Hyperoxia during extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest is associated with severe circulatory failure and increased mortality.

BACKGROUND: High levels of arterial oxygen pressures (PaO2) have been associated with increased mortality in extracorporeal cardiopulmonary resuscitation (ECPR), but there is limited information regarding possible mechanisms linking hyperoxia and death in this setting, notably with respect to its hemodynamic consequences. We aimed therefore at evaluating a possible association between PaO2, circulatory failure and death during ECPR. METHODS: We retrospectively analyzed 44 consecutive cardiac arrest (CA) patients treated with ECPR to determine the association between the mean PaO2 over the first 24 h, arterial blood pressure, vasopressor and intravenous fluid therapies, mortality, and cause of deaths. RESULTS: Eleven patients (25%) survived to hospital discharge. The main causes of death were refractory circulatory shock (46%) and neurological damage (24%). Compared to survivors, non survivors had significantly higher mean 24 h PaO2 (306 ± 121 mmHg vs 164 ± 53 mmHg, p < 0.001), lower mean blood pressure and higher requirements in vasopressors and fluids, but displayed similar pulse pressure during the first 24 h (an index of native cardiac recovery). The mean 24 h PaO2 was significantly and positively correlated with the severity of hypotension and the intensity of vasoactive therapies. Patients dying from circulatory failure died after a median of 17 h, compared to a median of 58 h for patients dying from a neurological cause. Patients dying from neurological cause had better preserved blood pressure and lower vasopressor requirements. CONCLUSION: In conclusion, hyperoxia is associated with increased mortality during ECPR, possibly by promoting circulatory collapse or delayed neurological damage.

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry.

BACKGROUND: Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality. METHODS: Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock). RESULTS: A total of 5912 patients were analyzed. The median age was 39 [26-55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50-0.70], p < 0.0001). CONCLUSION: In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.

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 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.

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.

Optimal Arterial Blood Oxygen Tension in the Early Postresuscitation Phase of Extracorporeal Cardiopulmonary Resuscitation: A 15-Year Retrospective Observational Study.

OBJECTIVES: Hyperoxia could lead to a worse outcome after cardiac arrest. Few studies have investigated the impact of oxygenation status on patient outcomes following extracorporeal cardiopulmonary resuscitation. We sought to delineate the association between oxygenation status and neurologic outcomes in patients receiving extracorporeal cardiopulmonary resuscitation. DESIGN: Retrospective analysis of a prospective extracorporeal cardiopulmonary resuscitation registry database. SETTING: An academic tertiary care hospital. PATIENTS: Patients receiving extracorporeal cardiopulmonary resuscitation between 2000 and 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 291 patients were included, and 80.1% were male. Their mean age was 56.0 years. The arterial blood gas data employed in the primary analysis were recorded from the first sample over the first 24 hours in the ICUs after return of spontaneous circulation. The mean PaO2 after initiation of venoarterial extracorporeal membrane oxygenation was 178.0 mm Hg, and the mean PaO2/FIO2 ratio was 322.0. Only 88 patients (30.2%) demonstrated favorable neurologic status at hospital discharge. Multivariate logistic regression analysis indicated that PaO2 between 77 and 220 mm Hg (odds ratio, 2.29; 95% CI, 1.01-5.22; p = 0.05) and PaO2/FIO2 ratio between 314 and 788 (odds ratio, 5.09; 95% CI, 2.13-12.14; p < 0.001) were both positively associated with favorable neurologic outcomes. CONCLUSIONS: Oxygenation status during extracorporeal membrane oxygenation affects neurologic outcomes in patients receiving extracorporeal cardiopulmonary resuscitation. The PaO2 range of 77 to 220 mm Hg, which is slightly narrower than previously defined, seems optimal. The PaO2/FIO2 ratio was also associated with outcomes in our analysis, indicating that both PaO2 and the PaO2/FIO2 ratio should be closely monitored during the early postcardiac arrest phase for postextracorporeal cardiopulmonary resuscitation patients.

Myocardial injury and mortality in patients with excessive oxygen administration before cardiac arrest.

INTRODUCTION: Hyperoxia after cardiac arrest may be associated with higher mortality, and trials have found that excess oxygen administration in patients with myocardial infarction is associated with increased infarct size. The effect of hyperoxia before cardiac arrest is sparsely investigated. Our aim was to assess the association between excessive oxygen administration before cardiac arrest and the extent of subsequent myocardial injury. METHODS: We performed a retrospective study including patients who had in-hospital cardiac arrest during 2014 in the Capital Region of Denmark. We excluded patients without peripheral oxygen saturation measurements within 48 hours before cardiac arrest. Patients were divided in three groups of pre-arrest oxygen exposure, based on average peripheral oxygen saturation and supplemental oxygen. Primary outcome was peak troponin concentration within 30 days. Secondary outcomes included 30-day mortality. Data were analyzed using multiple logistic regression and Wilcoxon rank sum test. RESULTS: Of 163 patients with cardiac arrest, 28 had excessive oxygen administration (17%), 105 had normal oxygen administration (64%) and 30 had insufficient oxygen administration (18%) before cardiac arrest. Peak troponin was median 224 ng/L in the excessive oxygen administration group vs 365 ng/L in the normal oxygen administration group (P = .54); 20 of 28 (71%) in the excessive oxygen administration group died within 30 days compared to 54 of 105 (51%) in the normal oxygen administration group. (OR 1.87, 95% CI 0.56-6.19) CONCLUSIONS: Excessive oxygen administration within 48 hours before in-hospital cardiac arrest was not statistically associated with significantly higher peak troponin or mortality.

Association between perioperative hyperoxia and cerebrovascular complications after laparotomy-A post-hoc follow-up study.

BACKGROUND: Perioperative hyperoxia has been linked to increased long-term mortality. Vasoconstrictive and cellular side effects to hyperoxia have been suggested to increase the risk of coronary and cerebral ischemia. The aim of this post-hoc analysis of a large randomized trial was to compare the effects of 80% vs 30% perioperative oxygen on the long-term risk of stroke or transient cerebral ischemia (TCI) in patients undergoing abdominal surgery. METHODS: A total of 1386 patients were randomized to 80% or 30% perioperative oxygen during acute or elective open abdominal surgery. Median follow-up was 3.9 years. Primary outcome was a composite of the long-term occurrence of stroke or TCI. Secondary outcomes included long-term mortality without stroke or TCI, and incidences of neurological admission, psychiatric admission, and dementia. Outcomes were analyzed in Cox regression models. RESULTS: Stroke or TCI occurred in 20 (3.0%) patients given 80% oxygen vs 22 (3.2%) patients given 30% oxygen with an adjusted hazard ratio (HR) of 0.96 [95% CI 0.52-1.76]. Composite secondary outcome of death, stroke, or TCI had a HR of 1.21 [95% CI 1.00-1.47] for 80% compared to 30% oxygen. HRs for secondary outcomes were HR 1.14 [95% CI 0.79-1.64] for neurological admission, 1.34 [95% CI 0.95-1.88] for psychiatric admission and 0.54 [95% CI 0.16-1.80] for dementia. CONCLUSION: Stroke or TCI did not seem related to perioperative inspiratory oxygen fraction. Due to few events, this study cannot exclude that perioperative hyperoxia increases risk of mortality, stroke, or TCI after abdominal surgery.

Emergency department hyperoxia is associated with increased mortality in mechanically ventilated patients: a cohort study.

BACKGROUND: Providing supplemental oxygen is fundamental in the management of mechanically ventilated patients. Increasing amounts of data show worse clinical outcomes associated with hyperoxia. However, these previous data in the critically ill have not focused on outcomes associated with brief hyperoxia exposure immediately after endotracheal intubation. Therefore, the objectives of this study were to evaluate the impact of isolated early hyperoxia exposure in the emergency department (ED) on clinical outcomes among mechanically ventilated patients with subsequent normoxia in the intensive care unit (ICU). METHODS: This was an observational cohort study conducted in the ED and ICUs of an academic center in the USA. Mechanically ventilated normoxic (partial pressure of arterial oxygen (PaO2) 60-120 mm Hg) ICU patients with mechanical ventilation initiated in the ED were studied. The cohort was categorized into three oxygen exposure groups based on PaO2 values obtained after ED intubation: hypoxia, normoxia, and hyperoxia (defined as PaO2 < 60 mmHg, PaO2 60-120 mm Hg, and PaO2 > 120 mm Hg, respectively, based on previous literature). RESULTS: A total of 688 patients were included. ED normoxia occurred in 350 (50.9%) patients, and 300 (43.6%) had exposure to ED hyperoxia. The ED hyperoxia group had a median (IQR) ED PaO2 of 189 mm Hg (146-249), compared to an ED PaO2 of 88 mm Hg (76-101) in the normoxia group, P < 0.001. Patients with ED hyperoxia had greater hospital mortality (29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%). After multivariable logistic regression analysis, ED hyperoxia was an independent predictor of hospital mortality (adjusted OR 1.95 (1.34-2.85)). CONCLUSIONS: ED exposure to hyperoxia is common and associated with increased mortality in mechanically ventilated patients achieving normoxia after admission. This suggests that hyperoxia in the immediate post-intubation period could be particularly injurious, and targeting normoxia from initiation of mechanical ventilation may improve outcome.

Association of Arterial Oxygen Tension During In-Hospital Cardiac Arrest With Return of Spontaneous Circulation and Survival.

BACKGROUND: Despite numerous advances in the delivery of resuscitative care, in-hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. We sought to study the impact of arterial oxygen tension (Pao2) on return of spontaneous circulation (ROSC) and survival to discharge in patients with IHCA. METHODS: The study population included 255 consecutive patients who underwent advanced cardiac life support-guided resuscitation from January 2012 to December 2013 for IHCA at an academic tertiary medical center. Of these patients, 167 underwent arterial blood gas testing at the time of the arrest. Baseline demographic, clinical, laboratory, and clinical outcome data were recorded. The primary outcome of interest was survival to hospital discharge. Secondary outcome of interest was presence of ROSC. RESULTS: Of the 167 patients studied, Pao2 categorization included the following: Pao2 < 60 mm Hg (n = 38), Pao2 of 60-92 mm Hg (n = 44), Pao2 of 93 to 159 mm Hg (n = 43), Pao2 of 160 to 299 mm Hg (n = 24), and Pao2 ≥ 300 mm Hg (n = 18). Patients with higher Pao2 levels during the time of cardiac arrest were noted to have higher rates of hypertension and chronic kidney disease. Clinical presentation of IHCA, in particular, the initial rhythm, location of IHCA, and duration of cardiopulmonary resuscitation, was similar in all groups. Patients with higher Pao2 levels had higher platelet count, higher arterial pH, and lower arterial carbon dioxide tension (Pco2). With respect to outcomes, patients with higher intra-arrest Pao2 levels had progressively higher rates of ROSC (58% vs 71% vs 72% vs 79% vs 100%, P = .021) and survival to discharge (16% vs 23% vs 30% vs 33% vs 56%, P = .031). In multivariate analysis, Pao2 ≥ 300 mm Hg was independently associated with higher survival to discharge (odds ratio 60.68; 95% confidence interval: 3.04-1210.28; P = .007; referent Pao2 < 60 mm Hg). CONCLUSION: Higher intra-arrest Pao2 is independently associated with higher rates of survival to discharge in adults with IHCA.

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.

Hyperoxia and Hypocapnia During Pediatric Extracorporeal Membrane Oxygenation: Associations With Complications, Mortality, and Functional Status Among Survivors.

OBJECTIVES: To determine the frequency of hyperoxia and hypocapnia during pediatric extracorporeal membrane oxygenation and their relationships to complications, mortality, and functional status among survivors. DESIGN: Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network. SETTING: Eight Collaborative Pediatric Critical Care Research Network-affiliated hospitals. PATIENTS: Age less than 19 years and treated with extracorporeal membrane oxygenation. INTERVENTIONS: Hyperoxia was defined as highest PaO2 greater than 200 Torr (27 kPa) and hypocapnia as lowest PaCO2 less than 30 Torr (3.9 kPa) during the first 48 hours of extracorporeal membrane oxygenation. Functional status at hospital discharge was evaluated among survivors using the Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Of 484 patients, 420 (86.7%) had venoarterial extracorporeal membrane oxygenation and 64 (13.2%) venovenous; 69 (14.2%) had extracorporeal membrane oxygenation initiated during cardiopulmonary resuscitation. Hyperoxia occurred in 331 (68.4%) and hypocapnia in 98 (20.2%). Hyperoxic patients had higher mortality than patients without hyperoxia (167 [50.5%] vs 48 [31.4%]; p < 0.001), but no difference in functional status among survivors. Hypocapnic patients were more likely to have a neurologic event (49 [50.0%] vs 143 (37.0%]; p = 0.021) or hepatic dysfunction (49 [50.0%] vs 121 [31.3%]; p < 0.001) than patients without hypocapnia, but no difference in mortality or functional status among survivors. On multivariable analysis, factors independently associated with increased mortality included highest PaO2 and highest blood lactate concentration in the first 48 hours of extracorporeal membrane oxygenation, congenital diaphragmatic hernia, and being a preterm neonate. Factors independently associated with lower mortality included meconium aspiration syndrome. CONCLUSIONS: Hyperoxia is common during pediatric extracorporeal membrane oxygenation and associated with mortality. Hypocapnia appears to occur less often and although associated with complications, an association with mortality was not observed.

Oxygen Thresholds and Mortality During Extracorporeal Life Support in Adult Patients.

OBJECTIVES: Extracorporeal life support can lead to rapid reversal of hypoxemia and shock; however, it can also result in varying degrees of hyperoxia. Recent data have suggested an association between hyperoxia and mortality; however, this conclusion has not been consistent across the literature. We evaluated the association between oxygenation thresholds and mortality in three cohorts of extracorporeal life support patients. DESIGN: We performed a retrospective cohort study using the Extracorporeal Life Support Organization Registry. SETTING: We evaluated the relationship between oxygenation measured 24 hours after extracorporeal membrane oxygenation onset and mortality (2010-2015). PATIENTS: The extracorporeal life support cohorts were as follows: 1) veno-venous extracorporeal membrane oxygenation for respiratory failure, 2) veno-arterial extracorporeal membrane oxygenation for cardiogenic shock, and 3) extracorporeal cardiopulmonary resuscitation. INTERVENTIONS: The relationships between hypoxemia (PaO2 < 60mm Hg), normoxia (PaO2 60-100mm Hg), moderate hyperoxia (PaO2 101-300mm Hg), extreme hyperoxia (PaO2 > 300 mm Hg), and mortality were evaluated across three extracorporeal life support cohorts. MEASUREMENTS AND MAIN RESULTS: Seven hundred sixty-five patients underwent veno-venous extracorporeal membrane oxygenation, 775 patients underwent veno-arterial extracorporeal membrane oxygenation, and 412 underwent extracorporeal cardiopulmonary resuscitation. During veno-venous extracorporeal membrane oxygenation, hypoxemia (odds ratio, 1.68; 95% CI, 1.09-2.57) and moderate hyperoxia (odds ratio, 1.66; 95% CI, 1.11-2.50) were associated with increased mortality compared with normoxia. There was no association between oxygenation and mortality for veno-arterial extracorporeal membrane oxygenation. Moderate hyperoxia was associated with increased mortality during extracorporeal cardiopulmonary resuscitation compared with normoxia (odds ratio, 1.77; 95% CI, 1.03-3.30). An exploratory analysis did not find more specific PaO2 thresholds associated with mortality within moderate hyperoxia. CONCLUSIONS: Moderate hyperoxia was associated with increased mortality in patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure and extracorporeal cardiopulmonary resuscitation. Hypoxemia was associated with an increased mortality in veno-venous extracorporeal membrane oxygenation. No association was seen between oxygenation and mortality in veno-arterial extracorporeal membrane oxygenation which may be due to early death driven by the underlying disease.

Admission PaO2 and Mortality in Critically Ill Children: A Cohort Study and Systematic Review.

OBJECTIVE: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. DESIGN: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: "hyperoxia," "hypoxia," "critically ill children," "pediatric intensive care," "mortality," and/or "survival." SETTING: Tertiary PICU. PATIENTS: Patients younger than 18 years of age. INTERVENTIONS: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, < 60 torr [8 kPa] or peripheral oxygen saturations, < 90%) to mortality in critically ill children was explored. MEASUREMENTS AND MAIN RESULTS: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group (< 8 kPa) to 5.3% (287/5,385) with normoxia and 9.1% (64/701) in the hyperoxic group (> 40 kPa). Nonlinear regression displayed a "U-shaped" relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79-5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42-3.17; p = 0.77). CONCLUSIONS: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.

Hyperoxia Is Associated With Poor Outcomes in Pediatric Cardiac Patients Supported on Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Patients who require venoarterial extracorporeal membrane oxygenation because of cardiac failure frequently have supranormal blood oxygen tensions (hyperoxia). Recent studies have suggested worse outcomes in patients with hyperoxia after resuscitation from cardiac or respiratory arrests, presumably because of oxidative stress. There are limited data regarding the effect of hyperoxia on outcomes in pediatric patients on venoarterial extracorporeal membrane oxygenation. DESIGN: Retrospective chart review. SETTING: Pediatric cardiothoracic ICU. PATIENTS: Cardiac surgery patients less than 1 year old requiring venoarterial extracorporeal membrane oxygenation in the postoperative period from 2007 to 2013. MEASUREMENTS AND MAIN RESULTS: In 93 infants (median time on extracorporeal membrane oxygenation, 5 d), mortality at 30 days post surgery (primary outcome) was 38%. Using a receiver operating characteristic curve, a mean PaO2 of 193 mm Hg in the first 48 hours of extracorporeal membrane oxygenation was determined to have good discriminatory ability with regard to 30-day mortality. Univariate analysis identified a mean PaO2 greater than 193 mm Hg (p = 0.001), longer cardiopulmonary bypass times (p = 0.09), longer duration of extracorporeal membrane oxygenation (p < 0.0001), and higher extracorporeal membrane oxygenation pump flows (p = 0.052) as possible risk factors for 30-day mortality. In multivariable analysis controlling for the variables listed above, a mean PaO2 greater than 193 mm Hg remained an independent risk factor for mortality (p = 0.03). In addition, a mean PaO2 greater than 193 mm Hg was associated with the need for renal dialysis (p = 0.02) but not with neurologic injury (p = 0.41) during the hospitalization. CONCLUSIONS: In infants with congenital heart disease who are placed on venoarterial extracorporeal membrane oxygenation postoperatively, hyperoxia (defined as a mean PaO2 > 193 mm Hg in the first 48 hr of extracorporeal membrane oxygenation) was an independent risk factor for 30-day mortality after surgery. Future studies are needed to delineate the causative or associative role of hyperoxia with outcomes, especially in children with baseline cyanosis who may be more susceptible to the effects of oxidative stress.

Associations of arterial carbon dioxide and arterial oxygen concentrations with hospital mortality after resuscitation from cardiac arrest.

INTRODUCTION: Arterial concentrations of carbon dioxide (PaCO2) and oxygen (PaO2) during admission to the intensive care unit (ICU) may substantially affect organ perfusion and outcome after cardiac arrest. Our aim was to investigate the independent and synergistic effects of both parameters on hospital mortality. METHODS: This was a cohort study using data from mechanically ventilated cardiac arrest patients in the Dutch National Intensive Care Evaluation (NICE) registry between 2007 and 2012. PaCO2 and PaO2 levels from arterial blood gas analyses corresponding to the worst oxygenation in the first 24 h of ICU stay were retrieved for analyses. Logistic regression analyses were performed to assess the relationship between hospital mortality and both categorized groups and a spline-based transformation of the continuous values of PaCO2 and PaO2. RESULTS: In total, 5,258 cardiac arrest patients admitted to 82 ICUs in the Netherlands were included. In the first 24 h of ICU admission, hypocapnia was encountered in 22 %, and hypercapnia in 35 % of included cases. Hypoxia and hyperoxia were observed in 8 % and 3 % of the patients, respectively. Both PaCO2 and PaO2 had an independent U-shaped relationship with hospital mortality and after adjustment for confounders, hypocapnia and hypoxia were significant predictors of hospital mortality: OR 1.37 (95 % CI 1.17-1.61) and OR 1.34 (95 % CI 1.08-1.66). A synergistic effect of concurrent derangements of PaCO2 and PaO2 was not observed (P = 0.75). CONCLUSIONS: The effects of aberrant arterial carbon dioxide and arterial oxygen concentrations were independently but not synergistically associated with hospital mortality after cardiac arrest.

Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice.

Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Neonatal mice exposed to hyperoxia develop a simplified lung structure that resembles BPD. Sustained activation of the transcription factor NF-κB and increased expression of protective target genes attenuate hyperoxia-induced mortality in adults. However, the effect of enhancing hyperoxia-induced NF-κB activity on lung injury and development in neonatal animals is unknown. We performed this study to determine whether sustained NF-κB activation, mediated through IκBß overexpression, preserves lung development in neonatal animals exposed to hyperoxia. Newborn wild-type (WT) and IκBß-overexpressing (AKBI) mice were exposed to hyperoxia (>95%) or room air from day of life (DOL) 0-14, after which all animals were kept in room air. Survival curves were generated through DOL 14. Lung development was assessed using radial alveolar count (RAC) and mean linear intercept (MLI) at DOL 3 and 28 and pulmonary vessel density at DOL 28. Lung tissue was collected, and NF-κB activity was assessed using Western blot for IκB degradation and NF-κB nuclear translocation. WT mice demonstrated 80% mortality through 14 days of exposure. In contrast, AKBI mice demonstrated 60% survival. Decreased RAC, increased MLI, and pulmonary vessel density caused by hyperoxia in WT mice were significantly attenuated in AKBI mice. These findings were associated with early and sustained NF-κB activation and expression of cytoprotective target genes, including vascular endothelial growth factor receptor 2. We conclude that sustained hyperoxia-induced NF-κB activation improves neonatal survival and preserves lung development. Potentiating early NF-κB activity after hyperoxic exposure may represent a therapeutic intervention to prevent BPD.

Association between hyperoxia and mortality after stroke: a multicenter cohort study.

OBJECTIVE: To test the hypothesis that hyperoxia was associated with higher in-hospital mortality in ventilated stroke patients admitted to the ICU. DESIGN: Retrospective multicenter cohort study. SETTING: Primary admissions of ventilated stroke patients with acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage who had arterial blood gases within 24 hours of admission to the ICU at 84 U.S. ICUs between 2003 and 2008. Patients were divided into three exposure groups: hyperoxia was defined as PaO2 ≥ 300 mm Hg (39.99 kPa), hypoxia as any PaO2<60 mm Hg (7.99 kPa) or PaO2/FiO2 ratio ≤ 300, and normoxia, not defined as hyperoxia or hypoxia. The primary outcome was in-hospital mortality. PARTICIPANTS: Two thousand eight hundred ninety-four patients. METHODS: Patients were divided into three exposure groups: hyperoxia was defined as PaO2 more than or equal to 300 mm Hg (39.99 kPa), hypoxia as any PaO2 less than 60 mm Hg (7.99 kPa) or PaO2/FIO2 ratio less than or equal to 300, and normoxia, not defined as hyperoxia or hypoxia. The primary outcome was in-hospital mortality. INTERVENTIONS: Exposure to hyperoxia. RESULTS: Over the 5-year period, we identified 554 ventilated patients with acute ischemic stroke (19%), 936 ventilated patients with subarachnoid hemorrhage (32%), and 1,404 ventilated patients with intracerebral hemorrhage (49%) of whom 1,084 (38%) were normoxic, 1,316 (46%) were hypoxic, and 450 (16%) were hyperoxic. Mortality was higher in the hyperoxia group as compared with normoxia (crude odds ratio 1.7 [95% CI 1.3-2.1]; p < 0.0001) and hypoxia groups (crude odds ratio, 1.3 [95% CI, 1.1-1.7]; p < 0.01). In a multivariable analysis adjusted for admission diagnosis, other potential confounders, the probability of being exposed to hyperoxia, and hospital-specific effects, exposure to hyperoxia was independently associated with in-hospital mortality (adjusted odds ratio, 1.2 [95% CI, 1.04-1.5]). CONCLUSION: In ventilated stroke patients admitted to the ICU, arterial hyperoxia was independently associated with in-hospital death as compared with either normoxia or hypoxia. These data underscore the need for studies of controlled reoxygenation in ventilated critically ill stroke populations. In the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in ventilated stroke patients.

Significance of arterial hyperoxia and relationship with case fatality in traumatic brain injury: a multicentre cohort study.

OBJECTIVE: In this retrospective multi-centre cohort study, we tested the hypothesis that hyperoxia was not associated with higher in-hospital case fatality in ventilated traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU). METHODS: Admissions of ventilated TBI patients who had arterial blood gases within 24 h of admission to the ICU at 61 US hospitals between 2003 and 2008 were identified. Hyperoxia was defined as PaO2 ≥300 mm Hg (39.99 kPa), hypoxia as any PaO2 <60 mm Hg (7.99 kPa) or PaO2/FiO2 ratio ≤300 and normoxia, not defined as hyperoxia or hypoxia. The primary outcome was in-hospital case fatality. RESULTS: Over the 5-year period, we identified 1212 ventilated TBI patients, of whom 403 (33%) were normoxic, 553 (46%) were hypoxic and 256 (21%) were hyperoxic. The case-fatality was higher in the hypoxia group (224/553 [41%], crude OR 2.3, 95% CI 1.7-3.0, p<.0001) followed by hyperoxia (80/256 [32%], crude OR 1.5, 95% CI 1.1-2.5, p=.01) as compared to normoxia (87/403 [23%]). In a multivariate analysis adjusted for other potential confounders, the probability of being exposed to hyperoxia and hospital-specific characteristics, exposure to hyperoxia was independently associated with higher in-hospital case fatality adjusted OR 1.5, 95% CI 1.02-2.4, p=0.04. CONCLUSIONS: In ventilated TBI patients admitted to the ICU, arterial hyperoxia was independently associated with higher in-hospital case fatality. In the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in critically ill ventilated TBI patients.