Oxygen therapy is a crucial treatment method for maintaining vital signs in patients in the intensive care unit. However, several controversial issues have emerged regarding its clinical application. This article analyzes current research trends in oxygen therapy in the intensive care unit and provides guidance and recommendations. Relevant literature was retrieved from the Web of Science Core Collection, and keyword co-occurrence and highly cited literature hotspot analyses were conducted using VOSviewer 1.6.19 software. The key topics related to oxygen therapy in the intensive care unit primarily focus on four areas: oxygen therapy and mechanical ventilation in the intensive care unit, extracorporeal membrane oxygenation therapy for coronavirus disease 2019 and its role in reducing mortality, research on hypoxia and oxygen saturation monitoring, and oxygen inhalation therapy in the intensive care unit. The analysis of highly cited literature indicates that the main research hotspots regarding oxygen therapy used in the intensive care unit focus primarily on conservative oxygen therapy, high-flow nasal oxygen therapy, comparisons of high- and low-oxygenation strategies, and research on hyperbaric oxygen therapy. First, the potential of conservative oxygen therapy to reduce mortality rates in the intensive care unit has attracted considerable attention; however, further clinical studies are needed to validate its optimal parameters and suitable patient populations. Second, high-flow nasal oxygen therapy has been shown to be effective in alleviating respiratory distress and reducing the need for intubation. This therapy can deliver oxygen flows of up to 60 L/min, effectively improving respiratory distress and decreasing intubation demands. In patients subjected to high-risk extubation, the combination of high-flow nasal oxygen therapy and noninvasive ventilation significantly lowers the rate of reintubation, making the combined approach one of the best strategies to prevent respiratory failure after extubation in the intensive care unit. Third, there are differences between lower and higher oxygenation strategies regarding their effects on patient mortality, long-term outcomes, and clinician preferences; however, there is currently no clear evidence indicating which strategy is superior. Clinicians' preferences regarding various oxygenation targets may impact the design of future studies. Finally, hyperbaric oxygen therapy is recognized as an effective supportive treatment for various critical conditions and has significant application value in acute severe traumatic brain injury, cerebral resuscitation, and cardiopulmonary resuscitation. Currently, researchers are continually exploring the latest oxygen therapies in the intensive care unit. Several randomized controlled clinical trials investigating automated oxygen control, novel high-flow nasal oxygen therapy, and combined oxygen therapy are underway. The results of these trials should be closely observed. Overall, this article provides a systematic review and valuable reference for the scientific and rational application of oxygen therapy in the intensive care unit. Future research should focus on verifying the optimal parameters of conservative oxygen therapy, assessing oxygen needs in different patient populations, evaluating the long-term effects of oxygen treatment, and developing novel oxygen therapy technologies and devices.

Oxygen supplementation is widely used to enhance oxygen delivery and to treat or prevent hypoxia; however, it requires careful management to avoid the harmful effects of excessive oxygen exposure. Both hyperoxia (inspiratory oxygen fraction exceeding 0.21) and hyperoxemia (arterial oxygen tension oxygen partial pressure [PaO2] > 100 mmHg) can contribute to lung injury, promote systemic vasoconstriction, and increase the production of reactive oxygen species, which can impair macromolecular and cellular functions. Conversely, in certain situations, hyperoxemia may provide benefits, such as hemodynamic stabilization in hyperdynamic shock, immunomodulation, and bactericidal effects. The literature presents conflicting evidence regarding the impact of different oxygen targets (i.e., PaO2 and/or peripheral saturation of oxygen [SpO2]) on both short- and long-term outcomes in patients with acute critical conditions, such as acute respiratory distress syndrome, sepsis, cardiac arrest, and acute central nervous system injuries. These discrepancies may stem from the small differences between the oxygenation targets used in randomized trials, the physiological limitations of PaO2 and SpO2 targets, which reflect blood oxygen content rather than oxygen delivery, the lack of measurements of microvascular function or oxygen delivery, and the heterogeneity in treatment response. Furthermore, advanced analytical methods (e.g., machine learning) are emerging as promising tools to implement population enrichment strategies. By refining patient sub-group identification, these approaches can significantly optimize precision medicine, enabling more personalized oxygen therapy tailored to individual patient characteristics.

Supplemental oxygen is commonly used to treat newborns with respiratory disorders. It has been explored that hyperoxia increases oxidative stress, and have the potential adverse effects on developing organs. Mitochondrial biogenesis plays a crucial role in maintaining mitochondrial homeostasis, and resveratrol (Res) has its unique advantage in promoting mitochondrial biogenesis. However, the molecular mechanisms controlling mitochondrial biogenesis in hyperoxia-induced kidney injury remain unclear. The aim of this study was to evaluate the protective effect and it's mechanisms of Res on hyperoxia-induced kidney injury in neonatal rats.

Sprague-Dawley rats were housed in normoxia or hyperoxia (85% O2) and randomized to receive saline, dimethyl sulfoxide, and Res administered intraperitoneally from postnatal days 1∼14(All medicine is scheduled to be given at six o'clock every afternoon). Split the rats into six groups, and on postnatal days 1, 7 and 14, kidney samples were acquired for HE staining and PAS staining to assess kidney development, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to detect apoptosis, and real-time quantitative polymerase chain reaction and immunoblotting to detect the expression levels of SIRT1, PGC-1α, NRF1, NRF2 and TFAM.

Hyperoxia induced tubular and glomerular injury, increased renal tissue apoptosis, decreased Silent information regulator 2-related enzyme 1(SIRT1), Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), nuclear respiratory factor 1(Nrf1), Nrf2, mitochondrial transcription factor A (TFAM) protein levels in the kidney, and inhibited TFAM mRNA expression in mitochondria, diminished ND1 copy number and ND4/ND1 ratio. In contrast, Res reduced renal injury and attenuated renal tissue apoptosis in neonatal rats and increased the levels of the corresponding indexes.

Res protects neonatal rats from hyperoxia-induced kidney injury by promoting mitochondrial biogenesis, possibly in part through activation of the SIRT1/PGC-1α signaling pathway.

Neurological morbidity and mortality remain high in children requiring extracorporeal membrane oxygenation (ECMO). Although the severity of illness at the time of ECMO initiation and the nature of the underlying disease are strongly linked to the development of acute brain injury, several important factors are associated with neurological complications during ECMO support. Many of these factors, particularly those encountered during the early phase of ECMO initiation (first 24 hours), may be modifiable and represent potential targets for interventional studies aiming for improvement of neurological outcomes in pediatric ECMO patients. In this review from the European Extracorporeal Life Support Organization (EuroELSO) Working Group on Neurologic Monitoring and Outcome, we aim to summarize current knowledge on modifiable factors associated with brain injury during ECMO and their potential impact on outcome.

Whether low peripheral oxygen saturation (SpO2) directed oxygen therapy is associated with lower mortality in critically ill patients needs further exploration. Adult critically ill patients from 11 intensive care units in China were screened. Participants were randomly assigned to the low SpO2 (90%-95%) group or the high SpO2 (≥96%) -group. The primary outcome was 28-day all-cause mortality. The secondary outcomes were hours free from ventilators and from renal replacement therapy (RRT) within 14 days. Note that 857 patients in the low SpO2 group and 849 in the high SpO2 group were included. In the low SpO2 group versus the high SpO2 group, the time-weighted average of the fraction of inspired oxygen (FiO2) was significantly lower (33.5 ± 9.7% vs. 39.6 ± 9.3%, p < 0.001), and so was the time-weighted average of SpO2 (95.9 ± 1.8% vs. 98.0 ± 1.9%, p < 0.001). Within 28 days after randomization, 172 (20.1%) in the low SpO2 group and 193 (22.7%) in the high SpO2 group died (p = 0.180). Ventilator-free time and RRT-free time were not significantly different within 14 days. In critically ill patients, low SpO2directed oxygen therapy did not decrease 28-day mortality, 14-day ventilator-free time, or 14-day RRT-free time.

Oxygen therapy is ubiquitous in critical illness but oxygenation targets to guide therapy remain controversial despite several large randomised controlled trials (RCTs). Findings from RCTs evaluating different approaches to oxygen therapy in critical illness present a confused picture for several reasons. Differences in both oxygen target measures (e.g. oxygen saturation or partial pressure) and the numerical thresholds used to define lower and higher targets complicate comparisons between trials. The duration of and adherence to oxygenation targets is also variable with consequent substantial variation in both the dose and the dose separation. Finally, heterogeneity of treatment effects (HTE) may also be a significant factor. HTE is defined as non-random variation in the benefit or harm of a treatment, in which the variation is associated with or attributable to patient characteristics. This narrative review aims to make the case that such heterogeneity is likely in relation to oxygen therapy for critically ill patients and that this has significant implications for the design and interpretation of trials of oxygen therapy in this context. HTE for oxygen therapy amongst critically ill patients may explain the contrasting results from different clinical trials of oxygen therapy. Individualised oxygen therapy may overcome this challenge, and future studies should incorporate ways to evaluate this approach.

The current technology of high-velocity nasal insufflation (HVNI) can be equipped with an oxygen assist module (OAM) that continuously monitors and automatically adjusts the inspired oxygen fraction (FiO2) to maintain oxygen saturation by pulse oximetry (SpO2) within the target range. This study aimed to evaluate the use of HVNI with OAM compared to conventional HVNI in patients after endotracheal extubation.

This randomized crossover study enrolled 16 mechanically ventilated subjects who were ready to wean. The subjects were randomized to protocol A (HVNI with OAM for 60 min, followed by conventional HVNI for another 60 min) or protocol B (conventional HVNI for 60 min, followed by HVNI with OAM for another 60 min) after extubation. In HVNI with OAM, the target SpO2 was set at 94% with a range of 92-98%, temperature of 37 °C and flow rate of 40 L/min. In the conventional HVNI group, the attending physician adjusted the FiO2 to maintain an SpO2 of at least 94%. The primary outcome was the time in the SpO2 range between the two groups. The secondary outcomes included FiO2, transcutaneous carbon dioxide pressure (PtcCO2), respiratory rate oxygenation (ROX) index, and hemodynamic variables.

HVNI with OAM significantly maintained SpO2 within the target range compared to conventional HVNI [99.4% (97.4-99.8%) vs. 5.3% (1.5-68.1%); P=0.001]. The use of FiO2 was significantly lower and the ROX index was significantly higher at the end of the study in the HVNI with OAM group than in the conventional HVNI group [0.22 (0.21-0.25) vs. 0.40 (0.40-0.40); P=0.001 and 22.26 (15.94-26.46) vs. 13.01 (10.72-14.66); P=0.001, respectively]. No differences in breathing frequency, PtcCO2 or hemodynamic variables were observed between the two groups.

HVNI with OAM can maintain SpO2 within the target range while using a lower FiO2 and providing a higher ROX index than conventional HVNI in patients after extubation.

This study was registered in the Thai Clinical Trial Registry (TCTR20220801007) before the inclusion of the first patient.

Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support.

These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels.

We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts.

The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Although pulse oximetry technology, which is considered the standard of care to ensure optimum oxygenation, is indispensable in clinical practice, especially in the detection of hypoxemia, it has some limitations in the detection of hyperoxemia. Oxygen Reserve Index can provide clinicians with a crucial pathway in detecting and preventing hyperoxia, noninvasively. Our aim in this study is to determine the hyperoxia detection ability of ORi and to investigate the effectiveness of ORi and SpO2-guided FiO2 titration in preventing hyperoxia.

This prospective randomized study was conducted in the operating theater of Health Sciences University İzmir Tepecik Training and Research Hospital from September 1, 2020, to December 1, 2022. Patients undergoing major abdominal surgery were divided into two groups: the control group and the SpO2 + ORi group. FiO2 titration was performed in the SpO2 + ORi group to maintain the ORi between 0.00 and 95% < SpO2 ≤ 98%. Parameters were recorded before induction, 10 min after intubation, and every hour during the operation.

A positive linear relationship of 75.8% (r = 0.758) was found between PaO2 and ORi in the ORi + SpO2 group (p < 0.001). Moderate hyperoxemia was observed in 31.6% of patients in the control group, while it was not observed in the ORi + SpO2 group at the 3rd hour. PaO2 values decreased significantly over time in the ORi + SpO2 group with FiO2 titration (p < 0.001).

The combined use of SpO2 and ORi has been demonstrated to successfully guide FiO2 titration for optimal oxygenation and reduce hyperoxemia.

The effects of oxygenation targets (partial pressure of arterial oxygen [Pa o2 ], arterial oxygen saturation [Sa o2 ]/peripheral oxygen saturation [Sp o2 ], or inspiratory oxygen concentration [Fi o2 ] on clinical outcomes in critically ill patients remains controversial. We reviewed the existing literature to assess the effects of lower and higher oxygenation targets on the mortality rates of critically ill intensive care unit (ICU) patients.

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched from their dates of inception to December 31, 2022, for randomized controlled trials (RCTs) comparing lower and higher oxygenation targets for critically ill patients ≥18 years of age undergoing mechanical ventilation, nasal cannula, oxygen mask, or high-flow oxygen therapy in the ICU. Data extraction was conducted independently, and RoB 2.0 software was used to evaluate the quality of each RCT. A random-effects model was used for the meta-analysis to calculate the relative risk (RR). We used the I 2 statistic as a measure of statistical heterogeneity. Certainty of evidence was assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.

We included 12 studies with a total of 7416 patients participating in RCTs. Oxygenation targets were extremely heterogeneous between studies. The meta-analysis found no differences in mortality between lower and higher oxygenation targets for critically ill ICU patients (relative risk [RR], 1.00; 95% confidence interval [CI], 0.93-1.09; moderate certainty). The incidence of serious adverse events (RR, 0.93; 95% CI, 0.85-1.00; high certainty), mechanical ventilation-free days through day 28 (mean difference [MD], -0.05; 95%CI, -1.23 to 1.13; low certainty), the number of patients requiring renal replacement therapy (RRT) (RR, 0.96; 95% CI, 0.84-1.10; low certainty), and ICU length of stay (MD, 1.05; 95% CI, -0.04 to 2.13; very low certainty) also did not differ among patients with lower or higher oxygenation targets.

Critically ill ICU patients ≥18 years of age managed with lower and higher oxygenation targets did not differ in terms of mortality, RRT need, mechanical ventilation-free days through day 28, or ICU length of stay. However, due to considerable heterogeneity between specific targets in individual studies, no conclusion can be drawn regarding the effect of oxygenation targets on ICU outcomes.

The aim of this study is the evaluation of a closed-loop oxygen control system in pediatric patients undergoing invasive mechanical ventilation (IMV).

Cross-over, multicenter, randomized, single-blind clinical trial. Patients between the ages of 1 month and 18 years who were undergoing IMV therapy for acute hypoxemic respiratory failure (AHRF) were assigned at random to either begin with a 2-hour period of closed-loop oxygen control or manual oxygen titrations. By using closed-loop oxygen control, the patients' SpO2 levels were maintained within a predetermined target range by the automated adjustment of the FiO2. During the manual oxygen titration phase of the trial, healthcare professionals at the bedside made manual changes to the FiO2, while maintaining the same target range for SpO2. Following either period, the patient transitioned to the alternative therapy. The outcomes were the percentage of time spent in predefined SpO2 ranges ±2% (primary), FiO2, total oxygen use, and the number of manual adjustments.

The median age of included 33 patients was 17 (13-55.5) months. In contrast to manual oxygen titrations, patients spent a greater proportion of time within a predefined optimal SpO2 range when the closed-loop oxygen controller was enabled (95.7% [IQR 92.1-100%] vs. 65.6% [IQR 41.6-82.5%]), mean difference 33.4% [95%-CI 24.5-42%]; P < 0.001). Median FiO2 was lower (32.1% [IQR 23.9-54.1%] vs. 40.6% [IQR 31.1-62.8%]; P < 0.001) similar to total oxygen use (19.8 L/h [IQR 4.6-64.8] vs. 39.4 L/h [IQR 16.8-79]; P < 0.001); however, median SpO2/FiO2 was higher (329.4 [IQR 180-411.1] vs. 246.7 [IQR 151.1-320.5]; P < 0.001) with closed-loop oxygen control. With closed-loop oxygen control, the median number of manual adjustments reduced (0.0 [IQR 0.0-0.0] vs. 1 [IQR 0.0-2.2]; P < 0.001).

Closed-loop oxygen control enhances oxygen therapy in pediatric patients undergoing IMV for AHRF, potentially leading to more efficient utilization of oxygen. This technology also decreases the necessity for manual adjustments, which could reduce the workloads of healthcare providers.

This research has been submitted to ClinicalTrials.gov (NCT05714527).

Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support.

These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels.

We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts.

The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Circulatory shock, defined as decreased tissue perfusion, leading to inadequate oxygen delivery to meet cellular metabolic demands, remains a common condition with high morbidity and mortality. Rapid restitution and restoration of adequate tissue perfusion are the main treatment goals. To achieve this, current hemodynamic strategies focus on adjusting global physiological variables such as cardiac output (CO), hemoglobin (Hb) concentration, and arterial hemoglobin oxygen saturation (SaO2). However, it remains a challenge to identify optimal targets for these global variables that best support microcirculatory function. Weighting up the risks and benefits is especially difficult for choosing the amount of oxygen supplementation in critically ill patients. This review assesses the physiological basis for oxygen delivery to the tissue and provides an overview of the relevant literature to emphasize the importance of considering risks and benefits and support decision making at the bedside.

Oxygen must reach the tissue to enable oxidative phosphorylation. The human body timely detects hypoxia via different mechanisms aiming to maintain adequate tissue oxygenation. In contrast to the pulmonary circulation, where the main response to hypoxia is arteriolar vasoconstriction, the regulatory mechanisms of the systemic circulation aim to optimize oxygen availability in the tissues. This is achieved by increasing the capillary density in the microcirculation and the capillary hematocrit thereby increasing the capacity of oxygen diffusion from the red blood cells to the tissue. Hyperoxia, on the other hand, is associated with oxygen radical production, promoting cell death.

Clinical trials in critically ill patients have primarily focused on comparing macrocirculatory endpoints and outcomes based on stroke volume and oxygenation targets. Some earlier studies have indicated potential benefits of conservative oxygenation. Recent trials show contradictory results regarding mortality, organ dysfunction, and ventilatory-free days. Empirical studies comparing various targets for SaO2, or partial pressure of oxygen indicate a U-shaped curve balancing positive and negative effects of oxygen supplementation.

To optimize risk-benefit ratio of resuscitation measures in critically ill patients with circulatory shock in addition to individual targets for CO and Hb concentration, a primary aim should be to restore tissue perfusion and avoid hyperoxia. In the future, an individualized approach with microcirculatory targets will become increasingly relevant. Further studies are needed to define optimal targets.

Objectives Whether a higher or lower partial pressure of oxygen (PaO2) could impact outcomes in patients with coronavirus disease 2019 (COVID-19) remains a matter of debate. So, we planned this retrospective analysis to determine if a higher or lower partial pressure of oxygen in blood had any effect on outcomes in COVID-19 patients. Material and method The records of COVID-19 patients from the beginning of 2020 to the end of 2022 were scanned. Patients were sub-grouped into two groups based on the partial pressure of oxygen (PaO2) values on arterial blood gas (ABG), i.e., high PaO2 group, PaO2 value of 80-100 mm Hg, and low PaO2 group, PaO2 value of 60-80 mm Hg for the first 48 hours after the initiation of oxygenation and/or mechanical ventilation. The two groups were compared in terms of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen (FiO2) concentration (P/F ratio), Sequential Organ Failure Assessment (SOFA) score at presentation and after 48 hours, and clinical outcomes, including mortality, time of mortality, extubation, acute kidney injury (AKI), and change in Glasgow Coma Scale (GCS). Results SOFA score was significantly higher in the low PaO2 group as compared to the high PaO2 group both at baseline (4.59 {1.79} versus 5.51 {1.15}; p-value: 0.005) and at 48 hours (3.06 {1.39} versus 5.11 {2.13}; p-value: 0.007). However, the change in SOFA score over 48 hours did not achieve statistical significance (-1.000 {0.97} versus 0.53 {2.34}; p-value: 0.257). Out of a total of 37 patients, 21 patients died in the high PaO2 group, while 18 patients died in the low PaO2 group. Conclusion Our study highlights that targeting either low or high arterial oxygen content while considering oxygen therapy for COVID-19 patients did not significantly alter the outcomes.

One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation.

"POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU.

POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients.

Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pa o2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure.

Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020.

Newborns supported by ECMO for respiratory indication were included.

None.

Pa o2 24 hours after ECMO initiation (H24 Pa o2 ) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pa o2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pa o2 < 60 mm Hg) and moderate hyperoxia (Pa o2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045.

Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure.

The impact of closed-loop control systems to titrate oxygen flow in critically ill patients, including their effectiveness, efficacy, workload and safety, remains unclear. This systematic review investigated the utilization of closed-loop oxygen systems for critically ill patients in comparison to manual oxygen titration systems focusing on these topics.

A search was conducted across several databases including MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, LOVE, ClinicalTrials.gov, and the World Health Organization on March 3, 2022, with subsequent updates made on June 27, 2023. Evidence databases were searched for randomized clinical parallel or crossover studies investigating closed-loop oxygen control systems for critically ill patients. This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The analysis was conducted using Review Manager software, adopting the mean difference or standardized mean difference with a 95% confidence interval (95% CI) for continuous variables or risk ratio with 95% CI for dichotomous outcomes. The main outcome of interest was the percentage of time spent in the peripheral arterial oxygen saturation target. Secondary outcomes included time for supplemental oxygen weaning, length of stay, mortality, costs, adverse events, and workload of healthcare professional. A total of 37 records from 21 studies were included in this review with a total of 1,577 participants. Compared with manual oxygen titration, closed-loop oxygen control systems increased the percentage of time in the prescribed SpO2 target, mean difference (MD) 25.47; 95% CI 19.7, 30.0], with moderate certainty of evidence. Current evidence also shows that closed-loop oxygen control systems have the potential to reduce the percentage of time with hypoxemia (MD -0.98; 95% CI -1.68, -0.27) and healthcare workload (MD -4.94; 95% CI -7.28, -2.61) with low certainty of evidence.

Closed-loop oxygen control systems increase the percentage of time in the preferred SpO2 targets and may reduce healthcare workload.

PROSPERO: CRD42022306033.

Although several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO2) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension.

From the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO2 (PaO2 ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO2 (PaO2 < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality.

The median values of PaO2 over the first three ICU days in 1211 liberal and 1211 conservative PaO2 groups were, respectively, 107.2 (92.0-134.0) and 84.4 (71.2-112.0) in day 1110.0 (93.4-132.0) and 80.0 (71.0-100.0) in day 2, and 106.0 (91.9-127.4) and 78.0 (69.0-94.5) in day 3 (all p-values < 0.001). The liberal PaO2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65-0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67-0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73-0.97; p-value = 0.020) were lower in the liberal PaO2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO2 of around 100 mm Hg.

In critically ill patients with sepsis, higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO2.

We determined the prevalences of hyperoxemia and excessive oxygen use, and the epidemiology, ventilation characteristics and outcomes associated with hyperoxemia in invasively ventilated patients with coronavirus disease 2019 (COVID-19).

Post hoc analysis of a national, multicentre, observational study in 22 ICUs. Patients were classified in the first two days of invasive ventilation as 'hyperoxemic' or 'normoxemic'. The co-primary endpoints were prevalence of hyperoxemia (PaO2 > 90 mmHg) and prevalence of excessive oxygen use (FiO2 ≥ 60% while PaO2 > 90 mmHg or SpO2 > 92%). Secondary endpoints included ventilator settings and ventilation parameters, duration of ventilation, length of stay (LOS) in ICU and hospital, and mortality in ICU, hospital, and at day 28 and 90. We used propensity matching to control for observed confounding factors that may influence endpoints.

Of 851 COVID-19 patients, 225 (26.4%) were classified as hyperoxemic. Excessive oxygen use occurred in 385 (45.2%) patients. Acute respiratory distress syndrome (ARDS) severity was lowest in hyperoxemic patients. Hyperoxemic patients were ventilated with higher positive end-expiratory pressure (PEEP), while rescue therapies for hypoxemia were applied more often in normoxemic patients. Neither in the unmatched nor in the matched analysis were there differences between hyperoxemic and normoxemic patients with regard to any of the clinical outcomes.

In this cohort of invasively ventilated COVID-19 patients, hyperoxemia occurred often and so did excessive oxygen use. The main differences between hyperoxemic and normoxemic patients were ARDS severity and use of PEEP. Clinical outcomes were not different between hyperoxemic and normoxemic patients.

Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) patients with COVID-19.

Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 hours of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria.

In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): -0.26 (-0.45, -0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): -1.55 (-2.42, -0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality.

Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients.

Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies.

Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality.

11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]).

In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Administration of oxygen therapy is common, yet there is a lack of knowledge on its ability to prevent cellular hypoxia as well as on its potential toxicity. Consequently, the optimal oxygenation targets in clinical practice remain unresolved. The novel PpIX technique measures the mitochondrial oxygen tension in the skin (mitoPO2) which allows for non-invasive investigation on the effect of hypoxemia and hyperoxemia on cellular oxygen availability.

During hypoxemia, SpO2 was 80 (77-83)% and PaO2 45(38-50) mmHg for 15 min. MitoPO2 decreased from 42(35-51) at baseline to 6(4.3-9)mmHg (p < 0.001), despite 16(12-16)% increase in cardiac output which maintained global oxygen delivery (DO2). During hyperoxic breathing, an FiO2 of 40% decreased mitoPO2 to 20 (9-27) mmHg. Cardiac output was unaltered during hyperoxia, but perfused De Backer density was reduced by one-third (p < 0.01). A PaO2 < 100 mmHg and > 200 mmHg were both associated with a reduction in mitoPO2.

Hypoxemia decreases mitoPO2 profoundly, despite complete compensation of global oxygen delivery. In addition, hyperoxemia also decreases mitoPO2, accompanied by a reduction in microcirculatory perfusion. These results suggest that mitoPO2 can be used to titrate oxygen support.

Hyperoxemia, often overlooked in critically ill patients, is common and may have adverse consequences.

To evaluate the incidence of hyperoxemia induced by oxygen therapy in nonsurgical critically ill patients at intensive care unit (ICU) admission and the association of hyperoxemia with hospital mortality.

This prospective cohort study included all consecutive admissions of nonsurgical patients aged 18 years or older who received oxygen therapy on admission to the Hospital Santa Luzia Rede D'Or São Luiz adult ICU from July 2018 through June 2021. Patients were categorized into 3 groups according to Pao2 level at ICU admission: hypoxemia (Pao2<60 mm Hg), normoxemia (Pao2= 60-120 mm Hg), and hyperoxemia (Pao2 >120 mm Hg).

Among 3088 patients, hyperoxemia was present in 1174 (38.0%) and was independently associated with hospital mortality (odds ratio [OR], 1.32; 95% CI, 1.04-1.67; P=.02). Age (OR, 1.02; 95% CI, 1.02-1.02; P<.001) and chronic kidney disease (OR, 1.55; 95% CI, 1.02-2.36; P=.04) were associated with a higher rate of hyperoxemia. Factors associated with a lower rate of hyperoxemia were Sequential Organ Failure Assessment score (OR, 0.88; 95% CI, 0.83-0.93; P<.001); late-night admission (OR, 0.80; 95% CI, 0.67-0.96; P=.02); and renal/metabolic (OR, 0.22; 95% CI, 0.13-1.39; P<.001), neurologic (OR, 0.02; 95% CI, 0.01-0.05; P<.001), digestive (OR, 0.23; 95% CI, 0.13-0.41; P<.001), and soft tissue/skin/orthopedic (OR, 0.32; 95% CI, 0.13-0.79; P=.01) primary reasons for hospital admission.

Hyperoxemia induced by oxygen therapy was common in critically ill patients and was linked to increased risk of hospital mortality. Health care professionals should be aware of this condition because of its potential risks and unnecessary costs.

Comparative effectiveness research is meant to determine which commonly employed medical interventions are most beneficial, least harmful, and/or most costly in a real-world setting. While the objectives for comparative effectiveness research are clear, the field has failed to develop either a uniform definition of comparative effectiveness research or an appropriate set of recommendations to provide standards for the design of critical care comparative effectiveness research trials, spurring controversy in recent years. The insertion of non-representative control and/or comparator arm subjects into critical care comparative effectiveness research trials can threaten trial subjects' safety. Nonetheless, the broader scientific community does not always appreciate the importance of defining and maintaining critical care practices during a trial, especially when vulnerable, critically ill populations are studied. Consequently, critical care comparative effectiveness research trials sometimes lack properly constructed control or active comparator arms altogether and/or suffer from the inclusion of "unusual critical care" that may adversely affect groups enrolled in one or more arms. This oversight has led to critical care comparative effectiveness research trial designs that impair informed consent, confound interpretation of trial results, and increase the risk of harm for trial participants.

We propose a novel approach to performing critical care comparative effectiveness research trials that mandates the documentation of critical care practices prior to trial initiation. We also classify the most common types of critical care comparative effectiveness research trials, as well as the most frequent errors in trial design. We present examples of these design flaws drawn from past and recently published trials as well as examples of trials that avoided those errors. Finally, we summarize strategies employed successfully in well-designed trials, in hopes of suggesting a comprehensive standard for the field.

Flawed critical care comparative effectiveness research trial designs can lead to unsound trial conclusions, compromise informed consent, and increase risks to research subjects, undermining the major goal of comparative effectiveness research: to inform current practice. Well-constructed control and comparator arms comprise indispensable elements of critical care comparative effectiveness research trials, key to improving the trials' safety and to generating trial results likely to improve patient outcomes in clinical practice.

Hypoxia and hyperoxia (pulse oximetry [SpO2] > 96%) are associated with increased mortality in critically ill patients. However, provider practices regarding oxygenation in traumatic brain injury (TBI) patients are unknown. This study assesses views on oxygenation of critically ill trauma patients with and without TBI and how this varies between Neurological ICU (NeuroICU) and Surgical-Trauma ICU (STICU) providers.

This is a cross-sectional survey of Level I trauma center's NeuroICU and STICU providers. We used Likert scales, yes-no questions, and multiple-choice case-based scenarios to characterize provider views on oxygenation with descriptive statistics to characterize responses. Significant differences regarding TBI and non-TBI patients or NeuroICU and STICU providers were determined using Fisher's exact test and a P-value of .05.

A total of 83 providers initiated the survey, and 53 providers completed it. Most providers identified a threshold SpO2 < 92% for the administration of supplemental oxygen in critically ill TBI patients. A total of 9% of providers "somewhat or completely agreed" that they were more likely to give supplemental oxygen to a critically ill trauma patient with TBI than one without TBI and the same SpO2. A total of 48% of providers selected an SpO2 < 90% as the point at which supplemental oxygen should be initiated in patients without TBI, compared to 27% of providers in patients with TBI (P < .01). This threshold for supplemental oxygen use varied by provider type for non-TBI patients, but not for TBI patients (30% NeuroICU and 69% STICU providers selected SpO2 < 90% in non-TBI, P < .05; 30% NeuroICU and 35% STICU providers selected SpO2 < 90% in TBI, P = .85).

Critical care providers at UCHealth University of Colorado Hospital approach the oxygenation of critically ill trauma patients with and without TBI differently. Specifically, critical care respondents accepted a different lower oxygen saturation threshold for TBI and non-TBI patients. NeuroICU and STICU respondents differed in their threshold for the down-titration of supplemental oxygen. Targeted education for critical care providers may reduce these discrepancies and optimize oxygen use.

Acute hypoxic respiratory failure (AHRF) is a prominent feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) critical illness. The severity of gas exchange impairment correlates with worse prognosis, and AHRF requiring mechanical ventilation is associated with substantial mortality. Persistent impaired gas exchange leading to hypoxemia often warrants the prolonged administration of a high fraction of inspired oxygen (FiO2). In SARS-CoV-2 AHRF, systemic vasculopathy with lung microthrombosis and microangiopathy further exacerbates poor gas exchange due to alveolar inflammation and oedema. Capillary congestion with microthrombosis is a common autopsy finding in the lungs of patients who die with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome. The need for a high FiO2 to normalise arterial hypoxemia and tissue hypoxia can result in alveolar hyperoxia. This in turn can lead to local alveolar oxidative stress with associated inflammation, alveolar epithelial cell apoptosis, surfactant dysfunction, pulmonary vascular abnormalities, resorption atelectasis, and impairment of innate immunity predisposing to secondary bacterial infections. While oxygen is a life-saving treatment, alveolar hyperoxia may exacerbate pre-existing lung injury. In this review, we provide a summary of oxygen toxicity mechanisms, evaluating the consequences of alveolar hyperoxia in COVID-19 and propose established and potential exploratory treatment pathways to minimise alveolar hyperoxia.

Oxygen is the commonest intervention provided to critically ill patients requiring mechanical ventilation. Despite this, it is unclear how much oxygen should be administered to patients in order to promote the best clinical outcomes and it has been suggested that a strategy of conservative oxygen therapy (COT) may be advantageous. We therefore sought to answer the question of whether COT versus usual or liberal oxygen therapy was beneficial to adult patients receiving mechanical ventilation on an intensive care unit (ICU) by performing a systematic review and meta-analysis.

Studies were included if they were randomised controlled trials comparing COT to liberal or usual oxygen therapy strategies in acutely ill adults (aged ⩾18 years) admitted to an ICU, and reported an outcome of interest. Studies were excluded if they were limited to a specific single disease diagnosis. The review was registered on PROSPERO (CRD42022308436). Risk of bias was assessed using a modified Cochrane Risk of Bias assessment tool. Effect estimates were pooled using a random effects model with the between study variance estimated using restricted maximum likelihood and standard errors calculated using the method of Hartung-Knapp/Sidik-Jonkman. Between study heterogeneity was quantified using the I2 statistic. The certainty in the body of evidence was assessed using GRADE criteria.

Nine eligible studies with 5727 participants fulfilled all eligibility criteria. Trials varied in their definitions of COT and liberal or usual oxygen therapy. The pooled estimate of risk ratio for 90 day mortality for COT versus comparator was 0.99 (95% confidence interval 0.88-1.12, 95% prediction interval 0.82-1.21). There was low heterogeneity among studies (I2 = 22.4%). The finding that mortality was similar for patients managed with COT or usual/liberal oxygen therapy was graded as moderate certainty.

In critically ill adults admitted to an ICU, COT is neither beneficial nor harmful when compared to usual or liberal oxygen therapy. Trials to date have been inconsistent in defining both COT and liberal or usual oxygen therapy, which may have had an impact on the results of this meta-analysis. Future research should focus on unifying definitions and outcome measures.

To compare the effects of conservative oxygen therapy and conventional oxygen therapy on the mortality of critically ill patients in ICU.

Searching for randomized controlled clinical trials (RCT) on the effect of conservative oxygen therapy and conventional oxygen therapy on the mortality of critically ill patients in computer databases, including PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang, with postdate before August 2022. We have two researchers evaluating the quality of the literature included and extracting data as per the inclusion and exclusion criteria and then analyzed it with RevMan 5.4 statistical software. Primary outcome included short-term mortality (28-day mortality or ICU mortality); secondary outcome included 90-day mortality, ICU length of stay, hospital length of stay, incidence of new organ dysfunction in ICU, incidence of new infection in ICU, and incidence of ICUAW.

A total of 5779 subjects were included in 10 articles, including 2886 in the conservative oxygen therapy group and 2893 in the conventional oxygen therapy group. The meta-analysis showed that conservative oxygen therapy had an advantage over conventional oxygen therapy in terms of short-term mortality (P=0.03). Subgroup analysis based on different conservative oxygen targets showed that this advantage was statistically significant when the target is set above 90% (RR = 0.76, 95% CI = 0.62∼0.94, P=0.01), while there was no significant difference between conservative oxygen therapy and conventional oxygen therapy when the target is set below 90% (RR = 0.95, 95% CI = 0.79∼1.16, P=0.63). In addition, in terms of the incidence of new infections in the ICU (P=0.03) and the incidence of ICUAW (P=0.03), conservative oxygen therapy also had advantages over conventional oxygen therapy, and the difference was statistically significant. But in terms of 90-day mortality (P=0.61), ICU length of stay (P=0.96), hospital length of stay (P=0.47), and incidence of new organ dysfunction in ICU (P=0.61), there was no significant difference between conservative oxygen therapy and conventional oxygen therapy.

Compared with conventional oxygen therapy, conservative oxygen therapy can reduce the short-term mortality of severe patients, especially when the conservative oxygen therapy target is set above 90%. And it can also reduce the incidence of ICU new infections and ICUAW, while having no effect on 90-day mortality, ICU length of stay, and hospital length of stay.

Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (PaO2, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).