Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial

Shah, Akshay; Chester-Jones, Mae; Dutton, Susan; Marian, Ioana R; Barber, Vicki S; Griffith, David; Singleton, Jo; Wray, Katherine; James, Tim; Drakesmith, Hal; Robbins, Peter A.; Frise, Matthew C.; Young, J D; Walsh, Timothy; McKechnie, Stuart; Stanworth, Simon; Hutton, Paula; Bashyal, Archana; Chapman, George; Donovan, Killian; James, Christie; Rea, Nicola; Clark, Sarah L.; Barclay, Lucy; Priestley, Kate; Hope, David; McCulloch, Corrienne; Jacques, Nicola; Bartley, Shauna; Bhachu, Parminder; Black, Joanna; Haines, Emma; Eldridge, Lucy; Hill, Quentin A.; Walden, Andrew; Richards, Toby

doi:10.1016/j.bja.2021.11.010

Cited by 21 publications

(19 citation statements)

References 40 publications

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“…Further phenotyping of patients at follow-up time points will be required to identify the factors driving anaemia and the therapeutic utility of iron supplementation in this setting. Treating anaemia of inflammation, particularly during the recovery phase of critical illness, with intravenous iron has been shown to be efficacious ( Shah et al ., 2022 ) but there are no comparable data in patients recovering from COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19

Frost

Hamilton²,

Arnold³

et al. 2022

Wellcome Open Res

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Background: Marked reductions in serum iron concentrations are commonly induced during the acute phase of infection. This phenomenon, termed hypoferremia of inflammation, leads to inflammatory anemia, but could also have broader pathophysiological implications. In patients with coronavirus disease 2019 (COVID-19), hypoferremia is associated with disease severity and poorer outcomes, although there are few reported cohorts. Methods: In this study, we leverage a well characterised prospective cohort of hospitalised COVID-19 patients and perform a set of analyses focussing on iron and related biomarkers and both acute severity of COVID-19 and longer-term symptomatology. Results: We observed no associations between acute serum iron and long-term outcomes (including fatigue, breathlessness or quality of life); however, lower haemoglobin was associated with poorer quality of life. We also quantified iron homeostasis associated parameters, demonstrating that among 50 circulating mediators of inflammation IL-6 concentrations were strongly associated with serum iron, consistent with its central role in inflammatory control of iron homeostasis. Surprisingly, we observed no association between serum hepcidin and serum iron concentrations. We also observed elevated erythroferrone concentrations in COVID-19 patients with anaemia of inflammation. Conclusions: These results enhance our understanding of the regulation and pathophysiological consequences of disturbed iron homeostasis during SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19

Frost

Hamilton²,

Arnold³

et al. 2022

Wellcome Open Res

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“…Surprisingly, the same number of patients received intravenous iron in both groups and the recommendations for intravenous iron treatment were not fully followed. This is important as treating iron deficiency may improve post-ICU outcomes [22,23]. The choice of systematically giving iron together with erythropoietin could be an option, as this could be done easily if the study is not double-blinded.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin to treat anaemia in critical care patients: a multicentre feasibility study

et al. 2023

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Anaemia is common and associated with poor outcomes during and after critical illness. The use of erythropoietin to treat such anaemia is controversial with older studies showing mixed results. In this study, we aimed to evaluate the feasibility of performing a large multicentre randomised controlled trial of erythropoietin in this setting. We randomly allocated patients staying in the ICU for ≥ 72 h with haemoglobin ≤ 120 g.l -1 to either a weekly injection of erythropoietin (40,000 iu, maximum of five injections) or placebo (saline). The primary endpoint was feasibility (as measured by recruitment, randomisation and follow-up rates, and protocol compliance). Secondary endpoints included biological efficacy and clinical outcomes. Forty-two participants were recruited and randomly allocated, all participants received the allocated intervention, but one withdrew their consent and refused the use of their data, leaving 20 in the erythropoietin group and 21 in placebo group. Follow-up was completed for all patients who survived. The overall recruitment rate was 73.7% with 8.4 participants recruited on average per month. The last haemoglobin measured before hospital discharge (or death) was similar between the groups with a mean (SD) haemoglobin of 107 (21) vs. 95 (25) g.l -1 , mean difference (95%CI) 11 (-4-26), g.l -1 , p = 0.154. A large, multicentre randomised controlled trial of erythropoietin to treat anaemia in ICU patients is feasible and necessary to determine effects of erythropoietin on mortality in ICU anaemic patients.

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“…Hospital re‐admission within 30 days of discharge was more frequent among people who had anaemia at discharge, suggesting that more comprehensive investigation and follow‐up of patients with anaemia is needed 15 . Post‐operative anaemia — associated with reduced likelihood of re‐admission as a secondary endpoint in PREVENTT 6 — could be a target for intravenous iron therapy, including after discharge from critical care 16 …”

Section: Discussionmentioning

confidence: 99%

“… 15 Post‐operative anaemia — associated with reduced likelihood of re‐admission as a secondary endpoint in PREVENTT 6 — could be a target for intravenous iron therapy, including after discharge from critical care. 16 …”

Section: Discussionmentioning

confidence: 99%

The management of peri‐operative anaemia in patients undergoing major abdominal surgery in Australia and New Zealand: a prospective cohort study

2022

Medical Journal of Australia

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Objectives To assess the prevalence and management of anaemia in patients undergoing major abdominal surgery, and the influence of guideline adherence on patient outcomes. Design Prospective observational cohort study. Setting 56 hospitals in Australia and New Zealand. Participants People aged 18 years or more who underwent major abdominal surgery during two 2‐week periods in July 2021. Main outcome measures Proportions of patients managed according to Australian National Blood Authority patient blood management guidelines. Secondary outcomes: anaemia prevalence, post‐operative complications, length of hospital stay, re‐admission within 30 days of discharge. Results Data were available for 2730 eligible patients (mean age, 56.7 years; SD, 17.3 years), including 1558 women (57.1%). Haemoglobin levels prior to surgery were documented for 2461 of 2727 patients (90.2%), 689 of whom had anaemia (28.0%). Pre‐operative anaemia assessment and management were associated with lower likelihood of intra‐operative (adjusted odds ratio [aOR], 0.33; 95% CI, 0.19–0.57) and post‐operative blood transfusion (aOR, 0.36; 95% CI, 0.25–0.53), and of post‐operative complications (aOR, 0.79; 95% CI, 0.63–0.99). Tranexamic acid was administered during 128 of 2728 procedures (4.7%); a restrictive transfusion strategy was followed for 96 of the 167 patients who received post‐operative blood transfusions (58%). Post‐operative anaemia was identified in 1227 of 2069 patients (59.3%) in whom haemoglobin was assessed prior to discharge. The proportion of people re‐admitted to hospital within 30 days was larger for patients with anaemia at discharge (169 of 1207 patients followed up, 14.0% v 61 of 825, 7.4%). Haemoglobin assessments were recorded by 30 days after discharge for only 288 patients with post‐operative anaemia (24.3%). Conclusions The management of peri‐operative anaemia differs between hospitals in Australia and New Zealand, with consequences for patient outcomes. Patients are often discharged after surgery with anaemia, which is therefore a potential therapeutic target. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621001517864 (retrospective).

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Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial

Cited by 21 publications

References 40 publications

Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19

Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19

Erythropoietin to treat anaemia in critical care patients: a multicentre feasibility study

The management of peri‐operative anaemia in patients undergoing major abdominal surgery in Australia and New Zealand: a prospective cohort study

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