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Practice review: Evidence-based and effective management of anaemia in palliative care patients
Neoh K, Page A, Chin-Yee N, Doree C, Bennett MI
Palliative medicine. 2022;:2692163221081967
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Editor's Choice
Abstract
BACKGROUND Anaemia is a common sequela of advanced disease and is associated with significant symptom burden. No specific guidance exists for the investigation and management of anaemia in palliative care patients. AIM: We aim to offer a pragmatic overview of the approaches to investigate and manage anaemia in advanced disease, based on guidelines and evidence in disease specific patient groups, including cancer, heart failure and chronic kidney disease. DESIGN Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia in patients with advanced disease. DATA SOURCES A search for guidelines was performed in 2020. National or international guidelines were examined if they described the investigation or management of anaemia in adult patients with health conditions seen by palliative care services written within the last 5 years in the English language. Searches of MEDLINE, the Cochrane library and WHO guidance were made in 2019 to identify key publications that provided additional primary data. RESULTS Evidence supports patient-centred investigation of anaemia, results of which should guide targeted intervention. Blanket use of blood transfusion should be avoided, with evidence supporting a more restrictive approach to transfusion. Routine use of oral iron and erythropoetin stimulating agents (ESAs) are not recommended. Insufficient evidence exists to determine the effectiveness of IV iron in this patient group. CONCLUSION We advocate early consideration and investigation of anaemia, guided by symptom burden and patient preferences. Correction of reversible causes should be the mainstay of treatment, with a restrictive approach to blood transfusion. Research is required to evaluate the efficacy of IV iron in these patients.
PICO Summary
Population
Palliative care patients (6 guidelines).
Intervention
Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia.
Comparison
Outcome
Evidence supported patient-centred investigation of anaemia. There was insufficient evidence to determine the effectiveness of intravenous iron in this patient group.
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Efficacy and Safety of Intravenous Iron Therapy for Treating Anaemia in Critically ill Adults: A Rapid Systematic Review With Meta-Analysis
Geneen LJ, Kimber C, Doree C, Stanworth S, Shah A
Transfusion medicine reviews. 2021
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Editor's Choice
Abstract
Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P = .0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at <10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron + subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and <10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.
PICO Summary
Population
Critically ill adults admitted to intensive care or high dependency units (8 studies, n= 1,198).
Intervention
Intravenous (IV) iron therapy; IV iron and subcutaneous erythropoietin (EPO); Hepcidin and targeted IV iron treatment (with and without EPO).
Comparison
Placebo/no iron therapy, or EPO therapy; Standard care.
Outcome
Seven trials (n= 748) comparing IV vs. control, found evidence of an effect in favour of IV iron in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL). There was no evidence of an effect in either direction for hospital duration, intensive care unit duration, hospital readmission, infection, and mortality. For the two trials (n= 104) comparing IV iron and subcutaneous erythropoietin (EPO) vs. control, the reported outcomes showed no evidence of effect in either direction (Hb concentration at 10-30 days, and <10 days, infection, mortality). One trial (n= 399) comparing hepcidin-guided treatment with IV iron or iron and EPO vs. standard care reported evidence of an effect in favour of the intervention for 90-day mortality, but no other group differences for Hb concentration at 10-30 days, hospital duration, and HRQoL.
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Safety and efficacy of iron therapy on reducing red blood cell transfusion requirements and treating anaemia in critically ill adults: A systematic review with meta-analysis and trial sequential analysis
Shah A, Fisher SA, Wong H, Roy NB, McKechnie S, Doree C, Litton E, Stanworth SJ
Journal of Critical Care. 2018;49:162-171.
Abstract
PURPOSE To evaluate the safety (risk of infection) and efficacy (transfusion requirements, changes in haemoglobin (Hb)) of iron therapy in adult intensive care unit (ICU) patients. MATERIALS AND METHODS We systematically searched seven databases for all relevant studies until January 2018 and included randomized (RCT) studies comparing iron, by any route, with placebo/no iron. RESULTS 805 participants from 6 RCTs were included. Iron therapy, by any route, did not decrease the risk of requirement for a red blood cell (RBC) transfusion (Risk ratio (RR) 0.91, 95% CI 0.80 to 1.04, p=0.15) or mean number of RBCs transfused per participant (mean difference (MD) -0.30, 95% CI -0.68 to 0.07, p=0.15). Iron therapy did increase mean Hb concentration (MD 0.31g/dL, 95% CI 0.04 to 0.59, p=0.03). There was no difference in infection (RR 0.95, 95% CI 0.79 to 1.19, p=0.44). Trial Sequential Analysis suggests that the required participant numbers to detect or reject a clinically important effect of iron therapy on transfusion requirements or infection in ICU patients has not yet been reached. CONCLUSION Iron therapy results in a modest increase in Hb. The current evidence is inadequate to exclude an important effect on transfusion requirements or infection.
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What is the effect of perioperative intravenous iron therapy in patients undergoing non-elective surgery? A systematic review with meta-analysis and trial sequential analysis
Shah A, Palmer AJR, Fisher SA, Rahman SM, Brunskill S, Doree C, Reid J, Sugavanam A, Stanworth SJ
Perioperative Medicine (London, England). 2018;7:30.
Abstract
Background: Guidelines to treat anaemia with intravenous (IV) iron have focused on elective surgical patients with little attention paid to those undergoing non-elective/emergency surgery. Whilst these patients may experience poor outcomes because of their presenting illness, observational data suggests that untreated anaemia may also be a contributing factor to poor outcomes. We conducted a systematic review to investigate the safety and efficacy of IV iron in patients undergoing non-elective surgery. Methods: We followed a pre-defined review protocol and included randomised controlled trials (RCTs) in patients undergoing non-elective surgery who received IV iron. Primary outcomes were all-cause infection and mean difference in haemoglobin (Hb) at follow-up. Secondary outcomes included transfusion requirements, hospital length of stay (LOS), health-related quality of life (HRQoL), mortality and adverse events. Results: Three RCTs (605 participants) were included in this systematic review of which two, in both hip fracture (HF) patients, provided data for meta-analysis. Both of these RCTs were at low risk of bias. We found no evidence of a difference in the risk of infection (RR 0.99, 95% CI 0.55 to 1.80, I (2) = 9%) or in the Hb concentration at 'short-term' (≤ 7 days) follow-up (mean difference - 0.32 g/L, 95% CI - 3.28 to 2.64, I (2) = 37%). IV iron did not reduce the risk of requiring a blood transfusion (RR 0.90, 95% CI 0.73 to 1.11, p = 0.46, I (2) = 0%), and we observed no difference in mortality, LOS or adverse events. One RCT reported on HRQoL and found no difference between treatment arms. Conclusion: We found no conclusive evidence of an effect of IV iron on clinically important outcomes in patients undergoing non-elective surgery. Further adequately powered trials to evaluate its benefit in emergency surgical specialties with a high burden of anaemia are warranted. Trial registration: This systematic review was registered on PROSPERO (CRD42018096288).
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Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis
Shah A, Roy NB, McKechnie S, Doree C, Fisher SA, Stanworth SJ
Critical Care (London, England). 2016;20((1)):306.
Abstract
BACKGROUND Anaemia affects 60-80 % of patients admitted to intensive care units (ICUs). Allogeneic red blood cell (RBC) transfusions remain the mainstay of treatment for anaemia but are associated with risks and are costly. Our objective was to assess the efficacy and safety of iron supplementation by any route, in anaemic patients in adult ICUs. METHODS Electronic databases (CENTRAL, MEDLINE, EMBASE) were searched through March 2016 for randomized controlled trials (RCT)s comparing iron by any route with placebo/no iron. Primary outcomes were red blood cell transfusions and mean haemoglobin concentration. Secondary outcomes included mortality, infection, ICU and hospital length of stay, mean difference (MD) in iron biomarkers, health-related quality of life and adverse events. RESULTS Five RCTs recruiting 665 patients met the inclusion criteria; intravenous iron was tested in four of the RCTs. There was no difference in allogeneic RBC transfusion requirements (relative risk 0.87, 95 % confidence interval (CI) 0.70 to 1.07, p = 0.18, five trials) or mean number of RBC units transfused (MD -0.45, 95 % CI -1.34 to 0.43, p = 0.32, two trials) in patients receiving or not receiving iron. Similarly, there was no difference between groups in haemoglobin at short-term (up to 10 days) (MD -0.25, 95 % CI -0.79 to 0.28, p = 0.35, three trials) or mid-term follow up (last measured time point in hospital or end of trial) (MD 0.21, 95 % CI -0.13 to 0.55, p = 0.23, three trials). There was no difference in secondary outcomes of mortality, in-hospital infection, or length of stay. Risk of bias was generally low although three trials had high risk of attrition bias; only one trial had low risk of bias across all domains. CONCLUSION Iron supplementation does not reduce RBC transfusion requirements in critically ill adults, but there is considerable heterogeneity between trials in study design, nature of interventions, and outcomes. Well-designed trials are needed to investigate the optimal iron dosing regimens and strategies to identify which patients are most likely to benefit from iron, together with patient-focused outcomes. TRIAL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42015016627 . Registered 2 March 2015.