Harms of off-label erythropoiesis-stimulating agents for critically ill people

Mesgarpour, Bita; Heidinger, Benedikt H.; Roth, Dominik von; Schmitz, Susanne; Walsh, Cathal; Herkner, Harald

doi:10.1002/14651858.cd010969.pub2

Cited by 26 publications

(28 citation statements)

References 136 publications

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“…EPO has not only successfully been used to treat or prevent anemia (the approved indication) but also for various other conditions, ranging from brain to different other organ diseases, in both human trials and numerous animal studies. Overall, in critically ill patients, EPO was safe and probably efficient, as summarized in recent meta-analyses (Litton et al 2019;Mesgarpour et al 2017).…”

Section: Introductionmentioning

confidence: 88%

Erythropoietin as candidate for supportive treatment of severe COVID-19

Ehrenreich

Weißenborn

Begemann

et al. 2020

Mol Med

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In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.

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Section: Introductionmentioning

confidence: 88%

Erythropoietin as candidate for supportive treatment of severe COVID-19

Ehrenreich

Weißenborn

Begemann

et al. 2020

Mol Med

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“…Several meta-analyses [57][58][59][60][61] [60]. However, the authors of these meta-analyses downgraded the GRADE score in view of the high risk of bias, the inconsistency and the imprecision of the studies.…”

Section: Rationalementioning

confidence: 99%

“…However, the authors of these meta-analyses downgraded the GRADE score in view of the high risk of bias, the inconsistency and the imprecision of the studies. In the meta-analysis by Mesgarpour [59], the randomised controlled trials included 10 trials conducted in critical care patients designed to treat anemia with a potential effect on mortality [59,[62][63][64][65][66][67][68][69], 3 trials in traumatic brain injury patients [70][71][72] and 13 trials in which ESA was administered as adjuvant therapy for ST segment elevation myocardial infarction. Variable weekly treatment regimens, intravenous and/or subcutaneous routes of administration, and timing of the start of treatment made the results difficult to interpret.…”

Section: Rationalementioning

confidence: 99%

Management and prevention of anemia (acute bleeding excluded) in adult critical care patients

Lasocki

Pène

Ait‐Oufella

et al. 2020

Ann. Intensive Care

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Objective: Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay. Methods: A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology. Results: The SFAR-SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus. Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy).

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“…It is thus largely plausible that treating ID improved post-ICU survival. In addition, EPO treatment has also been shown to reduce mortality in critically ill patients and may have contributed to the decreased mortality observed [33,34]. It is now recommended (low grade recommendation) by the French societies of critical care to treat anemia with erythropoietin in ICU [35].…”

Section: Discussionmentioning

confidence: 99%

Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

Lasocki

Asfar

Jaber

et al. 2020

Preprint

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Background: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnosed in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. Methods: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm patients were treated with intravenous iron (1g of ferric carboxymaltose) when hepcidin was <20 μg/l and with intravenous iron and erythropoietin for 20≤ hepcidin <41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue and day 90 mortality. Results: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). 220(55%) had ID at discharge (i.e. an hepcidin <41 μg/l). Primary endpoint was not different (medians(IQR) post-ICU LOS 33(13;90) vs 33(11;90) days for intervention and control respectively, median difference -1(-3;1) days, p=0.78). D90 mortality was significantly lower in the intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference -8.7 (-15.1 to -2.3)%, p=0.008). Conclusion: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but may reduce the long-term mortality in critically ill patients about to be discharged after a prolonged stay. Trial Registration: www.clinicaltrial.gov NCT02276690 (October 28, 2014; Retrospectively registered)

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Harms of off-label erythropoiesis-stimulating agents for critically ill people

Cited by 26 publications

References 136 publications

Erythropoietin as candidate for supportive treatment of severe COVID-19

Erythropoietin as candidate for supportive treatment of severe COVID-19

Management and prevention of anemia (acute bleeding excluded) in adult critical care patients

Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

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