Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients — insights from the PRoVENT-COVID study: a national, multicenter, observational cohort analysis
Authors: Ahuja Sanchit , de Grooth Harm-Jan , Paulus Frederique , van der Ven Fleur L. , Serpa Neto Ary , Schultz Marcus J. , Tuinman Pieter R. ,   PRoVENT-COVID Study Collaborative Group* ‘PRactice of VENTilation in COVID–19’, Ahuja S. , van Akkeren J. P. , Algera A. G. , Algoe C. K. , van Amstel R. B. , Artigas A. , Baur O. L. , van de Berg P. , van den Berg A. E. , Bergmans D. C. J. J. , van den Bersselaar D. I. , Bertens F. A. , Bindels A. J. G. H. , de Boer M. M. , den Boer S. , Boers L. S. , Bogerd M. , Bos L. D. J. , Botta M. , Breel J. S. , de Bruin H. , de Bruin S. , Bruna C. L. , Buiteman-Kruizinga L. A. , Cremer O. L. , Determann R. M. , Dieperink W. , Dongelmans D. A. , Franke H. S. , Galek-Aldridge M. S. , de Graaff M. J. , Hagens L. A. , Haringman J. J. , van der Heide S. T. , van der Heiden P. L. J. , Heijnen N. F. L. , Hiel S. J. P. , Hoeijmakers L. L. , Hol L. , Hollmann M. W. , Hoogendoorn M. E. , Horn J. , van der Horst R. , Ie E. L. K. , Ivanov D. , Juffermans N. P. , Kho E. , de Klerk E. S. , Koopman-van Gemert A. W. M. M. , Koopmans M. , Kucukcelebi S. , Kuiper M. A. , de Lange D. W. , van Mourik N. , Nijbroek S. G. , Onrust M. , Oostdijk E. A. N. , Paulus F. , Pennartz C. J. , Pillay J. , Pisani L. , Purmer I. M. , Rettig T. C. D. , Roozeman J. P. , Schuijt M. T. U. , Schultz M. J. , Serpa Neto A. , Sleeswijk M. E. , Smit M. R. , Spronk P. E. , Stilma W. , Strang A. C. , Tsonas A. M. , Tuinman P. R. , Valk C. M. A. , Veen-Schra F. L. , Veldhuis L. I. , van Velzen P. , van der Ven W. H. , Vlaar A. P. J. , van Vliet P. , van der Voort P. H. J. , van Welie L. , Wesselink H. J. F. T. , van der Wier-Lubbers H. H. , van Wijk B. , Winters T. , Wong W. Y. , van Zanten A. R. H. 
Published: June 2022

Abstract
Background
Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Methods
We analyzed data from the multicenter observational ‘PRactice of VENTilation in COVID-19 patients’ study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed.

Results
Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27–7.72 L), 0.78 L (0.26–1.27 L), and − 0.35 L (− 6.52–0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77–0.95, P = 0.0047). Sensitivity analyses showed similar results.

Conclusions
In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial.
Trial registration Clinicaltrials.gov (NCT04346342); Date of registration: April 15, 2020.

Graphical abstract