Neurological outcomes and mortality of hyperoxaemia in patients with acute brain injury: protocol for a systematic review and meta-analysis.

INTRODUCTION: Oxygen is frequently prescribed in neurocritical care units. Avoiding hypoxaemia is a key objective in patients with acute brain injury (ABI). However, several studies suggest that hyperoxaemia may also be related to higher mortality and poor neurological outcomes in these patients. The evidence in this direction is still controversial due to the limited number of prospective studies, the lack of a common definition for hyperoxaemia, the heterogeneity in experimental designs and the different causes of ABI. To explore the correlation between hyperoxaemia and poor neurological outcomes and mortality in hospitalised adult patients with ABI, we will conduct a systematic review and meta-analysis of observational studies and RCTs. METHODS AND ANALYSIS: The systematic review methods have been defined according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and follow the PRISMA-Protocols structure. Studies published until June 2024 will be identified in the electronic databases MEDLINE, Embase, Scopus, Web of Science, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov. Retrieved records will be independently screened by four authors working in pairs, and the selected variables will be extracted from studies reporting data on the effect of 'hyperoxaemia' versus 'no hyperoxaemia on neurological outcomes and mortality in hospitalised patients with ABI. We will use covariate-adjusted ORs as outcome measures when reported since they account for potential cofounders and provide a more accurate estimate of the association between hyperoxaemia and outcomes; when not available, we will use univariate ORs. If the study presents the results as relative risks, it will be considered equivalent to the OR as long as the prevalence of the condition is close to 10%. Pooled estimates of both outcomes will be calculated applying random-effects meta-analysis. Interstudy heterogeneity will be assessed using the I2 statistic; risk of bias will be assessed through Risk Of Bias In Non-Randomised Studies of Interventions, Newcastle-Ottawa or RoB2 tools. Depending on data availability, we plan to conduct subgroup analyses by ABI type (traumatic brain injury, postcardiac arrest, subarachnoid haemorrhage, intracerebral haemorrhage and ischaemic stroke), arterial partial pressure of oxygen values, study quality, study time, neurological scores and other selected clinical variables of interest. ETHICS AND DISSEMINATION: Specific ethics approval consent is not required as this is a review of previously published anonymised data. Results of the study will be shared with the scientific community via publication in a peer-reviewed journal and presentation at relevant conferences and workshops. It will also be shared key stakeholders, such as national or international health authorities, healthcare professionals and the general population, via scientific outreach journals and research institutes' newsletters.

Arterial hyperoxia and mortality in the cardiac intensive care unit.

BACKGROUND: Arterial hyperoxia (hyperoxemia), defined as a high arterial partial pressure of oxygen (PaO2), has been associated with adverse outcomes in critically ill populations, but has not been examined in the cardiac intensive care unit (CICU). We evaluated the association between exposure to hyperoxia on admission with in-hospital mortality in a mixed CICU cohort. METHODS: We included unique Mayo Clinic CICU patients admitted from 2007 to 2018 with admission PaO2 data (defined as the PaO2 value closest to CICU admission) and no hypoxia (PaO2 < 60mmHg). The admission PaO2 was evaluated as a continuous variable and categorized (60-100 mmHg, 101-150 mmHg, 151-200 mmHg, 201-300 mmHg, >300 mmHg). Logistic regression was used to evaluate predictors of in-hospital mortality before and after multivariable adjustment. RESULTS: We included 3,368 patients with a median age of 70.3 years; 70.3% received positive-pressure ventilation. The median PaO2 was 99 mmHg, with a distribution as follows: 60-100 mmHg, 51.9%; 101-150 mmHg, 28.6%; 151-200 mmHg, 10.6%; 201-300 mmHg, 6.4%; >300 mmHg, 2.5%. A J-shaped association between admission PaO2 and in-hospital mortality was observed, with a nadir around 100 mmHg. A higher PaO2 was associated with increased in-hospital mortality (adjusted OR 1.17 per 100 mmHg higher, 95% CI 1.01-1.34, p = 0.03). Patients with PaO2 >300 mmHg had higher in-hospital mortality versus PaO2 60-100 mmHg (adjusted OR 2.37, 95% CI 1.41-3.94, p < 0.001). CONCLUSIONS: Hyperoxia at the time of CICU admission is associated with higher in-hospital mortality, primarily in those with severely elevated PaO2 >300 mmHg.

Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. METHODS: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. RESULTS: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). CONCLUSION: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

Rationale: Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. Objectives: We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. Methods: An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021. Patients ⩽18 years old and with a corrected gestational age of ≥37 weeks who received chest compressions for cardiac arrest in one of the 18 intensive care units were included. Exposures during the first 24 hours postarrest were hypoxemia, hyperoxemia, or normoxemia-defined as lowest arterial oxygen tension/pressure (PaO2) <60 mm Hg, highest PaO2 ⩾200 mm Hg, or every PaO2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (PaCO2) <30 mm Hg, highest PaCO2 ⩾50 mm Hg, or every PaCO2 30-49 mm Hg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. Results: The hypoxemia group was less likely to survive to hospital discharge, compared with the normoxemia group (adjusted relative risk [aRR] = 0.71; 95% confidence interval [CI] = 0.58-0.87), whereas survival in the hyperoxemia group did not differ from that in the normoxemia group (aRR = 1.0; 95% CI = 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge, compared with the normocapnia group (aRR = 0.74; 95% CI = 0.64-0.84), whereas survival in the hypocapnia group did not differ from that in the normocapnia group (aRR = 0.91; 95% CI = 0.74-1.12). Conclusions: Postarrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

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.

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.

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.

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.

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.

Association of Severe Hyperoxemia Events and Mortality Among Patients Admitted to a Pediatric Intensive Care Unit.

Importance: A high Pao2, termed hyperoxemia, is postulated to have deleterious health outcomes. To date, the association between hyperoxemia during the ongoing management of critical illness and mortality has been incompletely evaluated in children. Objective: To examine whether severe hyperoxemia events are associated with mortality among patients admitted to a pediatric intensive care unit (PICU). Design, Setting, and Participants: A retrospective cohort study was conducted over a 10-year period (January 1, 2009, to December 31, 2018); all 23 719 PICU encounters at a quaternary children's hospital with a documented arterial blood gas measurement were evaluated. Exposures: Severe hyperoxemia, defined as Pao2 level greater than or equal to 300 mm Hg (40 kPa). Main Outcomes and Measures: The highest Pao2 values during hospitalization were dichotomized according to the definition of severe hyperoxemia and assessed for association with in-hospital mortality using logistic regression models incorporating a calibrated measure of multiple organ dysfunction, extracorporeal life support, and the total number of arterial blood gas measurements obtained during an encounter. Results: Of 23 719 PICU encounters during the inclusion period, 6250 patients (13 422 [56.6%] boys; mean [SD] age, 7.5 [6.6] years) had at least 1 measured Pao2 value. Severe hyperoxemia was independently associated with in-hospital mortality (adjusted odds ratio [aOR], 1.78; 95% CI, 1.36-2.33; P < .001). Increasing odds of in-hospital mortality were observed with 1 (aOR, 1.47; 95% CI, 1.05-2.08; P = .03), 2 (aOR, 2.01; 95% CI, 1.27-3.18; P = .002), and 3 or more (aOR, 2.53; 95% CI, 1.62-3.94; P < .001) severely hyperoxemic Pao2 values obtained greater than or equal to 3 hours apart from one another compared with encounters without hyperoxemia. A sensitivity analysis examining the hypothetical outcomes of residual confounding indicated that an unmeasured binary confounder with an aOR of 2 would have to be present in 37% of the encounters with severe hyperoxemia and 0% of the remaining cohort to fail to reject the null hypothesis (aOR of severe hyperoxemia, 1.31; 95% CI, 0.99-1.72). Conclusions and Relevance: Greater numbers of severe hyperoxemia events appeared to be associated with increased mortality in this large, diverse cohort of critically ill children, supporting a possible exposure-response association between severe hyperoxemia and outcome in this population. Although further prospective evaluation appears to be warranted, this study's findings suggest that guidelines for ongoing management of critically ill children should take into consideration the possible detrimental effects of severe hyperoxemia.

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.

An exploration of the deleterious effects of hyperoxemia on the morbidity and mortality of hospitalized adult patients.

BACKGROUND AND PURPOSE: To explore the deleterious effects of hyperoxia due to liberal oxygen use and clarify the significance of overuse and effects on morbidity and mortality in adult hospitalized patients. This literature review is also intended to bring awareness to nurse practitioners regarding the iatrogenic harm caused by excessive oxygenation and promote individualized patient care. METHODS: A review of existing literature was conducted using PubMed and CINAHL databases. The keywords "hyperoxia", "hyperoxemia", "oxygen toxicity," and "excessive oxygenation" were used to yield articles for consideration. RESULTS: Of the six studies compared for this review, five identified positive correlations between hyperoxia and adverse outcomes. The sixth study found no significant differences in morbidity or mortality with the use of liberal oxygenation versus a more conventional approach. CONCLUSIONS: Overwhelming evidence suggests that states of hyperoxemia lead to increased mortality and morbidity. However, there is considerable variability on the threshold at which hyperoxia occurs. Further research is required to define levels of hyperoxia to better protect patients from iatrogenic harm. IMPLICATIONS FOR PRACTICE: Nurse practitioners in all specialties can increase awareness of the dangers of excessive oxygenation and effect a change in practice through education.

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.

Harmful effects of early hyperoxaemia in patients admitted to general wards: an observational cohort study in South Korea.

OBJECTIVES: We evaluated the association between hyperoxaemia induced by a non-invasive oxygen supply for 3 days after emergency department (ED) arrival and the clinical outcomes at day 5 after ED arrival. DESIGN: Observational cohort study. SETTING AND PATIENTS: Consecutive ED patients ≥16 years of age with available arterial blood gas analysis results who were admitted to our hospital were enrolled from January 2010 to December 2016. INTERVENTIONS: The highest (PaO2MAX), average (PaO2AVG) and median (PaO2MED) PaO2 (arterial oxygen pressure) values within 72 hours and the area under the curve divided by the time elapsed between ED admittance and the last PaO2 result (AUC72) were used to assess hyperoxaemia. The AUC72 values were calculated using the trapezoid rule. OUTCOMES: The primary outcome was the 90-day in-hospital mortality rate. The secondary outcomes were intensive care unit (ICU) transfer and respiratory failure at day 5 after ED arrival, as well as new-onset cardiovascular, coagulation, hepatic and renal dysfunction at day 5 after ED arrival. RESULTS: Among the 10 141 patients, the mortality rate was 5.8%. The adjusted ORs of in-hospital mortality for PaO2MAX, PaO2AVG, PaO2MED and AUC72 were 0.79 (95% CI 0.61 to 1.02; p=0.0715), 0.92 (95% CI 0.69 to 1.24; p=0.5863), 0.82 (95% CI 0.61 to 1.11; p=0.2005) and 1.53 (95% CI 1.25 to 1.88; p<0.0001). All of the hyperoxaemia variables showed significant positive correlations with ICU transfer at day 5 after ED arrival (p<0.05). AUC72 was positively correlated with respiratory failure, as well as cardiovascular, hepatic and renal dysfunction (p<0.05). PaO2MAX was positively correlated with cardiovascular dysfunction. PaO2MAX and AUC72 were negatively correlated with coagulation dysfunction (p<0.05). CONCLUSIONS: Hyperoxaemia during the first 3 days in patients outside the ICU is associated with in-hospital mortality and ICU transfer at day 5 after arrival at the ED.