Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-Analysis

Shah, Akshay; Donovan, Killian; Seeley, Claire; Dickson, Edward; Palmer, A; Dorée, Carolyn; Brunskill, Susan J; Reid, Jack; Acheson, Austin G; Sugavanam, Anita; Litton, Edward; Stanworth, Simon

doi:10.2139/ssrn.3844778

Cited by 6 publications

(12 citation statements)

References 82 publications

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“…These are summarised in a recent meta-analysis of 154 randomised trials of intravenous iron that found an increased risk of infection (RR 1.16; 95% CI 1.03-1.29), although there was marked heterogeneity across studies, and intravenous iron was compared against both “no iron”, and iron supplementation. 12 As intravenous iron is associated with around a one SD increase in TSAT, our estimates are remarkable concordant with the trial data.…”

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

“…8 In adult settings, a recent meta-analysis of all randomised controlled trials of intravenous iron found increased risks of infection in those randomised to receive intravenous iron, but there was significant uncertainty around the effect size. 9 Here, we aimed to investigate the association between iron levels and sepsis using both an observational multi-cohort design and a Mendelian randomisation analysis, with independent validation, to determine whether changes in four iron biomarkers were causally associated with the risk of sepsis.…”

Section: Introductionmentioning

confidence: 99%

“…11 In adult settings, a recent meta-analysis of all randomised controlled trials of intravenous iron found increased risks of infection in those randomised to receive intravenous iron, but there was substantial uncertainty around the effect size. 12 Because of the limited number of studies, this meta-analysis was unable to compare oral iron vs no supplementation at all. Uncertainty therefore remains around whether increased iron is associated with increased rates of sepsis.…”

Section: Introductionmentioning

confidence: 99%

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Causal associations between iron status and sepsis: a Mendelian randomisation analysis

Hamilton

Mitchell

Ahmed

et al. 2022

Preprint

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ObjectiveTo evaluate the association between four iron biomarkers and sepsis.DesignAn observational cohort and two sample Mendelian randomisation (MR) study.SettingThe UK Biobank prospective cohort study (for the observational cohort and for MR outcomes), the FinnGEN cohort study (replication of MR outcomes) and three large genome wide association studies (GWAS, for iron exposures).Participants453,169 participants enrolled in UK Biobank, 356,000 participants enrolled in FinnGen and between 131,471 - 246,139 participants enrolled across the three iron biomarker GWAS.ExposuresIn the observational cohort, iron status was determined using ferritin levels recorded in general practice data. In the MR analyses, four iron biomarkers were used: serum iron, serum ferritin, the total iron binding capacity (TIBC), and transferrin saturation (TSAT).Main outcome measuresHospital admission with an ICD-10 coded sepsis diagnosis.ResultsIn the observational cohort, the odds of sepsis increased as ferritin levels increased, with odds ratios of >1 once ferritin was more than >160 ug/L, within the normal accepted reference range for ferritin. Extremely low ferritin (<40ug/L) was also associated with increased odds of sepsis.In inverse-variance-weighted mendelian randomisation analyses, increases in all iron biomarkers were associated with increasing odds of sepsis (OR 1.10 for each SD increase in TSAT; 95% CI 1.03 to 1.17) with similar results for serum iron (OR 1.07; 95% CI 0.98 to 1.16), and ferritin (OR 1.09; 95% CI 0.99 to 1.2), with the opposite result for TIBC (OR 0.92; 95% CI 0.86 to 0.99). Effect estimates were slightly larger in those with iron deficiency or anaemia.Results were similar in the replication cohort (FinnGen) and were robust to sensitivity analyses of Mendelian randomisation.ConclusionsIncreasing measures of iron and related biomarkers are associated with increased risk of sepsis in a healthy adult volunteer cohort. MR analyses suggest this association is causal. Clinicians and policymakers should be aware of this potential risk when manipulating iron levels.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Causal associations between iron status and sepsis: a Mendelian randomisation analysis

Hamilton

Mitchell

Ahmed

et al. 2022

Preprint

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“…Accumulating evidence have shown that the administration of iron and erythropoietin cannot improve anaemia or reduce the requirement of blood transfusion in critically ill patients [30,31]. Moreover, the administration of iron has been implicated with an increased risk of infection [32]. In contrast, patient blood management, particularly the restriction of diagnostic phlebotomy, appears to be practical and actionable in critically ill surgical patients [33].…”

Section: Discussionmentioning

confidence: 99%

Week-One Anaemia was Associated with Increased One-Year Mortality in Critically Ill Surgical Patients

Wong

et al. 2022

International Journal of Clinical Practice

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Background. Anaemia has a deleterious effect on surgical patients, but the long-term impact of anaemia in critically ill surgical patients remains unclear. Methods. We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at a tertiary referral centre in central Taiwan between 2015 and 2020. We used both Cox proportional hazards analysis and propensity score-based analyses, including propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS) to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year mortality. Results. A total of 7,623 critically ill surgical patients were enrolled, and 29.9% (2,280/7,623) of them had week-one anaemia (haemoglobin <10 g/dL). We found that anaemia was independently associated with an increased risk of one-year mortality after adjustment for relevant covariates (aHR, 1.170; 95% CI, 1.045–1.310). We further identified a consistent strength of association between anaemia and one-year mortality in propensity score-based analyses, with the adjusted HRs in the PSM, IPTW, and CBPS were 1.164 (95% CI 1.025–1.322), 1.179 (95% CI 1.030–1.348), and 1.181 (1.034–1.349), respectively. Conclusions. We identified the impact on one-year mortality of anaemia in critically ill surgical patients, and more studies are needed to validate our findings.

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Clinical progress note: Inpatient management of iron deficiency anemia

Cool

Nelson

Freed

2022

Journal of Hospital Medicine

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Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-Analysis

Cited by 6 publications

References 82 publications

Causal associations between iron status and sepsis: a Mendelian randomisation analysis

Causal associations between iron status and sepsis: a Mendelian randomisation analysis

Week-One Anaemia was Associated with Increased One-Year Mortality in Critically Ill Surgical Patients

Clinical progress note: Inpatient management of iron deficiency anemia

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