Clinical Trial: Hyperoxia, Erythropoiesis and Microcirculation in Critically Ill Patient

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Hyperoxia, Erythropoiesis and Tissue Oxygenation in Critically Ill Patient

Brief Summary: Prospective observational study in 40 adult critically ill patients. Patients were eligible if they were mechanically ventilated with an FiO2 ≤0.5 and PaO2/FiO2 ≥200 mmHg and hemodynamically stable with a hemoglobin ≥9 g/dL, no acute bleeding or need for blood transfusions, no renal failure, no chronic obstructive pulmonary disease. Twenty patients (hyperoxia group) underwent a 2-hour exposure to normobaric hyperoxia (FiO2 1.0), 20 patients were evaluated as controls. Serum erythropoietin (EPO) was measured at baseline, 24h and 48h. Serum Glutathione (GSH) and reacting oxygen species (ROS) were assessed at baseline (t0), after 2 hours of hyperoxia (t1) and 2 hours after the return to baseline FiO2 (t2). Sidestream dark field videomicroscopy was applied sublingually to assess the microvascular response to hyperoxia. Near infrared spectroscopy with a vascular occlusion test was applied at t0, t1, t2.

Detailed Summary:

Interventions:

Forty patients were enrolled in total. The first 20 patients (hyperoxia group) underwent a 2-hour period of normobaric hyperoxia (FiO2 1.0), according to the protocol applied in. No variation in the FiO2 was applied for the other 20 patients (control group). All patients were enrolled in the morning and hyperoxia was performed in the time range between 10am-2pm in order to minimize variability due to the circadian rhythm of EPO production. No variations to sedation or vasopressor dose were applied during the study period.

Measurements:

On the study day, measurements were taken at 2-hour intervals: baseline (t0), under 1.0 FiO2 (t1) and after returning to baseline FiO2 (t2). These included: body temperature, heart rate (HR), mean arterial pressure (MAP), arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2), PaO2/FiO2, arterial pH, bicarbonate, base excess) and central venous saturation (ScvO2) blood gases, arterial lactates, evaluation of the sublingual microcirculation and tissue oxygenation. The same measurements were performed in the control group at 2-hour intervals. In 24 patients (12 patients per group), arterial blood samples (10 mL) were taken at each time point and immediately centrifuged; plasma and serum were stored at -70°C for subsequent analyses. Serum EPO, reticulocyte count, hemoglobin (Hb) and hematocrit were measured at 8am in all patients on the study day, at 24 and 48 hours.

Microcirculation measurements with sidestream dark field imaging The sublingual microcirculation was evaluated with sidestream dark field (SDF) videomicroscopy (Microscan, Microvision Medical, Amsterdam, NL). This technique has been described in details elsewhere.<
Sponsor: Università Politecnica delle Marche

Current Primary Outcome: Effectiveness of Normobaric Oxygen Hyperoxia in increasing serum erythropoietin levels in critically ill patients [ Time Frame: up to 2 day after FiO2=1 exposure ]

Blood samples to detect erythropoietin


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Effects of hyperoxia on the sublingual microcirculation [ Time Frame: Before FiO2, after 2 hours of FiO2=1 exposure, 2 hours after the end of FiO2=1 exposure ]
    SDF technique will be used to look at sublingual microcirculation, 20 seconds movies are registered and software is used to analyze them
  • Effects of hyperoxia on the peripheral microcirculation [ Time Frame: Before FiO2 = 1, after 2 hours of FiO2=1 exposure, 2 hours after the end of FiO2=1 exposure ]
    Near Infra-Red Spectroscopy is used to assess oxygen tissue saturation at thenar and vascular occlusion test is performed to assess the desaturation and resaturation curves
  • Hyperoxia and variations in circulating glutathione [ Time Frame: Before FiO2 = 1, after 2 hours of FiO2=1 exposure, 2 hours after the end of FiO2=1 exposure ]
    Blood samples
  • Hyperoxia and variations in circulating nitric oxide [ Time Frame: Before FiO2 = 1, after 2 hours of FiO2=1 exposure, 2 hours after the end of FiO2=1 exposure ]
    Blood samples
  • Hyperoxia and variations in circulating ROS [ Time Frame: Before FiO2 = 1, after 2 hours of FiO2=1 exposure, 2 hours after the end of FiO2=1 exposure ]
    Blood samples
  • Reticulocyte Count [ Time Frame: Before FiO2 = 1, at 1 day and 2 day after FiO2=1 exposure ]
  • Effectiveness of Normobaric Oxygen Hyperoxia in increasing serum erythropoietin levels in critically ill patients after 1 day [ Time Frame: Before FIO2 = 1 and at 1 day after FiO2 = 1 exposure ]


Original Secondary Outcome: Same as current

Information By: Università Politecnica delle Marche

Dates:
Date Received: June 15, 2015
Date Started: April 2013
Date Completion:
Last Updated: July 2, 2015
Last Verified: July 2015