Intravenous Iron for Treatment of Anaemia Before Cardiac Surgery

Preoperative anaemia is common (≈30%) in patients awaiting cardiac surgery, and is associated with increased complications, ICU and hospital stay, and mortality. The extent of anaemia is worsened by haemodilution occurring with cardiopulmonary bypass and surgical bleeding (average blood loss 0.5-1.5 litres), which in turn impair end-organ blood flow and tissue oxygen delivery. Further, the need for blood transfusion is greatly increased in anaemic patients, and is associated with poor outcomes. In addition, blood transfusions are costly (>$700 per unit), with around 50% of all transfusions used in surgery being for cardiac surgery. The investigators have identified high rates of bleeding complications and transfusion requirements in Australian cardiac surgery; and in another international collaboration, it was found that anaemia, transfusion and kidney injury are inter-related after cardiac surgery. After risk-adjustment, the combination of these three risk factors was associated with a 3.5-fold (95% CI 2.3-5.2) increased odds of kidney injury.

Both anaemia and red cell transfusion are independent risk factors in major surgery. Some of the investigators reviewed Australian cardiac surgery patients from six Victorian hospitals, 2005-2011. We linked the ANZ Society of Cardiothoracic Surgeons cardiac surgery database to laboratory data, including preoperative haemoglobin and all issued blood products (manuscript in preparation). Anaemia was defined according to the WHO definition (Hb <130 g/L for males and <120 g/L for females). There were 15,948 cardiac surgery patients available for inclusion in the analysis, of which 28% were anaemic. Anaemic patients were more likely to receive a red cell transfusion (71% vs. 40%, p<0.001), more transfused units of blood (median 4 [IQR 2-8] vs. 3 [2-5], p<0.001), and had higher 30-day mortality (5.4% vs. 1.9%, p<0.001), new renal failure (43% vs. 26%, p<0.001), and longer hospital stay in survivors (13 days [8-23] vs. 8 days [6-14], p<0.001). After multivariable adjustment, preoperative anaemia was an independent predictor of mortality (adj. OR 1.46, 95% CI 1.14-1.88, p=0.003). Similar results were obtained when restricted to elective surgery, but with hospital stay 9 days (7-17) vs. 7 days (6-11), p<0.001. Other large studies are consistent with this.

The investigators have also analysed data for patients undergoing major non-cardiac surgery from the American College of Surgeons' National Surgical Quality Improvement Program database (a validated outcomes registry from 211 hospitals worldwide). In 227,425 patients undergoing noncardiac surgery, and found that preoperative anaemia was associated with increased 30-day mortality (adj. OR 1.42, 95% CI 1.31-1.54) and morbidity (adj. OR 1.35, 1.30-1.40).

Alfred hospital (Melbourne) transfusion data for 2012-14 (n=2,091) show that anaemic (27% of cohort) and non-anaemic cardiac surgical patients had intraoperative red cell transfusion rates of 31% and 14%, respectively; p<0.01.

Iron deficiency is the commonest cause of anaemia worldwide, and iron deficiency per se independently worsens outcomes after surgery. The traditional textbook definition of iron deficiency anaemia refers to depletion of the body's iron stores due to dietary deficiency or chronic blood loss - an absolute iron deficiency. Chronic disease and inflammation have a direct effect in the pathway of iron absorption and metabolism leading to a state of functional iron deficiency and anaemia. Specifically, the iron regulatory protein hepcidin is upregulated, blocking pathways of iron transport. This prevents iron absorption from the gut, further uptake by the reticuloendothelial system increases stores (ferritin), but distribution and transfer to the bone marrow is blocked. Consequently, despite normal or even increased body iron stores (with normal ferritin levels), these are artifactual, and a state of 'functional iron deficiency' exists. This is commonly seen in renal and cardiac disease and increasingly recognised as a cause for anaemia in the surgical patient. Importantly, IV iron has been shown to overcome this functional deficiency and correct anaemia.