Effects of short-term hyperoxia on erythropoietin levels and microcirculation in critically Ill patients: a prospective observational pilot study

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Abstract

Background

The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of ‘relative hypoxia’ which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients.

Methods

In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO ₂) ≤0.5 and PaO ₂/FiO ₂ ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO ₂ 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO ₂ (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.

Results

EPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4–20.2] to 22.9 [14.1–37.2] IU/L ( p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79–90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO ₂.

Conclusions

A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis.

Trial registration

ClinicalTrials.gov ( www.clinicaltrials.gov), NCT02481843, registered 15th June 2015, retrospectively registered

Related collections

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Author and article information

Contributors

Abele Donati:

ORCID: http://orcid.org/0000-0001-6792-8741

+390715964603 , a.donati@univpm.it

Elisa Damiani: eli.dam86@alice.it

Samuele Zuccari: samuelezuccari@gmail.com

Roberta Domizi: robertadomizi@gmail.com

Claudia Scorcella: cla.scorcella83@alice.it

Massimo Girardis: girardis.massimo@unimo.it

Alessia Giulietti: a.giulietti@univpm.it

Arianna Vignini: a.vignini@univpm.it

Erica Adrario: e.adrario@univpm.it

Rocco Romano: viboval@yahoo.it

Laura Mazzanti: l.mazzanti@univpm.it

Paolo Pelaia: p.pelaia@univpm.it

Mervyn Singer: m.singer@ucl.ac.uk

Journal

Journal ID (nlm-ta): BMC Anesthesiol

Journal ID (iso-abbrev): BMC Anesthesiol

Title: BMC Anesthesiology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2253

Publication date (Electronic): 23 March 2017

Publication date PMC-release: 23 March 2017

Publication date Collection: 2017

Volume: 17

Electronic Location Identifier: 49

Affiliations

[1 ]ISNI 0000 0001 1017 3210, GRID grid.7010.6, Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, , Università Politecnica delle Marche, ; via Tronto 10, 6126 Torrette di Ancona, Italy

[2 ]ISNI 0000 0004 1769 5275, GRID grid.413363.0, Department of Anesthesiology and Intensive Care, , Modena University Hospital, ; L.go del Pozzo 71, 41100 Modena, Italy

[3 ]ISNI 0000 0001 1017 3210, GRID grid.7010.6, Department of Clinical Sciences, Section of Biochemistry, , Università Politecnica delle Marche, ; via Tronto 10, 60126 Torrette di Ancona, Italy

[4 ]ISNI 0000000121901201, GRID grid.83440.3b, Bloomsbury Institute of Intensive Care Medicine, , University College London, ; Gower Street, London, WC1E 6BT UK

Author information

Abele Donati http://orcid.org/0000-0001-6792-8741

Article

Publisher ID: 342

DOI: 10.1186/s12871-017-0342-2

PMC ID: 5364633

PubMed ID: 28335733

SO-VID: 2dd845ff-625e-4c00-934d-64f5eca5505f

License:

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