Abstract

Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis.

Highlights

  • Sepsis is the systemic inflammatory response to infection

  • Apoptosis is pivotal in the relative immunosuppression that can lead to secondary infection and superinfection in sepsis

  • Reliable clinical data in critically ill patients have led to useful information on the pharmacokinetics [84,85] and the potential for harm [87,88,91]

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Summary

Introduction

Sepsis is the systemic inflammatory response to infection. The clinical syndrome can range from mild constitutional upset to overt septic shock with the failure of multiple organ systems, reflecting the complex pathogenesis of sepsis involving immunological and coagulation pathways [1,2]. While positive results in animal models do not always correlate with clinical outcomes, it appears that EPO has significant cytoprotective effects mediated by anti-apoptotic and immune mechanisms that could be beneficial in sepsis syndromes. Rat models of haemorrhagic shock show improvements in haemodynamic stability and markers of organ dysfunction [62,90] These effects may underlie the improved outcome; clinically relevant thrombotic events were commoner in EPO-treated patients, with a hazard ratio of 1.41 (95% confidence interval, 1.06 to 1.86) occurring in 120/728 patients in the EPO-treated group versus 83/720 in the control group. Serious problems such as pure red cell aplasia due to EPO antibodies are rare [13] but clinicians using this drug in a new way should monitor closely for adverse side effects

Conclusion
14. Savill J
18. Remick DG
Findings
35. Fisher JW
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