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Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients : a systematic review

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Abstract
Background Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. Methods Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. Results Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. Conclusions It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.
Keywords
Systematic review, Elective surgery, Anemia, Preoperative care, Hematinics, Erythropoiesis-stimulating agents, Iron, Blood transfusion, Adverse events, RECOMBINANT-HUMAN-ERYTHROPOIETIN, COLORECTAL-CANCER PATIENTS, INTRAVENOUS IRON, BLOOD MANAGEMENT, DEFICIENCY ANEMIA, EPOETIN-ALPHA, TRANSFUSION REQUIREMENTS, OPEN-LABEL, SAFETY, SUPPLEMENTATION

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MLA
Laermans, Jorien, et al. “Adverse Events of Iron and/or Erythropoiesis-Stimulating Agent Therapy in Preoperatively Anemic Elective Surgery Patients : A Systematic Review.” SYSTEMATIC REVIEWS, vol. 11, no. 1, 2022, doi:10.1186/s13643-022-02081-5.
APA
Laermans, J., Van Remoortel, H., Avau, B., Bekkering, G., Georgsen, J., Manzini, P. M., … Vandekerckhove, P. (2022). Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients : a systematic review. SYSTEMATIC REVIEWS, 11(1). https://doi.org/10.1186/s13643-022-02081-5
Chicago author-date
Laermans, Jorien, Hans Van Remoortel, Bert Avau, Geertruida Bekkering, Jorgen Georgsen, Paola Maria Manzini, Patrick Meybohm, et al. 2022. “Adverse Events of Iron and/or Erythropoiesis-Stimulating Agent Therapy in Preoperatively Anemic Elective Surgery Patients : A Systematic Review.” SYSTEMATIC REVIEWS 11 (1). https://doi.org/10.1186/s13643-022-02081-5.
Chicago author-date (all authors)
Laermans, Jorien, Hans Van Remoortel, Bert Avau, Geertruida Bekkering, Jorgen Georgsen, Paola Maria Manzini, Patrick Meybohm, Yves Ozier, Emmy De Buck, Veerle Compernolle, and Philippe Vandekerckhove. 2022. “Adverse Events of Iron and/or Erythropoiesis-Stimulating Agent Therapy in Preoperatively Anemic Elective Surgery Patients : A Systematic Review.” SYSTEMATIC REVIEWS 11 (1). doi:10.1186/s13643-022-02081-5.
Vancouver
1.
Laermans J, Van Remoortel H, Avau B, Bekkering G, Georgsen J, Manzini PM, et al. Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients : a systematic review. SYSTEMATIC REVIEWS. 2022;11(1).
IEEE
[1]
J. Laermans et al., “Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients : a systematic review,” SYSTEMATIC REVIEWS, vol. 11, no. 1, 2022.
@article{01GQMMHTJKZT96BGQECJ906VWC,
  abstract     = {{Background
Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs.

Methods
Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence.

Results
Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting.

Conclusions
It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.}},
  articleno    = {{224}},
  author       = {{Laermans, Jorien and  Van Remoortel, Hans and  Avau, Bert and  Bekkering, Geertruida and  Georgsen, Jorgen and  Manzini, Paola Maria and  Meybohm, Patrick and  Ozier, Yves and  De Buck, Emmy and Compernolle, Veerle and  Vandekerckhove, Philippe}},
  issn         = {{2046-4053}},
  journal      = {{SYSTEMATIC REVIEWS}},
  keywords     = {{Systematic review,Elective surgery,Anemia,Preoperative care,Hematinics,Erythropoiesis-stimulating agents,Iron,Blood transfusion,Adverse events,RECOMBINANT-HUMAN-ERYTHROPOIETIN,COLORECTAL-CANCER PATIENTS,INTRAVENOUS IRON,BLOOD MANAGEMENT,DEFICIENCY ANEMIA,EPOETIN-ALPHA,TRANSFUSION REQUIREMENTS,OPEN-LABEL,SAFETY,SUPPLEMENTATION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{17}},
  title        = {{Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients : a systematic review}},
  url          = {{http://doi.org/10.1186/s13643-022-02081-5}},
  volume       = {{11}},
  year         = {{2022}},
}

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