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

Sanchit Ahuja, Harm-Jan de Grooth, Frederique Paulus, Fleur L van der Ven, Ary Serpa Neto, Marcus J Schultz, Pieter R Tuinman, PRoVENT-COVID Study Collaborative Group* ‘PRactice of VENTilation in COVID–19’, S Ahuja, J P van Akkeren, A G Algera, C K Algoe, R B van Amstel, A Artigas, 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 L 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, Sanchit Ahuja, Harm-Jan de Grooth, Frederique Paulus, Fleur L van der Ven, Ary Serpa Neto, Marcus J Schultz, Pieter R Tuinman, PRoVENT-COVID Study Collaborative Group* ‘PRactice of VENTilation in COVID–19’, S Ahuja, J P van Akkeren, A G Algera, C K Algoe, R B van Amstel, A Artigas, 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 L 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

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.

Keywords: ARDS; COVID-19; Critical care; Cumulative fluid balance; Liberation of ventilation.

Conflict of interest statement

All authors declare no competing interests related to the submitted work.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of the study
Fig. 2
Fig. 2
Survival and marginal effect plots. a Survival plots (unadjusted and adjusted) showing predicted probability of successful liberation of invasive ventilation as a function of day 3 fluid balance—separated in tertiles. b Marginal effect (unadjusted and adjusted) of day 3 cumulative fluid balance on the hazard of successful liberation from invasive ventilation after adjustment for predefined confounding variables. A higher day 3 cumulative fluid balance was associated with a lower hazard (i.e., a lower probability over time) of successful liberation
Fig. 3
Fig. 3
Sensitivity analysis showing the consistency of main effect over ARDS severity. ARDS acute respiratory distress syndrome

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