Arterial Hyperoxia Research Articles

Association between arterial oxygen tension with clinical outcomes in patients undergoing VA-ECMO support: a systematic review and dose-response meta-analysis

Abstract Background Arterial hyperoxia has been associated with a worse prognosis in critically ill patients. However, studies conducted in patients undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) used inconsistent and arbitrary thresholds for defining hyperoxia, which impeded the determination of the optimal target for arterial oxygen tension (PaO2) in this population. Purpose To investigate and visualise the dose-response relationship between post-ECMO level of PaO2 with early mortality (in-hospital and 1-month) and poor neurological outcomes in adult patients undergoing VA-ECMO support, including Extracorporeal Cardiopulmonary Resuscitation (ECPR). Methods A systematic search was conducted through Pubmed and Embase to include studies that stratified patients based on PaO2 levels and evaluated relevant outcomes. We utilised either adjusted Odds Ratio (OR) with 95% Confidence Interval (CI) when available, or unadjusted OR against the lowest exposure category. The median, mean, or midpoint value of PaO2 was assigned as the corresponding dose. A random-effects one-stage dose-response meta-analysis was performed to assess linear association for every 10 mmHg increase in PaO2, while potential non-linear relationship was explored with restricted cubic splines at 3 knots (10th, 50th, and 90th percentile). Non-linearity was assessed by using Wald test with p value <0.05 considered significant. Statistical analyses were performed using STATA 17.0. Results Fourteen eligible records were identified (cardiogenic shock/CS = 5 records; ECPR = 8 records; both = 1 record). Only four studies classified a separate category for hypoxemic patients (<60 mmHg). PaO2 levels were measured within 24-72 hours of VA-ECMO initiation, except in one study. PaO2 level was not associated with early mortality (9 studies; OR 1.021 [95% CI 0.988–1.055]; p for non-linearity = 0.893), but found to have a linear association with composite poor neurological outcomes (6 studies; OR 1.016 [1.009–1.024]; p for non-linearity = 0.346). Subgroup analysis of CS patients revealed a linear association between PaO2 >100 mmHg and early mortality (4 studies; OR 1.025 [95%CI 1.018–1.032]; p for non-linearity = 0.255). For ECPR patients, a J-shaped relationship was observed between PaO2 and early mortality (5 studies; p for non-linearity = 0.004), with the lowest odds being at PaO2 level of 110-210 mmHg, while PaO2 level >110 mmHg showed a linear trend towards higher odds of poor neurological function (4 studies; OR 1.091 [95%CI 0.938–1.269]; p for non-linearity = 0.257). Conclusion Pooled data from observational studies suggest that PaO2 >100 mmHg should be avoided in CS patients on VA-ECMO support, given its linear association with mortality, but it cannot be extrapolated to hypoxemic patients. In ECPR patients, PaO2 level around 110-210 mmHg conferred the best clinical outcomes. However, these findings should be confirmed through randomised controlled trials.

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan

IntroductionCritically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. DesignThe BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and settingPatients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. InterventionThe study compares a conservative oxygenation strategy (target arterial saturations 92–96%) with a liberal oxygenation strategy (target 97–100%). Main Outcome MeasuresThe primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. ConclusionsThis paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

Exposure to Arterial Hyperoxia During Extracorporeal Membrane Oxygenator Support and Mortality in Patients With Cardiogenic Shock.

Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock. We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60-150 mmHg), mild hyperoxia (PaO2 151-300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression. Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23-1.53]; P<0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92-2.52]; P<0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12-1.16]; P<0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age. Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO.

ARTERIAL HYPEROXIA AND MORTALITY IN PATIENTS UNDERGOING VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can easily lead to supranormal oxygenation. The impact of hyperoxygenation beyond the early VA-ECMO support phase is unexplored. We sought to investigate its association with short- and long-term mortality. Methods: A total of 10,615 arterial blood gases of 179 patients undergoing VA-ECMO between 2013 and 2018 in our cardiosurgical tertiary center were analyzed for partial pressure of oxygen (PaO2) and its association with in-hospital, 90-day, and 1-year mortality. Patients were stratified into terciles (T) based on PaO2. Results: The median systemic PaO2 during VA-ECMO was 122 mm Hg (Q1-Q3, 111-158 mm Hg) and was significantly higher in 90-day nonsurvivors versus survivors (134 mm Hg [Q1-Q3, 114-175 mm Hg] vs. 114 mm Hg [Q1-Q3, 109-136 mm Hg]; P < 0.001). The incidence of mortality increased at all time points tested after VA-ECMO implantation along with the increasing terciles of PaO2. The lowest mortality rates were noted for patients with median PaO2 values of <115 mm Hg (T1), whereas patients with median PaO2 values of >144 mm Hg (T3) had the highest mortality rates. Bonferroni multiple testing analysis found the T3 of PaO2 to be a predictor of decreased 90-day survival in comparison with T1 (P < 0.001) and T2 (P = 0.002). Multivariable Cox regression analyses for in-hospital, 90-day, and 1-year mortality showed a significant association of the T3 compared with the T2 and the T1 of PaO2 to mortality across all endpoints. Conclusion: Hyperoxygenation during VA-ECMO might be associated with increased all-cause mortality. The results of our study further document the known toxicity of hyperoxygenation in general critical care patients and mark the need to focus specifically on VA-ECMO patients.

P116 Association between arterial hyperoxia after return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) and prognosis.

P116 Association between arterial hyperoxia after return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) and prognosis.

Association of Arterial Hyperoxia With Outcomes in Critically Ill Children

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. To evaluate the association of arterial hyperoxia with clinical outcome in critically ill children among studies using varied definitions of hyperoxia. A systematic search of EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception to February 1, 2021, was conducted. 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. 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. 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. 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. 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.

Association Between Oxygen Partial Pressure Trajectories and Short-Term Outcomes in Patients With Hemorrhagic Brain Injury.

Objectives: Arterial hyperoxia is reportedly a risk factor for poor outcomes in patients with hemorrhagic brain injury (HBI). However, most previous studies have only evaluated the effects of hyperoxia using static oxygen partial pressure (PaO2) values. This study aimed to investigate the association between overall dynamic oxygenation status and HBI outcomes, using longitudinal PaO2 data.Methods: Data were extracted from the Medical Information Mart for Intensive Care III database. Longitudinal PaO2 data obtained within 72 h of admission to an intensive care unit were analyzed, using a group-based trajectory approach. In-hospital mortality was used as the primary outcomes. Multivariable logistic models were used to explore the association between PaO2 trajectory and outcomes.Results: Data of 2,028 patients with HBI were analyzed. Three PaO2 trajectory types were identified: Traj-1 (mild hyperoxia), Traj-2 (transient severe hyperoxia), and Traj-3 (persistent severe hyperoxia). The initial and maximum PaO2 of patients with Traj-2 and Traj-3 were similar and significantly higher than those of patients with Traj-1. However, PaO2 in patients with Traj-2 decreased more rapidly than in patients with Traj-3. The crude in-hospital mortality was the lowest for patients with Traj-1 and highest for patients with Traj-3 (365/1,303, 209/640, and 43/85 for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001), and the mean Glasgow Coma Scale score at discharge (GCSdis) was highest for patients with Traj-1 and lowest in patients with Traj-3 (13 [7–15], 11 [6–15], and 7 [3–14] for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001). The multivariable model revealed that the risk of death was higher in patients with Traj-3 than in patients with Traj-1 (odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9–5.8) but similar for patients with Traj-1 and Traj-2. Similarly, the logistic analysis indicated the worst neurological outcomes in patients with Traj-3 (OR: 3.6, 95% CI: 2.0–6.4, relative to Traj-1), but similar neurological outcomes for patients in Traj-1 and Traj-2.Conclusion: Persistent, but not transient severe arterial hyperoxia, was associated with poor outcome in patients with HBI.

Arterial Oxygenation in Traumatic Brain Injury-Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome.

Background:Ischemic and hypoxic secondary brain insults are common and detrimental in traumatic brain injury (TBI). Treatment aims to maintain an adequate cerebral blood flow with sufficient arterial oxygen content. It has been suggested that arterial hyperoxia may be beneficial to the injured brain to compensate for cerebral ischemia, overcome diffusion barriers, and improve mitochondrial function. In this study, we investigated the relation between arterial oxygen levels and cerebral energy metabolism, pressure autoregulation, and clinical outcome.Methods:This retrospective study was based on 115 patients with severe TBI treated in the neurointensive care unit, Uppsala university hospital, Sweden, 2008 to 2018. Data from cerebral microdialysis (MD), arterial blood gases, hemodynamics, and intracranial pressure were analyzed the first 10 days post-injury. The first day post-injury was studied in particular.Results:Arterial oxygen levels were higher and with greater variability on the first day post-injury, whereas it was more stable the following 9 days. Normal-to-high mean pO2 was significantly associated with better pressure autoregulation/lower pressure reactivity index (P = .02) and lower cerebral MD-lactate (P = .04) on day 1. Patients with limited cerebral energy metabolic substrate supply (MD-pyruvate below 120 µM) and metabolic disturbances with MD-lactate-/pyruvate ratio (LPR) above 25 had significantly lower arterial oxygen levels than those with limited MD-pyruvate supply and normal MD-LPR (P = .001) this day. Arterial oxygenation was not associated with clinical outcome.Conclusions:Maintaining a pO2 above 12 kPa and higher may improve oxidative cerebral energy metabolism and pressure autoregulation, particularly in cases of limited energy substrate supply in the early phase of TBI. Evaluating the cerebral energy metabolic profile could yield a better patient selection for hyperoxic treatment in future trials.

Arterial Hyperoxia Is Associated with Poor Functional Outcome and Cognitive Impairment After TBI: A Retrospective Multi-center Cohort Study (1272)

Arterial Hyperoxia Is Associated with Poor Functional Outcome and Cognitive Impairment After TBI: A Retrospective Multi-center Cohort Study (1272)

The relation between arterial hyperoxia and mortality among intensive care unit patients with septic shock

Context Oxygen should be regarded as any other drug with potential dose and time-dependent adverse effects. Health care practitioners are more likely to accept supranormal arterial oxygen levels as a wider safety buffer. Furthermore, the latest guidelines in the management of septic shock did not define upper limits for oxygenation in mechanically ventilated patients with septic shock.Aim To investigate whether hyperoxia is associated with higher mortality in patients with septic shock.Patients and methods This study was carried out on 200 patients with septic shock. After fulfilling the inclusion criteria, we recorded the clinical data, severity scoring systems, source of sepsis, ventilatory data, oxygenation status data, and the outcome parameters. We categorized the patients into two groups: group I (nonhyperoxic group), whose arterial oxygen tension was less than 120 mmHg in all arterial blood gas analyses during the ICU stay, and group II (hyperoxic group), whose arterial oxygen tension was more than or equal to 120 mmHg in at least one arterial blood gas analysis during ICU stay.Results Group I included 40 patients, whereas group II included 160 patients. Mortality rate was 57.5 and 89.4% in groups I and II, respectively. In group II, there were 16 patients who were exposed to 1 day of hyperoxia with a mortality rate of 75%, whereas there were 144 patients who were exposed to hyperoxia more than 1 day with a mortality rate of 91%.Conclusion Hyperoxia was associated with increased mortality, number of mechanical ventilation days, length of ICU stay, and hospital stay.

Abstract 275: Oxygen Weaning is Slow and Highly Variable Among Mechanically Ventilated Patients After Out-Of-Hospital Cardiac Arrest

Introduction: Arterial hyperoxia at 6 h following resuscitation from out-of-hospital cardiac arrest (OHCA) may be associated with worsened survival and neurologic outcome. While global resuscitation guidelines call for prompt weaning of inhaled oxygen fraction (FiO2) following return of spontaneous circulation, with titration to oxygen saturation (SaO2) &gt;92%, the burden of hyperoxia (both FiO2 and duration) among OHCA patients in the emergency department (ED) and critical care setting is unknown. Objectives: We sought to characterize oxygen weaning behavior in a cohort of resuscitated and mechanically ventilated OHCA patients from two hospitals, with “hyperoxic exposure burden” defined as cumulative treatment hours with FiO2&gt;0.6. We hypothesized that the majority of these patients receive at least 6 h of hyperoxic exposure despite concomitant SaO2&gt;92% during and after weaning. Methods: A retrospective study of post-arrest care was performed at two academic hospitals from 1/2018-12/2018; both hospitals have well-developed post-arrest care protocols that include oxygen weaning instructions. Consecutive non-traumatic, adult (age&gt;17 y) OHCA patients treated in the emergency department that achieved sustained ROSC and received mechanical ventilation were included. Demographic data, as well as data on FiO2, SaO2 and arterial blood gas results, were collected for the first 24 h of post-arrest care. Results: 70 adult OHCA patients were included. Mean age was 61 y (SD 16.4), 51% were male, and 20% had initial shockable arrest rhythms. Survival to discharge was 21%. Median ED patient care time before ICU transfer was 2.7 h (IQR: 1.9-4.0). FiO2&gt;=0.6 was administered to 52% of the cohort for at least 6 h; the median duration of hyperoxic exposure burden was 8.7 h (IQR: 3.9-15.0) with a wide range from 0.6-92 h. Among all patients with 6 h or more with FiO2&gt;=0.6, median partial pressure of arterial oxygen was 136 mm Hg (IQR: 94-301) as measured during this period. Conclusions: Most resuscitated OHCA patients received substantial exposure to hyperoxia, and the timing of oxygen weaning was highly variable. Additional clinical investigation is required to understand the barriers to rapid weaning and to test the effect of improved weaning on clinical outcomes.

Postnatal Cerebral Hyperoxia Is Associated with an Increased Risk of Severe Retinopathy of Prematurity

Background: High arterial oxygen saturation (SaO₂) is associated with the development of retinopathy of prematurity (ROP), but difficult to avoid. Objective: To assess the association between severe ROP and a burden of cerebral and arterial hyperoxia. Methods: We retrospectively analyzed 225 preterm infants born ≤30 weeks’ gestation. The cerebral oxygen saturation (r_cSO₂) and SaO₂ were measured within the first 96 h after birth. We determined the burden of both cerebral and arterial hyperoxia, which was defined as the percentage of time spent at saturation thresholds exceeding 85 and 90%, respectively. Their association with severe ROP (prethreshold disease type 1) was tested using logistic regression analyses. Results: Median gestational age (GA) was 28.0 weeks (interquartile range 26.7–29.0) and mean birth weight 1,032 g (±281 SD). Eight infants developed severe ROP. Infants with severe ROP spent more time at cerebral hyperoxic levels than infants without severe ROP (medians 30 vs. 16%). Adjusted for GA, for every 10% increase in burden of cerebral hyperoxia, the OR for developing ROP was 1.50 (95% CI 1.09 – 2.06, p = 0.013). A burden of arterial hyperoxia was not associated with ROP. Infants with severe ROP experienced even less arterial hyperoxia, although not statistically significant. Conclusions: Cerebral hyperoxia may be a better early predictor of severe ROP than arterial hyperoxia. Moreover, under strict oxygen management, cerebral hyperoxia in these infants may result from cerebral immaturity rather than a high SaO₂. Whether reducing cerebral hyperoxia is feasible and might prevent ROP needs to be further examined.

Abstract 275: Arterial Hyperoxia Exposure and Survival Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest. Jaam-ohca Registry in Japan

Background: The effect of hyperoxia for outcomes in resuscitated patients with out-of-hospital cardiac arrest (OHCA) is still controversial. Objective: To assess the relationship between the post-ROSC hyperoxia exposure volume (HEV) and survival among resuscitated OHCA patients. Methods: The JAAM-OHCA Registry was a multicenter prospective observation using the OHCA database obtained from 73 critical care medical centers in Japan, and the study period were between June 2014 and December 2015. In this study, patients who sustained a cardiac arrest in a prehospital setting, for whom resuscitation was attempted, and who were then transported to participating institutions were included. Patients receiving extracorporeal cardiopulmonary resuscitation and who was dead in emergency room were excluded. Arterial blood gases were sampled on hospital arrival, ROSC, ICU admission, and at least 24-hours post-ROSC. In addition to the 4 sampling times mentioned above, arterial blood gases were sampled, as and when required. Hyperoxia was defined as a PaO2 value of &gt;=300 mm Hg. Hyperoxia exposure time (HET) was defined as the time of a sustained PaO2 value of &gt;=300 mmHg, and hyperoxia excess level (HEL) was defined as the highest PaO2 level from hospital arrival to 24-hours post-ROSC. HEV was calculated by HET*HEV/2. Primary outcome was one-month survival. Multivariable logistic regression adjusting for age, sex, initial shockable rhythm, bystander witness, bystander CPR, time from call to hospital arrival, tracheal intubation, and targeted temperature management was performed to assess the association between HEV and survival. Results: A total of 1751 patients were included and 414 (23.6%) had hyperoxia. Among the hyperoxia patients, survival gradually decreased from 50.0% to 44.2% as HEV increased. The adjusted odds ratio of minimum HEV groups or maximum HEV groups for one-month survival compared with non-hyperoxia group was 2.50 (95% confidence interval [CI], 1.33-4.70) and 1.16 (95% CI, 0.62-2.18), respectively. Conclusions: Among resuscitated OHCA patients, excessive amounts of HEV was associated with decreased one-month survival.

Excess oxygen in acute illness: adding fuel to the fire

Oxygen is essential for life and is the third most abundant element in the universe. This abundance is evident in the treatment of acutely ill adults admitted to intensive and progressive care units around the world, in whom excess oxygen is frequently provided for inhalation. The typical motivation for liberal oxygen administration is the prevention of hypoxaemia. By contrast, few health-care providers are concerned about hyperoxaemia—ie, highly elevated arterial oxygen concentrations (arterial oxygen tension >100 mm Hg). As a cardiologist working in cardiac intensive care, I am familiar with the panic often incited by a patient with hypoxaemia. Bedside alarms ring, nurses justifiably fret, and pagers vibrate. However, I have never been called to treat a patient with hyperoxaemia. On the basis of accumulating observational evidence 1 Damiani E Adrario E Girardis M et al. Arterial hyperoxia and mortality in critically ill patients: a systematic review and meta-analysis. Crit Care. 2014; 18: 711 Crossref PubMed Scopus (210) Google Scholar , 2 Helmerhorst HJ Roos-Blom MJ van Westerloo DJ de Jonge E Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015; 43: 1508-1519 Crossref PubMed Scopus (198) Google Scholar , 3 Aggarwal NR Brower RG Hager DN et al. Oxygen exposure resulting in arterial oxygen tensions above the protocol goal was associated with worse clinical outcomes in acute respiratory distress syndrome. Crit Care Med. 2018; 46: 517-524 Crossref PubMed Scopus (55) Google Scholar and a compelling meta-analysis of randomised trials by Derek K Chu and colleagues in The Lancet, 4 Chu DK Kim LH-Y Young PJ et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018; 391: 1693-1705 Summary Full Text Full Text PDF PubMed Scopus (411) Google Scholar perhaps that is about to change. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysisIn acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy. Full-Text PDF

Using an Interactive Computer App to Quantify the Marginal Increase in Oxygen Loading Elicited by Arterial Hyperoxia During ARDS

Using an Interactive Computer App to Quantify the Marginal Increase in Oxygen Loading Elicited by Arterial Hyperoxia During ARDS

Hyperoxia: At what level of SpO2 is a patient safe? A study in mechanically ventilated ICU patients

BackgroundConcerns have been expressed regarding a possible association between arterial hyperoxia and adverse outcomes in critically ill patients. Oxygen status is commonly monitored noninvasively by peripheral saturation monitoring (SpO2). However, the risk of hyperoxia above specific SpO2 levels in critically ill patients is unknown. The purpose of this study was to determine a threshold value of SpO2 above which the prevalence of arterial hyperoxia distinctly increases. MethodsThis is a cross-sectional study in adult mechanically ventilated intensive care patients in a tertiary referral center. In 100 patients, we collected 200 arterial blood gases (ABG) and simultaneously registered SpO2 levels, as well as hemodynamic and ventilation parameters and vasoactive medication. Patients under therapeutic hypothermia were excluded. ResultsThe risk of arterial hyperoxia, defined as PaO2>100mmHg or >125mmHg, was negligible when SpO2 was ≤95% or ≤96%, respectively. The majority (89% and 54%, respectively for PaO2>100mmHg and 125mmHg) of ICU patients with SpO2 of 100% had arterial hyperoxia. The relation between SpO2 and PaO2 was not clearly affected by hemodynamic or other clinical variables (pH, pCO2, body temperature, recent blood transfusion). ConclusionIn critically ill patients, the prevalence of arterial hyperoxia increases when SpO2 is >95%. Above this saturation level, supplemental oxygen should be administered with caution in patients potentially susceptible to adverse effects of hyperoxia.

Hemodynamic effects of short-term hyperoxia after coronary artery bypass grafting

BackgroundAlthough oxygen is generally administered in a liberal manner in the perioperative setting, the effects of oxygen administration on dynamic cardiovascular parameters, filling status and cerebral perfusion have not been fully unraveled. Our aim was to study the acute hemodynamic and microcirculatory changes before, during and after arterial hyperoxia in mechanically ventilated patients after coronary artery bypass grafting (CABG) surgery.MethodsThis was a single-center physiological study in a tertiary care ICU in the Netherlands. Twenty-two patients scheduled for ICU admission after elective CABG were enrolled in the study between September 2014 and September 2015.In the ICU, patients were exposed to a fraction of inspired oxygen (FiO2) of 90% allowing a 15-min wash-in period. Various hemodynamic parameters were measured using direct pressure signals and continuous arterial waveform analysis at three sequential time points: before, during and after hyperoxia.ResultsDuring a 15-min exposure to a fraction of inspired oxygen (FiO2) of 90%, the partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO2) were significantly higher. The systemic resistance increased (P < 0.0001), without altering the heart rate. Stroke volume variation and pulse pressure variation decreased slightly. The cardiac output did not significantly decrease (P = 0.08). Mean systemic filling pressure and arterial critical closing pressure increased (P < 0.01), whereas the percentage of perfused microcirculatory vessels decreased (P < 0.01). Other microcirculatory parameters and cerebral blood flow velocity showed only slight changes.ConclusionsWe found that short-term hyperoxia affects hemodynamics in ICU patients after CABG. This was translated in several changes in central circulatory variables, but had only slight effects on cardiac output, cerebral blood flow and the microcirculation.Clinical trial registration Netherlands Trial Register: NTR5064

Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial

There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO2) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality. This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO2 at 1·0 (hyperoxia) or FiO2 set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422. Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia [n=223] or hyperoxia [n=219]; isotonic [n=224] or hypertonic [n=218]). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio [HR] 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 [85%]) and normoxia groups (165 [76%]; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 [11%] vs 13 [6%]; p=0·06) and atelectasis (26 [12%] vs 13 [6%]; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23). In patients with septic shock, setting FiO2 to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival. The French Ministry of Health.

Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care.

Emerging evidence has shown the potential risks of arterial hyperoxia, but the lack of a clinical definition and methodologic limitations hamper the interpretation and clinical relevance of previous studies. Our purpose was to evaluate previously used and newly constructed metrics of arterial hyperoxia and systematically assess their association with clinical outcomes in different subgroups in the ICU. Observational cohort study. Three large tertiary care ICUs in the Netherlands. A total of 14,441 eligible ICU patients. None. In total, 295,079 arterial blood gas analyses, including the PaO2, between July 2011 and July 2014 were extracted from the patient data management system database. Data from all admissions with more than one PaO2 measurement were supplemented with anonymous demographic and admission and discharge data from the Dutch National Intensive Care Evaluation registry. Mild hyperoxia was defined as PaO2 between 120 and 200 mm Hg; severe hyperoxia as PaO2 greater than 200 mm Hg. Characteristics of existing and newly constructed metrics for arterial hyperoxia were examined, and the associations with hospital mortality (primary outcome), ICU mortality, and ventilator-free days and alive at day 28 were retrospectively analyzed using regression models in different subgroups of patients. Severe hyperoxia was associated with higher mortality rates and fewer ventilator-free days in comparison to both mild hyperoxia and normoxia for all metrics except for the worst PaO2. Adjusted effect estimates for conditional mortality were larger for severe hyperoxia than for mild hyperoxia. This association was found both within and beyond the first 24 hours of admission and was consistent for large subgroups. The largest point estimates were found for the exposure identified by the average PaO2, closely followed by the median PaO2, and these estimates differed substantially between subsets. Time spent in hyperoxia showed a linear and positive relationship with hospital mortality. Our results suggest that we should limit the PaO2 levels of critically ill patients within a safe range, as we do with other physiologic variables. Analytical metrics of arterial hyperoxia should be judiciously considered when interpreting and comparing study results and future studies are needed to validate our findings in a randomized fashion design.

Effect of Hyperoxia on Cerebral Blood Flow Velocity and Regional Oxygen Saturation in Patients Operated on for Severe Traumatic Brain Injury–The Influence of Cerebral Blood Flow Autoregulation

The effect of normobaric hyperoxia on brain oxygenation in the presence or absence of intact autoregulation has not been studied previously in acute traumatic brain injury (TBI). In this prospective clinical investigation of 50 patients operated on for severe TBI, cerebral blood flow (CBF) velocity in the middle cerebral artery was measured using transcranial Doppler. Regional cerebral oxygen saturation using near-infrared spectroscopy at 3 different fractions of inspired oxygen (Fio2) (0.4, 0.6, and 1) was measured in the last 25 of these patients. There was no difference in the hemodynamic and respiratory variables except for Pao2, which increased with increasing Fio2. The CBF velocities and pulsatility indices did not vary at different levels of Fio2 (0.4, 0.6, and 1) both on the operated and on the nonoperated side. The regional cerebral oxygen saturation as evaluated by bifrontal near-infrared spectroscopy sensors increased with increasing Fio2 on the operated (pathologic) side with impaired cerebral autoregulation and not with intact autoregulation. In severe TBI, middle cerebral artery CBF velocity is not affected by hyperoxia in both the pathologic and the normal side. The cerebral oxygen saturation increased with increasing arterial hyperoxia in the operated cerebral hemisphere and remained within baseline range in the nonoperated hemisphere. Impairment in the cerebral autoregulation in the pathologic hemisphere contributes to this luxury oxygenation.