Longitudinal changes in haemoglobin, iron stores, and inflammatory markers following surgery and in critical illness: an analysis from the Practical Anaemia Bundle for Sustained Blood Recovery randomised clinical trial

Abstract

Background: Intravenous iron improves haemoglobin recovery after surgery and in critical illness. However, the impact on longitudinal markers of iron status and inflammation are unknown. Further, it is unknown if iron studies obtained early in acute illness may moderate i.v. iron treatment responses.

Methods: This is a planned analysis from a randomised clinical trial of critically ill adults with haemoglobin levels <10 g dl^-1 receiving i.v. iron vs standard care on haemoglobin recovery and clinical outcomes through 3 months post-hospitalisation. Iron assays, erythropoietin levels, haemoglobin, and inflammatory markers were obtained at enrollment and 1 and 3 months post-hospitalisation. Between-group differences and correlations between laboratory values were evaluated at each timepoint. Treatment-related haemoglobin responses were evaluated by baseline laboratory parameters in interaction analyses.

Results: A total of 100 patients were included: 49 intervention and 51 standard care. The intervention group achieved higher haemoglobin (adjusted mean difference, 0.69 [95% confidence interval, 0.13-1.25] g dl^-1, P=0.015 at 1 month) and ferritin (multiple increase, 2.7 [95% confidence interval, 1.9-3.9] ng/ml, P<0.001 at 1 month) values post-hospitalisation. There were no significant differences in other laboratory values over time. Ferritin and transferrin saturation, but not soluble transferrin receptor, correlated with inflammatory markers. Inflammatory markers positively correlated with erythropoietin and negatively correlated with haemoglobin. The soluble transferrin receptor-log ferritin index, specifically values ≥1.5, identified patients likely to experience the greatest haemoglobin responses to i.v. iron.

Conclusions: Intravenous iron increases haemoglobin and ferritin concentrations through 3 months following critical illness. Traditional iron assays are influenced by inflammation, impeding utility in iron deficiency detection. The soluble transferrin receptor-log ferritin index measured early in critical illness has potential to identify differential i.v. iron treatment responses.

Keywords: anaemia; critical illness; inflammation; intensive care; intravenous iron; iron; soluble transferrin receptor; surgery.