Early Hyperoxemia Research Articles

Association Between Early Hyperoxemia Exposure and Intensive Care Unit Mortality in Intracerebral Hemorrhage: An Observational Cohort Analysis.

Supraphysiologic levels of oxygen could have potential adverse effects on the brain that may be dose and time dependent in patients with brain injury. We therefore aimed to assess whether exposure to excess supplemental oxygen, measured as time-weighted mean exposure to hyperoxemia, was associated with intensive care unit (ICU) mortality in patients with intracerebral hemorrhage (ICH). In this single-center retrospective cohort study, we included all patients admitted to our ICU with a diagnosis of primary spontaneous ICH. To provide a longitudinal measure of hyperoxemia exposure, we calculated the hyperoxemia dose, defined as the area under the partial pressure of oxygen in arterial blood (PaO2) time curve above the threshold PaO2 value of 100mm Hg (13.3kPa) divided by the number of hours of potential exposure. To provide consistent potential exposure windows and limit bias from informative censoring, nested subsets were created with progressively longer exposure periods (0-1day, 0-2days, 0-3days, 0-4days, 0-5days, 0-6days, 0-7days). We used multivariable Cox regression, with hyperoxemia dose as a time-dependent covariate, to model ICU mortality. Admission ICH and Acute Physiology and Chronic Health Evaluation II scores were included as predictor covariables. A step-function extended Cox model was also fitted. Between September 2019 and July 2022, 275 patients met the inclusion criteria, with 24,588 arterial blood gas results available for analysis. The mean age was 57.19years (± 13.99), 59.64% were male, 23.64% had an infratentorial origin of hemorrhage, and ICU mortality was 35.64%. Almost all patients (97.45%) were exposed to hyperoxemia during their ICU admission. Cox regression modeling showed an association between hyperoxemia dose and ICU mortality (hazard ratio 1.15, confidence interval 1.05-1.25, p = 0.003). This association was observed in the 0-1day subset in the step-function extended Cox model (hazard ratio 1.19, confidence interval 1.06-1.35, p = 0.005) but not in any of the subsequent exposure periods. In patients with ICH admitted to the ICU, we observed an association between hyperoxemia dose and ICU mortality. Further prospective study is required to inform guidance on early systemic oxygen targets in ICH.

Early Hyperoxemia and 2-year Outcomes in Infants with Hypoxic-ischemic Encephalopathy: A Secondary Analysis of the Infant Cooling Evaluation Trial

ObjectiveTo determine the causal relationship between exposure to early hyperoxemia and death or major disability in infants with hypoxic-ischemic encephalopathy (HIE). Study designWe analyzed data from the Infant Cooling Evaluation (ICE) trial that enrolled newborns ≥35 weeks' gestation with moderate-severe HIE, randomly allocated to hypothermia or normothermia. The primary outcome was death or major sensorineural disability at 2 years. We included infants with arterial pO2 measured within 2 hours of birth. Using a directed acyclic graph, we established that markers of severity of perinatal hypoxia-ischemia and pCO2 were a minimally sufficient set of variables for adjustment in a regression model to estimate the causal relationship between arterial pO2 and death/disability. ResultsAmong 221 infants, 116 (56%) had arterial pO2 and primary outcome data. The unadjusted analysis revealed a U-shaped relationship between arterial pO2 and death or major disability. Among hyperoxemic infants (pO2 100–500 mmHg) the proportion with death or major disability was 40/58 (0.69), while the proportion in normoxemic infants (pO2 40 – 99mmHg) was 20/48 (0.42). In the adjusted model, hyperoxemia increased the risk of death or major disability (adjusted risk ratio 1.61, 95% CI 1.07 – 2.00, p= 0.03) in relation to normoxemia. ConclusionEarly hyperoxemia increased the risk of death or major disability among infants who had an early arterial pO2 in the ICE trial. Limitations include the possibility of residual confounding and other causal biases. Further work is warranted to confirm this relationship in the era of routine therapeutic hypothermia.

The effects of exposure to severe hyperoxemia on neurological outcome and mortality after cardiac arrest.

Hyperoxemia during cardiac arrest (CA) may increase chances of successful resuscitation. However, episodes of severe hyperoxemia after intensive care unit admission occurs frequently (up to 60%), and these have been associated with higher mortality in CA patients. The impact of severe hyperoxemia on neurological outcome is more unclear. We conducted a systematic review and meta-analysis on Pubmed and EMBASE to evaluate the effects of severe hyperoxemia according to arterial blood gas analysis on neurological outcome and mortality in patients resuscitated from CA and admitted to intensive care unit. Thirteen observational studies were included, eight of them reporting data on neurological outcome and ten on mortality. Most studies reported odds ratio adjusted for confounders. Severe hyperoxemia was associated with worse neurological outcome (OR 1.37 [95%CI 1.01,1.86], P=0.04) and higher mortality at longest follow-up (OR 1.32 [95%CI 1.11,1.57], P=0.002). Subgroup analyses according to timing of hyperoxemia showed that any hyperoxemia during the first 36 hours was associated with worse neurological outcome (OR 1.52 [95%CI 1.12,2.08], P=0.008) and higher mortality (OR 1.40 [95%CI 1.18,1.66], P=0.0001), whilst early hyperoxemia was not (neurological: P=0.29; mortality: P=0.19). Sensitivity analyses mostly confirmed the results of the primary analyses. Severe hyperoxemia is associated with worse neurological outcome and lower survival in CA survivors admitted to intensive care unit. Clinical efforts should be made to avoid severe hyperoxemia during at least the first 36 hours after cardiac arrest.

Effect of early hyperoxemia on mortality in mechanically ventilated septic shock patients according to Sepsis-3 criteria: analysis of the MIMIC-III database.

Hyperoxemia may be associated with increased mortality in emergency room or ICU patients. However, its effect during septic shock is still debated. To evaluate the effect of hyperoxemia on ICU mortality, during the first 24 h of ICU stay, in mechanically ventilated patients with septic shock according to SEPSIS-3 criteria. A retrospective cohort study of ICU admissions recorded in the Medical Information Mart for Intensive Care-III, a retrospective ICU database, was performed. Two oxygen exposures during the first 24 h were compared: average PaO2 (TWA-PaO2) between 70 and 120 mmHg in the normoxemia group and above 120 mmHg in the hyperoxemia group. The primary outcome was mortality during ICU stay. Four hundred eighty-eight ICU admissions met the inclusion criteria: 214 in the normoxemia group and 274 in the hyperoxemia group. The median TWA-PaO2 was 99.1 (88.9-107.6) mmHg in the normoxemia group and 151.5 (133.6-180.2) mmHg in the hyperoxemia group. ICU mortality was lower in the hyperoxemia group than in the normoxemia group in univariate analysis [29.6 vs. 39.7%, respectively; OR 0.64 (0.44-0.93); P = 0.024], but not in multivariate analysis [OR 0.98 (0.62-1.56); P = 0.93]. There was no difference between the two groups in ICU length of stay [8.0 (4.3-15.0) vs. 8.4 (4.7-15.0) days; P = 0.82]. We did not find any impact of early hyperoxemia on mortality in this population of mechanically ventilated patients with SEPSIS-3 septic shock criteria.

Hyperoxemia and Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm. This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO2 values or died within 96h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO2 measured within 72h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale. Three hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt-Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO2 by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO2 between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage. Hyperoxemia within 72h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO2 and may represent a modifiable risk factor for vasospasm.

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

BackgroundHyperoxemia 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.MethodsUsing 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).ResultsA 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).ConclusionIn 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.

Effect of early hyperoxemia on the outcome in servere blunt chest trauma: A propensity score-based analysis of a single-center retrospective cohort.

Our study aimed to explore the association between early hyperoxemia of the first 24h on outcomes in patients with severe blunt chest trauma. In a level I trauma center, we conducted a retrospective study of 426 consecutive patients. Hyperoxemic groups were classified in severe (average PaO2≥200mmHg), moderate (≥150 and<200mmHg) or mild (≥ 100 and<200mmHg) and compared to control group (≥60 and<100mmHg) using a propensity score based analysis. The first endpoint was the incidence of a composite outcome including death and hospital-acquired pneumonia occurring from admission to day 28. The secondary endpoints were the incidence of death, the number of hospital-acquired pneumonia, mechanical ventilation-free days and intensive care unit-free day at day 28. The incidence of the composite endpoint was lower in the severe hyperoxemia group(OR, 0.25; 95%CI, 0.09-0.73; P<0.001) compared with control. The 28-day mortality incidence was lower in severe (OR, 0.23; 95%CI, 0.08-0.68; P<0.001) hyperoxemia group (OR, 0.41; 95%CI, 0.17-0.97; P=0.04). Significant association was found between hyperoxemia and secondary outcomes. In our cohort early hyperoxemia during the first 24h of admission after severe blunt chest trauma was not associated with worse outcome.

Early Hyperoxemia and Outcome Among Critically Ill Children.

To identify whether a high PaO2 (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality. Single-center observational study. Quaternary-care PICU. Encounters admitted between January 1, 2009, and December 31, 2018. None. 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). 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.

Early hyperoxemia is not associated with cardiac arrest outcome

AimStudies suggest that hyperoxemia increases short-term mortality after cardiopulmonary resuscitation (CPR), but the effect of hyperoxemia on long-term outcomes is unclear. We determined the prevalence of early hyperoxemia after CPR and its association with long-term neurological outcome and mortality. MethodsWe analysed data from adult cardiac arrest patients treated after CPR in tertiary ICUs during 2005–2013. We retrieved data from the resuscitation and the first arterial blood sample collected after return of spontaneous circulation (ROSC) (severe hyperoxemia defined as PaO2 > 40 kPa and moderate as PaO2 16–40 kPa). We inspected two outcomes, neurological performance at one year after resuscitation according to the Cerebral Performance Category and one-year mortality. We used logistic regression to test associations between hyperoxemia and the outcome and interaction analyses to test the effect of hyperoxemia exposure on the outcomes in smaller subgroups. ResultsOf 1110 patients 11% had severe hyperoxemia, prevalence was 10% for out-of-hospital arrests, 13% for in-hospital arrests and 9% for in-ICU arrests. In total 585(53%) patients had an unfavourable neurological outcome. Compared to normoxemia, severe (Odds ratio [OR] 0.81, 95% confidence interval [CI] 0.50–1.30) and moderate hyperoxemia (OR 0.94 95%CI 0.69–1.27) did not associate with neurological outcome. Additionally, hyperoxemia had no association with mortality. In subgroup analyses there were no significant associations between severe hyperoxemia and outcomes regardless of cardiac arrest location, initial rhythm or time-to-ROSC. ConclusionWe found no association between early post-arrest hyperoxemia and unfavourable outcome. Subgroup analysis found no differential effect depending on arrest location, initial rhythm or time-to-ROSC.

Abstract 56: The Association Between Early Hyperoxemia and Oxygen Exposure with Development of Pulmonary Dysfunction, Survival and Neurological Outcomes After Cardiac Arrest

Introduction: Prior studies inconsistently report an association between hyperoxemia and worse outcomes after cardiac arrest (CA), but are methodologically limited. We used a high-resolution CA-specific database to control for cumulative early oxygen exposure, disease-specific covariates and care processes to test if rigorous adjustment would eliminate any association between hyperoxemia and outcomes. We also tested if exposure to higher inspired oxygen (FiO2) was associated with development of lung dysfunction. Methods: We included patients surviving and ventilated for &gt;24 hours after ROSC. To test the association between hyperoxemia and outcomes, we categorized PaO2 hourly for 24h as severe hyperoxemia (&gt;300mmHg), moderate hyperoxemia (101-299mmHg), normoxia (60-100mmHg) or hypoxia (&lt;60mmHg). We controlled for CA-specific covariates and markers of potentially less attentive care (time to first FiO2 wean, number of weans, etc). We used multiple logistic regression to test the association between PaO2 and survival and discharge CPC. To test for development of lung dysfunction, we calculated oxygen exposure as the area under the curve of the FiO2 x hour (FiO2AUC) for each patient over 24h. Our main outcomes in this analysis were change in the respiratory SOFA score (SOFA-R) and change in dynamic lung compliance from baseline to 48h. Results: Of 184 patients overall mortality was 54% and 36% had severe hyperoxemia. The first PaO2:FiO2 ratio was 241±137, and at baseline 85% had pulmonary failure and 55% had cardiovascular failure as assessed by SOFA. Only severe hyperoxemia was independently associated with decreased survival to hospital discharge (adjusted OR 0.83 per hour, P=0.04) and worse discharge CPC. Higher FiO2AUC was not associated with worsened SOFA-R or lung compliance over 48h but was associated with decreased survival to discharge and worse discharge CPC. This was driven by 50% decreased survival in the highest quartile of FiO2AUC (FIO2&gt;80%/24h) compared to other quartiles. Conclusion: Despite rigorous adjustment, severe hyperoxemia was independently associated with decreased survival to hospital discharge and discharge CPC. We did not observe toxicity at lower levels. High FiO2 was not associated with pulmonary toxicity.

Early hyperoxemia may not increase mortality after cardiac arrest: a pilot study

ObjectiveInternational Liaison Committee on Resuscitation guidelines advocate an arterial saturation of 94% to 96% after return of spontaneous circulation (ROSC). However, a few clinical trials have investigated the impact of postresuscitative O2 therapy after cardiac arrest. We studied whether early hyperoxemia is associated with a poor post-ROSC outcome after in-hospital cardiac arrest.MethodsWe retrospectively reviewed patients who experienced an in-hospital cardiac arrest from January 2005 to January 2011. Based on the results of the first arterial blood gas analysis (ABGA) within 10 minutes and a second ABGA from 60 to 120 minutes after ROSC, patients were classified into three groups: hyperoxemia (PaO2 ≥ 300 mmHg), normoxemia (300 mmHg > PaO2 ≥ 60 mmHg), and hypoxemia (PaO2 < 60 mmHg or ratio of PaO2 to fraction of inspired oxygen < 300). We examined whether early hyperoxemia was associated with survival and neurological outcome.ResultsThere were 792 patients who met the inclusion criteria: 638 (80.6%) in the hypoxemia group, 62 (7.8%) in the normoxemia group, and 92 (11.6%) in the hyperoxemia group. Multiple logistic regression analysis showed that hyperoxemia was not associated with survival (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.30 to 3.84) or neurological outcome (OR, 1.03; 95% CI, 0.31 to 3.40).ConclusionPostresuscitation hyperoxemia was not associated with survival or neurological outcome in patients with ROSC after in-hospital cardiac arrest.

Perinatal Asphyxia with Hyperoxemia within the First Hour of Life Is Associated with Moderate to Severe Hypoxic-Ischemic Encephalopathy

To determine whether early hyperoxemia in neonates with severe perinatal acidemia is associated with the development of hypoxic-ischemic encephalopathy (HIE). We identified 120 infants at ≥ 36 weeks gestational age with perinatal acidosis born at Parkland Hospital who qualified for a screening neurologic exam for cooling therapy. Based on a PaO2 measurement during the first hour of life, the cohort was divided into infants with hyperoxemia (PaO2 >100 mmHg) and those without hyperoxemia (PaO2 ≤ 100 mmHg). The rate of moderate-severe encephalopathy was compared between the groups using χ(2) analysis, as well as multiple logistic regression, taking into account baseline characteristics and confounding variables. Thirty-six infants (30%) had an initial PaO2 >100 mmHg. Infants with and without hyperoxemia had similar baseline maternal and infant characteristics. Infants with hyperoxemia had a higher incidence of HIE than those without hyperoxemia (58% vs 27%; P = .003). Admission hyperoxemia was associated with a higher risk of HIE (OR, 4; 95% CI, 1.4-10.5; adjusted P = .01). Among the neonates with moderate-severe HIE during the first 6 hours of life, those with hyperoxemia had a higher incidence of abnormal brain magnetic resonance imaging results, consistent with hypoxic ischemic injury, compared with those without hyperoxemia (79% vs 33%; P = .015). In neonates with perinatal acidemia, admission hyperoxemia is associated with a higher incidence of HIE. Among neonates with HIE, admission hyperoxemia is associated with abnormal brain magnetic resonance imaging findings. The judicious use of oxygen during and after resuscitation is warranted.