In patients undergoing elective major surgery, preoperative anemia is a common morbidity that may necessitate allogeneic blood transfusion in a substantial proportion of patients depending on the degree of anemia. Allogeneic blood transfusion has potential adverse outcomes. Preoperative intravenous iron (IV) monotherapy has been recommended as a bloodless therapy to decrease perioperative blood transfusion; however, class 1A evidence is lacking due to the absence of meta-analysis and systematic

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... reviews, and high quality randomized controlled trials. The aim was to evaluate the efficacy and safety of preoperative IV monotherapy injection versus placebo/oral iron (standard of care) as a strategy to increase the hemoglobin concentration to minimize the necessity of blood transfusion. Therefore, this systematic review and meta-analysis of the randomized controlled trials was conducted. The results of the meta-analysis study in this thesis showed that preoperative IV iron supplementation was found to be effective in decreasing allogeneic blood transfusion by 17% in patients who received IV iron therapy compared to who did not receive it. This reduction in transfusion rate was statistically significant (risk ratio [RR]: 0.83, 95% confidence interval [CI]: 0.70, 0.98, p = 0.03). Concomitantly, pre-operative IV iron therapy was also associated with increases in the hemoglobin concentrations prior to surgery compared with not receiving pre-operative IV iron therapy (mean difference [MD] between the study groups: 6.65, 95% CI: 0.83, 12.47 g/L, p = 0.03). Because some of the trials started administration of IV iron 3-4 weeks before surgery and some studies started the IV injection 1-2 days before surgery, the hemoglobin rise showed a bi-phasic pattern with the first wave appeared before surgery and the second wave existed 4 weeks after iii surgery. Moreover, the blood loss perioperatively interrupted this hemoglobin concentration growth throughout the hospital stay. As a follow-up > 4 weeks postoperatively, the second wave existed and the hemoglobin level increased significantly again in favor of the IV group (6.46, 95% CI: 3.11, 9.80 g/L, p = 0.0002) indicating an augmented/new effect of the injected IV iron later by the other trials. Intravenous iron administration was able to restore the depleted iron stores and increased serum ferritin levels significantly pre-surgery, at hospital discharge, and > 4 weeks postoperatively, (MD between groups: 108.03, 95 % CI: 45.58, 170.49 ng/mL, p = 0.0007), (MD between groups: 547.77, 95 % CI: 36.61, 1058.94 ng/mL, p = 0.04), and (MD between groups: 391.00, 95 % CI: 271.44, 510.56 ng/mL, p < 0.00001), respectively. There were no differences in non-serious and serious adverse effects between the two groups (RR: 1.17, 95% CI: 0.80, 1.71, p = 0.42) and (RR: 0.89, 95% CI: 0.40, 1.99, p = 0.77) respectively. Similar results were obtained from the case series of the thesis where is IV iron treatment was capable to increase Hb level significantly from 125.70 ± 11 g/L at baseline to be 132.30 ± 16 g/L at the time of surgery with p = 0.007, with mean difference of 6.6 g/L (95% confidence interval [CI]: 2.00, 11.11 g/L). Moreover, depleted iron stores were restored, and serum ferritin level increased significantly from 25.43 ± 18.47 ng/mL at baseline to be 239.80 ± 18.47 ng/ml at surgery (p = 0.004). Allogeneic perioperative red blood cell transfusion occurred in 9 (29%) patients, which is lower than a recent Canadian report. Preoperative intravenous iron monotherapy is a safe and efficacious intervention. It successfully lowers the transfusion rate and increases hemoglobin concentration preiv surgery and at four weeks postoperatively. However, further randomized controlled trials are required to establish its effectiveness, potential adverse effects, and to show which intravenous iron preparation has better cost-effectiveness than the other preparations to reduce blood transfusion. v PREFACE