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Iron supplementation for patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials
Yang SS, Al Kharusi L, Gosselin A, Chirico A, Baradari PG, Cameron MJ
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2021
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Editor's Choice
Abstract
PURPOSE Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for its potential to increase baseline hemoglobin and decrease red blood cell transfusion during cardiac surgery. This study's main objective was to evaluate the current evidence for iron administration in cardiac surgery patients. METHODS We searched MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar from inception to 19 November 2020 for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. The RCTs were assessed using a risk of bias assessment and the quality of evidence was assessed using the grading of recommendations, assessments, development, and evaluations. RESULTS We reviewed 1,767 citations, and five studies (n = 554) met the inclusion criteria. The use of iron showed no statistical difference in incidence of transfusion (risk ratio, 0.86; 95% confidence interval, 0.65 to 1.13). Trial sequential analysis suggested an optimal information size of 1,132 participants, which the accrued information size did not reach. CONCLUSION The current literature does not support or refute the routine use of iron therapy in cardiac surgery patients. TRIAL REGISTRATION PROSPERO (CRD42020161927); registered 19 December 2019.
PICO Summary
Population
Patients undergoing cardiac surgery (5 studies, n= 554).
Intervention
Iron therapy.
Comparison
Placebo, or no-treatment.
Outcome
Based on the pooling of data from four trials (n= 449), the use of iron showed no statistical difference in the incidence of transfusion (RR, 0.86). There was low heterogeneity between studies (I2 = 0%). One trial (n= 60) reported a significant decrease in the number of red blood cells transfused (mean differences, -1.0 units). All five trials (n= 554) showed no difference in serious adverse events using iron therapy (risk difference, 0.0).
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Intravenous iron therapy for patients with preoperative iron deficiency or anaemia undergoing cardiac surgery reduces blood transfusions: a systematic review and meta-analysis
Gupta S, Panchal P, Gilotra K, Wilfred AM, Hou W, Siegal D, Whitlock RP, Belley-Cote EP
Interact Cardiovasc Thorac Surg. 2020
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Editor's Choice
Abstract
OBJECTIVES The benefits of preoperative intravenous (IV) iron treatment in cardiac surgery patients with preoperative anaemia or iron deficiency have not been well-established. We performed a systematic review and meta-analysis to determine the effects of treating preoperative anaemia or iron deficiency with IV iron in adult cardiac surgery patients. METHODS We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online and Excerpta Medica Database for randomized controlled trials (RCTs) and observational studies comparing IV iron to oral iron or no iron. We performed title and abstract, full-text screening, data extraction and risk of bias assessment independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence. RESULTS We identified 4 RCTs and 7 observational studies. Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality [relative risk 0.39, 95% confidence interval (CI) 0.23-0.65; P < 0.001, very low quality], units transfused per patient (mean difference -1.22, 95% CI -1.85 to -0.60; P < 0.001, very low quality), renal injury (relative risk 0.50, 95% CI 0.36-0.69; P < 0.001, very low quality) and hospital length of stay (mean difference -4.24 days, 95% CI -6.86 to -1.63; P = 0.001, very low quality). Pooled data from RCTs demonstrated a reduction in the number of patients transfused with IV iron compared to oral or no iron (relative risk 0.81, 95% CI 0.70-0.94; P = 0.005, moderate quality). The pooled estimates of effect from RCTs for mortality, hospital length of stay, units transfused per patient and renal injury were consistent in direction with observational studies. CONCLUSIONS This meta-analysis suggests that IV iron improves postoperative morbidity in adult cardiac surgery patients with preoperative anaemia or iron deficiency. A large, rigorous, placebo-controlled, double-blinded, multicentre trial is needed to clarify the role of IV iron in this patient population. CLINICAL TRIAL REGISTRATION International prospective register of systematic reviews ID Number CRD42019122844.
PICO Summary
Population
Adult cardiac surgery patients with preoperative anaemia or iron deficiency (11 studies, n= 1657).
Intervention
Intravenous (IV) iron treatment.
Comparison
Oral iron or no iron.
Outcome
Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality, units transfused per patient, renal injury and hospital length of stay. Pooled data from randomised controlled trials (RCTs) demonstrated a reduction in the number of patients transfused with IV iron compared to oral or no iron. The pooled estimates of effect from RCTs for mortality, hospital length of stay, units transfused per patient and renal injury were consistent in direction with observational studies.
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The Impact of Preoperative Intravenous Iron Therapy on Perioperative Outcomes in Cardiac Surgery: A Systematic Review
Tankard KA, Park B, Brovman EY, Bader AM, Urman RD
Journal of hematology. 2020;9(4):97-108
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Editor's Choice
Abstract
BACKGROUND Anemia is common in cardiac surgery affecting 25-40% of patients and associated with increased blood transfusions, morbidity, mortality, and higher hospital costs. Higher rates of stroke, acute renal injury, and total number of adverse postoperative outcomes have also been reported to be associated with preoperative anemia. This systematic review assessed the current evidence for preoperative intravenous iron on major outcomes following cardiac surgery. METHODS Outcome measures included postoperative hemoglobin, transfusion rates, major adverse events, and mortality. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and articles were identified using PubMed, Cochrane, CLINAHL, WOS, and EMBASE databases. Articles were included if they compared patients with and without preoperative anemia based on treatment with intravenous iron. Quality was assessed using Cochrane Risk of Bias Tool and Newcastle-Ottawa scale, and strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS Of the articles reviewed, six met inclusion criteria. These included four randomized double-blind prospective cohort studies, one randomized non-blinded prospective study, and one non-randomized non-blinded prospective study with historical control. Across studies, 1,038 patients were enrolled. Two studies showed higher hemoglobin with iron therapy, and only one study showed significant differences in multiple outcomes such as transfusion and morbidity. CONCLUSIONS Given the paucity of studies and biases within them, the current evidence for treatment with intravenous iron prior to cardiac surgery is weak. More evidence is needed to support the administration of preoperative intravenous iron in cardiac surgery patients.
PICO Summary
Population
Cardiac surgery patients with or without preoperative anaemia (6 studies, n= 1,038).
Intervention
Preoperative intravenous iron.
Comparison
Oral iron; Placebo.
Outcome
Two studies showed higher hemoglobin with iron therapy, and only one study showed significant differences in multiple outcomes such as transfusion and morbidity.
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Preoperative Anemia and Postoperative Mortality in Patients with Aortic Stenosis Treated with Transcatheter Aortic Valve Implantation (TAVI): A Systematic Review and Meta-Analysis
Lv Z, Zhou B, Yang C, Wang H
Medical science monitor : international medical journal of experimental and clinical research. 2019;25:7251-7257
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Editor's Choice
Abstract
BACKGROUND Patients with severe aortic stenosis who have comorbidities that prevent general anesthesia and open cardiothoracic surgery are candidates for transcatheter aortic valve implantation (TAVI). However, TAVI can result in patient mortality following the procedure. This systematic review of the literature and meta-analysis aimed to determine the relationship between preoperative anemia and postoperative mortality in patients following TAVI. MATERIAL AND METHODS PubMed, EMBASE, the Cochrane Library, and the Web of Science were systematically searched from their inception to February 2019 for relevant published studies that included patients with bicuspid aortic valve stenosis and tricuspid aortic valve stenosis who underwent TAVI and who had preoperative data on hemoglobin levels. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated using a random-effects generic inverse variance method. RESULTS Six published studies that involved 6,406 patients with aortic stenosis were included in the meta-analysis. There was no significant difference observed for the final pooled result for patients with and without anemia for the short-term 30-day postoperative mortality (OR, 1.34; 95% CI, 0.77-2.35). However, long-term mortality rates were significantly worse in patients with preoperative anemia compared with those without anemia (OR, 1.77; 95% CI, 1.34-2.35). CONCLUSIONS Systematic review of the literature and meta-analysis showed that pre-procedural anemia reduced long-term mortality following TAVI. This finding supports the need to correct preoperative anemia in patients with aortic stenosis to improve patient outcome following TAVI.
PICO Summary
Population
Patients with aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) (n=6,046, 6 studies).
Intervention
Patients with pre-operative anaemia (defined as a hemoglobin level of <12 g/dl for women and hemoglobin of <13 g/dl in men).
Comparison
Patients without pre-operative anaemia.
Outcome
There was no significant difference observed for the final pooled result for patients with and without anaemia for short-term 30-day postoperative mortality. However, long-term mortality rates were significantly worse in patients with preoperative anaemia compared with those without anaemia.
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5.
Preoperative anemia and outcomes in cardiovascular surgery: systematic review and meta-analysis
Padmanabhan H, Siau K, Curtis J, Ng A, Menon S, Luckraz H, Brookes MJ
The Annals of thoracic surgery. 2019
Abstract
BACKGROUND Pre-operative anemia is common in patients scheduled for cardiac surgery. However, its effect on postoperative outcomes remains controversial. This meta-analysis aimed to clarify the impact of anemia on outcomes following cardiac surgery. METHODS A literature search was conducted on MEDLINE, Embase, Cochrane, and Web of Science databases. The primary outcome was 30-day postoperative or in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), stroke, blood transfusion, and infection. A meta-analytic model was used to determine the differences in the above postoperative outcomes between anemic and non-anemic patients. RESULTS Out of 1103 studies screened, 22 met the inclusion criteria. A total of 23624 (20.6%) out of 114277 patients were anemic. Anemia was associated with increased mortality (odds ratio [OR] 2.74, 95% confidence interval [CI] 2.32-3.24; I(2)=69.6%; p<0001), AKI (OR 3.13, 95% CI 2.37-4.12; I(2)=71.1%; p<0001), stroke (OR 1.46, 95% CI 1.24-1.72; I(2)=21.6%; p<0001), and infection (OR 2.65, 95% CI 1.98-3.55; I(2)=46.7%; p<0001). More anemic patients were transfused than non-anemic (33.3 versus 11.9%). No statistically significant association was found between mortality and blood transfusion (OR 1.35, 95% CI 0.92-1.98; I(2)=83.7%; p=0.12) but we were not able to compare mortality with or without transfusion in those who were or were not anemic. CONCLUSIONS Preoperative anemia is associated with adverse outcomes following cardiac surgery. These findings support the addition of preoperative anemia to future risk prediction models, and as a target for risk modification.
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The impact of anaemia and intravenous iron replacement therapy on outcomes in cardiac surgery
Hogan M, Klein AA, Richards T
European Journal of Cardio-Thoracic Surgery. 2015;47((2):):218-26.
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Abstract
Anaemia is common in patients with cardiac disease and also in those undergoing cardiac surgery. There is increasing evidence that preoperative anaemia is associated with increased patient morbidity and mortality following surgery. We performed a systematic literature review to assess the impact of anaemia and intravenous (IV) iron supplementation on outcomes in cardiac surgery. Sixteen studies examined preoperative anaemia in detail. One study examined the role of preoperative IV iron administration and a further three, the effect of postoperative iron supplementation on haemoglobin (Hb) levels and the need for transfusion. Preoperative anaemia was associated with higher mortality, more postoperative blood transfusions, longer intensive care unit (ICU) and total hospital stay and also a greater incidence of postoperative cardiovascular events. In the single study that examined preoperative IV iron in combination with erythropoietin treatment, there was decreased blood transfusion, shorter hospital stay and an increase in patient survival. However, this was a small retrospective cohort study, with the observation and treatment groups analysed over different time periods. Postoperative administration of IV iron therapy, either alone or in combination with erythropoietin, was not effective in raising Hb levels or reducing red cell concentrate transfusion. On the basis of currently available evidence, the effect of perioperative administration of IV iron to cardiac surgery patients, alone or in combination with erythropoietin, remains unproven. Well-designed and appropriately powered prospective randomized controlled trials are needed to evaluate perioperative iron supplementation in the context of cardiac surgery. Copyright © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Does the use of erythropoietin reduce the risk of exposure to allogeneic blood transfusion in cardiac surgery? A systematic review and meta-analysis
Alghamdi AA, Albanna MJ, Guru V, Brister SJ
Journal of Cardiac Surgery. 2006;21((3):):320-6.
