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



In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0.5 and PaO2/FiO2≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO21.0). 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 FiO2(t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.



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 FiO2.



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.



ClinicalTrials.gov ( www.clinicaltrials.gov ), NCT02481843 , registered 15th June 2015, retrospectively registered.
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy. a.donati@univpm.it.
Abele
0000-0001-6792-8741
A
Donati
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Elisa
E
Damiani
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Samuele
S
Zuccari
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Roberta
R
Domizi
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Claudia
C
Scorcella
Department of Anesthesiology and Intensive Care, Modena University Hospital, L.go del Pozzo 71, 41100, Modena, Italy.
Massimo
M
Girardis
Department of Clinical Sciences, Section of Biochemistry, Università Politecnica delle Marche, via Tronto 10, 60126, Torrette di Ancona, Italy.
Alessia
A
Giulietti
Department of Clinical Sciences, Section of Biochemistry, Università Politecnica delle Marche, via Tronto 10, 60126, Torrette di Ancona, Italy.
Arianna
A
Vignini
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Erica
E
Adrario
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Rocco
R
Romano
Department of Clinical Sciences, Section of Biochemistry, Università Politecnica delle Marche, via Tronto 10, 60126, Torrette di Ancona, Italy.
Laura
L
Mazzanti
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Paolo
P
Pelaia
Bloomsbury Institute of Intensive Care Medicine, University College London, Gower Street, London, WC1E 6BT, UK.
Mervyn
M
Singer
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016638:Critical Illness; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005978:Glutathione / Q000097:blood; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D018496:Hyperoxia / Q000097:blood* / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D018715:Microscopy, Video; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000097:blood; D019265:Spectroscopy, Near-Infrared
D017382:Reactive Oxygen Species; D004921:Erythropoietin; D005978:Glutathione
Anemia; Erythropoietin; Microcirculation; Normobaric hyperoxia