Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 May;50(5):678-686.
doi: 10.1007/s00134-024-07385-9. Epub 2024 Apr 10.

Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial

Christian Ahlstedt  1   2   3 , Praleene Sivapalan  4   5   6 , Miroslav Kriz  7 , Gustaf Jacobson  8 , Tine Sylvest Meyhoff  4   5 , Benjamin Skov Kaas-Hansen  4 , Manne Holm  8 , Jacob Hollenberg  9   10 , Marek Nalos  5   7   11 , Olav Rooijackers  8   12 , Morten Hylander Møller  4   5   6 , Maria Cronhjort  5   9   13 , Anders Perner  4   5   6 , Jonathan Grip  8   12
Affiliations
Randomized Controlled Trial

Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial

Christian Ahlstedt et al. Intensive Care Med. 2024 May.

Abstract

Purpose: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload.

Methods: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis.

Results: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results.

Conclusion: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

Keywords: Fluid therapy; Hyperlactatemia; Lactate; Sepsis; Septic shock.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig. 1
Fig. 1
CONSORT flow chart. Assessment, randomization and follow-up
Fig. 2
Fig. 2
Top graph: Median plasma lactate concentrations in mmol/L (interpolated to hourly resolution) with the interquartile range illustrated as a ribbon in the first 3 days after randomization in the restrictive fluid (red) and standard fluid (blue) groups (days). Bottom graph: The number of patients within the restrictive fluid (red) and standard fluid (blue) group contributing to the measured lactate values above. Example: The number of patients contributing with lactate values constituted 118 in each group around the eighth hour of the first day
Fig. 3
Fig. 3
Cumulative probability with 95% confidence intervals for the competing risk outcomes (resolution, discharge, or death) in the restrictive fluid (red) and standard fluid (blue) groups
See this image and copyright information in PMC

References

    1. Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA. 2016;315(8):775–787. doi: 10.1001/jama.2016.0289. - DOI - PMC - PubMed
    1. Hernandez G, Bellomo R, Bakker J. The ten pitfalls of lactate clearance in sepsis. Intensive Care Med. 2019;45(1):82–85. doi: 10.1007/s00134-018-5213-x. - DOI - PMC - PubMed
    1. Bakker J, de Backer D, Hernandez G. Lactate-guided resuscitation saves lives: we are not sure. Intensive Care Med. 2016;42(3):472–474. doi: 10.1007/s00134-016-4220-z. - DOI - PubMed
    1. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49(11):e1063–e1143. doi: 10.1097/CCM.0000000000005337. - DOI - PubMed
    1. Kushimoto S, Akaishi S, Sato T, Nomura R, Fujita M, Kudo D, et al. Lactate, a useful marker for disease mortality and severity but an unreliable marker of tissue hypoxia/hypoperfusion in critically ill patients. Acute Med Surg. 2016;3(4):293–297. doi: 10.1002/ams2.207. - DOI - PMC - PubMed

Publication types

LinkOut - more resources