• Shodai Yoshihiro, Takashi Hongo, Mariko Yamamoto, Shunsuke Taito, and Yuki Kataoka.
• Department of Pharmaceutical Services, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan.
• Crit. Care Med. 2024 Apr 1; 52 (4): 618625618-625.

ObjectivesTo determine optional therapeutic strategies by comparing monotherapies and combination therapies to reduce RBC transfusion requirement for patients in the ICU.Data SourcesMEDLINE, CENTRAL, and Embase were searched for studies published from database inception until July 2023.Data ExtractionWe included randomized controlled trials comparing erythropoiesis-stimulating agents (Epo), iron, combination therapy with iron and Epo, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), vitamin D 3 (VD3), and placebo/no treatment. A frequentist network meta-analysis (NMA) was performed using a random effects model, and the confidence in NMA was rated.Data SynthesisOf 117 eligible studies, 75 studies (15,091 patients) were included in the quantitative analysis. Compared with placebo/no treatment, the combination therapy reduces the requirement for RBC transfusion (risk ratio [RR]: 0.60; 95% CI, 0.49-0.74; confidence rating: moderate). The Epo or iron monotherapy may reduce the requirement for RBC transfusion (RR: 0.81; 95% CI, 0.63-1.04; confidence rating: low; RR: 0.83; 95% CI, 0.70-0.98; confidence rating: low, respectively). Combination therapy may not increase the prevalence of both venous thromboembolism (VTE) (RR: 0.73; 95% CI, 0.25-2.08; confidence rating: low) and infection. Epo monotherapy may not increase the prevalence of VTE but may increase that of infections (RR: 1.27; 95% CI, 0.94-1.73; confidence rating: low). Iron monotherapy may not increase the prevalence of both VTE and infection. Evidence for VD3 and HIF-PHI remains uncertain.ConclusionsCombination therapy with iron and Epo likely reduces the requirement for RBC transfusion and may be less harmful than other therapies.Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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