

Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.

Figures

Box 1
Box 1
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Fig. 1
Fig. 1
Group assignment, positive end-expiratory pressure and FiO2 in the higher (pink) and lower (green) positive end-expiratory pressure groups, before (left panels) and after (right panels) matching. The figure shows the median, lowest and highest positive end-expiratory pressure and FiO2 values. Horizontal bars inside boxes represent medians; box tops and bottoms, interquartile ranges. Whiskers extend to 1.5 times the interquartile range beyond the first and third quartiles per the conventional Tukey method. Circles represent means.
Fig. 2
Fig. 2
Mortality and pattern of extubation in the higher (pink) and lower (green) positive end-expiratory pressure groups, before (left panels) and after (right panels) matching. HR, hazard ratio.

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Source: PubMed

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