Iron supplementation for patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Yang, Stephen Su; Kharusi, Latifa Al; Gosselin, Adam; Chirico, Anissa; Baradari, Pouya Gholipour; Cameron, Matthew

doi:10.1007/s12630-021-02113-z

Cited by 13 publications

(10 citation statements)

References 42 publications

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“…Seven recently published systematic reviews with metaanalyses of RCTs answered a similar PICO question and confirmed our conclusions regarding no effect of preoperative iron monotherapy [25][26][27][28] or a reduced effect of ESAs in addition to oral/IV iron supplementation on blood transfusion rate. [29][30][31] On the contrary, one review found that IV iron supplementation is associated with a significant decrease in blood transfusion rate in both anemic and nonanemic patients undergoing major elective surgery.…”

Section: Comparison With Other Recent Systematic Reviews and Meta-ana...supporting

confidence: 82%

Evidence-Based Medicine: Principles and Values as Illustrated by the Case of Patient Blood Management

et al. 2023

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Evidence-based medicine is considered 1 of the 15 great inventions in medicine. It aims to remove bias in medical decision-making as much as possible through a rigorous process. In this article, the principles of evidence-based medicine are illustrated using the case of patient blood management (PBM). Acute or chronic bleeding, iron deficiency, and renal and oncological diseases may lead to preoperative anemia. To compensate for severe and life-threatening blood loss during surgery, doctors transfuse red blood cells (RBCs). PBM is an approach to take care of patients at risk for anemia, which includes detecting and treating anemia before surgery. Alternative interventions to treat preoperative anemia are the use of iron supplementation with or without erythro-stimulating agents (ESAs). The best available scientific evidence today indicates that preoperative intravenous (IV) or oral iron monotherapy may not be effective to reduce RBC utilization (low-certainty evidence). Preoperative IV iron supplementation in addition to ESAs is probably effective to reduce RBC utilization (moderate-certainty evidence), whereas oral iron supplementation in addition to ESAs may be effective to reduce RBC utilization (low-certainty evidence). The adverse events of preoperative oral/IV iron and/or ESAs and their impact on patient-important outcomes (morbidity, mortality, quality of life) remain unclear (very low-certainty evidence). Since PBM is a patient-centered approach, emphasis on monitoring and evaluation of patient-important outcomes in future research is urgently needed. Finally, the cost-effectiveness of preoperative oral/IV iron monotherapy is unproven, whereas preoperative oral/IV iron in addition to ESAs is extremely cost-ineffective.

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Section: Comparison With Other Recent Systematic Reviews and Meta-ana...supporting

confidence: 82%

Evidence-Based Medicine: Principles and Values as Illustrated by the Case of Patient Blood Management

et al. 2023

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“…Because more than half of anemic patients undergoing cardiac surgery have iron deficiency, IV iron therapy preoperatively is recommended [ 2 , 28 , 29 ]. However, the evidence regarding the effect of IV iron on reducing the transfusion rate for cardiac surgery patients with preoperative anemia is limited and unclear [ 2 , 13 , 14 , 30 ].This systematic review and meta-analysis suggested that IV iron did not decrease transfusion rates compared with the control group, which was not consistent with Gupta et al [ 13 ] or Elhenawy et al [ 31 ] as they found a significant association of IV iron treatment with a reduced transfusion rate in cardiac surgery patients (RR 0.81, 95% CI 0.70–0.94, P = 0.005) or other major surgery patients (RR 0.84, 95% CI 0.70 to 0.99, P = 0.04). However, their meta-analysis [ 13 , 31 ] included studies exploring the efficacy of IV iron in nonanemic patients.…”

Section: Discussionmentioning

confidence: 99%

“…Taken together, future studies with a sufficiently large sample size are needed to focus on patients undergoing cardiac surgery. Further data are also required to examine the role of IV iron in three aspects: [ 1 ] applying IV iron with or without other agents (mainly EPO); [ 2 ] dosage of IV iron; and [ 3 ] time of IV iron administration preoperatively [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Anemia is a common condition observed in patients scheduled for cardiac surgery with its incidence ranging 20–50% in different circumstances [ 1 , 2 ]. Anemia remains an independent risk factor for perioperative allogeneic blood transfusion (ABT), associated with increased hospital length of stay (LOS), postoperative morbidity and mortality [ 3 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

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The efficacy of intravenous iron for treatment of anemia before cardiac surgery: An updated systematic review and meta-analysis with trial sequential analysis

Tang

et al. 2023

J Cardiothorac Surg

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Background Preoperative anemia is common in patients undergoing cardiac surgery with various etiologies, among which iron deficiency is the leading cause. However, the benefit of intravenous (IV) iron for the treatment of anemia before cardiac surgery is uncertain. This updated meta-analysis aimed to evaluate the efficacy of IV iron in adult cardiac surgery patients with preoperative anemia. Methods This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched Embase, PubMed and the Cochrane Central Register of Controlled Trials to identify eligible randomized controlled trials (RCTs) and observational studies. Quality was assessed using the Cochrane Collaboration risk of bias tool and Newcastle–Ottawa scale, and the strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Trial sequential analysis was performed on the primary outcome (transfusion rate) to confirm whether firm evidence was reached. Results Six RCTs (936 patients) and 5 observational studies (1350 patients) were included in this meta-analysis. The IV iron group and the control group were comparable in terms of transfusion rate [55.1% vs 60.9%, risk ratio (RR) = 0.91, 95% confidence interval (CI) 0.81–1.03, P = 0.13, low quality]. There were no significant differences in units transfused per patient, ICU stay and hospital length of stay between the two groups. And pooled data showed a benefit of IV iron compared to the control group on mortality (2.76% vs 3.75%, RR = 0.58, 95% CI 0.36–0.95, P = 0.03, moderate quality) and no mortality reduction existed when including only RCTs. Conclusions This meta-analysis suggested that IV iron treatment for patients with anemia before cardiac surgery did not reduce the transfusion requirement (low quality), but it was associated with decreased mortality (moderate quality). More large-scale, high-quality randomized clinical trials are warranted to confirm or refute our findings. PROSPERO registry reference: CRD42022331875.

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“…Studies exploring IV iron supplementation prior to cardiac surgery have typically focused on a transfusion-sparing effect [14][15][16]. Systematic reviews published in 2015 [17] and 2022 [18] have concluded that perioperative administration of IV iron in this setting is of uncertain benefit, whilst a recent observational study reported that IV iron therapy increased hemoglobin but had no effect on postoperative outcomes [19].…”

Section: Introductionmentioning

confidence: 99%

Non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement: a single-centre retrospective study

Frise

Holdsworth

Sandhu

et al. 2022

J Cardiothorac Surg

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Background Iron deficiency has deleterious effects in patients with cardiopulmonary disease, independent of anemia. Low ferritin has been associated with increased mortality in patients undergoing cardiac surgery, but modern indices of iron deficiency need to be explored in this population. Methods We conducted a retrospective single-centre observational study of 250 adults in a UK academic tertiary hospital undergoing median sternotomy for non-emergent isolated aortic valve replacement. We characterised preoperative iron status using measurement of both plasma ferritin and soluble transferrin receptor (sTfR), and examined associations with clinical outcomes. Results Measurement of plasma sTfR gave a prevalence of iron deficiency of 22%. Patients with non-anemic iron deficiency had clinically significant prolongation of total hospital stay (mean increase 2.2 days; 95% CI: 0.5–3.9; P = 0.011) and stay within the cardiac intensive care unit (mean increase 1.3 days; 95% CI: 0.1–2.5; P = 0.039). There were no deaths. Defining iron deficiency as a plasma ferritin < 100 µg/L identified 60% of patients as iron deficient and did not predict length of stay. No significant associations with transfusion requirements were evident using either definition of iron deficiency. Conclusions These findings indicate that when defined using sTfR rather than ferritin, non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement. Further studies are required to clarify the role of contemporary laboratory indices in the identification of preoperative iron deficiency in patients undergoing cardiac surgery. An interventional study of intravenous iron targeted at preoperative non-anemic iron deficiency is warranted.

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Iron supplementation for patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Cited by 13 publications

References 42 publications

Evidence-Based Medicine: Principles and Values as Illustrated by the Case of Patient Blood Management

Evidence-Based Medicine: Principles and Values as Illustrated by the Case of Patient Blood Management

The efficacy of intravenous iron for treatment of anemia before cardiac surgery: An updated systematic review and meta-analysis with trial sequential analysis

Non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement: a single-centre retrospective study

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