What question did this study set out to answer?

To investigate the impact of restrictive versus standard IV fluid therapy on NTproBNP levels in ICU patients with septic shock.

April 17, 2026Open Access

Restrictive versus standard intravenous fluid therapy and NTproBNP in ICU patients with septic shock – a sub-study of the randomised CLASSIC trial

Key Points

To investigate the impact of restrictive versus standard IV fluid therapy on NTproBNP levels in ICU patients with septic shock.
Prospective exploratory sub-study of the CLASSIC trial
Enrolled adult ICU patients with septic shock from Danish and Swedish ICUs
Patients randomized to restrictive or standard IV fluid therapy
Measured plasma NTproBNP at multiple timepoints: T0, T1, T2, T3
Used mixed models to assess differences between groups across timepoints.
No significant differences in NTproBNP levels between groups at any timepoint
At T1, NTproBNP levels: 7667 ng/L (restrictive) vs. 8913 ng/L (standard)
Estimated between-group difference at T1 was -1245 ng/L (95% CI -4065–1575)
Levels elevated across the board suggest NTproBNP reflects systemic inflammation rather than fluid loading
Findings interpreted with caution due to small sample size.

Abstract

Cardiac dysfunction is common in septic shock and may be influenced by intravenous (IV) fluid therapy. We aimed to investigate the effects of restrictive versus standard IV fluid therapy on plasma N-terminal pro B-type natriuretic peptide (NTproBNP), a marker of cardiac dysfunction, in adult intensive care unit (ICU) patients with septic shock. This prospective exploratory sub-study of the randomised CLASSIC trial enrolled adult ICU patients with septic shock at one Danish and one Swedish ICU between February 2020 and October 2021. Patients were randomised to restrictive versus standard IV fluid therapy. Plasma NTproBNP was measured at randomisation (T0), the following morning (T1), the morning after (T2), and at ICU discharge or day 90 (T3). The exploratory outcome was the between-group difference in NTproBNP across timepoints assessed using mixed models. Fifty-four patients were included. NTproBNP levels did not differ significantly between groups at any timepoint. At T1, mean NTproBNP levels were 7667 ng/L in the restrictive group and 8913 ng/L in the standard group, with an estimated between-group difference of -1245 (95% CI -4065–1575). Similarly, no statistically significant differences were observed at T2 and T3. No group-by-time interaction was observed (p = 0.925). No statistically significant difference in plasma NTproBNP between adult ICU patients with septic shock randomised to restrictive versus standard IV fluid therapy was seen. Uniformly elevated levels could suggest that NTproBNP in septic shock primarily reflects systemic inflammation rather than fluid-induced cardiac loading. Results should be interpreted with caution due to the small sample size. ClinicalTrials.gov NCT04282252. Registered 31 January 2020.

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