A South African Multi-centre Pilot Trial to Assess the Feasibility and Clinical Efficacy of Preoperative Oral Iron to Treat Preoperative Iron-deficiency Anaemia in Children Undergoing Elective Noncardiac Surgery

Studies in both paediatric and adult patients have shown an association between preoperative anaemia and increased postoperative morbidity and mortality, and transfusion rates. The incidence of preoperative anaemia in the secondary analysis of the SAPSOS cohort of children who underwent noncardiac surgery was 46.2%. IDA has been shown to represent up to 30% of preoperative anaemia in adults. Iron deficiency and IDA are of even greater concern in children, because of the negative impact it may have on cognitive performance.

A recent Cochrane review on the role of preoperative iron in reducing perioperative blood transfusion in adult patients found no significant reduction in the administration of allogeneic blood transfusion in patients who had received preoperative iron compared with those who did not. These findings were supported by the Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT) trial which found no difference in blood transfusion or death between the patients who did and did not receive intravenous iron. However, these findings have generated much discussion in the literature and concerns have been raised about the clinical application of this study. The mean haemoglobin (Hb) difference between the two groups post intervention (0.47g.dl-1) highlights the need for greater understanding of the impact of an intervention on the absolute or relative increase in Hb when designing trials looking at the impact of iron treatment on perioperative outcomes. Dosing regimens of preoperative oral iron varies widely between studies further complicating the ability to draw conclusions of the role of oral iron in the treatment of preoperative anaemia.

In contrast with the findings of the Cochrane review and the PREVENTT trial, a meta-analysis of patient blood management programme (PBM) studies, many of which include preoperative iron treatment as a component, found that there was a reduction in exposure to red cell transfusions. Although, the meta-analysis also found the implementation of PBM was not associated with a reduction on in-hospital mortality or 30-day mortality, there was no additive benefit from multiple interventions and no trial showed that PBM were cost-effective. Not included in this meta-analysis were recently published studies on the implementation of preoperative anaemia screening clinics in adults in elective colorectal surgery and major surgery which demonstrated reductions in red cell transfusions, length of stay, and net costs in patients with IDA who were treated with preoperative intravenous iron. Similarly, a large study from Western Australia reported significant reductions in cost associated with the use of blood products, and improved patient outcomes, after implementation of a PBM.

Studies investigating the impact of increasing preoperative Hb on perioperative outcomes in children are primarily focused on blood loss and blood transfusion rates in surgery in which significant bleeding and frequent blood transfusion are anticipated and most of the children in these studies received preoperative erythopoeitin. The impact of preoperative oral iron as a stand-alone intervention to increases preoperative Hb are limited to 2 studies. A single retrospective study has reported on the impact of the introduction of preoperative oral iron without erythropoeitin (EPO) in children undergoing spinal surgery. They found a significant difference in intraoperative transfusion rates in patients who received a longer duration of preoperative oral iron therapy. The major limitation of the study was a lack of preintervention Hb, precluding the ability to assess the effect of iron supplementation on delta Hb. A subsequent study reviewing the impact of preoperative oral iron in paediatric cardiac patients found that iron supplementation resulted in an increase in preoperative Hb levels which was associated with reduced red blood cell transfusion volumes.

Given the high incidence of preoperative anaemia in children having surgery in South Africa in the public sector and its association with poorer postoperative outcomes, it is important to assess the feasibility of a pragmatic intervention to treat preoperative anaemia in the context of a resource-constrained setting. Although intravenous iron in combination with EPO may be more effective and have fewer side effects, oral iron is relatively inexpensive and widely available in South Africa. Regular deworming may also play an important role in the treatment of preoperative anaemia and has been shown to be an effective intervention to increase baseline Hb in school age children from low- and middle- income countries. We hypothesise that the implementation of preoperative anaemia screening and treatment of anaemic patients with a minimum of 6 weeks supplementation with oral iron will have a clinically significant effect on increasing the Hb in patients with preoperative IDA.