Associations Between Nonanemic Iron Deficiency and Postoperative Outcomes in Cardiac Surgery: A Systematic Review and Meta-Analysis

BACKGROUND: Preoperative screening for iron deficiency is a part of patient blood management protocols. This systematic review, meta-analysis, and meta-regression reviews the association between nonanemic iron deficiency and postoperative outcomes in patients undergoing cardiac surgery. We aimed to determine whether preoperative screening for nonanemic iron deficiency should be recommended in patients undergoing cardiac surgery. METHODS: Electronic databases MEDLINE (Ovid), Embase (Ovid), and Scopus were searched from inception until December 9, 2022. Studies were considered for inclusion if they (1) used an observational study design; (2) enrolled adult patients undergoing cardiac surgery; and (3) included an iron-deficient and iron-replete group, defined using serum ferritin and/or transferrin saturation. The primary outcome was the length of acute hospital stay. Secondary outcomes included length of intensive care unit stay, requirement for allogeneic red blood cell transfusion, number of red blood cell units transfused, days alive and at home at postoperative days 30 and 90, all-cause postoperative complications, postoperative infection, mortality, and hospital readmission. Meta-regression was performed to assess the effects of study and patient-level factors on the associations between nonanemic iron deficiency and specific outcomes. Individual study quality was assessed using the Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to determine the quality of evidence for each outcome. RESULTS: Eight studies (2683 patients) were included. No significant association was observed between nonanemic iron deficiency and any of the primary or secondary outcomes except for an increased requirement for allogeneic red blood cell transfusion (odds ratio [OR], 1.39 [95% confidence interval, CI, 1.16–1.68; P < .001; I 2 2.8%]). Meta-regression did not identify any potential sources of heterogeneity to explain variation in individual study results. The quality of evidence was rated as “low” or “very low” for all outcomes. CONCLUSIONS: Few high-quality studies are available to assess associations between nonanemic iron deficiency and outcomes after cardiac surgery. Acknowledging these limitations, the presence of preoperative nonanemic iron deficiency was not associated with a change in the primary outcome of length of hospital stay, or any patient-centered secondary outcome compared to those without iron deficiency. There was an association with increased requirement for allogeneic red blood cell transfusion, but this did not impact the reported patient-centered outcomes.