3.4 Effect of non-transfusion interventions to increase haemoglobin concentration

3.4.2 Effect of erythropoiesis-stimulating agents

Thirty-two studies investigated the effect of ESAs on morbidity, mortality and need for RBC transfusion in a perioperative population. All 32 studies combined ESAs with oral or intravenous iron therapy. Of these, 14 were Level II studies (some of which were included in 2 Level I studies); these formed the evidence base.

Of the 14 RCTs investigating the efficacy of erythropoietin in an anaemic perioperative patient population, 2 were in cardiac surgery, as postoperative therapy.104,105 The remaining 12 studies were in noncardiac surgery,106–116 with only 1 as postoperative therapy.117 These studies used a variety of ESA treatment doses and regimens, and were of fair to good quality.

Morbidity and mortality

The studies were too small to detect any effect of perioperative ESA therapy on mortality.

No difference was observed in the incidence of morbidity outcomes between ESA-treated and control patients, including the incidence of thrombotic vascular events,106,108 or the incidence of infections.113 However, the studies investigating thrombotic vascular events were underpowered to detect a difference in this outcome. Therefore, no conclusion could be drawn regarding the safety of perioperative use of ESAs.

Haemoglobin concentration and incidence of transfusion

The results of ESA treatment on haemoglobin concentration and transfusion use varied between surgical populations.

In noncardiac surgery patients, preoperative erythropoietin treatment resulted in higher haemoglobin levels preoperatively110,113,116,118 and postoperatively.112–116 The effect on transfusion requirements in oncology surgery patients remains uncertain;107,110–112,114 however, in patients who underwent orthopaedic surgery, treatment with preoperative ESA reduced both the use106,108,115 and rate108 of blood transfusion.

Postoperative treatment with ESA plus intravenous iron in patients who were anaemic following cardiac surgery was compared to intravenous iron alone or standard care.104,105 Treatment with ESA did not affect postoperative haemoglobin levels or decrease the incidence of transfusion or number of units transfused per patient.

A small, single study in orthopaedic surgery found a modest increase in haemoglobin concentration in patients treated postoperatively with ESA and oral iron.117

EVIDENCE STATEMENTS – iron and erythropoiesis-stimulating agents	Evidence	Consistency	Clinical impact	Generalisability	Applicability
In paediatric and adult cardiac surgery patients with postoperative anaemia, postoperative oral iron had no effect on haemoglobin.			X
In patients with preoperative anaemia undergoing noncardiac surgery, preoperative oral iron increases haemoglobin levels.
In patients with preoperative anaemia undergoing noncardiac surgery, preoperative oral iron reduces the incidence of transfusion requirements.
In noncardiac surgery patients without preoperative anaemia, there is insufficient evidence to determine whether oral iron treatment before surgery affects the incidence of transfusion.		NA
In noncardiac surgery patients with postoperative anaemia, postoperative oral iron is not clinically effective.			X
In noncardiac surgery patients, preoperative and postoperative intravenous iron may reduce mortality and hospital length of stay, risk of infection and incidence of transfusion.	X		X
In cardiac and orthopaedic surgery patients, the effectiveness of postoperative intravenous iron plus oral iron compared with postoperative oral iron alone on the incidence of transfusion and postoperative haemoglobin levels and ferritin levels is uncertain.		NA	X
In gynaecological surgical patients with iron deficiency anaemia, preoperative intravenous iron is more effective than preoperative oral iron at increasing postoperative haemoglobin and ferritin levels.	X	NA	X
In noncardiac surgery patients, there is insufficient evidence to determine the effect on morbidity of preoperative treatment with an ESA in combination with oral iron.
In orthopaedic surgery patients, preoperative treatment of anaemia with an ESA in combination with oral iron reduces the incidence of transfusion.
In colorectal surgery patients, preoperative treatment of anaemia with an ESA in combination with oral iron starting less than 10 days before surgery has an inconsistent effect on incidence of transfusion.
In noncardiac surgery patients, preoperative treatment of anaemia with an ESA in combination with iron increases preoperative haemoglobin levels.
In noncardiac surgery patients, preoperative treatment of anaemia with an ESA in combination with oral iron does not affect hospital length of stay.
In orthopaedic surgery patients with anaemia, preoperative administration of an ESA (epoetin alfa) weekly is no different to daily administration in combination with oral iron at increasing preoperative haemoglobin levels.		NA
In cardiac and orthopaedic surgery patients, treatment of postoperative anaemia with an ESA in combination with intravenous iron may not decrease the incidence of transfusion compared with intravenous iron plus oral iron, or oral iron alone.		NA	X
In orthopaedic surgery patients with postoperative anaemia, treatment with an ESA in combination with oral iron increases haemoglobin levels.		NA	X

ESA, erythropoiesis-stimulating agent

(See Table 2.2)

RECOMMENDATION – iron and erythropoiesis-stimulating agents

R4 Grade B	In surgical patients with, or at risk of, iron-deficiency anaemia, preoperative oral iron therapy is recommended (Grade B). Refer to the preoperative haemoglobin assessment and optimisation template [Appendix F] for further information on the optimal dosing strategy.
R5 Grade B	In patients with preoperative anaemia, where an ESA is indicated, it must be combined with iron therapy (Grade A).
R6 Grade B	In patients with postoperative anaemia, early oral iron therapy is not clinically effective; its routine use in this setting is not recommended (Grade B).

PRACTICE POINTS – iron and erythropoiesis-stimulating agents

PP4	All surgical patients should be evaluated as early as possible to manage and optimise haemoglobin and iron stores.
PP5	Elective surgery should be scheduled to allow optimisation of patients’ haemoglobin and iron stores.
PP6	Surgical patients with suboptimal iron stores (as defined by a ferritin level <100 μg/L) in whom substantial blood loss (blood loss of a volume great enough to induce anaemia that would require therapy) is anticipated, should be treated with preoperative iron therapy. Refer to the preoperative haemoglobin assessment and optimisation template [Appendix F] for further information on the evaluation and management of preoperative patients.
PP7	In patients with preoperative iron-deficiency anaemia or depleted iron stores, treatment should be with iron alone. In patients with anaemia of chronic disease (also known as anaemia of inflammation), ESAs may be indicated. Refer to the preoperative haemoglobin assessment and optimisation template [Appendix F] for further information on the evaluation and management of preoperative patients.

ESA, erythropoiesis-stimulating agent