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Unrecognised iron deficiency in critical illness
RESEARCH LETTERS
Research letters
Unrecognised iron deficiency in critical illness M C Bellamy, J A Gedney
In functional iron deficiency there is a decrease in iron available for metabolic processes. Functional iron deficiency is present when more than 10% of red blood cells show hypochromasia.1 These changes are seen before changes in ferritin, transferrin, and haemoglobin. In several groups of patients, functional iron deficiency is associated with poor outcome. We studied prevalence of functional iron deficiency in patients presenting to intensive care, and its relation with outcome.1,2 In a prospective observational study, we studied 51 consecutive adult patients presenting to the general intensive care unit of a tertiary referral teaching hospital over 6 weeks. Exclusion criteria were: massive haemorrhage or exchange transfusion (>8 units) in the 2 weeks before admission, pregnancy or lactation, age older than 80 years, haematological malignant disorders, or existing bone marrow depression. We recorded age, sex, diagnosis, scores for acute physiological and chronic health evaluation (APACHE II) and sepsis-related organ failure assessment (SOFA),3 haemoglobin, ferritin, transferrin, and percentage hypochromasia, and elective or emergency admission. We measured the proportion of hypochromic red blood cells by flow cytometry with a haematology analyser (Bayer, Tarrytown, USA). Functional iron deficiency was presented in 35% (95% CI 22–48) of patients at admission. In comparisons of patients with and without functional iron deficiency, emergency admission (15/18 vs 23/33), mean age (60·5 [range 48–74] vs 59 [42–67] years), ferritin (342 [66–703] vs 292 [132–1640] g/L), haemoglobin (10·7 [9·3–11·5] vs 10·8 [9·4–12·1] g/L), and APACHE II score (18·0 [14·5–24·0] vs 18·5 [11·0–25·0]) were similar in the two Patients in intensive care (%)
100
p⬍0·0007
groups (p=0·78). Likewise, there was no difference in B12 (541 [309–1442] vs 568 [223–1987] ng/L) or folate (5·1 [3·9–6·6] vs 5 [2·6–9·6] g/L). Patients with functional iron deficiency had long stays in intensive care compared with patients without functional iron deficiency. Mean length of stay was 7·6 days (95% CI 4·4–10·8) compared with 3·3 days (2·0–4·5, p<0·0007; figure). After correction for survival, time to discharge for live patients was similarly longer in patients with functional iron deficiency than for those without. Severity of hypochromasia correlated with duration of stay (r=0·33, p=0·017). Six of 17 patients in the functional iron deficiency group died (35% [12–58]), as did 11 of 31 in the group without functional iron deficiency (35 [18–52] p=0·76). Time of death was similar by Kaplan-Meier analysis (p=0·91). Duration of episodes of systemic inflammatory response syndrome was longer in the functional iron deficiency group than in the group without functional iron deficiency (8·4 [5·4–11·4] vs 4·6 days [2·6–6·5] p<0·02). SOFA scores were non-significantly lower in the group without iron deficiency. There are many potential explanations for these findings. Functional iron deficiency may be a marker of nutritional status or general health. Research in animals and human beings has suggested that adequate iron scores are important for immune function, 4 and a deficiency may, therefore, predict patients with inappropriate immune responses. Patients may also develop functional iron deficiency in response to immune activation.5 Further study is required of the relation between functional iron deficiency and immune function in critical illness. 1
Functional iron deficiency group No functional iron deficiency
80
2
60
3
40 20
4 5
0 0
5 10 15 Stay in intensive care (days)
Length of stay in intensive care
THE LANCET • Vol 352 • December 12, 1998
20
MacDougall IC, Cavill I, Hulme B, et al. Detection of functional iron deficiency during erythropoietin treatment: a new approach. BMJ 1992; 304: 225–26. Kumar R. Mechanisms of the anaemia of chronic infection: a re-examination of the role of functional iron deficiency in its causation. Indian J Med Res 1976; 64: 1046–56. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the Working Group on SepsisRelated Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22: 707–10. Scrimshaw NS, SanGiovanni JP. Synergism of nutrition, infection, and immunity: an overview. Am Clin Nutr 1997; 66: 464S–77. Fuchs D, Hausen A, Reinegger G, et al. Immune activation and the anaemia associated with chronic inflammatory disorders. Eur J Haematol 1991; 46: 65–70.
Intensive Care Unit, Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds LS9 7TF, UK (M C Bellamy; e-mail [email protected])
1903
Research letters
Unrecognised iron deficiency in critical illness M C Bellamy, J A Gedney
In functional iron deficiency there is a decrease in iron available for metabolic processes. Functional iron deficiency is present when more than 10% of red blood cells show hypochromasia.1 These changes are seen before changes in ferritin, transferrin, and haemoglobin. In several groups of patients, functional iron deficiency is associated with poor outcome. We studied prevalence of functional iron deficiency in patients presenting to intensive care, and its relation with outcome.1,2 In a prospective observational study, we studied 51 consecutive adult patients presenting to the general intensive care unit of a tertiary referral teaching hospital over 6 weeks. Exclusion criteria were: massive haemorrhage or exchange transfusion (>8 units) in the 2 weeks before admission, pregnancy or lactation, age older than 80 years, haematological malignant disorders, or existing bone marrow depression. We recorded age, sex, diagnosis, scores for acute physiological and chronic health evaluation (APACHE II) and sepsis-related organ failure assessment (SOFA),3 haemoglobin, ferritin, transferrin, and percentage hypochromasia, and elective or emergency admission. We measured the proportion of hypochromic red blood cells by flow cytometry with a haematology analyser (Bayer, Tarrytown, USA). Functional iron deficiency was presented in 35% (95% CI 22–48) of patients at admission. In comparisons of patients with and without functional iron deficiency, emergency admission (15/18 vs 23/33), mean age (60·5 [range 48–74] vs 59 [42–67] years), ferritin (342 [66–703] vs 292 [132–1640] g/L), haemoglobin (10·7 [9·3–11·5] vs 10·8 [9·4–12·1] g/L), and APACHE II score (18·0 [14·5–24·0] vs 18·5 [11·0–25·0]) were similar in the two Patients in intensive care (%)
100
p⬍0·0007
groups (p=0·78). Likewise, there was no difference in B12 (541 [309–1442] vs 568 [223–1987] ng/L) or folate (5·1 [3·9–6·6] vs 5 [2·6–9·6] g/L). Patients with functional iron deficiency had long stays in intensive care compared with patients without functional iron deficiency. Mean length of stay was 7·6 days (95% CI 4·4–10·8) compared with 3·3 days (2·0–4·5, p<0·0007; figure). After correction for survival, time to discharge for live patients was similarly longer in patients with functional iron deficiency than for those without. Severity of hypochromasia correlated with duration of stay (r=0·33, p=0·017). Six of 17 patients in the functional iron deficiency group died (35% [12–58]), as did 11 of 31 in the group without functional iron deficiency (35 [18–52] p=0·76). Time of death was similar by Kaplan-Meier analysis (p=0·91). Duration of episodes of systemic inflammatory response syndrome was longer in the functional iron deficiency group than in the group without functional iron deficiency (8·4 [5·4–11·4] vs 4·6 days [2·6–6·5] p<0·02). SOFA scores were non-significantly lower in the group without iron deficiency. There are many potential explanations for these findings. Functional iron deficiency may be a marker of nutritional status or general health. Research in animals and human beings has suggested that adequate iron scores are important for immune function, 4 and a deficiency may, therefore, predict patients with inappropriate immune responses. Patients may also develop functional iron deficiency in response to immune activation.5 Further study is required of the relation between functional iron deficiency and immune function in critical illness. 1
Functional iron deficiency group No functional iron deficiency
80
2
60
3
40 20
4 5
0 0
5 10 15 Stay in intensive care (days)
Length of stay in intensive care
THE LANCET • Vol 352 • December 12, 1998
20
MacDougall IC, Cavill I, Hulme B, et al. Detection of functional iron deficiency during erythropoietin treatment: a new approach. BMJ 1992; 304: 225–26. Kumar R. Mechanisms of the anaemia of chronic infection: a re-examination of the role of functional iron deficiency in its causation. Indian J Med Res 1976; 64: 1046–56. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the Working Group on SepsisRelated Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22: 707–10. Scrimshaw NS, SanGiovanni JP. Synergism of nutrition, infection, and immunity: an overview. Am Clin Nutr 1997; 66: 464S–77. Fuchs D, Hausen A, Reinegger G, et al. Immune activation and the anaemia associated with chronic inflammatory disorders. Eur J Haematol 1991; 46: 65–70.
Intensive Care Unit, Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds LS9 7TF, UK (M C Bellamy; e-mail [email protected])
1903