Iron deficiency and infection: another pathway to explore in critically ill patients?

Swenson, Erik R.; Porcher, Raphaël; Piagnerelli, Michaël

doi:10.1007/s00134-018-5438-8

Cited by 10 publications

(14 citation statements)

References 17 publications

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“…Recent initiatives, such as the updated Sepsis-3 definition 202 Imbalances of iron homeostasis, including both iron deficiency and overload, can affect the risk of developing infection, but the effect of therapeutic iron on this remains unclear. 204 The effects are likely to be context specific, depending on the patient's preexisting iron status, exposure to potential infections and genetic background, and type of iron preparation administerd. 205,206 We observed no evidence of an interaction between baseline iron status (as measured by ferritin, transferrin saturation, and hemoglobin) and the risk of developing infection, although the number of studies reporting this information in a way that could be analyzed for metaregression ranged from 29 to 40.…”

Section: Jama Network Open | Hematologymentioning

confidence: 99%

Risk of Infection Associated With Administration of Intravenous Iron

et al. 2021

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IMPORTANCEIntravenous iron is recommended by many clinical guidelines based largely on its effectiveness in reducing anemia. However, the association with important safety outcomes, such as infection, remains uncertain. OBJECTIVE To examine the risk of infection associated with intravenous iron compared with oral iron or no iron. DATA SOURCES Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials (RCTs) from 1966 to January 31, 2021. Ongoing trials were sought from ClinicalTrials.gov, CENTRAL, and the World Health Organization International Clinical Trials Search Registry Platform. STUDY SELECTION Pairs of reviewers identified RCTs that compared intravenous iron with oral iron or no iron across all patient populations, excluding healthy volunteers. Nonrandomized studies published since January 1, 2007, were also included. A total of 312 full-text articles were assessed for eligibility. DATA EXTRACTION AND SYNTHESIS Data extraction and risk of bias assessments were performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) and Cochrane recommendations, and the quality of evidence was assessed using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Two reviewers extracted data independently. A random-effects model was used to synthesize data from RCTs. A narrative synthesis was performed to characterize the reporting of infection. MAIN OUTCOMES AND MEASURESThe primary outcome was risk of infection. Secondary outcomes included mortality, hospital length of stay, and changes in hemoglobin and red blood cell transfusion requirements. Measures of association were reported as risk ratios (RRs) or mean differences.RESULTS A total of 154 RCTs (32 920 participants) were included in the main analysis. Intravenous iron was associated with an increased risk of infection when compared with oral iron or no iron (RR, 1.17; 95% CI, 1.04-1.31; I 2 = 37%; moderate certainty of evidence). Intravenous iron also was associated with an increase in hemoglobin (mean difference, 0.57 g/dL; 95% CI, 0.50-0.64 g/dL; I 2 = 94%) and a reduction in the risk of requiring a red blood cell transfusion (RR, 0.93; 95% CI, 0.76-0.89; I 2 = 15%) when compared with oral iron or no iron. There was no evidence of an effect on mortality or hospital length of stay. (continued) Key Points Question In patients who require treatment with intravenous iron, what is the evidence that this intervention increases the risk of developing a new infection? Findings In this systematic review and meta-analysis of 154 randomized clinical trials that included 32 920 participants, intravenous iron was associated with an increased risk of infection. Meaning The results of this study suggest that, despite broad advocacy in clinical guidelines, intravenous iron may increase the risk of infection, which must be balanced with the potential benefits of treating anemia and reducing blood transfusion requirements.

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Section: Jama Network Open | Hematologymentioning

confidence: 99%

Risk of Infection Associated With Administration of Intravenous Iron

et al. 2021

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“…This work suggests that infection susceptibility may be dependent on the level of iron deficiency. This has been described as a U-shaped relationship, with infection risk being increased from either extreme of iron levels (54). The plateau of the U likely represents the desirable level of iron which maintains immune function without promoting infection.…”

Section: Role Of Iron In Immune Defensementioning

confidence: 99%

Role of reactive oxygen species and iron in host defense against infection

Dickson

2020

Front Biosci

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“…The role of iron status in the context of infectious diseases has long been noted (1, 2, 10, 11). Both iron deficiency (5, 6), iron overload (8), and iron fortification programs without adequate infection surveillance (43), have been linked to increased risk of infections.…”

Section: Discussionmentioning

confidence: 99%

“…Genetically-predicted iron status may not perfectly reflect this time-varying exposure (51). The U-shaped risk relationship that has been proposed for the extremes of iron status (10, 15) might cause an attenuated association when evaluated in a linear model as in the two-sample MR methods. Non-linear MR methods could be more suitable to explore this U-shaped relationship but requires large GWAS with both measurements of iron biomarkers as well as the outcomes of interest (37).…”

Section: Discussionmentioning

confidence: 99%

Iron status and the risk of sepsis and severe COVID-19: A two-sample Mendelian randomization study

Mohus

Flatby

Liyanarachi

et al. 2022

Preprint

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Introduction: Observational studies have indicated an association between iron status and risk of sepsis and severe COVID-19. However, these findings may be affected by residual confounding, reverse causation. Methods: In a two-sample Mendelian randomization study using inverse variance weighted method, we estimated the effect of genetically-predicted iron biomarkers (serum iron, transferrin saturation (TSAT), total iron binding capacity (TIBC) and ferritin) on risk of sepsis and risk of being hospitalized with COVID-19. For the COVID-19 outcomes we additionally conducted sex-stratified analyses. Weighted median, Weighted mode and MR Egger were used as sensitivity analyses. Results: For risk of sepsis, one standard deviation increase in genetically-predicted serum iron was associated with odds ratio (OR) of 1.14 (95% confidence interval (CI) 1.01 to 1.29, P=0.031). The findings were supported in the analyses for transferrin saturation and total iron binding capacity, while the estimate for ferritin was inconclusive. We found a tendency of higher risk of hospitalization with COVID-19 for serum iron; OR 1.29 (CI 0.97-1.72, P=0.08), where sex stratified analyses showed OR 1.63 (CI 0.94-2.86, P=0.09) for women and OR 1.21 (CI 0.92-1.62, P=0.17) for men. Sensitivity analyses supported the main findings and did not suggest bias due to pleiotropy. Conclusions: Our findings suggest a causal effect of genetically-predicted higher iron status and risk of hospitalization due to sepsis and indications of an increased risk of being hospitalized with COVID-19. These findings warrant further studies to assess iron status in relation to severe infections, including the potential of improved management.

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Iron deficiency and infection: another pathway to explore in critically ill patients?

Cited by 10 publications

References 17 publications

Risk of Infection Associated With Administration of Intravenous Iron

Risk of Infection Associated With Administration of Intravenous Iron

Role of reactive oxygen species and iron in host defense against infection

Iron status and the risk of sepsis and severe COVID-19: A two-sample Mendelian randomization study

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