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Comment
. 2023 Jul;49(7):820-830.
doi: 10.1007/s00134-023-07114-8. Epub 2023 Jun 18.

Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock

Maj-Brit Nørregaard Kjær  1   2 , Tine Sylvest Meyhoff  3   4 , Praleene Sivapalan  3   4 , Anders Granholm  3   4 , Peter Buhl Hjortrup  3   5 , Martin Bruun Madsen  3   5 , Morten Hylander Møller  3   4 , Ingrid Egerod  3   4 , Jørn Wetterslev  4   6 , Theis Lange  4   7 , Maria Cronhjort  8 , Jon Henrik Laake  9   10 , Stephan M Jakob  11 , Marek Nalos  12 , Marlies Ostermann  13 , Doug Gould  14 , Maurizio Cecconi  15   16 , Manu L N G Malbrain  17   18   19 , Christian Ahlstedt  20 , Louise Bendix Kiel  21 , Morten H Bestle  22   23 , Lars Nebrich  24 , Thomas Hildebrandt  25 , Lene Russell  26 , Marianne Vang  27 , Michael Lindhart Rasmussen  28 , Christoffer Sølling  29 , Anne Craveiro Brøchner  4   30 , Mette Krag  4   23   31 , Carmen Pfortmueller  11 , Miroslav Kriz  12 , Martin Siegemund  32 , Giovanni Albano  33 , Søren Rosborg Aagaard  34 , Helle Bundgaard  27 , Vera Crone  31 , Sine Wichmann  22 , Bror Johnstad  35 , Yvonne Karin Martin  36 , Philipp Seidel  37 , Johan Mårtensson  38 , Jacob Hollenberg  39 , Mats Wistrand  40   41 , Abele Donati  42 , Enrico Barbara  43 , Thomas Karvunidis  12 , Alexa Hollinger  32 , Andrea Carsetti  42   44 , Nuttha Lumlertgul  13   45 , Eva Joelsson-Alm  8 , Nikolas Lambiris  38 , Tayyba Naz Aslam  9   10   46   47 , Fredrik Femtehjell Friberg  35   48 , Gitte Kingo Vesterlund  3   4 , Camilla Bekker Mortensen  24 , Stine Rom Vestergaard  34 , Sidsel Fjordbak Caspersen  24 , Diana Bertelsen Jensen  21 , Morten Borup  30 , Bodil Steen Rasmussen  4   34 , Anders Perner  3   4
Affiliations
Comment

Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock

Maj-Brit Nørregaard Kjær et al. Intensive Care Med. 2023 Jul.

Abstract

Purpose: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial.

Methods: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function.

Results: Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups.

Conclusions: Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.

Trial registration: ClinicalTrials.gov NCT03668236.

Keywords: Cognitive function; Critical illness; Intravenous fluid; Long-term outcomes; Quality of life; Sepsis; Septic shock.

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Conflict of interest statement

MBNK, TSM, PS, AG, PBH, MBM, MHM, GVK, and AP are affiliated with the Department of Intensive Care at Rigshospitalet, which has received funding for other projects from The Novo Nordisk Foundation, Pfizer, and Fresenius Kabi, Sygeforsikringen “danmark”, and has conducted contract research for AM-Pharma (the REVIVAL trial). AP has received an honorarium from Novartis for the participation in an advisory board. MHB and SW are affiliated with the Department of Anaesthesia and Intensive Care at Copenhagen University Hospital – North Zealand, which has received funding for other research projects from The Novo Nordisk Foundation, Sygeforsikringen “danmark”, Toyota Foundation, A.P. Moeller Foundation, Frimodt-Heineke Foundation, Svend Andersen Foundation, Ehrenreich Foundation, and Olga Bryde Nielsen Foundation, and has conducted contract research for AM-Pharma (the REVIVAL trial) and Inotrem (ASTONISH trial). MHB has received an honorarium from AM-Pharma for participation in an advisory board. All other authors have no conflicts to disclose.

Figures

Fig. 1
Fig. 1
CONSORT diagram of the patient flow in the CLASSIC trial. Details up to day 90 were presented in the primary report [6]. We included all patients randomised (n = 1554) except for 5 patients excluded before day 90 (n = 1549). There were patients who withdrew consent up to day 90 follow-up (n = 32) where the primary outcome was published [6] for whom no further data were obtained. For nonrespondents we registered reasons for being lost to follow at 1 year with a detailed description of missing data available in Tables S4 and S5 in the ESM1. Patients who responded, but had incomplete data was due to partly fulfilled HRQoL questionnaire or partly performed cognitive test
Fig. 2
Fig. 2
One-year survival curves in the two interventions groups (A). One patient in each group had died at day 90, but dates of death were unknown due to lack of consent. This resulted in 766 patients in the restrictive group and 781 patients in the standard group to be presented in the survival curves. The four patients who were lost to follow-up at day 90 [4] were included in the survival curves until the last day they were known to be alive. B Stacked heat maps for EQ VAS, EQ-5D-5L index, and Mini MoCA values in all patients after imputations (nonsurvivors assigned zero and multiple imputation of missing data) in the restrictive (Res.) vs standard (Std.) groups. Red represents worse outcomes and blue better outcomes. The horizontal axes represent the cumulated proportion of the patients scoring at or below the value on the secondary axes which represents the score ranges of the tools used; EQ VAS from 0 to 100, EQ-5D-5L index value from below 0 (corresponding to health states valued worse than death) to 1 and Mini MoCA from 0 to 30. In total, 1.5% (restricted-fluid group) and 1.6% (standard-fluid group) of the EQ-5D-5L index values were below zero; these were included as zero in heat map. The plots were done by calculating the proportions after stacking all 50 imputed datasets. Heat maps for survivors only are presented in the ESM1
Fig. 3
Fig. 3
Distribution of the health state levels in the 5 HRQoL domains from all respondents being alive at 1-year (n = 749) in the restrictive (Res.) vs. standard (Std.) groups. Relatives responded on behalf of 55/749 (7.3%) of the surviving patients. The numeric data corresponding to the Figure are presented in Table S3 in the ESM1
See this image and copyright information in PMC

Comment on

  • Long-term patient-important outcomes after septic shock: A protocol for 1-year follow-up of the CLASSIC trial.
    Kjaer MN, Meyhoff TS, Madsen MB, Hjortrup PB, Møller MH, Egerod I, Wetterslev J, Lange T, Cronhjort M, Laake JH, Jakob SM, Nalos M, Pettilä V, van der Horst ICC, Ostermann M, Mouncey P, Cecconi M, Ferrer R, Malbrain MLNG, Ahlstedt C, Hoffmann S, Bestle MH, Gyldensted L, Nebrich L, Russell L, Vang M, Sølling C, Brøchner AC, Rasmussen BS, Perner A. Kjaer MN, et al. Acta Anaesthesiol Scand. 2020 Mar;64(3):410-416. doi: 10.1111/aas.13519. Epub 2019 Dec 26. Acta Anaesthesiol Scand. 2020. PMID: 31828753

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