Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit

Background: In COVID-19 patients requiring mechanical ventilation, the administration of high oxygen (O2) doses for prolonged time periods may be necessary. Although life-saving in most cases, O2 may exert deleterious effects if administered in excessive concentrations. We aimed to describe the prevalence of hyperoxemia and excessive O2 administration in mechanically ventilated patients with SARS-CoV-2 pneumonia and determine whether hyperoxemia is associated with mortality in the Intensive Care Unit (ICU) or the onset of ventilator-associated pneumonia (VAP). Materials and methods: Retrospective single-center study on adult patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation for ≥48 h. Patients undergoing extracorporeal respiratory support were excluded. We calculated the excess O2 administered based on the ideal arterial O2 tension (PaO2) target of 55–80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed through multivariate analyses. Results: One hundred thirty-four patients were included. For each day of mechanical ventilation, each patient received a median excess O2 of 1,121 [829–1,449] L. Hyperoxemia was found in 38 [27–55]% of arterial blood gases, hyperoxia + hyperoxemia in 11 [5–18]% of cases. The FiO2 was not reduced in 69 [62–76]% of cases of hyperoxemia. Adjustments were made more frequently with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (OR 1.300 95% CI [1.097–1.542]), time of exposure to hyperoxemia (OR 2.758 [1.406–5.411]), hyperoxia + hyperoxemia (OR 1.144 [1.008–1.298]), and daily excess O2 (OR 1.003 [1.001–1.005]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006–1.061]), time of exposure to hyperoxemia (OR 1.108 [1.018–1.206]), hyperoxia + hyperoxemia (OR 1.038 [1.003–1.075]), and daily excess O2 (OR 1.001 [1.000–1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents (before VAP), prolonged prone positioning and mean PaO2/FiO2 before VAP. Conclusion: Excess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 pneumonia. The exposure to hyperoxemia may be associated with ICU-mortality and greater risk for VAP

Near-infrared spectroscopy for assessing tissue oxygenation and microvascular reactivity in critically ill patients: a prospective observational study

Impaired microcirculatory perfusion and tissue oxygenation during critical illness are associated with adverse outcome. The aim of this study was to detect alterations in tissue oxygenation or microvascular reactivity and their ability to predict outcome in critically ill patients using thenar near-infrared spectroscopy (NIRS) with a vascular occlusion test (VOT)

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

Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

Introduction: Microvascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2)-delivery but rarely improves tissue O2 uptake in septic patients. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused-RBCs on microcirculation in septic patients. Methods: In a prospective randomized trial, 20 septic patients were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark-field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2-saturation (StO2) and tissue haemoglobin index (THI) were determined with near-infrared spectroscopy (NIRS), and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage and glycocalyx compounds (syndecan-1, hyaluronan, heparan sulfate) were measured in the serum. Results: No differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When looking at within-group changes, microcirculatory improvement was only observed in patients that received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01) and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2-upslope increased in both groups. StO2 and StO2-downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03). Conclusions: This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in septic patients, although it suggests a more favourable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings. © 2014 Donati et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit

BackgroundIn COVID-19 patients requiring mechanical ventilation, the administration of high oxygen (O2) doses for prolonged time periods may be necessary. Although life-saving in most cases, O2 may exert deleterious effects if administered in excessive concentrations. We aimed to describe the prevalence of hyperoxemia and excessive O2 administration in mechanically ventilated patients with SARS-CoV-2 pneumonia and determine whether hyperoxemia is associated with mortality in the Intensive Care Unit (ICU) or the onset of ventilator-associated pneumonia (VAP).Materials and methodsRetrospective single-center study on adult patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation for ≥48 h. Patients undergoing extracorporeal respiratory support were excluded. We calculated the excess O2 administered based on the ideal arterial O2 tension (PaO2) target of 55–80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed through multivariate analyses.ResultsOne hundred thirty-four patients were included. For each day of mechanical ventilation, each patient received a median excess O2 of 1,121 [829–1,449] L. Hyperoxemia was found in 38 [27–55]% of arterial blood gases, hyperoxia + hyperoxemia in 11 [5–18]% of cases. The FiO2 was not reduced in 69 [62–76]% of cases of hyperoxemia. Adjustments were made more frequently with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (OR 1.300 95% CI [1.097–1.542]), time of exposure to hyperoxemia (OR 2.758 [1.406–5.411]), hyperoxia + hyperoxemia (OR 1.144 [1.008–1.298]), and daily excess O2 (OR 1.003 [1.001–1.005]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006–1.061]), time of exposure to hyperoxemia (OR 1.108 [1.018–1.206]), hyperoxia + hyperoxemia (OR 1.038 [1.003–1.075]), and daily excess O2 (OR 1.001 [1.000–1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents (before VAP), prolonged prone positioning and mean PaO2/FiO2 before VAP.ConclusionExcess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 pneumonia. The exposure to hyperoxemia may be associated with ICU-mortality and greater risk for VAP

From Macrohemodynamic to the Microcirculation

ICU patients need a prompt normalization of macrohemodynamic parameters. Unfortunately, this optimization sometimes does not protect patients from organ failure development. Prevention or treatment of organ failure needs another target to be pursued: the microcirculatory restoration. Microcirculation is the ensemble of vessels of maximum 100 m in diameter. Nowadays the Sidestream Dark Field (SDF) imaging technique allows its bedside investigation and a recent round-table conference established the criteria for its evaluation. First, microcirculatory derangements have been studied in sepsis: they are mainly characterized by a reduction of vessel density, an alteration of flow, and a heterogeneous distribution of perfusion. Endothelial malfunction and glycocalyx rupture were proved to be the main reasons for the observed microthrombi, capillary leakage, leukocyte rolling, and rouleaux phenomenon, even if further studies are necessary for a better explanation. Therapeutic approaches targeting microcirculation are under investigation. Microcirculatory alterations have been recently demonstrated in other diseases such as hypovolemia and cardiac failure but this issue still needs to be explored. The aim of this paper is to gather the already known information, focus the reader’s attention on the importance of microvascular physiopathology in critical illness, and prompt him to actively participate to achieve a more comprehensive understanding of the issue

Evaluation of the Microcirculation in Critically Ill Patients

Abstract: The first goal of therapies in critically ill patients is to improve tissue perfusion and oxygenation. Hemodynamic monitoring has long been limited to measure-ments of cardiac output and global oxygen delivery. The clinical introduction of hand-held vital microscopes in the late 1990s enabled the real-time, non-invasive, bedside ob-servation of blood flow in the microcirculation (vessels with diameter <100 µm), i.e. the real site of oxygen and nutrient exchange between blood and cells. Microcirculatory alter-ations have been described during sepsis and shock states and were associated with mor-tality. These can occur independently of systemic hemodynamic alterations. Sublingual videomicroscopy allowed evaluating the microvascular response to resuscitation proce-dures, including oxygen therapy, fluids, blood transfusions, vasopressors. Future re-search directions should be aimed to integrate microcirculatory monitoring with standard hemodynamic measurements and verify the utility of microcirculation as a therapeutic tar-get. Continuous technological developments are imperative to facilitate the introduction of sublingual videomicroscopy in the clinical practice