VENTILATION MANAGEMENT AND OUTCOME

Michaela Botta, Anissa M. Tsonas, Janesh Pillay, Leonoor S. Boers, Anna Geke Algera, Lieuwe D. Bos, Dave A. Dongelmans, Markus W. Hollmann, Janneke Horn, Alexander P. Vlaar, Marcus J. Schultz, Ary Serpa Neto and Frederique Paulus, for the PRoVENT-COVID Collaborative Group

Research in context

Evidence before this study

We conducted a search of MEDLINE, Embase, CINAHL, and Web of Science with the terms (‘mechanical ventilation’) AND (‘coronavirus’ OR ‘COVID–19’), with no date or language restrictions. Studies including patients not receiving ventilation were excluded, as those reporting on paediatric and single–centre populations. The only two studies that reported detailed ventilator settings and outcomes was one multi–centre observational study from Italy in 1150 invasively ventilated COVID–19 patients and one multi–centre observational study from Spain in 742 invasively ventilated COVID–19 patients. In the Italian study, reporting was restricted to one single time point, and contained only information on positive end–expiratory pressure (PEEP), adjunctive treatments for refractory hypoxemia, and oxygenation parameters. The Spanish study reported values during the whole period of ventilatory support, but restricted data collection to ‘worst’ values on each ventilation day. The search did not identify studies that used regression models to identify factors independently associated with outcome, or studies assessing outcomes after 28 days.

Added value of this study

Our study provides a detailed description of various important ventilation variables and parameters, adjunctive treatments for refractory hypoxemia, and outcomes in a large set of hospitals in the Netherlands. In addition, we report on these variables and parameters over four consecutive calendar days, which allows a better insight in ventilation practice over time. Our study was retrospective, but included consecutive patients in the first month of the outbreak in the Netherlands. Furthermore, in contrast to several studies in COVID–19 patients, it included mortality at day 90.

Implications of all the available evidence

Most patients receiving invasive ventilation for respiratory failure due to COVID–19 had moderate or severe ARDS. Respiratory system compliance was low in all patients. Protective ventilation was used often, especially with regard to the use of lower tidal volumes and the use of prone positioning as an adjunctive treatment for refractory hypoxemia. The level of PEEP varied widely and did not change over the first days of ventilation. Of the ventilatory variables, a higher tidal volume and a lower compliance in the first day of ventilation were associated with higher 28–day mortality. Mortality was high, but comparable to what has been reported for other cohorts. Our results add to existing knowledge about epidemiological characteristics and outcomes, and could be useful in planning future studies and understanding previous findings about invasive ventilation in COVID–19 patients.

Summary

Background

Ventilation management in COVID–19 is unknown. We aimed to ascertain ventilation management and outcomes in invasively ventilated COVID–19 patients.

Methods

PRoVENT–COVID is a national, multicentre study in ICUs in the Netherlands. Consecutive patients ≥ 18 years were eligible for participation if they had received invasive ventilation for COVID–19 during the first month of the national outbreak. We collected ventilator variables and parameters during 4 calendar days. In addition, we captured use of adjunctive treatments for refractory hypoxemia, and outcomes like ventilator–free days and alive at day 28 (VFD–28), duration of ventilation, duration of ICU and hospital stay, and mortality.

Findings

553 patients were included, of which 75% had moderate–to–severe ARDS. Median V_T was 6.3 mL/kg predicted body weight (IQR 5.7–7.1), PEEP and ΔP were 14.0 cmH₂O (IQR 11.0–15.0) and 14.0 cmH₂O (IQR 11.2–16.0), respectively. Respiratory system compliance was 31.9 ml/cmH₂O (IQR 26.0–39.9). Of the adjunctive treatments for refractory hypoxemia, prone positioning was most often used (51.4%). The number of VFD–28 was 0 (IQR 0–15); mortality at day 28 was 35.1%. Predictors of 28-day mortality were gender, age, and V_T, respiratory system compliance, arterial pH and heart rate at the first day of invasive ventilation.

Interpretation

Lung–protective ventilation with low V_T and low ΔP is broadly applied and prone positioning is often used. The applied PEEP varies widely despite an invariably low respiratory system compliance. Of the ventilatory variables, a higher V_T and a lower respiratory system compliance in the first day of invasive ventilation were associated with higher 28-day mortality. The findings of this study could function as a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID–19. In addition, these data help better interpretation of findings of other studies in COVID–19.

Full list of investigators

(in alphabetic order) J.P. van Akkeren; A.G. Algera; C.K. Algoe; R.B. van Amstel; O.L. Baur; P. van de Berg; A.E. van den Berg; D.C.J.J. Bergmans; D.I. van den Bersselaar; F.A. Bertens; A.J.G.H. Bindels;M.M. de Boer; S. den Boer; L.S. Boers; M. Bogerd; L.D.J. Bos; M. Botta; J.S. Breel; H. de Bruin; S. de Bruin; C.L. Bruna; L.A. Buiteman–Kruizinga; O. Cremer; R.M. Determann; W. Dieperink; D.A. Dongelmans; H.S. Franke; M.S. Galek-Aldridge; M.J. de Graaff; L.A. Hagens; J.J. Haringman;; S.T. van der Heide; P.L.J. van der Heiden; N.F.L. Heijnen; S.J.P. Hiel; L.L. Hoeijmakers; L. Hol; M. W. Hollmann; M.E. Hoogendoorn; J. Horn; R. van der Horst; E.L.K. Ie; D. Ivanov; N.P. Juffermans; E. Kho; E.S. de Klerk; A.W.M.M Koopman-van Gemert; M. Koopmans; S. Kucukcelebi; M.A. Kuiper; D.W. de Lange; N. van Mourik; S.G. Nijbroek; M. Onrust; E.A.N. Oostdijk; F. Paulus; C.J. Pennartz; J. Pillay; L. Pisani; I.M. Purmer; T.C.D. Rettig; J.P Roozeman; M.T.U. Schuijt; M.J. Schultz; A. Serpa Neto; M.E. Sleeswijk; M.R. Smit; P.E. Spronk; W. Stilma; A.C. Strang; A. M. Tsonas; P.R Tuinman; C.M.A. Valk; F.L. Veen-Schra; L.I. Veldhuis; P. van Velzen; W.H. van der Ven; A.P.J. Vlaar; P. van Vliet; P.H.J. van der Voort; L. van Welie; H.J.F.T. Wesselink; H.H. van der Wier-Lubbers; B. van Wijk; T. Winters; W.Y. Wong; A.R.H. van Zanten.