PMID- 36253838 OWN - NLM STAT- MEDLINE DCOM- 20221019 LR - 20221215 IS - 2046-4053 (Electronic) IS - 2046-4053 (Linking) VI - 11 IP - 1 DP - 2022 Oct 17 TI - Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review. PG - 224 LID - 10.1186/s13643-022-02081-5 [doi] LID - 224 AB - 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. CI - (c) 2022. The Author(s). FAU - Laermans, Jorien AU - Laermans J AUID- ORCID: 0000-0002-6695-6019 AD - Centre for Evidence-Based Practice, Belgian Red Cross, Mechelen, Belgium. jorien.laermans@cebap.org. AD - Department of Public Health and Primary Care, Leuven Institute for Healthcare Policy, KU Leuven, Leuven, Belgium. jorien.laermans@cebap.org. FAU - Van Remoortel, Hans AU - Van Remoortel H AD - Centre for Evidence-Based Practice, Belgian Red Cross, Mechelen, Belgium. AD - Department of Public Health and Primary Care, Leuven Institute for Healthcare Policy, KU Leuven, Leuven, Belgium. FAU - Avau, Bert AU - Avau B AD - Centre for Evidence-Based Practice, Belgian Red Cross, Mechelen, Belgium. FAU - Bekkering, Geertruida AU - Bekkering G AD - Department of Public Health and Primary Care, Leuven Institute for Healthcare Policy, KU Leuven, Leuven, Belgium. AD - Center for Evidence-Based Medicine, Leuven, Belgium. AD - Cochrane Belgium, Leuven, Belgium. FAU - Georgsen, Jorgen AU - Georgsen J AD - South Danish Transfusion Service, Odense University Hospital, Odense C, Denmark. FAU - Manzini, Paola Maria AU - Manzini PM AD - SC Banca del Sangue Servizio di Immunoematologia, University Hospital Citta della Salute e della Scienza di Torino, Torino, Italy. FAU - Meybohm, Patrick AU - Meybohm P AD - Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany. FAU - Ozier, Yves AU - Ozier Y AD - University Hospital of Brest, Brest, France. FAU - De Buck, Emmy AU - De Buck E AD - Centre for Evidence-Based Practice, Belgian Red Cross, Mechelen, Belgium. AD - Department of Public Health and Primary Care, Leuven Institute for Healthcare Policy, KU Leuven, Leuven, Belgium. FAU - Compernolle, Veerle AU - Compernolle V AD - Blood Services, Belgian Red Cross, Mechelen, Belgium. AD - Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. FAU - Vandekerckhove, Philippe AU - Vandekerckhove P AD - Department of Public Health and Primary Care, Leuven Institute for Healthcare Policy, KU Leuven, Leuven, Belgium. AD - Belgian Red Cross, Mechelen, Belgium. AD - Centre for Evidence-Based Health Care, Stellenbosch University, Cape Town, South Africa. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20221017 PL - England TA - Syst Rev JT - Systematic reviews JID - 101580575 RN - 0 (Hematinics) RN - FZ7NYF5N8L (Ferric Oxide, Saccharated) SB - IM MH - Adult MH - *Anemia/drug therapy/etiology MH - Elective Surgical Procedures/adverse effects MH - Erythropoiesis MH - Ferric Oxide, Saccharated/therapeutic use MH - *Hematinics/adverse effects MH - Humans PMC - PMC9578279 OTO - NOTNLM OT - Adverse events OT - Anemia OT - Blood transfusion OT - Elective surgery OT - Erythropoiesis-stimulating agents OT - Hematinics OT - Iron OT - Preoperative care OT - Systematic review COIS- Financial competing interests directly related to this review: PMM received personal fees from Ethos Srl (Advisory Board on PBM) and SUMMEET Srl (Speaker in a meeting on PBM). PM received grants from Vifor Pharma, SerumWerke Bernburg, csl Behring, Fresenius Medical, and B.Baun. PM received personal fees from Vifor Pharma and Pharmacosmos. HV, JL, BA, EDB, GB, JG, VC, YO, and PV declared not having any relevant direct financial competing interest. Financial competing interests not directly related to this review: HV, JL, BA, EDB, VC, and PV are employees of Belgian Red Cross-Flanders, which is responsible for supplying adequate quantities of safe blood products to hospitals in Flanders and Brussels on a continuous basis and is being paid for this activity by the Ministry of Social Affairs. Belgian Red Cross-Flanders received a grant from the European Blood Alliance to conduct this review. PMM received personal fees from Editree Srl (creation of training course on porphyria), Eleuthera Srl (AHP Advisory Board), Collage SpA (speaker in a meeting on Erythrocytosis), IQVIA (Advisory Board on porphyria), and Alnylam (Advisory Board on porphyria). GB, JG, PM, and YO declared not having any other financial competing interest. Non-financial competing interests: JL, HVR, BA, GB, PMM, YO, EDB, VC, and PV declared not having any non-financial competing interests. PM declared to be involved in the implementation of PBM programs. JG declared to be involved in The Danish Health Authority-National Clinical Guideline-Indication for Transfusion with Blood Components-Copenhagen 2018 (https://www.sst.dk/da/udgivelser/2018/nkr-indikation-for-transfusion-med-blodkomponenter). EDAT- 2022/10/18 06:00 MHDA- 2022/10/20 06:00 PMCR- 2022/10/17 CRDT- 2022/10/17 23:47 PHST- 2021/09/23 00:00 [received] PHST- 2022/09/25 00:00 [accepted] PHST- 2022/10/17 23:47 [entrez] PHST- 2022/10/18 06:00 [pubmed] PHST- 2022/10/20 06:00 [medline] PHST- 2022/10/17 00:00 [pmc-release] AID - 10.1186/s13643-022-02081-5 [pii] AID - 2081 [pii] AID - 10.1186/s13643-022-02081-5 [doi] PST - epublish SO - Syst Rev. 2022 Oct 17;11(1):224. doi: 10.1186/s13643-022-02081-5.