Non-invasive assessment of oxygenation status using the oxygen reserve index in dogs.

BACKGROUND: The oxygen reserve index (ORi) is a real-time, continuous index measured with multi-wavelength pulse CO-oximetry technology. It estimates mild hyperoxemia in humans, which is defined as a partial pressure of oxygen (PaO2) level between 100 and 200 mmHg. The objectives of this study were to assess the correlation between ORi and PaO2, as well as to determine its ability in detecting mild hyperoxemia in dogs. METHODS: This prospective observational study enrolled 37 anaesthetised and mechanically ventilated dogs undergoing elective procedures. Simultaneous measurements of ORi and PaO2 were collected, using a multi-wavelength pulse CO-oximeter with a probe placed on the dog's tongue, and a blood gas analyser, respectively. A mixed-effects model was used to calculate the correlation (r2) between simultaneous measurements of ORi and PaO2. The trending ability of ORi to identify dependable and proportional changes of PaO2 was determined. The diagnostic performances of ORi to detect PaO2 ≥ 150 mmHg and ≥ 190 mmHg were estimated using the area under the receiver operating characteristic curve (AUROC). The effects of perfusion index (PI), haemoglobin (Hb), arterial blood pH and partial pressure of carbon dioxide (PaCO2) on AUROC for PaO2 ≥ 150 mmHg were evaluated. RESULTS: A total of 101 paired measurements of ORi and PaO2 were collected. PaO2 values ranged from 74 to 258 mmHg. A strong positive correlation (r2 = 0.52, p < 0.001) was found between ORi and PaO2. The trending ability ORi was 90.7%, with 92% sensitivity and 89% specificity in detecting decreasing PaO2. An ORi value ≥ 0.53 and ≥ 0.76 indicated a PaO2 ≥ 150 and ≥ 190 mmHg, respectively, with ≥ 82% sensitivity, ≥ 77% specificity and AUROC ≥ 0.75. The AUROC of ORi was not affected by PI, Hb, pH and PaCO2. CONCLUSIONS: In anaesthetised dogs, ORi may detect mild hyperoxaemia, although it does not replace blood gas analysis for measuring the arterial partial pressure of oxygen. ORi monitoring could be used to non-invasively assess oxygenation in dogs receiving supplemental oxygen, limiting excessive hyperoxia.

Dangers of hyperoxia.

Oxygen (O2) toxicity remains a concern, particularly to the lung. This is mainly related to excessive production of reactive oxygen species (ROS). Supplemental O2, i.e. inspiratory O2 concentrations (FIO2) > 0.21 may cause hyperoxaemia (i.e. arterial (a) PO2 > 100 mmHg) and, subsequently, hyperoxia (increased tissue O2 concentration), thereby enhancing ROS formation. Here, we review the pathophysiology of O2 toxicity and the potential harms of supplemental O2 in various ICU conditions. The current evidence base suggests that PaO2 > 300 mmHg (40 kPa) should be avoided, but it remains uncertain whether there is an "optimal level" which may vary for given clinical conditions. Since even moderately supra-physiological PaO2 may be associated with deleterious side effects, it seems advisable at present to titrate O2 to maintain PaO2 within the normal range, avoiding both hypoxaemia and excess hyperoxaemia.

Hyperoxaemia and hypoxaemia are associated with harm in patients with ARDS.

BACKGROUND: Oxygen therapy is routinely administered to mechanically ventilated patients. However, there remains uncertainty about the optimal oxygen titration target in patients with the acute respiratory distress syndrome (ARDS). METHODS: Prospectively identified adult patients meeting the Berlin definition of ARDS between 1st January 2014 and 13th December 2016 were analyzed. Oxygen exposure variables were collected at 6-hourly intervals. The primary exposure was the average time-weighted partial pressure of arterial oxygen (PaO2) calculated over a maximum of 7 days from meeting ARDS criteria. The primary outcome was ICU mortality. Univariable and multivariable logistic regression analyses were performed to assess the impact of exposure variables on clinical outcomes. Results are presented as odds ratio [95% confidence interval]. RESULTS: 202 patients were included in the final analysis. Overall ICU mortality was 31%. The average time-weighted PaO2 during the first 7 days of ARDS was similar between non-survivors and survivors (11.3 kPa [10.2, 12.5] (84.8 mmHg [76.5, 93.8]) vs. 11.9 kPa [10.9, 12.6] (89.3 mmHg [81.8, 94.5]); p = 0.08). In univariable and multivariable analysis, average time-weighted PaO2 demonstrated a U-shaped relationship with ICU mortality. There was a similar relationship identified with hospital mortality. CONCLUSIONS: In patients with ARDS, the predicted probability of both ICU and hospital mortality was lowest when the average time-weighted PaO2 was between 12.5 and 14 kPa (93.8-105.0 mmHg), suggesting this is a reasonable oxygenation target for clinicians to aim for.

Oxygen therapy for critically Ill and post-operative patients.

Nearly all patients receiving treatment in a peri-operative or intensive care setting receive supplemental oxygen therapy. It is biologically plausible that the dose of oxygen used might affect important patient outcomes. Most peri-operative research has focussed on oxygen regimens that target higher than normal blood oxygen levels. Whereas, intensive care research has mostly focussed on conservative oxygen regimens which assiduously avoid exposure to higher than normal blood oxygen levels. While such conservative oxygen therapy is preferred for spontaneously breathing patients with chronic obstructive pulmonary disease, the optimal oxygen regimen in other patient groups is not clear. Some data suggest that conservative oxygen therapy might be preferred for patients with hypoxic ischaemic encephalopathy. However, unless oxygen supplies are constrained, routinely aggressively down-titrating oxygen in either the peri-operative or intensive care setting is not necessary based on available data. Targeting higher than normal levels of oxygen might reduce surgical site infections in the perioperative setting and/or improve outcomes for intensive care patients with sepsis but further research is required and available data are not sufficiently strong to warrant routine implementation of such oxygen strategies.

Restrictive vs liberal oxygen for trauma patients-the TRAUMOX1 pilot randomised clinical trial.

INTRODUCTION: Hyperoxaemia is commonly observed in trauma patients but has been associated with pulmonary complications and mortality in some patient populations. The objectives of this study were to evaluate whether maintenance of normoxia is feasible using a restrictive oxygen strategy in the initial phase after trauma and to evaluate the incidence of 30-day mortality and/or major pulmonary complications. METHODS: Forty-one adult trauma patients admitted to our trauma centre were randomised to 24 hours of restrictive oxygen therapy (no supplemental oxygen if the arterial oxyhaemoglobin saturation (SpO2 ) was at least 94%, n = 21) or liberal oxygen therapy (intubated patients: FiO2 1.0 in the trauma bay, 0.8-1.0 elsewhere; spontaneously breathing patients: 15 L/min via a non-rebreather mask, n = 20). Two blinded anaesthesiologists evaluated major in-hospital pulmonary complications within 30 days. RESULTS: Protocol compliance was high, as the median arterial oxygen tension was significantly lower in the restrictive group (10.8 kPa [9.7-12.0] vs 30.4 kPa [23.7-39.0], P < 0.0001). There were seven episodes of SpO2 below 90% in the restrictive group and one episode in the liberal group. Thirty-day mortality and/or major in-hospital pulmonary complications occurred in 4/20 (20%) in the restrictive group and in 6/18 (33%) in the liberal group: two patients in each group died within 30 days and the incidence of major in-hospital pulmonary complications was 2/20 (10%) in the restrictive group and 4/18 (22%) in the liberal group. CONCLUSION: Maintenance of normoxia using a restrictive oxygen strategy following trauma is feasible. This pilot study serves as the basis for a larger clinical trial.

Oxygen alert wristbands (OxyBand) and controlled oxygen: a pilot study.

Despite the introduction of Oxygen Alert Cards, guidelines and audits, oxygen therapy remains overused in NHS practice, and this may lead to iatrogenic mortality. This pilot study aimed to examine the use of Oxygen Alert Wristbands (OxyBand) designed to alert health professionals who are delivering oxygen to patients to ensure that the oxygen is administered and titrated safely to the appropriate target saturations. Patients at risk of hypercapnic acidosis were asked to wear OxyBands while presenting to paramedics and health professionals in hospitals. Inappropriate prescription of oxygen reduced significantly after the OxyBands were used. A questionnaire-based assessment showed that the clinicians involved had a good understanding of the risks of uncontrolled oxygen. Forty-two patients found the wrist band comfortable to wear, and only two did not. OxyBands may have the potential to improve patient safety over Oxygen Alert Cards.

Oxygen supplementation for critically ill patients-A protocol for a systematic review.

BACKGROUND: In critically ill patients, hypoxaemia is a common clinical manifestation of inadequate gas exchange in the lungs. Supplemental oxygen is therefore given to all critically ill patients. This can result in hyperoxaemia, and some observational studies have identified harms with hyperoxia. The objective of this systematic review is to critically assess the evidence of randomised clinical trials on the effects of higher versus lower inspiratory oxygen fractions or targets of arterial oxygenation in critically ill adult patients. METHODS: We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and Trial Sequential Analysis. To assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Supplemental oxygen administration is widely recommended in international guidelines despite lack of robust evidence of its effectiveness. To our knowledge, no systematic review of randomised clinical trials has investigated the effects of oxygen supplementation in critically ill patients. This systematic review will provide reliable evidence to better inform future trialists and decision-makers on clinical practice on supplemental oxygen administration in critically ill patients.

Improving manual oxygen titration in preterm infants by training and guideline implementation.

To study oxygen saturation (SpO2) targeting before and after training and guideline implementation of manual oxygen titration, two cohorts of preterm infants <30 weeks of gestation needing respiratory support and oxygen therapy were compared. The percentage of the time spent with SpO2 within the target range (85-95%) was calculated (%SpO2-wtr). SpO2 was collected every minute when oxygen is >21%. ABCs where oxygen therapy was given were identified and analyzed. After training and guideline implementation the %SpO2-wtr increased (median interquartile range (IQR)) 48.0 (19.6-63.9) % vs 61.9 (48.5-72.3) %; p < 0.005, with a decrease in the %SpO2 > 95% (44.0 (27.8-66.2) % vs 30.8 (22.6-44.5) %; p < 0.05). There was no effect on the %SpO2 < 85% (5.9 (2.8-7.9) % vs 6.2 (2.5-8) %; ns) and %SpO2 < 80% (1.9 (1.0-3.0) % vs 1.7 (0.8-2.6) %; ns). In total, 186 ABCs with oxygen therapy before and 168 ABCs after training and guideline implementation occurred. The duration of SpO2 < 80% reduced (2 (1-2) vs 1 (1-2) minutes; p < 0.05), the occurrence of SpO2 > 95% did not decrease (73% vs 64%; ns) but lasted shorter (2 (0-7) vs 1 (1-3) minute; p < 0.004). CONCLUSION: Training and guideline implementation in manual oxygen titration improved SpO2 targeting in preterm infants with more time spent within the target range and less frequent hyperoxaemia. The durations of hypoxaemia and hyperoxaemia during ABCs were shorter. What is Known: • Oxygen saturation targeting in preterm infants can be challenging and the compliance is low when oxygen is titrated manually. • Hyperoxaemia often occurs after oxygen therapy for oxygen desaturation during apnoeas. What is New: • Training and implementing guidelines improved oxygen saturation targeting and reduced hyperoxaemia. • Training and implementing guidelines improved manual oxygen titration during ABC.

Compliance in oxygen saturation targeting in preterm infants: a systematic review.

During oxygen therapy in preterm infants, targeting oxygen saturation is important for avoiding hypoxaemia and hyperoxaemia, but this can be very difficult and challenging for neonatal nurses. We systematically reviewed the qualitative and quantitative studies investigating the compliance in targeting oxygen saturation in preterm infants and factors that influence this compliance. We searched PubMed, Embase, Web of Science, Cochrane, CINAHL and ScienceDirect from 2000 to January 2015. Sixteen studies were selected, which involved a total of 2935 nurses and 574 infants. The studies varied in methodology, and we have therefore used a narrative account to describe the data. The main finding is that there is a low compliance in oxygen targeting; the upper alarm limits are inappropriately set, and maintaining the saturation (SpO2) below the upper limit presented particular difficulties. Although there is little data available, the studies indicate that training, titration protocols and decreasing workload could improve awareness and compliance. Automated oxygen regulations have been shown to increase the time that SpO2 is within the target range. CONCLUSION: The compliance in targeting oxygen during oxygen therapy in preterm infants is low, especially in maintaining the SpO2 below the upper limit. WHAT IS KNOWN: • The use of oxygen in preterm infants is vital, but the optimal strategyremains controversial. • Targeting SpO2 during oxygen therapy in preterm infants has beenshown to reduce mortality and morbidity. WHAT IS NEW: • Review of the literature showed that the compliance in targeting SpO2and alarm settings is low. • Creating awareness of risks of oxygen therapy and benefits in targeting,decreasing nurse/patient ratio and automated oxygen therapy couldincrease compliance.

Automated control of inspired oxygen in ventilated preterm infants: crossover physiological study.

AIM: To evaluate the efficacy of automated control of the fraction of inspired oxygen (FiO2 ) in comparison with manual FiO2 control in maintaining target pulse oxygen saturation (SpO2 ) range. METHODS: Crossover physiological study involving preterm infants requiring mechanical ventilation and supplemental oxygen. Each infant was studied for two consecutive 12 hours in a random sequence. Outcome measures included the proportion of time with SpO2 within and outside the target range of 90-95%, extreme hypoxaemia (< 80%) and hyperoxaemia (≥ 98%). RESULTS: Complete data set was available in 27 infants. The percentage of time (median, IQR) within the target range was higher during automated control 72.8 (58.8-82.6) compared to manual control 59.6 (49.3-73.3), p = 0.031. Corresponding reduction in per cent time below the target range was 18.1 (12.7-23.6) versus 25.9 (17.8-30.7), p = 0.028, and above the target range 4.8 (3-16) versus 10.1 (6.4-22.5), p = 0.026. Median (IQR) per cent time spent with severe hypoxaemia (SpO2 < 80%) and severe hyperoxaemia (SpO2 ≥ 98%) was 1.3 (0.1-2.9) versus 3.2 (1.4-6.1), p = 0.022 and 0.08 (0.05-0.36) versus 1.7 (0.7-6.8), p = 0.001, respectively. Median number of manual adjustments of FiO2 per 12 hour was 0 and 63, respectively. CONCLUSION: Automated control of FiO2 significantly improved compliance of oxygen saturation targeting and significantly reduced exposure to hypoxaemia as well as hyperoxaemia.

The medical use of oxygen: a time for critical reappraisal.

Oxygen treatment has been a cornerstone of acute medical care for numerous pathological states. Initially, this was supported by the assumed need to avoid hypoxaemia and tissue hypoxia. Most acute treatment algorithms, therefore, recommended the liberal use of a high fraction of inspired oxygen, often without first confirming the presence of a hypoxic insult. However, recent physiological research has underlined the vasoconstrictor effects of hyperoxia on normal vasculature and, consequently, the risk of significant blood flow reduction to the at-risk tissue. Positive effects may be claimed simply by relief of an assumed local tissue hypoxia, such as in acute cardiovascular disease, brain ischaemia due to, for example, stroke or shock or carbon monoxide intoxication. However, in most situations, a generalized hypoxia is not the problem and a risk of negative hyperoxaemia-induced local vasoconstriction effects may instead be the reality. In preclinical studies, many important positive anti-inflammatory effects of both normobaric and hyperbaric oxygen have been repeatedly shown, often as surrogate end-points such as increases in gluthatione levels, reduced lipid peroxidation and neutrophil activation thus modifying ischaemia-reperfusion injury and also causing anti-apoptotic effects. However, in parallel, toxic effects of oxygen are also well known, including induced mucosal inflammation, pneumonitis and retrolental fibroplasia. Examining the available 'strong' clinical evidence, such as usually claimed for randomized controlled trials, few positive studies stand up to scrutiny and a number of trials have shown no effect or even been terminated early due to worse outcomes in the oxygen treatment arm. Recently, this has led to less aggressive approaches, even to not providing any supplemental oxygen, in several acute care settings, such as resuscitation of asphyxiated newborns, during acute myocardial infarction or after stroke or cardiac arrest. The safety of more advanced attempts to deliver increased oxygen levels to hypoxic or ischaemic tissues, such as with hyperbaric oxygen therapy, is therefore also being questioned. Here, we provide an overview of the present knowledge of the physiological effects of oxygen in relation to its therapeutic potential for different medical conditions, as well as considering the potential for harm. We conclude that the medical use of oxygen needs to be further examined in search of solid evidence of benefit in many of the current clinical settings in which it is routinely used.

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with sepsis in the intensive care unit (Mega-ROX Sepsis).

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial. Design setting and participants: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of patients discharged home. Results and conclusions: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias.

Does closed-loop automated oxygen control reduce the duration of supplementary oxygen treatment and the amount of time spent in hyperoxia? A randomised controlled trial in ventilated infants born at or near term.

BACKGROUND: Ventilated infants frequently require supplemental oxygen, but its use should be monitored carefully due to associated complications. The achievement of oxygen saturation (SpO2) targets can be challenging as neonates experience frequent fluctuations of their oxygen levels that further increase the risk of complications. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets, reduce hyperoxaemic episodes and facilitate weaning of the inspired oxygen concentration in ventilated infants born at or near term. This study investigates whether CLAC compared with manual oxygen control reduces the time spent in hyperoxia and the overall duration of supplemental oxygen treatment in ventilated infants born at or above 34 weeks gestation. METHODS: This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at or above 34 weeks of gestation and within 24 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment till successful extubation. The primary outcome is the percentage of time spent in hyperoxia (SpO2 > 96%). The secondary outcomes are the overall duration of supplementary oxygen treatment, the percentage of time spent with an oxygen requirement above thirty per cent, the number of days on mechanical ventilation and the length of neonatal unit stay. The study is performed following informed parental consent and was approved by the West Midlands-Edgbaston Research Ethics Committee (Protocol version 1.2, 10/11/2022). DISCUSSION: This trial will investigate the effect of CLAC on the overall duration of oxygen therapy and the time spent in hyperoxia. These are important clinical outcomes as hyperoxic injury is related to oxidative stress that can adversely affect multiple organ systems. TRIAL REGISTRATION: ClinicalTrials.Gov NCT05657795. Registered on 12/12/2022.

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains).

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial. Design setting and participants: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home. Results and conclusions: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

Hyperoxemia Is Associated With Mortality in Critically Ill Children.

Multiple studies among adults have suggested a non-linear relationship between arterial partial pressure of oxygen (PaO2) and clinical outcomes. Meta-analyses in this population suggest that high levels of supplemental oxygen resulting in hyperoxia are associated with mortality. This mini-review focuses on the non-neonatal pediatric literature examining the relationship between PaO2 and mortality. While only one pilot pediatric randomized-controlled trials exists, over the past decade, there have been at least eleven observational studies examining the relationship between PaO2 values and mortality in critically ill children. These analyses of mixed-case pediatric ICU populations have generally reported a parabolic ("u-shaped") relationship between PaO2 and mortality, similar to that seen in the adult literature. However, the estimates of the point at which hyperoxemia becomes deleterious have varied widely (300-550 mmHg). Where attempted, this effect has been robust to analyses restricted to the first PaO2 value obtained, those obtained within 24 h of admission, anytime during admission, and the number of hyperoxemic blood gases over time. These findings have also been noted when using various methods of risk-adjustment (accounting for severity of illness scores or complex chronic conditions). Similar relationships were found in the majority of studies restricted to patients undergoing care after cardiac arrest. Taken together, the majority of the literature suggests that there is a robust parabolic relationship between PaO2 and risk-adjusted pediatric ICU mortality, but that the exact threshold at which hyperoxemia becomes deleterious is unclear, and likely beyond the typical target value for most clinical indications. Findings suggest that clinicians should remain judicious and thoughtful in the use of supplemental oxygen therapy in critically ill children.

Target arterial PO2 according to the underlying pathology: a mini-review of the available data in mechanically ventilated patients.

There is an ongoing discussion whether hyperoxia, i.e. ventilation with high inspiratory O2 concentrations (FIO2), and the consecutive hyperoxaemia, i.e. supraphysiological arterial O2 tensions (PaO2), have a place during the acute management of circulatory shock. This concept is based on experimental evidence that hyperoxaemia may contribute to the compensation of the imbalance between O2 supply and requirements. However, despite still being common practice, its use is limited due to possible oxygen toxicity resulting from the increased formation of reactive oxygen species (ROS) limits, especially under conditions of ischaemia/reperfusion. Several studies have reported that there is a U-shaped relation between PaO2 and mortality/morbidity in ICU patients. Interestingly, these mostly retrospective studies found that the lowest mortality coincided with PaO2 ~ 150 mmHg during the first 24 h of ICU stay, i.e. supraphysiological PaO2 levels. Most of the recent large-scale retrospective analyses studied general ICU populations, but there are major differences according to the underlying pathology studied as well as whether medical or surgical patients are concerned. Therefore, as far as possible from the data reported, we focus on the need of mechanical ventilation as well as the distinction between the absence or presence of circulatory shock. There seems to be no ideal target PaO2 except for avoiding prolonged exposure (> 24 h) to either hypoxaemia (PaO2 < 55-60 mmHg) or supraphysiological (PaO2 > 100 mmHg). Moreover, the need for mechanical ventilation, absence or presence of circulatory shock and/or the aetiology of tissue dysoxia, i.e. whether it is mainly due to impaired macro- and/or microcirculatory O2 transport and/or disturbed cellular O2 utilization, may determine whether any degree of hyperoxaemia causes deleterious side effects.

Frequency of hyperoxaemia during and after major surgery.

The oxygen concentration (FiO2) and arterial oxygen tension (PaO2) delivered in patients undergoing major surgery is poorly understood. We aimed to assess current practice with regard to the delivered FiO2 and the resulting PaO2 in patients undergoing major surgery. We performed a retrospective cohort study in a tertiary hospital. Data were collected prospectively as part of a larger randomised controlled trial but were analysed retrospectively. Patients were included if receiving controlled mandatory ventilation and arterial line monitoring. Anaesthetists determined the FiO2 and the oxygenation saturation (SpO2) targets. An arterial blood gas (ABG) was obtained 15-20 minutes after induction of anaesthesia, immediately before the emergence phase of anaesthesia and 15 minutes after arrival in the post-anaesthesia care unit (PACU). We defined hyperoxaemia as a PaO2 of >150 mmHg and included a further threshold of PaO2 >200 mmHg. We studied 373 patients. The median (interquartile range (IQR)) lowest intraoperative FiO2 and SpO2 values were 0.45 (IQR 0.4-0.5) and 97% (IQR 96-98%), respectively, with a median PaO2 on the first and second ABG of 237 mmHg (IQR 171-291 mmHg) and 189 mmHg (IQR 145-239 mmHg), respectively. In the PACU, the median lowest oxygen flow rate was 6 L/min (IQR 3-6 L/min), and the PaO2 was 158 mmHg (IQR 120-192 mmHg). Hyperoxaemia occurred in 82%, 73% and 54% of participants on the first and second intraoperative and postoperative ABGs respectively. A PaO2 of >200 mmHg occurred in 64%, 41% and 21% of these blood gases, respectively. In an Australian tertiary hospital, a liberal approach to FiO2 and PaO2 was most common and resulted in a high incidence of perioperative hyperoxaemia.

Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX).

PURPOSE: Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. METHODS: We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. RESULTS: Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO2 ≥ 97% (23.5 h [interquartile range (IQR) 8-70] vs. 47 h [IQR 11-93], absolute difference, 23 h; 95% CI 8-38), and more time receiving an FiO2 of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1-79] vs. 0 h [IQR 0-10], absolute difference, 20 h; 95% CI 14-26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI - 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy. CONCLUSIONS: Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group. CLINICAL TRIALS REGISTRY: ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594.

Conservative or liberal oxygen therapy in adults after cardiac arrest: An individual-level patient data meta-analysis of randomised controlled trials.

AIM: The effect of conservative versus liberal oxygen therapy on mortality rates in post cardiac arrest patients is uncertain. METHODS: We undertook an individual patient data meta-analysis of patients randomised in clinical trials to conservative or liberal oxygen therapy after a cardiac arrest. The primary end point was mortality at last follow-up. RESULTS: Individual level patient data were obtained from seven randomised clinical trials with a total of 429 trial participants included. Four trials enrolled patients in the pre-hospital period. Of these, two provided protocol-directed oxygen therapy for 60 min, one provided it until the patient was handed over to the emergency department staff, and one provided it for a total of 72 h or until the patient was extubated. Three trials enrolled patients after intensive care unit (ICU) admission and generally continued protocolised oxygen therapy for a longer period, often until ICU discharge. A total of 90 of 221 patients (40.7%) assigned to conservative oxygen therapy and 103 of 206 patients (50%) assigned to liberal oxygen therapy had died by this last point of follow-up; absolute difference; odds ratio (OR) adjusted for study only; 0.67; 95% CI 0.45 to 0.99; P = 0.045; adjusted OR, 0.58; 95% CI 0.35 to 0.96; P = 0.04. CONCLUSION: Conservative oxygen therapy was associated with a statistically significant reduction in mortality at last follow-up compared to liberal oxygen therapy but the certainty of available evidence was low or very low due to bias, imprecision, and indirectness. PROSPERO REGISTRATION NUMBER: CRD42019138931.

Most impactful predictors for hyperoxaemia in exacerbation of chronic obstructive pulmonary disease managed by Emergency Medical Services and Emergency Department.

INTRODUCTION: Hyperoxemia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) leads to adverse outcomes. It remains prevalent in the pre-hospital Emergency Medical Services (EMS) and Emergency Department (ED). OBJECTIVE: To determine the key predictors for hyperoxemia in AECOPD in EMS and ED. METHODS: This was a prospective observational study of AECOPD patients in EMS and two EDs. Hyperoxemia was defined as PaO2 > 65 mm Hg (corresponds to SpO2 > 92%). We determined apriori candidate factors in Patient, Organization and Staff domains. Primary outcomes were the key predictors for hyperoxemia. Secondary outcomes were in-hospital mortality and mechanical ventilation rates in hyperoxemic versus non-hyperoxemic groups. We generated a logistic regression model for each domain. We reported the adjusted odds ratios (AORs), 95% CIs and p values. We selected the output factors using AOR ≥2.0 and ≥2.5 for modifiable and non-modifiable factors, respectively. These selected factors were fed into a final model with eventual factors selected based on: threshold AORs as stated above and/or 95% CIs including these AORs. RESULTS: Three hundred and twenty-six patients were analysed; 60.7% had hyperoxemia. We found three eventual modifiable factors; first, ED SpO2 > 95% [AOR 2.62 (95% CIs: 1.61-4.33); P < 0.001], EMS non-rebreathing mask [AOR 2.01 (95% CIs: 1.06-3.97); P = 0.04]; and ED nasal cannula [AOR 1.69 (95% CIs: 1.05-2.72); P = 0.03]. Secondary outcomes did not differ between groups. CONCLUSION: We identified three key modifiable predictors. We intend to conduct an interventional study using them to reduce hyperoxemia rate in AECOPD.