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

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 (FiO2) \ue2\u89\ua40.5 and PaO2/FiO2\ue2\u80\u89\ue2\u89\ua5\ue2\u80\u89200\uc2\ua0mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24\uc2\ua0h and 48\uc2\ua0h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2\uc2\ua0h of hyperoxia (t1) and 2\uc2\ua0h 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.RESULTS: EPO increased within 48\uc2\ua0h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p\ue2\u80\u89=\ue2\u80\u890.022). 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\uc2\ua0h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2.CONCLUSIONS: A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48\uc2\ua0h. 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

Changes in Cytokines, Haemodynamics and Microcirculation in Patients with Sepsis/Septic Shock Undergoing Continuous Renal Replacement Therapy and Blood Purification with CytoSorb

BACKGROUND Extracorporeal blood purification therapies have been proposed as a strategy to remove inflammatory mediators during sepsis, thus improving outcome. OBJECTIVES: We aimed to evaluate changes in cytokines, haemodynamics and microcirculation during blood purification with Cytosorb adsorber in septic patients. METHODS: Prospective observational study on critically ill adult patients with sepsis/septic shock underwent renal replacement therapy (RRT) for acute renal failure and haemoadsorption with Cytosorb as adjunctive therapy for 24 h. Measurements were taken at baseline, after 6 and 24 h: haemodynamic parameters, arterial and central venous blood gases, plasma levels of tumour necrosis factor alpha, interleukin (IL) 1-beta, IL-6, IL-8 and IL-10. The sublingual microcirculation was assessed with sidestream dark field videomicroscopy to evaluate the perfused vessel density (PVD) and microvascular flow quality. Tissue oxygenation and microvascular reactivity were assessed with thenar near infrared spectroscopy (NIRS) with a vascular occlusion test. RESULTS: Nine patients; plasma levels of IL-8 decreased at 24 h (p < 0.05 versus 6 h); no significant variation was found for other cytokines. Haemodynamic remained stable throughout the observation. Microvascular perfusion improved over time, with an increase in PVDs at 6 and 24 h (from 13.9 [13.3-16.4] to 15.7 [15-17.3] and 17 [14.8-18.6] mm/mm2 respectively, p = 0.003) and total vessel densities at 24 h (14.9 [13.9-16.9] vs. 17.9 [15.3-20], p = 0.0015). No significant variation was detected in NIRS-derived parameters. The Sequential Organ Failure Assessment score decreased from 12 ± 3 to 10 ± 1 at 24 h (p = 0.039). CONCLUSIONS: In septic patients undergoing RRT, haemoadsorption with Cytosorb seems to determine a decreasing in plasma levels of IL-8, although levels of other cytokines did not vary significantly, and an improvement of microcirculation despite no significant variation in macro-haemodynamics