Brain and Lung Biomarker Responses to Hyperoxic Hypobaric Decompression.

INTRODUCTION: Biomarker responses to intensive decompression indicate systemic proinflammatory responses and possible neurological stress. To further investigate responses, 12 additional brain and lung biomarkers were assayed.METHODS: A total of 15 healthy men (20 to 50 yr) undertook consecutive same-day ascents to 25,000 ft (7620 m), following denitrogenation, breathing 100% oxygen. Venous blood was sampled at baseline (T0), after the second ascent (T8), and next morning (T24). Soluble protein markers of brain and lung insult were analyzed by enzyme-linked immunosorbent assay with plasma microparticles quantified using flow cytometry.RESULTS: Levels of monocyte chemoattractant protein-1 and high mobility group box protein 1 were elevated at T8, by 36% and 16%, respectively, before returning to baseline. Levels of soluble receptor for advanced glycation end products fell by 8%, recovering by T24. Brain-derived neurotrophic factor rose by 80% over baseline at T24. Monocyte microparticle levels rose by factors of 3.7 at T8 and 2.7 at T24 due to early and late responses in different subjects. Other biomarkers were unaffected or not detected consistently.DISCUSSION: The elevated biomarkers at T8 suggest a neuroinflammatory response, with later elevation of brain-derived neurotrophic factor at T24 indicating an ongoing neurotrophic response and incomplete recovery. A substantial increase at T8 in the ratio of high mobility group box protein 1 to soluble receptor for advanced glycation end products suggests this axis may mediate the systemic inflammatory response to decompression. The mechanism of neuroinflammation is unclear but elevation of monocyte microparticles and monocyte chemoattractant protein-1 imply a key role for activated monocytes and/or macrophages.Connolly DM, Madden LA, Edwards VC, Lee VM. Brain and lung biomarker responses to hyperoxic hypobaric decompression. Aerosp Med Hum Perform. 2024; 95(9):667-674.

Acute Hyperoxia Improves Spinal Cord Oxygenation and Circulatory Function Following Cervical Spinal Cord Injury in Rats.

Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1-2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats through optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) conditions. The results showed that contused animals had significantly lower spinal cord oxygenation levels than uninjured animals during normoxia. Peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure are significantly reduced following cervical spinal cord contusion. Notably, spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia elevated blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function in the acute phase after cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.

Oxidative Stress Reaction to Hypobaric-Hyperoxic Civilian Flight Conditions.

BACKGROUND: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude. AIM: We hypothesized that hypobaric-hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals. METHODS: Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at -21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test. RESULTS: Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO2) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500 m altitude. CONCLUSION: Supplemental oxygen of 60% FiO2 in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m-4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.

Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry.

BACKGROUND: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence. METHODS: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO2 and PaCO2 with ABI. RESULTS: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89). CONCLUSIONS: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Association of Arterial Hyperoxia With Outcomes in Critically Ill Children: A Systematic Review and Meta-analysis.

Importance: Oxygen supplementation is a cornerstone treatment in pediatric critical care. Accumulating evidence suggests that overzealous use of oxygen, leading to hyperoxia, is associated with worse outcomes compared with patients with normoxia. Objectives: To evaluate the association of arterial hyperoxia with clinical outcome in critically ill children among studies using varied definitions of hyperoxia. Data Sources: A systematic search of EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception to February 1, 2021, was conducted. Study Selection: Clinical trials or observational studies of children admitted to the pediatric intensive care unit that examined hyperoxia, by any definition, and described at least 1 outcome of interest. No language restrictions were applied. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology guideline and Newcastle-Ottawa Scale for study quality assessment were used. The review process was performed independently by 2 reviewers. Data were pooled with a random-effects model. Main Outcomes and Measures: The primary outcome was 28-day mortality; this time was converted to mortality at the longest follow-up owing to insufficient studies reporting the initial primary outcome. Secondary outcomes included length of stay, ventilator-related outcomes, extracorporeal organ support, and functional performance. Results: In this systematic review, 16 studies (27 555 patients) were included. All, except 1 randomized clinical pilot trial, were observational cohort studies. Study populations included were post-cardiac arrest (n = 6), traumatic brain injury (n = 1), extracorporeal membrane oxygenation (n = 2), and general critical care (n = 7). Definitions and assessment of hyperoxia differed among included studies. Partial pressure of arterial oxygen was most frequently used to define hyperoxia and mainly by categorical cutoff. In total, 11 studies (23 204 patients) were pooled for meta-analysis. Hyperoxia, by any definition, showed an odds ratio of 1.59 (95% CI, 1.00-2.51; after Hartung-Knapp adjustment, 95% CI, 1.05-2.38) for mortality with substantial between-study heterogeneity (I2 = 92%). This association was also found in less heterogeneous subsets. A signal of harm was observed at higher thresholds of arterial oxygen levels when grouped by definition of hyperoxia. Secondary outcomes were inadequate for meta-analysis. Conclusions and Relevance: These results suggest that, despite methodologic limitations of the studies, hyperoxia is associated with mortality in critically ill children. This finding identifies the further need for prospective observational studies and importance to address the clinical implications of hyperoxia in critically ill children.

Effect of cardiopulmonary bypass reoxygenation on myocardial dysfunction following pediatric tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. METHODS: We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6-72 months who underwent complete repair of tetralogy of Fallot in 2012-2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. RESULTS: This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5-39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3-16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040-3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. CONCLUSIONS: Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. TRIAL REGISTRATION: Clinical Trials. gov number NCT03568357. June 26, 2018.

Effects of high-intensity interval exercise under hyperoxia on HSP27 and oxidative stress responses.

Hypoxia in working muscles during exercise may be associated with increased oxidative stress. Inhalation of hyperoxic gas diminishes the hypoxia within working muscles during exercise. Exposure to hyperoxia increases the expression of the antioxidant HSP27. We investigated the effects of acute high-intensity interval exercise (HIE) under hyperoxia on HSP27 levels and oxidative stress responses. Eight male subjects participated in two experiments: 1) normoxic HIE (NHIE) and 2) hyperoxic (60 % oxygen) HIE (HHIE). HIE consisted of four 30-s all-out cycling bouts with 4-min rest between bouts. Levels of serum oxidative stress markers (d-ROMs and LPO), HSP27, BAP, IL-6, and TNF-α significantly increased after both trials. The HIE-induced changes in d-ROMs, LPO, and HSP27 levels were significantly lower in the HHIE trial than in the NHIE trial. These findings suggest that inhaling hyperoxic gas during exercise might diminish oxidative stress induced by all-out HIE.

The effect of hyperoxia on inflammation and platelet responses in an ex vivo extracorporeal membrane oxygenation circuit.

Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses. Nine ex vivo ECMO circuits were tested using fresh healthy human whole blood, with two oxygen levels: 21% inspired fraction of oxygen (FiO2 ; mild hyperoxia; n = 5) and 100% FiO2 (severe hyperoxia; n = 4). Serial blood samples were taken for analysis of platelet aggregometry, leukocyte activation, inflammatory, and oxidative stress markers. ECMO resulted in reduced adenosine diphosphate- (P < .05) and thrombin receptor activating peptide-induced (P < .05) platelet aggregation, as well as increasing levels of the neutrophil activation marker, neutrophil elastase (P = .013). Additionally, levels of the inflammatory chemokine interleukin-8 were elevated (P < .05) and the activity of superoxide dismutase, a marker of oxidative stress, was increased (P = .002). Hyperoxia did not augment these responses, with no significant differences detected between mild and severe hyperoxia. Our ex vivo model of ECMO revealed that the circuit itself triggers a pro-inflammatory and oxidative stress response, however, exposure to supra-physiologic oxygen does not amplify that response. Extended-duration studies and inclusion of an endothelial component could be beneficial in characterizing longer term changes.

Effect of practical hyperoxic high-intensity interval training on exercise performance.

This study investigated the effect of a practical hyperoxic high-intensity interval training (HIIT) on aerobic and anaerobic exercise capacity. Sixteen male athletes were randomized into 2 groups: normoxic HIIT (NHIIT, n = 8) group or hyperoxic HIIT (HHIIT, n = 8) group and trained for 3 weeks (2 days/week) on a cycle ergometer (2-min intervals, with 2-min rest between intervals) at maximal workload, which was obtained during a maximal graded exercise test under normoxia. All training sessions were performed until exhaustion. Participants performed maximal graded exercise, submaximal exercise, and 90-s maximal exercise tests before and after the training period. Maximal oxygen uptake (P < 0.01) increased significantly in both groups. Blood lactate curve during submaximal exercise improved significantly only in the HHIIT group (P < 0.01). Mean power output during maximal exercise increased significantly only in the HHIIT group (P = 0.02). This study demonstrated that a practical hyperoxic HHIIT might be effective for improving aerobic capacity and anaerobic performance.

Extracellular vesicle miRNA-21 is a potential biomarker for predicting chronic lung disease in premature infants.

Premature infants are often exposed to positive pressure ventilation and supplemental oxygen, which leads to the development of chronic lung disease (CLD). There are currently no standard serum biomarkers used for prediction or early detection of patients who go on to develop CLD. MicroRNAs (miRNAs) are a novel class of naturally occurring, short, noncoding substances that regulate gene expression at the posttranscriptional level and cause translational inhibition and/or mRNA degradation and present in body fluids packaged in extracellular vesicles (EVs), rendering them remarkably stable. Our aim was to evaluate miRNAs identified in serum EVs of premature infants as potential biomarkers for CLD. Serum EVs were extracted from premature infants at birth and on the 28th day of life (DOL). Using a human miRNA array, we identified 62 miRNAs that were universally expressed in CLD patients and non-CLD patients. Of the 62 miRNAs, 59 miRNAs and 44 miRNAs were differentially expressed on DOL0 and DOL28 in CLD and non-CLD patients, respectively. Of these miRNAs, serum EV miR-21 was upregulated in CLD patients on DOL28 compared with levels at birth and downregulated in non-CLD patients on DOL28 compared with levels at birth. In neonatal mice exposed to hyperoxia for 7days, as a model of CLD, five miRNAs (miR-34a, miR-21, miR-712, miR-682, and miR-221) were upregulated, and 7 miRNAs (miR-542-5p, miR-449a, miR-322, miR-190b, miR-153, miR-335-3p, miR-377) were downregulated. MiR-21 was detected as a common miRNA that changed in CLD patients and in the hyperoxia exposed mice. We conclude that EV miR-21 may be a biomarker of CLD.

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats.

BACKGROUND: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases. METHODS: Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology. RESULTS: Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group. CONCLUSION: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.

Association between hyperoxemia and mortality in patients treated by eCPR after out-of-hospital cardiac arrest.

OBJECTIVE: Assess whether elevated oxygen partial arterial pressure (PaO2) measured after the initiation of extra-corporeal cardiopulmonary resuscitation (eCPR), is associated with mortality in patients suffering from refractory out-of-hospital cardiac arrest (rOHCA). METHODS: Retrospective cohort study including rOHCA admitted to the ICU. Patients were divided into 3 groups, defined according to the PaO2 measured from arterial blood gas analysis 30 min after the initiation of eCPR. Hyperoxemia was defined as PaO2 ≥ 300 mmHg, hypoxemia as PaO2 ≤ 60 mmHg and normoxemia, as 60 < PaO2 < 300 mmHg. The main outcome was the mortality rate on day 28 after hospital admission. RESULTS: Sixty-six consecutive rOHCA, 77% male, with a mean age of 51 ±â€¯14 years, were admitted to the ICU. rOHCA were mainly due to acute coronary syndrome (67%), hypertrophic cardiomyopathy (8%) and cardiotoxic overdose (8%). Mortality at day 28 reached 61%. In the overall population, the mean PaO2 was 227 ±â€¯124 mmHg. An association between mortality and PaO2 was observed (OR = 1.01 [1.01-1.02]). The AUC for PaO2 after starting eCPR was 0.77 [0.65-0.89]. After adjustment for witnessed arrest, bystander's CPR, location, no-flow, low-flow, lactate and pH, age, and PaCO2, hyperoxemia had an ORa of 1.89 (CI95 [1.74-2.07]). CONCLUSION: We found an association between mortality and hyperoxemia in patients admitted to the ICU for rOHCA requiring eCPR. These data underline the potential toxicity of high dose of oxygen and suggest that controlled oxygen administration for these patients is crucial.

The effect of the fraction of inspired oxygen on the NIRS-derived deoxygenated hemoglobin "breakpoint" during ramp-incremental test.

During ramp-incremental (RI) exercise to exhaustion, the near-infrared spectroscopy-derived deoxygenated hemoglobin ([HHb]) signal in the vastus lateralis muscle shows a linear increase up to a point at which a plateau-like response is manifested ([HHb]bp). This study investigated if 1) the [HHb]bp is affected by different fractions of inspired O2 (FIO2) [hypoxia (16%; HYPO); normoxia (21%; NORM); hyperoxia (30%; HYPER)]; and 2) an abrupt change to hyperoxic-inspired gas just before the occurrence of the [HHb]bp (HYPERSWITCH) would affect the [HHb] plateau-like response. Ten physically active male participants reported to the laboratory on four separate occasions to perform an RI test to exhaustion in NORM, HYPO, and HYPER and an RI test to exhaustion with an abrupt increase in FIO2 (30%; HYPERSWITCH) 15 W before the power output (PO) associated with [HHb]bp in normoxia. PO, [HHb], tissue O2 (StO2), and pulse O2 saturation (SpO2) were recorded continuously. Peak PO was significantly lower in HYPO (290 ± 21 W) and higher in HYPER (321 ± 22 W) and HYPERSWITCH (320 ± 19 W) compared with NORM (311 ± 18 W). The PO associated with [HHb]bp was not different between NORM and HYPER (246 ± 23 vs. 247 ± 24 W), but it was lower in HYPO (198 ± 31 W) than NORM and HYPER. The PO associated with the [HHb]bp in HYPERSWITCH (240 ± 23) was not different compared with NORM. HYPER and HYPERSWITCH resulted in greater StO2 and SpO2 compared with NORM. These results suggest that the [HHb]bp response is not dependent of O2 driving pressure and that other physiological mechanisms might determine its occurrence.

Association of Early Oxygenation Levels with Mortality in Acute Ischemic Stroke - A Retrospective Cohort Study.

BACKGROUND: Ischemic stroke is an emergency with elevated risk for morbidity and mortality. Hypoxia is harmful in acute ischemic stroke. Recent evidence raises concerns regarding hyperoxia as well in acute illness, and for supplemental oxygen therapy when SpO2greater than 92%. Current AHA/ASA guidelines recommend maintaining SpO2greater than 94%. In this study, we aimed to assess the relationship between the oxygenation levels within the first 6-hour of ischemic stroke admission and mortality. METHODS: With the approval of the Human Studies Committee (IRB #: 13.0396), we performed a retrospective cohort study of ischemic stroke patients consecutively admitted to our hospital in the years 2013-14 and 2017-18 (n = 1479). Relationship between the first 6 hours oxygenation status and in-house mortality was assessed. SpO2/FiO2 ratio was used as the oxygenation outcome parameter. Patients who were intubated at admission were excluded. Additionally, demographics, baseline confounding factors, neurological status, and laboratory values on admission were examined for their association with mortality in a multivariate logistic regression analysis. RESULTS: Mean age of patients was 64 ± 15 years. Time interval from last seen normal to hospital admission was 7 ± 5 hours (mean ± standard deviation). NIHSS on arrival was 41-9 (median-IQR). Fourteen percent of patients received IV alteplase and 6% were treated with mechanical thrombectomy. Baseline SpO2 was 97 ± 2%, and 47% of the patients required supplemental oxygen treatment per AHA/ASA guidelines. In hospital mortality rate of this cohort was 5.7%. Lower mean SpO2 /FiO2 levels were strongly correlated with increasing mortality rates (R2 = .973). Age (1.048 [1.028-1.068]), NIHSS (1.120 [1.088-1.154]), WBC (1.116 [1.061-1.175]) and Mean SpO2/FiO2 (.995 [.992-.999]) independently risk associated with mortality. CONCLUSIONS: Baseline oxygenation varies within the acute ischemic stroke patient population. In this retrospective cohort study, we are reporting a strong association between lower SpO2/FiO2 levels in the first few hours of admission and mortality. In the light of these results, we plan to prospectively assess the role of oxygenation further in the context of recanalization status of stroke.

Metabolomic changes of blood plasma associated with two phases of rat OIR.

Although acute hyperoxia/hypoxia alternation can shift sharply physiological processes of vessel development, e.g. oxygen induced retinopathy (OIR), very little is known of metabolic products resulted from the neovascularization disorder. In this study, the influence of abnormal oxygen exposures on the plasma metabolomic profiles of rats with OIR was investigated by the gas chromatography mass spectrometry (GC-MS). Rat pups were divided into four groups, each with 12 individuals: (i) reared in room air and sampled at P12 (CT1); (ii) exposed to high oxygen for 5 days and sampled at P12 (HO1, simulating the vaso-obeliteration process (phase I)); (iii) reared in room air and sampled at P17 (CT2); (iv) exposed to high oxygen for 5 days then followed by room air for 5 days and sampled at P17 (HO2, simulating the neovasculization one (phase II)). Plasma samples were analyzed with GC-MS, resulted in 122 metabolite species. Distinct differences in the plasma metabolome were found between groups of CT1 vs. HO1, and HO1 vs. HO2, by using univariate and multivariate analyses. Alternating hyperoxia/hypoxia conditions induced significant changes of richness of proline, ornithine and glutamine, that were important components of 'arginine and proline metabolism' pathway. These metabolites contributed largely to plasma sample classification, determined with receiver operating characteristic curve analysis and were involved profoundly in the proline-dependent production of reactive oxygen species (ROS) related to the cellular redox reactions. Our results from the rat OIR model suggest proline and 'arginine and proline metabolism' pathway as the potential biomarkers for human retinopathy of prematurity (ROP) diagnosis.

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia.

Oxygen (O2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO2) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO2 = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO2 = 0.80 group with respect to both the FiO2 = 0.40 group and the baseline values (p ≤ 0.05, Student's t-test). HbSSG in red blood cells was also higher in the FiO2 = 0.80 group at the end of the surgery. NOx was higher in the FiO2 = 0.80 group than the FiO2 = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO2, may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery.

The "Just Right" Amount of Oxygen. Improving Oxygen Use in a Rwandan Emergency Department.

Rationale: Despite oxygen's classification as an essential medication by the World Health Organization, it is inconsistently available in many resource-constrained settings. Hypoxemia is associated with increased mortality, and mounting evidence suggests that hyperoxia may also be associated with adverse outcomes.Objectives: To determine if overuse of oxygen for some patients in a Rwandan tertiary care hospital emergency department might coexist with oxygen shortages and underuse of oxygen for other patients, and whether an educational intervention coupled with provision of pulse oximeters could improve the distribution of limited oxygen resources.Methods: We screened all patients in the adult emergency department (ED) of the University Teaching Hospital of Kigali for hypoxemia and receipt of oxygen therapy for 5 weeks. After completing baseline data collection, we provided pulse oximeters and conducted a didactic training with pre- and posttests on oxygen titration, with a chosen target oxygen saturation (SpO2) of 90% to 95%. Four and 12 weeks after the intervention, we evaluated all patients in the ED again for SpO2 and receipt of oxygen therapy for 4 weeks each period. We also recorded ED oxygen use and availability of reserve oxygen for the hospital during the three study periods.Results: During all data collection periods, 214 of 1,765 (12.1%) unique patients screened were hypoxemic. The proportion of patient-days with appropriately titrated oxygen therapy (SpO2, 90-95%) increased from 18.7% at baseline to 38.5% and 42.0% at 4 and 12 weeks postintervention (P < 0.001). On a multiple-choice examination testing knowledge of appropriate oxygen titration, clinicians' scores improved from average 60% (interquartile range [IQR], 40-80%) correct to 80% (IQR, 60-80%) correct immediately after the educational intervention (P < 0.001). Oxygen use in the ED decreased from a median of 32.0 (IQR, 28.0-35.0) tanks per day to 25.5 (IQR, 24.0-29.0) and 16.0 (IQR, 12.5-21.0) tanks per day at Weeks 4 and 12, respectively (P < 0.001), and the median daily number of tanks in reserve for the hospital appeared to increase, although this did not reach statistical significance (30.0 [IQR, 9.0-46.0], 86.5 [IQR, 74.0-92.0], and 75.5 [IQR, 8.5-88.5], respectively; P = 0.07).Conclusions: Among patients in a Rwandan adult ED, 12.1% of patients were hypoxemic and 81.3% of patient-days were either under- or overtreated with oxygen during baseline data collection on the basis of our defined target of SpO2 90% to 95%. Follow-up results at 4 and 12 weeks postintervention demonstrated sustained improvement in oxygen titration and likely increased availability of oxygen resources.

Sex Hormones Response to Physical Hyperoxic and Hyperbaric Stress in Male Scuba Divers: A Pilot Study.

The use of hyperbaric oxygen plays a significant role in many aspects of medicine. However, there are few studies that analyzed the role of hyperbaric oxygen, in addition to physical exercise, on the endocrine profile. The aim of this study was to compare changes in plasma male sex hormones after hyperbaric physical exercise with different hyperbaric oxygen pre-conditionings. We recruited six healthy, well-trained recreational male divers. Concentrations of prolactin (PRL), follicle-stimulating hormone (FSH), luteotrophic hormone (LH), cortisol, 17-ß estradiol (E2), and total testosterone (TT) were measured in venous blood immediately after four different study conditions. Exercise increased PRL and hyperbaric oxygen potentiated this effect. Hyperbaria stimulated the E2 reduction and hyperoxia partially inhibited this reduction. Hyperbaria, but not hyperoxia, stimulated the TT reduction. There were no changes in FSH, LH, and cortisol. The increase in PRL likely reflects a stress response after physical exercise, amplified by hyperbaric oxygen. TT reduction may be interpreted as an acute and transient fertility impairment. Age, blood pressure, and BMI were taken into account as covariates for statistical analyses, and they significantly affected the results, in particular TT. These data open new insight into the role of E2 and PRL in male endocrine adaptive responses.

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia.

BACKGROUND: While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats. METHODS: Newborn Wistar rats were exposed to 21% or 80% oxygen for 3 (P3) or 5 (P5) postnatal days with or without recovery on room air until postnatal day 15 (P15) and treated with vehicle or caffeine (10 mg/kg) every 48 h beginning on the day of birth. The lung tissue of the rat pups was examined for oxidative stress response at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR. RESULTS: Lungs of newborn rats, corresponding to the saccular stage of lung development and to the human lung developmental stage of preterms, showed increased rates of total glutathione and hydrogen peroxide, oxidative damage to DNA and lipids, and induction of second-phase mediators of antioxidative stress response (superoxide dismutase, heme oxygenase-1, and the Nrf2/Keap1 system) in response to hyperoxia. Caffeine reduced oxidative DNA damage and had a protective interference with the oxidative stress response. CONCLUSION: In addition to the pharmacological antagonism of adenosine receptors, caffeine appears to be a potent antioxidant and modulates the hyperoxia-induced pulmonary oxidative stress response and thus protective properties in the BPD-associated animal model. Free-radical-induced damage caused by oxidative stress seems to be a biological mechanism progress of newborn diseases. New aspects of antioxidative therapeutic strategies to passivate oxidative stress-related injury should be in focus of further investigations.