Efficacy of perioperative intravenous iron therapy for transfusion in orthopedic surgery: A systematic review and meta-analysis

Abstract

Perioperative anemia frequently occurs in patients undergoing orthopedic surgery. We aimed to evaluate the efficacy of perioperative intravenous iron therapy (IVIT) on transfusion and recovery profiles during orthopedic surgery. We searched PubMed, Embase, Cochrane, and Google Scholar for eligible clinical trials (randomized controlled trials, RCTs; case-control studies, CCSs) in comparing IVIT and no iron therapy, up to September 2018. Primary outcomes were the effects of IVIT on the proportion of patients transfused and units of red blood cells (RBCs) transfused perioperatively. Secondary outcomes were the effects of IVIT on recovery profiles, such as length of hospital stay (LOS), post-operative infection, and mortality. Subgroup analysis was performed based on iron dose (low: ≤ 300 mg, high: > 400 mg), IVIT period (pre-operative, post-operative, perioperative), and study design. We identified 12 clinical trials (4 RCTs with 616 patients and 8 CCSs with 1,253 patients). IVIT significantly reduced the proportion of patients transfused by 31% (RR, 0.69; P = 0.0002), and units of RBCs transfused by 0.34 units/person (MD, −0.34; P = 0.0007). For subgroup analysis by iron dose, low- or high-dose IVIT significantly reduced the proportion of patients transfused (RR, 0.73, P = 0.005; RR, 0.68, P = 0.008), and RBC units transfused (MD, −0.47, P < 0.0001; MD, −0.28, P = 0.04). For subgroup analysis by period, IVIT administered post-operatively significantly reduced the proportion of patients transfused (post-operative: RR, 0.60, P = 0.002; pre-operative: RR, 0.74, P = 0.06) and RBC units transfused (post-operative: MD, −0.44, P <0.00001; pre-operative: MD, −0.29, P = 0.06). For subgroup analysis by study design, IVIT decreased the proportion of patients transfused and RBC units transfused in the group of CCSs, but IVIT in the group of RCTs did not. IVIT significantly shortened LOS by 1.6 days ( P = 0.0006) and reduced post-operative infections by 33% ( P = 0.01). IVIT did not change mortality. Perioperative IVIT during orthopedic surgery, especially post-operatively, appears to reduce the proportion of patients transfused and units of RBCs transfused, with shorter LOS and decreased infection rate, but no change in mortality rate. These were only found in CCSs and not in RCTs due to the relatively small number of RCTs with low to high risk of bias.

Intravenous iron infusion as an alternative to minimize blood transfusion in peri-operative patients

“…Functional IDA is a common feature of most major surgeries. Despite adequate iron stores in functional IDA, the unavailability of iron for erythropoiesis is due to the altered release of iron from macrophages and its subsequent incorporation into transferrin 38 – 42 . Results from various studies support the use of high dose IV iron infusion regimens to overcome this iron immobilization issue, wherein the iron saturated macrophages circumvent the hepcidin block by causing over-expression of ferroportin and the subsequent increase in transferrin saturation 43 .…”

“…Results from various studies support the use of high dose IV iron infusion regimens to overcome this iron immobilization issue, wherein the iron saturated macrophages circumvent the hepcidin block by causing over-expression of ferroportin and the subsequent increase in transferrin saturation 43 . Therefore, preoperative IV iron administration can prevent postoperative anemia in patients with functional IDA 42 , 44 . Still, most often RBC transfusion is the strategy of choice to tackle perioperative IDA in the management of patients undergoing major surgeries, a finding that is also reported by Shin et al 42 .…”

“…Therefore, preoperative IV iron administration can prevent postoperative anemia in patients with functional IDA 42 , 44 . Still, most often RBC transfusion is the strategy of choice to tackle perioperative IDA in the management of patients undergoing major surgeries, a finding that is also reported by Shin et al 42 .…”

Pre-operative hemoglobin level and use of sedative-hypnotics are independent risk factors for post-operative delirium following total knee arthroplasty

“…It reduced the rate of transfusion and length of hospital stay, but there is no conclusive evidence at present to suggest that correcting pre-operative anemia results in reduced risk of delirium post-operatively. [40] Although no definitive preventative measures for delirium exist, its multi-factorial nature suggests that for elderly patients with either low Hb or sedative-hypnotics, particular consideration is necessary to reduce other potential risk factors such as peri-operative bleeding and dehydration. Current hospital practice involves minimizing blood loss intra-operatively by administering tranexamic acid and avoiding dehydration by administration of intravenous fluids peri-operatively.…”

Pre-operative hemoglobin level and use of sedative-hypnotics are independent risk factors for post-operative delirium following total knee arthroplasty

“…It reduced the rate of transfusion and length of hospital stay, but whether correcting pre-operative anemia results in reducing the risk of delirium remains to be elucidated. [37] Although no definitive preventative measures for delirium exist, its multi-factorial nature suggests that for elderly patients with either low Hb or sedative-hypnotics, particular consideration is necessary to reduce other potential risk factors such as intra-operative bleeding and dehydration.…”