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Diuretic therapy for critically ill patients: a systematic review and network meta-analysis

In brief

Tolvaptan cuts acute kidney injury risk by about 90% versus standard loop diuretics in ICU patients

In a network meta-analysis of 26 trials (1,652 critically ill adults), tolvaptan monotherapy markedly lowered the odds of developing acute kidney injury compared with bolus or continuous loop diuretics, though the evidence is low certainty. Other diuretic strategies, including continuous infusion, showed no clear mortality benefit and may prolong ICU stay, leaving optimal fluid-removal practice uncertain.

Journal
Annals of intensive care (Q1)
Published
21 July 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Akira Kuriyama, Kamil Polok, Nikita Malhotra, Naoyuki Kuse, Tyler Pitre, Devan Lakhanpal, et al.
PMID
42604106
DOI
10.1016/j.aicoj.2026.100120

Why clinicians should know about it

Abstract

BACKGROUND: Fluid overload is common in critically ill patients and is associated with worse outcomes. Diuretics are the mainstay of active fluid removal in patients with preserved renal function. The optimal diuretic strategy for fluid removal remains uncertain. METHODS: We conducted a systematic review and Bayesian random-effects network meta-analysis of randomized controlled trials comparing two or more diuretic strategies for fluid removal in critically ill adults. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials via Ovid, as well as trial registries, from inception to November 20, 2025. Two reviewers independently extracted data and assessed risk of bias using ROBUST-RCT. Certainty of evidence was evaluated using the GRADE approach for network meta-analysis. Treatment effects were summarized as odds ratios (ORs) or mean differences (MDs) with 95% credible intervals (CrIs). RESULTS: Twenty-six randomized controlled trials involving 1,652 participants were included. Evaluated interventions included bolus loop diuretics (19 studies), continuous loop infusion (15 studies), oral loop diuretics (5 studies), and loop diuretics combined with tolvaptan (8 studies), spironolactone (3 studies), thiazides (2 studies), acetazolamide (1 study), or triamterene (1 study). Compared with bolus loop diuretics, continuous loop infusion had an uncertain effect on mortality (OR 1.26; 95% CrI 0.62 to 2.55; very low certainty) and may increase ICU length of stay (MD 1.56 days; 95% CrI -0.02 to 3.16; low certainty). Tolvaptan monotherapy may reduce acute kidney injury compared with bolus or continuous loop diuretics (OR 0.12; 95% CrI 0.01 to 0.87; low certainty), although no studies evaluated its effect on the need for renal replacement therapy. For most other comparisons and outcomes, the certainty of evidence was low or very low. CONCLUSIONS: Available evidence comparing diuretic strategies for fluid removal during ICU-level care is limited, clinically heterogeneous, and derived largely from heart failure and post-cardiovascular surgery populations. Bolus loop diuretics were at least comparable to alternate diuretic strategies for patient important outcomes in critically ill adults, but this was based mostly on low or very low certainty evidence. Tolvaptan monotherapy may decrease acute kidney injury, but its effect on subsequent need for RRT and mortality remains uncertain.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.