The Effect of Early Severe Hyperoxia in Adults Intubated in the Prehosptial Setting or Emergency Department: A Scoping Review.

BACKGROUND: The detrimental effects of hyperoxia exposure have been well-described in patients admitted to intensive care units. However, data evaluating the effects of short-term, early hyperoxia exposure in patients intubated in the prehospital setting or emergency department (ED) have not been systematically reviewed. OBJECTIVE: Our aim was to quantify and describe the existing literature examining the clinical outcomes in ED patients exposed to hyperoxia within the first 24 h of mechanical ventilation. METHODS: This review was performed in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Two rounds of review using Rayyan QCRI software were performed for title and abstract screening and full-text search. Of the 2739 articles, 27 articles were retrieved after initial screening, of which 5 articles were excluded during the full-text screening, leaving 22 articles for final review and data extraction. RESULTS: Of 22 selected publications, 9 described patients with traumatic brain injury, 6 with cardiac arrest, 3 with multisystem trauma, 1 with stroke, 2 with septic shock, and 1 was heterogeneous. Three studies were randomized controlled trials. The available data have widely heterogeneous definitions of hyperoxia exposure, outcomes, and included populations, limiting conclusions. CONCLUSIONS: There is a paucity of data that examined the effects of severe hyperoxia exposure in the acute, post-intubation phase of the prehospital and ED settings. Further research with standardized definitions is needed to provide more detailed guidance regarding early oxygen titration in intubated patients.

Association between short-term neurological outcomes and extreme hyperoxia in patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation: a retrospective observational study from a multicenter registry.

BACKGROUND: To investigate the impact of hyperoxia that developed immediately after extracorporeal membrane oxygenation (ECMO)-assisted cardiopulmonary resuscitation (ECPR) on patients' short-term neurological outcomes after out-of-hospital cardiac arrest (OHCA). METHODS: This study retrospectively analyzed data from the Japanese OHCA registry from June 2014 to December 2017. We analyzed adult patients (≥ 18 years) who had undergone ECPR. Eligible patients were divided into the following three groups based on their initial partial pressure of oxygen in arterial blood (PaO2) levels after ECMO pump-on: normoxia group, PaO2 ≤ 200 mm Hg; moderate hyperoxia group, 200 mm Hg < PaO2 ≤ 400 mm Hg; and extreme hyperoxia group, PaO2 > 400 mm Hg. The primary and secondary outcomes were 30-day favorable neurological outcomes. Logistic regression statistical analysis model of 30-day favorable neurological outcomes was performed after adjusting for multiple propensity scores calculated using pre-ECPR covariates and for confounding factors post-ECPR. RESULTS: Of the 34,754 patients with OHCA enrolled in the registry, 847 were included. The median PaO2 level was 300 mm Hg (interquartile range: 148-427 mm Hg). Among the eligible patients, 277, 313, and 257 were categorized as normoxic, moderately hyperoxic, and extremely hyperoxic, respectively. Moderate hyperoxia was not significantly associated with 30-day neurologically favorable outcomes compared with normoxia as a reference (adjusted odds ratio, 0.86; 95% confidence interval: 0.55-1.35; p = 0.51). However, extreme hyperoxia was associated with less 30-day neurologically favorable outcomes when compared with normoxia (adjusted odds ratio, 0.48; 95% confidence interval: 0.29-0.82; p = 0.007). CONCLUSIONS: For patients with OHCA who received ECPR, extreme hyperoxia (PaO2 > 400 mm Hg) was associated with 30-day poor neurological outcomes. Avoidance of extreme hyperoxia may improve neurological outcomes in patients with OHCA treated with ECPR.

Pulse Oximetry Saturation (Spo2) Monitoring in the Neonatal Intensive Care Unit (NICU): The Challenge for Providers: A Systematic Review.

BACKGROUND: In the neonatal intensive care unit (NICU), maintaining an oxygenation level that avoids both hypoxemia and hyperoxemia is challenging. Pulse oximetry has become fundamental for noninvasive monitoring of saturation of peripheral oxygen (Spo2) in preterm newborns. PURPOSE: The aim of this systematic review is to determine Spo2 target values in order to avoid hypoxemia or hyperoxemia and complications arising from these. METHOD AND SEARCH STRATEGY: For this systematic review, articles were audited from 2010 to 2020 using the PRISMA guidelines. PubMed, MEDLINE, Google Scholar, and Scopus databases were used, and search terms were related to use of pulse oximetry in the NICU. RESULTS: The result showed that 12 of 20 (60%) studies focused on target values but without a unanimous agreement on values, although 5 of 12 studies (41.66%) suggested a lower value target of 85% and 4 of 12 studies (33.33%) recommended 95% as the higher target value. Other authors showed no difference in the incidence of adverse events comparing different target values and focused the importance more on the fluctuation of the value than on the target value itself. IMPLICATION FOR PRACTICE: Reaching a balance in the oxygen administration so as to avoid potential complications associated with hypoxemia or hyperoxemia is a challenge for the clinicians. IMPLICATION FOR RESEARCH: Further studies on fluctuation of Spo2 comparing different starting targets could better clarify the role of fluctuations and the absolute target values.Video Abstract available at:https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=49.

A multicenter cluster randomized, stepped wedge implementation trial for targeted normoxia in critically ill trauma patients: study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen (SAVE-O2) trial.

BACKGROUND: Targeted normoxia (SpO2 90-96% or PaO2 60-100 mmHg) may help to conserve oxygen and improve outcomes in critically ill patients by avoiding potentially harmful hyperoxia. However, the role of normoxia for critically ill trauma patients remains uncertain. The objective of this study is to describe the study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen for Critically Ill Trauma Patients (SAVE-O2) clinical trial. METHODS: Design, setting, and participants: Protocol for a multicenter cluster randomized, stepped wedge implementation trial evaluating the effectiveness of a multimodal intervention to target normoxia in critically ill trauma patients at eight level 1 trauma centers in the USA. Each hospital will contribute pre-implementation (control) and post-implementation (intervention) data. All sites will begin in the control phase with usual care. When sites reach their randomly assigned time to transition, there will be a one-month training period, which does not contribute to data collection. Following the 1-month training period, the site will remain in the intervention phase for the duration of the trial. MAIN OUTCOME MEASURES: The primary outcome will be supplemental oxygen-free days, defined as the number of days alive and not on supplemental oxygen. Secondary outcomes include in-hospital mortality to day 90, hospital-free days to day 90, ventilator-free days (VFD) to day 28, time to room air, Glasgow Outcome Score (GOS), and duration of time receiving supplemental oxygen. DISCUSSION: SAVE-O2 will determine if a multimodal intervention to improve compliance with targeted normoxia will safely reduce the need for concentrated oxygen for critically injured trauma patients. These data will inform military stakeholders regarding oxygen requirements for critically injured warfighters, while reducing logistical burden in prolonged combat casualty care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04534959 . Registered September 1, 2020.

Predictive Intelligent Control of Oxygenation (PRICO) in preterm infants on high flow nasal cannula support: a randomised cross-over study.

OBJECTIVE: To investigate the efficacy of automated control of inspired oxygen (FiO2) by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining oxygen saturation (SpO2) in preterm infants on high flow nasal cannula (HFNC) support. DESIGN: Single-centre randomised two-period crossover study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: 27 preterm infants (gestational age (GA) <30 weeks) on HFNC support with FiO2 >0.25. INTERVENTION: A 24-hour period on automated FiO2-control with PRICO compared with a 24-hour period on routine manual control (RMC) to maintain a SpO2 level within target range of 88%-95% measured at 30 s intervals. MAIN OUTCOME MEASURES: Primary outcome: time spent within target range (88%-95%). SECONDARY OUTCOMES: time spent above and below target range, in severe hypoxia (SpO2 <80%) and hyperoxia (SpO2 >98%), mean SpO2 and FiO2 and manual FiO2 adjustments. RESULTS: 15 patients received PRICO-RMC and 12 RMC-PRICO. The mean time within the target range increased with PRICO: 10.8% (95% CI 7.6 to 13.9). There was a decrease in time below target range: 7.6% (95% CI 4.2 to 11.0), above target range: 3.1% (95% CI 2.9 to 6.2) and in severe hypoxia: 0.9% (95% CI 1.5 to 0.2). We found no difference in time spent in severe hyperoxia. Mean FiO2 was higher during PRICO: 0.019 (95% CI 0.006 to 0.030). With PRICO there was a reduction of manual adjustments: 9/24 hours (95% CI 6 to 12). CONCLUSION: In preterm infants on HFNC support, automated FiO2-control by PRICO is superior to RMC in maintaining SpO2 within target range. Further validation studies with a higher sample frequency and different ventilation modes are needed.

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.

Retinal oximetry with a prototype handheld oximeter during hyperoxia.

PURPOSE: Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient population including bedridden patients and newborn babies. The objective is to determine the sensitivity of this handheld oximeter in room air and during isocapnic hyperoxia. A comparison is made between the handheld oximeter and the Oxymap T1. METHODS: Thirteen young healthy subjects with a mean age of 25 ± 2 years were recruited at the Leiden University Medical Center. Retinal oximetry images were acquired during normoxia and during isocapnic hyperoxia for both the prototype oximeter and the OxymapT1. Isocapnic hyperoxia was induced with the dynamic end-tidal forcing technique. For both oximeters, the oxygen saturation and vessel width were measured with Oxymap Analyzer software. The hyperoxic state was verified with blood gas analysis. RESULTS: The mean oxygen saturation measured with the handheld oximeter in arterioles was 91.3% ± 3.9% during normoxia and 94.6% ± 3.9% during hyperoxia (p = 0.001). Oxygen saturation in venules was 56.3% ± 9.8% during normoxia and 82.2 ± 7.4% during hyperoxia (p < 0.001). For the Oxymap T1, the mean oxygen saturation for arterioles was 94.0% ± 2.6% during normoxia and 95.4%±3.2% during hyperoxia (p = 0.004). For the venules, the oxygen saturation was during normoxia 58.9%±3.2% and 84.3 ± 4.0% during hyperoxia (p < 0.001). CONCLUSION: The handheld retinal oximeter is sensitive to the changes in inhaled oxygen concentration. A small increase in oxygen saturation was measured in the arterioles and a larger increase in the venules. The handheld oximeter gives similar values as the 'gold standard' Oxymap T1 oximeter.

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.

The Impact of Hyperoxia on Outcome of Patients Treated with Noninvasive Respiratory Support.

Objective: Oxygen therapy is one of the most common treatment modalities for hypoxemic patients, but target goals for normoxemia are not clearly defined. Therefore, iatrogenic hyperoxia is a very common situation. The results from the recent clinical researches about hyperoxia indicate that hyperoxia can be related to worse outcomes than expected in some critically ill patients. According to our literature knowledge, there are not any reports researching the effect of hyperoxia on clinical course of patients who are not treated with invasive mechanical ventilation. In this study, we aimed to determine the effect of hyperoxia on mortality, and length of stay and also possible side effects of hyperoxia on the patients who are treated with oxygen by noninvasive devices. Materials and Methods: One hundred and eighty-seven patients who met inclusion criteria, treated in Dokuz Eylul University Medical Intensive Care Unit between January 1, 2016, and October 31, 2018, were examined retrospectively. These patients' demographic data, oxygen saturation (SpO2) values for the first 24 hours, APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, whether they needed intubation, if they did how many days they got ventilated, length of stay in intensive care unit and hospital, maximum PaO2 values of the first day, oxygen treatment method of the first 24 hours, and the rates of mortality were recorded. Results: Hyperoxemia was determined in 62 of 187 patients who were not treated with invasive mechanic ventilation in the first 24 hours of admission. Upon further investigation of the relation between comorbid situations and hyperoxia, hyperoxia frequency in patients with COPD was detected to be statistically low (16% vs. 35%, p < 0.008). Hospital mortality was significantly high (51.6% vs. 35.2%, p < 0.04) in patients with hyperoxia. When the types of oxygen support therapies were investigated, hyperoxia frequency was found higher in patients treated with supplemental oxygen (nasal cannula, oronasal mask, high flow oxygen therapy) than patients treated with NIMV (44.2% vs. 25.5%, p < 0.008). After exclusion of 56 patients who were intubated and treated with invasive mechanical ventilation after the first 24 hours, hyperoxemia was determined in 46 of 131 patients. Mortality in patients with hyperoxemia who were not treated with invasive mechanical ventilation during hospital stay was statistically higher when compared to normoxemic patients (41.3% vs 15.3%, p < 0.001). Conclusion: We report that hyperoxemia increases the hospital mortality in patients treated with noninvasive respiratory support. At the same time, we determined that hyperoxemia frequency was lower in COPD patients and the ones treated with NIMV. Conservative oxygen therapy strategy can be suggested to decrease the hyperoxia prevalence and mortality rates.

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.

Evaluation of hyperoxia-induced hypercapnia in obese patients after cardiac surgery: a randomized crossover comparison of conservative and liberal oxygen administration.

PURPOSE: Recent studies on patients with stable obesity-hypoventilation syndrome have raised concerns about hyperoxia-induced hypercapnia in this population. This study aimed to evaluate whether a higher oxygen saturation target would increase arterial partial pressure of carbon dioxide (PaCO2) in obese patients after coronary artery bypass grafting surgery (CABG). METHODS: Obese patients having CABG were recruited. With a randomized crossover design, we compared two oxygenation strategies for 30 min each, immediately after extubation: a peripheral oxygen saturation (SpO2) target of ≥ 95% achieved with manual oxygen titration (liberal) and a SpO2 target of 90% achieved with FreeO2, an automated oxygen titration device (conservative). The main outcome was end-of-period arterial PaCO2. RESULTS: Thirty patients were included. Mean (standard deviation [SD]) body mass index (BMI) was 34 (3) kg·m-2 and mean (SD) baseline partial pressure of carbon dioxide (PCO2) was 40.7 (3.1) mmHg. Mean (SD) end-of-period PaCO2 was 42.0 (5.4) mmHg in the conservative period, compared with 42.6 (4.6) mmHg in the liberal period [mean difference - 0.6 (95% confidence interval - 2.2 to 0.9) mmHg; P = 0.4]. Adjusted analysis for age, BMI, narcotics, and preoperative PaCO2 did not substantively change the results. Fourteen patients were retainers, showing an elevation in mean (SD) PaCO2 in the liberal period of 3.3 (4.1) mmHg. Eleven patients had the opposite response, with a mean (SD) end-of-period PaCO2 decrease of 1.8 (2.2) mmHg in the liberal period. Five patients had a neutral response. CONCLUSION: This study did not show a clinically important increase in PaCO2 associated with higher SpO2 values in this specific population of obese patients after CABG. Partial pressure of carbon dioxide increased with liberal oxygen administration in almost half of the patients, but no predictive factor was identified. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02917668); registered 25 September, 2016.

Early Hyperoxemia and Outcome Among Critically Ill Children.

OBJECTIVE: To identify whether a high PaO2 (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality. DESIGN: Single-center observational study. SETTING: Quaternary-care PICU. PATIENTS: Encounters admitted between January 1, 2009, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Encounters with a measured PaO2 were included. To account for severity of illness upon presentation, we calculated a modified Pediatric Risk of Mortality IV score excluding PaO2 for each encounter, calibrated for institutional data. Logistic regression was used to determine whether hyperoxemia (PaO2 ≥ 300 torr [39.99 kPa]) in the 12 hours surrounding PICU admission was associated with in-hospital mortality. We reperformed our analysis using a cutoff for hyperoxemia obtained by comparisons of observed versus predicted mortality when encounters were classified by highest PaO2 in 50 torr (6.67 kPa) bins. Results are reported as adjusted odds ratios with 95% CIs. Of 23,719 encounters, 4,093 had a PaO2 recorded in the period -6 to +6 hours after admission. Two hundred seventy-four of 4,093 (6.7%) had in-hospital mortality. The prevalence of hyperoxemia increased with rising modified Pediatric Risk of Mortality IV and was not associated with mortality in multivariable models (adjusted odds ratio, 1.38; 95% CI, 0.98-1.93). When using a higher cutoff of hyperoxemia derived from comparison of observed versus predicted rates of mortality of greater than or equal to 550 torr (73.32 kPa), hyperoxemia was associated with mortality (adjusted odds ratio, 2.78; 95% CI, 2.54-3.05). CONCLUSIONS: A conventional threshold for hyperoxemia at presentation to the PICU was not associated with in-hospital mortality in a model using a calibrated acuity score. Extreme states of hyperoxemia (≥ 73.32 kPa) were significantly associated with in-hospital mortality. Prospective research is required to identify if hyperoxemia before and/or after PICU admission contributes to poor outcomes.

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.

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.

Impact of hyperoxia on patients hospitalized in an intensive care unit for acute heart failure.

BACKGROUND: Oxygen therapy remains a cornerstone of treatment for acute heart failure in patients with pulmonary congestion. While avoiding hypoxaemia has long been a goal of critical care practitioners, less attention has been paid to the potential hazard related to excessive hyperoxia. AIM: To evaluate the impact of early hyperoxia exposure among critically ill patients hospitalized in an intensive care unit for acute heart failure. METHODS: In this preliminary study conducted in a Parisian intensive care unit, we assessed patients with acute heart failure admitted with pulmonary congestion and treated with oxygen therapy from 1 January 2015 to 31 December 2016. The hyperoxia group was defined by having at least one partial pressure of oxygen measurement>100mmHg on the first day following admission to the intensive care unit. The primary endpoint was 30-day all-cause mortality. Secondary endpoints were 30-day unplanned hospital admissions, occurrence of infections and intensive care unit and hospital lengths of stay. RESULTS: Seventy-five patients were included. Forty-three patients (57.3%) presented hyperoxia, whereas 32 patients (42.7%) did not (control group). The baseline clinical characteristics did not differ between the two groups. The primary endpoint was not statistically different between the two groups (14.0% in the hyperoxia group vs 18.8% in the control group; P=0.85). The secondary endpoints were also not significantly different between the two groups. In the multivariable analysis, hyperoxia was not associated with increased 30-day mortality (odds ratio 0.77, 95% confidence interval 0.24-2.41). CONCLUSION: In patients referred to an intensive care unit for acute heart failure, we did not find any difference in outcomes according to the presence of hyperoxia.

Improving preoperative identification of infants at risk for severe retinopathy of prematurity.

OBJECTIVE: To increase preoperative identification of at-risk infants for severe Retinopathy of prematurity (ROP) to >95% by August 2016, with a secondary aim of reducing the number of infants with 100% intraoperative peripheral oxygen saturation (SpO2) during the same time. STUDY DESIGN: Prospective quality improvement project centered on preterm surgical infants admitted to Primary Children's Hospital (n = 41). Preoperative ROP risk identification rates were analyzed using an annotated run chart, intraoperative SpO2 and laser intervention were compared using un-paired t test. RESULTS: Preoperative identification of ROP risk increased from 60 to 100% and no infant was exposed to 100% SpO2 intraoperatively during the study period. The incidence of laser intervention in this population decreased by 45% from 22 to 12% (p = 0.21). CONCLUSION: Simplifying our preoperative handoff increased our rates of correct identification and communication ROP risk in preterm infants while decreasing exposure to 100% SpO2.

Incidence of Hyperoxia in Combat Wounded in Iraq and Afghanistan: A Potential Opportunity for Oxygen Conservation.

INTRODUCTION: Oxygen supplementation is frequently used in critically injured trauma casualties in the combat setting. Oxygen supplies in the deployed setting are limited so excessive use of oxygen may unnecessarily consume this limited resource. We describe the incidence of supraphysiologic oxygenation (hyperoxia) within casualties in the Department of Defense Trauma Registry (DoDTR). METHODS: This is a subanalysis of previously published data from the DoDTR - we isolated casualties with a documented arterial blood gas (ABG) and categorized hyperoxia as an arterial oxygen >100 mmHg and extreme hyperoxia > 300 mmHg (a subset of hyperoxia). We defined serious injuries as those with an Abbreviated Injury Score (AIS) of 3 or greater. We defined a probable moderate traumatic brain injury of those with an AIS of 3 or greater for the head region and at least one Glasgow Coma Scale at 8 or less. RESULTS: Our initial search yielded 28,222 casualties, of which 10,969 had at least one ABG available. Within the 10,969, the proportion of casualties experiencing hyperoxia in this population was 20.6% (2,269) with a subset of 4.1% (452) meeting criteria for extreme hyperoxia. Among those with hyperoxia, the median age was 25 years (IQR 21-30), most were male (96.8%), most frequently US forces (41.4%), injured in Afghanistan (68.3%), injured by explosive (61.1%), with moderate injury scores (median 17, IQR 10-26), and most (93.8%) survived to hospital discharge. A total of 17.8% (1,954) of the casualties underwent endotracheal intubation: 27.5% (538 of 1,954) prior to emergency department (ED) arrival and 72.5% (1,416 of 1,954) within the ED. Among those intubated in the prehospital setting, upon ED arrival 35.1% (189) were hyperoxic, and a subset of 5.6% (30) that were extremely hyperoxic. Among those intubated in the ED, 35.4% (502) were hyperoxic, 7.9% (112) were extremely hyperoxic. Within the 1,277 with a probable TBI, 44.2% (565) experienced hyperoxia and 9.5% (122) met criteria for extreme hyperoxia. CONCLUSIONS: In our dataset, more than 1 in 5 casualties overall had documented hyperoxia on ABG measurement, 1 in 3 intubated casualties, and almost 1 in 2 TBI casualties. With limited oxygen supplies in theater and logistical challenges with oxygen resupply, efforts to avoid unnecessary oxygen supplementation may have material impact on preserving this scarce resource and avoid potential detrimental clinical effects from supraphysiologic oxygen concentrations.

Hypoxemic and hyperoxemic likelihood in pulse oximetry ranges: NICU observational study.

OBJECTIVE: Describe the likelihood of hypoxemia and hyperoxemia across ranges of oxygen saturation (SpO2), during mechanical ventilation with supplemental oxygenation. DESIGN: Retrospective observational study. SETTING: University affiliated tertiary care neonatal intensive care unit. PATIENTS: Two groups of neonates based on postmenstrual age (PMA): <32 weeks (n=104) and >36 weeks (n=709). MAIN MEASURES: Hypoxemia was defined as a PaO2 <40 mm Hg, hyperoxemia as a PaO2 of >99 mm Hg and normoxemia as a PaO2 of 50-80 mm Hg. Twenty-five per cent was defined as marked likelihood of hypoxemia or hyperoxemia. RESULTS: From these infants, 18 034 SpO2-PaO2 pairs were evaluated of which 10% were preterm. The PMA (median and IQR) of the two groups were: 28 weeks (27-30) and 40 weeks (38-41). With SpO2 levels between 90% and 95%, the likelihoods of hypoxemia and hyperoxemia were low and balanced. With increasing levels of SpO2, the likelihood of hyperoxemia increased. It became marked in the preterm group when SpO2 was 99%-100% (95% CI 29% to 41%) and in the term group with SpO2 levels of 96%-98% (95% CI 29% to 32%). The likelihood of hypoxemia increased as SpO2 decreased. It became marked in both with SpO2 levels of 80%-85% (95% CI 20% to 31%, 24% to 28%, respectively). CONCLUSIONS: The likelihood of a PaO2 <40 mm Hg is marked with SpO2 below 86%. The likelihood of a PaO2 >99 mm Hg is marked in term infants with SpO2 above 95% and above 98% in preterm infants. SpO2 levels between 90% and 95% are appropriate targets for term and preterm infants.

Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial.

PURPOSE: We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury. METHODS: Using a 23 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO2 and to normoxia (arterial oxygen tension [PaO2] 10-15 kPa) or moderate hyperoxia (PaO2 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months. RESULTS: In total 120 patients were included in the analyses. There was a clear separation in PaCO2 (p < 0.001) and PaO2 (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9-28.3 µg/l) in the low-normal PaCO2 group and 22.5 µg/l (14.2-34.9 µg/l) in the high-normal PaCO2 group, p = 0.400; and 22.3 µg/l (14.8-27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2-34.9 µg/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO2 and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes. CONCLUSIONS: Both high-normal PaCO2 and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected. REGISTRATION: ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.

Admission Hyperoxia Is a Risk Factor for Mortality in Pediatric Intensive Care.

OBJECTIVES: To determine whether the association between hyperoxia and increased risk-adjusted mortality in adult intensive care patients is also observed in a pediatric intensive care population. DESIGN: Single-center retrospective analysis of admissions to ICU over a 5-year period commencing January 1, 2012, examining the relationship between PaO2 measured within the first hour of admission and risk-adjusted mortality. Standardized mortality rates were calculated using the Pediatric Index of Mortality-3, and patients were grouped into 50 mm Hg (6.67 kPa) PaO2 bands to assess the relationship between initial PaO2 and risk-adjusted mortality. SETTING: Tertiary PICU with 17 beds and 1,100 annual admissions located in metropolitan Sydney, Australia. PATIENTS: A total of 1,447 patients 0-18 years old with PaO2 recorded at admission to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 5,176 patients admitted to the ICU during the study period and 1,447 (28%) with PaO2 recorded at admission. A U-shaped relationship between raw mortality and admission PaO2 was observed, with lowest mortality (2.3% and 2.6%, respectively) observed in the 101-150 (13.5-20.0 kPa) and 151-200 mm Hg (20.1-26.7 kPa) bands and the highest mortality observed in patients with PaO2 less than 50 mm Hg (6.67 kPa) with mortality of 5.3%, or greater than 350 mm Hg (46.7 kPa) with mortality of 18.2%. Hyperoxia at admission was associated with an increase in risk-adjusted mortality, with polynomial regression indicating a strong correlation between PaO2 band and risk-adjusted outcome (r = 0.845). When included in a multivariate model that included the Pediatric Index of Mortality-3 variables, the odds ratio for hyperoxia (defined as PaO2 > 250 mm Hg [33.3 kPa]) predicting death was 2.66 (p = 0.047). CONCLUSIONS: In this single-center study, hyperoxia at admission to the PICU was highly correlated with increased risk-adjusted mortality. Further investigation of these observations in a large multicenter cohort is warranted.