Date Published: May 6, 2019
Publisher: Public Library of Science
Author(s): Hye Won Shin, Jeong Jun Park, Hyun Jung Kim, Hae Sun You, Sung Uk Choi, Mee Ju Lee, Wen-Chih Wu.
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.
Perioperative anemia and intraoperative blood loss in patients undergoing orthopedic surgery are risk factors for requiring red blood cell (RBC) transfusions . Major orthopedic surgery, especially hip and knee arthroplasty, results in significant intraoperative bleeding . The most common cause of iron deficiency anemia (IDA) is absolute iron deficiency or functional iron deficiency . Functional IDA may be due to erythropoiesis blunted by inflammation in patients undergoing surgery . A surge in inflammatory cytokines increases the levels of the hormone hepcidin, which impairs the absorption and recycling of iron by iron sequestration in macrophages . As a regulator of iron erythropoiesis, hepcidin impairs the recycling of iron from erythrocytes, absorption of dietary iron by duodenal enterocytes, and storage of iron in hepatocytes . Allogenic blood transfusion is the most frequently used treatment for perioperative anemia and bleeding; however, it is associated with the risk of disease transmission, immunomodulation, allergic reaction, infection, and cancer recurrence .
In this meta-analysis of clinical trials, we evaluated the efficacy of perioperative IVIT during orthopedic surgery. This analysis was performed according to the recommendations of the PRISMA statement. This systematic review was registered in PROSPERO under the number CRD42018081647.
The present systematic review and meta-analysis of 12 clinical trials indicated that perioperative IVIT decreased the proportion of patients transfused by 31% and the RBCs transfused by 0.34 units among patients undergoing orthopedic surgery. IVIT also shortened LOS by 1.60 days and reduced the rate of post-operative infections by 33%, with no change in the mortality rate. IVIT administered in the post-operative period significantly reduced the proportion of patients who received transfusion and units of RBCs, as compared with the control group. However, the above results were only present in CCSs and not in RCTs.
In the systematic review using 8 CCSs, perioperative IVIT, especially post-operatively, is an effective alternative to transfusion and revealed good recovery profiles during orthopedic surgery. However, based on our meta-analysis using the results of 4 RCTs, we could not identify the definitive effect of IVIT on the profiles regarding transfusion and recovery. The small numbers of RCTs for all parameters are inadequate for satisfactory statistical analysis. Therefore, we recommend that there be large, prospective, well-designed RCTs to confirm the efficacy of perioperative IVIT in patients with functional IDA during major surgery.