Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery.

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml-1 or < 300 ng.ml-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127-141 [120-172]) g.l-1 , 143 (133-150 [120-179]) g.l-1 , p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77-82 [9-85]) days vs. 81 (79-83 [0-85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.

Iron deficiency without anaemia is a potential cause of fatigue: meta-analyses of randomised controlled trials and cross-sectional studies.

Fe deficiency is a prevalent nutritional disease, and fatigue is a common complaint in the general and patient population. The association between Fe deficiency without anaemia (IDNA) and fatigue is unclear. Here, we performed a meta-analysis to evaluate the therapeutic effect of Fe on fatigue in patients with IDNA and the association between IDNA and fatigue in the population. Articles from the PubMed database up to 19 January 2016 were systematically searched. A total of six relevant randomised controlled trials (RCT) and six relevant cross-sectional studies were identified. All outcomes were converted into effect sizes. In the meta-analysis of the six RCT, we identified a significant therapeutic effect of Fe in fatigue patients with IDNA (pooled effect size 0·33; 95 % CI 0·17, 0·48; I 2=0·0 %; P<0·0001). A sensitivity analysis found that the overall results (i.e. significant association) were robust. In the meta-analysis of the six cross-sectional studies, the association between IDNA and fatigue was not significant (pooled effect size 0·10; 95 % CI -0·11, 0·31; I 2=57·4 %; P=0·362). A sensitivity analysis found that the overall results (i.e. no significant association) were not robust; removal of one study made the outcomes significant. These meta-analyses suggest that improving Fe status may decrease fatigue. Further research is necessary to identify diagnostic criteria for selecting fatigue patients who might benefit from Fe therapy and to assess the prevalence of IDNA with fatigue in the general population.

Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review.

OBJECTIVE: To capture all data meeting a rigid definition of non-anaemic iron deficiency (NAID) and determine whether it is associated with poor outcomes compared with normal iron status and whether iron supplementation improves outcomes in NAID. DESIGN: Systematic review. DATA SOURCES: EMBASE, Medline, Web of Science, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014. ELIGIBILITY CRITERIA: Ferritin <16 µg/L (<12 µg/L if age <5 yr) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar, meta-analysis was undertaken. RESULTS: There were 21 studies included. NAID in pregnancy associated with reduction in birthweight (P = 0.028). Iron supplementation in NAID was associated with improvement in objective scores (P = 0.005) and self-rating (P = 0.03) of fatigue. Meta-analysis was limited and, where possible, was not statistically significant including the comparison of NAID with cardiovascular function in adults (VO2max P = 0.21, RERmax P = 0.68), educational attainment in children (P = 0.14), infant mental (P = 0.29) and psychomotor (P = 0.07) development, and iron supplementation in NAID with educational attainment in language (P = 0.31). CONCLUSIONS: There is emerging evidence that NAID is a disease in its own right, deserving of further research in the development of strategies for detection and treatment.

Non-anaemic iron deficiency in pregnancy: the views of health service users and health care professionals.

BACKGROUND: The prevalence of anaemia in pregnancy in Europe is 25% and that resulting from iron deficiency is estimated at 40%. The maternal and fetal morbidity of non-anaemic iron deficiency (NAID) in pregnancy is likely to be significant. OBJECTIVES: To determine the views and opinions of health service users and clinicians concerning NAID in pregnancy in order to inform future research. METHODS: Two semi-structured focus groups were carried out to determine health service users' views on anaemia and NAID in pregnancy. A questionnaire was administered to obstetricians, haematologists, midwives and anaesthetists to elucidate their views on NAID in pregnancy. RESULTS: The study indicated that health service users and clinicians were interested in implementing testing for NAID in pregnancy with serum ferritin, if proven to be effective at reducing the effects of anaemia and improving maternal and neonatal outcomes. Clinicians had reservations in the use of intravenous iron supplementation for NAID in pregnancy. CONCLUSION: NAID is now accepted as a target condition for research by health service users and clinicians. The focus of future research should be on screening for NAID and its treatment.

Intravenous Iron Replacement Improves Exercise Tolerance in COPD: A Single-Blind Randomized Trial.

INTRODUCTION: Iron deficiency affects exercise capacity because of the critical role iron plays in the optimal functioning of skeletal muscle metabolism. We hypothesized that intravenous iron may improve exercise tolerance, quality of life (QoL), and daily physical activity (DPA) in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a placebo-controlled, single-blind, parallel-group, randomized clinical trial. Iron deficiency was defined as a ferritin level<100ng/mL or a ferritin level between 100 and 299ng/mL with a transferrin saturation<20%, with or without mild anaemia. Patients were randomized at a 2:1 ratio to receive intravenous ferric carboxymaltose or placebo. The primary objective was to investigate whether intravenous iron replacement improved endurance time from baseline by at least 33%. The secondary objectives were to evaluate impact on QoL using the COPD Assessment Test (CAT) and on DPA by accelerometry. RESULTS: We included 66 patients, 44 (66.7%) in the intervention group and 22 (33.3%) in the placebo group. Among patients receiving ferric carboxymaltose, 23 (52.3%) achieved the primary endpoint compared to 4 (18.2%) in the placebo group [p=0.009; relative risk 3.12, (95% CI, 1.19-8.12)]. CAT score decreased -3 (-6.0-1.3) points from baseline in the intervention group (p=0.007), in contrast to placebo group [-1 (-4.0-2.3) points, p=0.236] with no differences in DPA and adverse events in both groups. CONCLUSIONS: Iron replacement improved exercise capacity and QoL in stable COPD patients with iron deficiency. The treatment was well tolerated. CLINICAL TRIAL REGISTRATION: EudraCT 2016-001238-89.

Intravenous Iron Replacement Improves Exercise Tolerance in COPD: A Single-Blind Randomized Trial

Introduction: Iron deficiency affects exercise capacity because of the critical role iron plays in the optimal functioning of skeletal muscle metabolism. We hypothesized that intravenous iron may improve exercise tolerance, quality of life (QoL), and daily physical activity (DPA) in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a placebo-controlled, single-blind, parallel-group, randomized clinical trial. Iron deficiency was defined as a ferritin level<100ng/mL or a ferritin level between 100 and 299ng/mL with a transferrin saturation<20%, with or without mild anaemia. Patients were randomized at a 2:1 ratio to receive intravenous ferric carboxymaltose or placebo. The primary objective was to investigate whether intravenous iron replacement improved endurance time from baseline by at least 33%. The secondary objectives were to evaluate impact on QoL using the COPD Assessment Test (CAT) and on DPA by accelerometry. Results: We included 66 patients, 44 (66.7%) in the intervention group and 22 (33.3%) in the placebo group. Among patients receiving ferric carboxymaltose, 23 (52.3%) achieved the primary endpoint compared to 4 (18.2%) in the placebo group [p=0.009; relative risk 3.12, (95% CI, 1.19–8.12)]. CAT score decreased −3 (−6.0–1.3) points from baseline in the intervention group (p=0.007), in contrast to placebo group [−1 (−4.0–2.3) points, p=0.236] with no differences in DPA and adverse events in both groups. Conclusions: Iron replacement improved exercise capacity and QoL in stable COPD patients with iron deficiency. The treatment was well tolerated. (AU)