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.

Comparison of two automated oxygen controllers in oxygen targeting in preterm infants during admission: an observational study.

OBJECTIVE: To compare the effect of two different automated oxygen control devices on time preterm infants spent in different oxygen saturation (SpO2) ranges during their entire stay in the neonatal intensive care unit (NICU). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Tertiary level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie 75 infants, CLiO2 111 infants) born at 24-29 weeks' gestation receiving at least 72 hours of respiratory support between October 2015 and November 2020. INTERVENTIONS: Inspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) between February 2019 and November 2020 and the CLiO2 controller (AVEA ventilator) between October 2015 and December 2018 as standard of care. MAIN OUTCOME MEASURES: Time spent within SpO2 target range (TR, 91-95% for either epoch) and other SpO2 ranges. RESULTS: Time spent within the SpO2 TR when receiving supplemental oxygen was higher during OxyGenie control (median 71.5 [IQR 64.6-77.0]% vs 51.3 [47.3-58.5]%, p<0.001). Infants under OxyGenie control spent less time in hypoxic and hyperoxic ranges (SpO2<80%: 0.7 [0.4-1.4]% vs 1.2 [0.7-2.3]%, p<0.001; SpO2>98%: 1.0 [0.5-2.4]% vs 4.0 [2.0-7.9]%, p<0.001). Both groups received a similar FiO2 (29.5 [28.0-33.2]% vs 29.6 [27.7-32.1]%, p=not significant). CONCLUSIONS: Oxygen saturation targeting was significantly different in the OxyGenie epoch in preterm infants, with less time in hypoxic and hyperoxic SpO2 ranges during their stay in the NICU.

Effectiveness of the oxygen reserve index in detecting and preventing hyperoxia in critically ill patients on mechanical ventilation: a randomized controlled trial.

AIM: To assess the effectiveness of fraction of inspired oxygen (FiO2) titration guided by oxygen reserve index (ORi) in preventing hyperoxia in intensive care unit (ICU) patients receiving mechanical ventilator support. METHODS: Patients aged 18 years and older who were admitted to a tertiary ICU and required mechanical ventilator support were randomly divided into two groups: the control group (n=30) and the oxygen saturation (SpO2) +ORi group (n=30). In the SpO2+ORi group, the goal was to maintain SpO2 between 95% and 98% and ORi at 0.00. In both groups, SpO2, ORi, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide, positive end-expiratory pressure, FiO2, and hemodynamic parameters were recorded every six hours for two consecutive days. RESULTS: A very strong positive linear correlation was found between PaO2 and ORi (r=0.937; P<0.001). In the ORi+SpO2 group, PaO2 values were significantly lower and decreased with FiO2 titration over time. Severe hyperoxia was observed in 24.8% of the control group and in only 3.3% of the ORi+SpO2 group. When PaO2>120 mm Hg, FiO2>0.40 was found in 83.5% of the control group, and in 40% of the ORi+SpO2 group. CONCLUSION: FiO2 titration guided by ORi+SpO2 effectively prevents hyperoxia and reduces the exposure time to hyperoxia in critically ill patients.

Does closed-loop automated oxygen control reduce the duration of mechanical ventilation? A randomised controlled trial in ventilated preterm infants.

BACKGROUND: Many preterm infants require supplemental oxygen in the newborn period but experience frequent fluctuations of their oxygen saturation levels. Intermittent episodes of hypoxia or hyperoxia increase the risk of complications. Compliance with achievement of oxygen saturation targets is variable, and the need for frequent adjustments of the inspired oxygen concentration increases workload. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets and reduce both episodes of hypoxia and hyperoxia and the number of manual adjustments. This study investigates whether CLAC compared with manual oxygen control reduces the duration of mechanical ventilation in preterm infants born at less than 31 weeks of gestation. METHODS: This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 70 infants born at less than 31 weeks of gestational age and within 48 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment until successful extubation. The primary outcome is the duration of mechanical ventilation, and secondary outcomes are the percentage of time spent within target oxygen saturation ranges, the time spent in hypoxia or hyperoxia, the number of manual adjustments required, the number of days on oxygen, the incidence of bronchopulmonary dysplasia and the length and cost of neonatal unit stay. The study is performed following informed parental consent and was approved by the Yorkshire and the Humber-Sheffield Research Ethics Committee (protocol version 1.1, 13 July 2021). DISCUSSION: This trial will investigate the effect of CLAC on the duration of mechanical ventilation, which is an important clinical outcome as prolonged mechanical ventilation is associated with important adverse outcomes, such as bronchopulmonary dysplasia. TRIAL REGISTRATION: ClinicalTrials.Gov NCT05030337 . Registered on 17 August 2021.

Automated versus manual oxygen control in preterm infants receiving respiratory support: a systematic review and meta-analysis.

BACKGROUND: Ventilated preterm infants are exposed to deviations from the intended arterial oxygen saturation range. Therefore, an automated control system was developed to rapidly modulate the fraction of inspired oxygen. The aim of this review is to compare the efficacy and safety of automated versus manual oxygen delivery control. METHODS: In December 2020, we systematically searched four electronic databases; PubMed, Cochrane Library, Scopus, and Web of Science for eligible randomized controlled trials. We extracted and pooled data as mean difference and 95% confidence interval in an inverse variance method using RevMan software. RESULTS: Thirteen trials were included in this systematic review and meta-analysis, enrolling 343 preterm infants on respiratory support. Automated oxygen control increased the time spent within the target arterial oxygen saturation range of 85-96% (MD = 8.96; 95% CI [6.26, 11.67], p<.00001), and 90-95% (MD = 18.25; 95% CI [4.58, 31.65], p = .008). In addition, it reduced the time of hypoxia (<80%); (MD = -1.24; 95% CI [-2.05, -0.43], p = .003), (MD = -0.82; 95% CI [-1.23, -0.41], p<.0001) with predetermined ranges of 85-96% and 90-95%, respectively. Automated control system reduced as well the time of hyperoxia (>98%) (MD = -0.99; 95% CI [-1.74, -0.25], p = .009) at intended range of 90-95%, and number of manual inspired oxygen fraction adjustments (MD = -2.82; 95% CI [-4.56, -1.08], p = .002). CONCLUSIONS: Automated oxygen delivery is rapid and effective in controlling infants' oxygen saturation. It can be used to reduce the load over the nurses, but not to substitute the clinical supervision. Further long-term trials of large-scale are required to evaluate the prolonged clinical outcomes.

Pulse Oximetry Saturation (Spo2) Monitoring in the Neonatal Intensive Care Unit (NICU): The Challenge for Providers: A Systematic Review.

BACKGROUND: In the neonatal intensive care unit (NICU), maintaining an oxygenation level that avoids both hypoxemia and hyperoxemia is challenging. Pulse oximetry has become fundamental for noninvasive monitoring of saturation of peripheral oxygen (Spo2) in preterm newborns. PURPOSE: The aim of this systematic review is to determine Spo2 target values in order to avoid hypoxemia or hyperoxemia and complications arising from these. METHOD AND SEARCH STRATEGY: For this systematic review, articles were audited from 2010 to 2020 using the PRISMA guidelines. PubMed, MEDLINE, Google Scholar, and Scopus databases were used, and search terms were related to use of pulse oximetry in the NICU. RESULTS: The result showed that 12 of 20 (60%) studies focused on target values but without a unanimous agreement on values, although 5 of 12 studies (41.66%) suggested a lower value target of 85% and 4 of 12 studies (33.33%) recommended 95% as the higher target value. Other authors showed no difference in the incidence of adverse events comparing different target values and focused the importance more on the fluctuation of the value than on the target value itself. IMPLICATION FOR PRACTICE: Reaching a balance in the oxygen administration so as to avoid potential complications associated with hypoxemia or hyperoxemia is a challenge for the clinicians. IMPLICATION FOR RESEARCH: Further studies on fluctuation of Spo2 comparing different starting targets could better clarify the role of fluctuations and the absolute target values.Video Abstract available at:https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=49.

Oxygen Toxicity in Critically Ill Adults.

Oxygen supplementation is one of the most common interventions in critically ill patients. Despite over a century of data suggesting both beneficial and detrimental effects of supplemental oxygen, optimal arterial oxygenation targets in adult patients remain unclear. Laboratory animal studies have consistently showed that exposure to a high FiO2 causes respiratory failure and early death. Human autopsy studies from the 1960s purported to provide histologic evidence of pulmonary oxygen toxicity in the form of diffuse alveolar damage. However, concomitant ventilator-induced lung injury and/or other causes of acute lung injury may explain these findings. Although some observational studies in general populations of critically adults showed higher mortality in association with higher oxygen exposures, this finding has not been consistent. For some specific populations, such as those with cardiac arrest, studies have suggested harm from targeting supraphysiologic PaO2 levels. More recently, randomized clinical trials of arterial oxygenation targets in narrower physiologic ranges were conducted in critically ill adult patients. Although two smaller trials came to opposite conclusions, the two largest of these trials showed no differences in clinical outcomes in study groups that received conservative versus liberal oxygen targets, suggesting that either strategy is reasonable. It is possible that some strategies are of benefit in some subpopulations, and this remains an important ongoing area of research. Because of the ubiquity of oxygen supplementation in critically ill adults, even small treatment effects could have a large impact on a global scale.

Predictive Intelligent Control of Oxygenation (PRICO) in preterm infants on high flow nasal cannula support: a randomised cross-over study.

OBJECTIVE: To investigate the efficacy of automated control of inspired oxygen (FiO2) by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining oxygen saturation (SpO2) in preterm infants on high flow nasal cannula (HFNC) support. DESIGN: Single-centre randomised two-period crossover study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: 27 preterm infants (gestational age (GA) <30 weeks) on HFNC support with FiO2 >0.25. INTERVENTION: A 24-hour period on automated FiO2-control with PRICO compared with a 24-hour period on routine manual control (RMC) to maintain a SpO2 level within target range of 88%-95% measured at 30 s intervals. MAIN OUTCOME MEASURES: Primary outcome: time spent within target range (88%-95%). SECONDARY OUTCOMES: time spent above and below target range, in severe hypoxia (SpO2 <80%) and hyperoxia (SpO2 >98%), mean SpO2 and FiO2 and manual FiO2 adjustments. RESULTS: 15 patients received PRICO-RMC and 12 RMC-PRICO. The mean time within the target range increased with PRICO: 10.8% (95% CI 7.6 to 13.9). There was a decrease in time below target range: 7.6% (95% CI 4.2 to 11.0), above target range: 3.1% (95% CI 2.9 to 6.2) and in severe hypoxia: 0.9% (95% CI 1.5 to 0.2). We found no difference in time spent in severe hyperoxia. Mean FiO2 was higher during PRICO: 0.019 (95% CI 0.006 to 0.030). With PRICO there was a reduction of manual adjustments: 9/24 hours (95% CI 6 to 12). CONCLUSION: In preterm infants on HFNC support, automated FiO2-control by PRICO is superior to RMC in maintaining SpO2 within target range. Further validation studies with a higher sample frequency and different ventilation modes are needed.

A quasiexperimental study of targeted normoxia in critically ill trauma patients.

BACKGROUND: Avoidance of hypoxia and hyperoxia may reduce morbidity and mortality in critically ill civilian and military trauma patients. The objective of this study was to determine if a multimodal quality improvement intervention increases adherence to a consensus-based, targeted normoxia strategy. We hypothesized that this intervention would safely improve compliance with targeted normoxia. METHODS: This is a pre/postquasiexperimental pilot study to improve adherence to normoxia, defined as a pulse oximetry (SpO2) of 90% to 96% or an arterial partial pressure oxygen (PaO2) of 60 to 100 mm Hg. We used a multimodal informatics and educational intervention guiding clinicians to safely titrate supplemental oxygen to normoxia based on SpO2 monitoring in critically ill trauma patients admitted to the surgical-trauma or neurosurgical intensive care unit within 24 hours of emergency department arrival. The primary outcome was effectiveness in delivering targeted normoxia (i.e., an increase in the probability of being in the targeted normoxia range and/or a reduction in the probability of being on a higher fraction-inspired oxygen concentration [FiO2]). RESULTS: Analysis included 371 preintervention subjects and 201 postintervention subjects. Preintervention and postintervention subjects were of similar age, race/ethnicity, and sex and had similar comorbidities and Acute Physiologic and Chronic Health Evaluation II scores. Overall, the adjusted probability of being hyperoxic while on supplemental oxygen was reduced during the postintervention period (adjusted odds ratio, 0.74; 95% confidence interval, 0.57-0.97). There was a higher probability of being on room air (FiO2, 0.21) in the postintervention period (adjusted odds ratio, 1.38; 95% confidence interval, 0.83-2.30). In addition, there was a decreased amount of patient time spent on higher levels of FiO2 (FiO2, >40%) without a concomitant increase in hypoxia. CONCLUSION: A multimodal intervention targeting normoxia in critically ill trauma patients increased normoxia and lowered the use of supplemental oxygen. A large clinical trial is needed to validate the impact of this protocol on patient-centered clinical outcomes. LEVEL OF EVIDENCE: Therapeutic/care management, level II.

Adjustment of oxygen reserve index (ORi™) to avoid excessive hyperoxia during general anesthesia.

The Oxygen Reserve Index (ORi™) is a non-invasive variable that reflects oxygenation continuously. The aims of this study were to examine the relationship between arterial partial pressure of oxygen (PaO2) and ORi during general anesthesia, and to investigate the usefulness of ORi as an indicator to avoid hyperoxia. Twenty adult patients who were scheduled for surgery under general anesthesia with arterial catheterization were enrolled. After induction of general anesthesia, inspired oxygen concentration (FiO2) was set to 0.33, and arterial blood gas analysis was performed. The PaO2 and ORi at the time of blood collection were recorded. After that, FiO2 was changed to achieve an ORi around 0.5, 0.2, and 0, followed by arterial blood gas analysis. The relationship between ORi and PaO2 was then investigated using the data obtained. Eighty datasets from the 20 patients were analyzed. When PaO2 was less than 240 mmHg (n = 69), linear regression analysis showed a relatively strong positive correlation (r2 = 0.706). The cut-off ORi value obtained from the receiver operating characteristic curve to detect PaO2 ≥ 150 mmHg was 0.21 (sensitivity 0.950, specificity 0.755). Four-quadrant plot analysis showed that the ORi trending of PaO2 was good (concordance rate was 100.0%). Hyperoxemia can be detected by observing ORi of patients under general anesthesia, and thus unnecessary administration of high concentration oxygen can possibly be avoided.

Simvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbits.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a frequent complication following preterm birth, affecting respiratory health throughout life. Transcriptome analysis in a preterm rabbit model for BPD revealed dysregulation of key genes for inflammation, vascular growth and lung development in animals exposed to hyperoxia, which could be prevented by simvastatin. METHODS: Preterm rabbits were randomized to either normoxia (21% O2) or hyperoxia (95% O2) and within each condition to treatment with 5 mg/kg simvastatin daily or control. Lung function, structure and mRNA-expression was assessed on day 7. RESULTS: Simvastatin partially prevented the effect of hyperoxia on lung function, without altering alveolar structure or inflammation. A trend towards a less fibrotic phenotype was noted in simvastatin-treated pups, and airways were less muscularized. Most importantly, simvastatin completely prevented hyperoxia-induced arterial remodeling, in association with partial restoration of VEGFA and VEGF receptor 2 (VEGFR2) expression. Simvastatin however decreased survival in pups exposed to normoxia, but not to hyperoxia. CONCLUSION: Repurposing of simvastatin could be an advantageous therapeutic strategy for bronchopulmonary dysplasia and other developmental lung diseases with pulmonary vascular disease. The increased mortality in the treated normoxia group however limits the translational value at this dose and administration route.

Supplemental Intraoperative Oxygen Does Not Promote Acute Kidney Injury or Cardiovascular Complications After Noncardiac Surgery: Subanalysis of an Alternating Intervention Trial.

BACKGROUND: Perioperative hyperoxia has been recommended by the World Health Organization and the Centers for Disease Control and Prevention for the prevention of surgical site infections. Based on animal studies and physiological concerns, the kidneys and heart may be at risk from hyperoxia. We therefore conducted 2 unplanned subanalyses of a previous alternating cohort trial in which patients having colorectal surgery were assigned to either 30% or 80% inspired intraoperative oxygen. Specifically, we tested 2 coprimary hypotheses: (1) hyperoxia increases the incidence of acute kidney injury (AKI) within 7 postoperative days (PODs); and (2) hyperoxia worsens a composite of myocardial injury, in-hospital cardiac arrest, and 30-day mortality. METHODS: The underlying controlled trial included 5749 colorectal surgeries in 4481 patients, with the exposure alternating between 30% and 80% fraction of inspired oxygen (FIO2) during general anesthesia at 2-week intervals over a period of 39 months. AKI was defined as a 1.5-fold increase in creatinine from the preoperative level to the highest value measured during the initial 7 PODs. Myocardial injury was defined by fourth-generation troponin-T level >0.03 ng/mL. We assessed the effect of 80% vs 30% oxygen on the outcomes using generalized estimating equation (GEE) logistic models that adjusted for the possible within-patient correlation across multiple potential operations for a patient on different visits. RESULTS: For the AKI outcome, 2522 surgeries were allocated to 80% oxygen and 2552 to 30% oxygen. Hyperoxia had no effect on the primary outcome of postoperative AKI, with an incidence of 7.7% in the 80% oxygen group and 7.7% in the 30% oxygen group (relative risk = 0.99; 95% confidence interval [CI], 0.82-1.2; P = .95). One thousand six hundred forty-seven surgeries (all with scheduled troponin monitoring) were analyzed for the composite cardiovascular outcome. Hyperoxia had no effect on the collapsed composite of myocardial injury, cardiac arrest, and 30-day mortality, nor on any of its components (estimated relative risk = 0.71; 95% CI, 0.44-1.16; P = .17). CONCLUSIONS: We found no evidence that intraoperative hyperoxia causes AKI or cardiovascular complications in adults undergoing colorectal surgery. Consequently, we suggest that clinicians select intraoperative inspired oxygen fraction based on other considerations.

Evaluation of hyperoxia-induced hypercapnia in obese patients after cardiac surgery: a randomized crossover comparison of conservative and liberal oxygen administration.

PURPOSE: Recent studies on patients with stable obesity-hypoventilation syndrome have raised concerns about hyperoxia-induced hypercapnia in this population. This study aimed to evaluate whether a higher oxygen saturation target would increase arterial partial pressure of carbon dioxide (PaCO2) in obese patients after coronary artery bypass grafting surgery (CABG). METHODS: Obese patients having CABG were recruited. With a randomized crossover design, we compared two oxygenation strategies for 30 min each, immediately after extubation: a peripheral oxygen saturation (SpO2) target of ≥ 95% achieved with manual oxygen titration (liberal) and a SpO2 target of 90% achieved with FreeO2, an automated oxygen titration device (conservative). The main outcome was end-of-period arterial PaCO2. RESULTS: Thirty patients were included. Mean (standard deviation [SD]) body mass index (BMI) was 34 (3) kg·m-2 and mean (SD) baseline partial pressure of carbon dioxide (PCO2) was 40.7 (3.1) mmHg. Mean (SD) end-of-period PaCO2 was 42.0 (5.4) mmHg in the conservative period, compared with 42.6 (4.6) mmHg in the liberal period [mean difference - 0.6 (95% confidence interval - 2.2 to 0.9) mmHg; P = 0.4]. Adjusted analysis for age, BMI, narcotics, and preoperative PaCO2 did not substantively change the results. Fourteen patients were retainers, showing an elevation in mean (SD) PaCO2 in the liberal period of 3.3 (4.1) mmHg. Eleven patients had the opposite response, with a mean (SD) end-of-period PaCO2 decrease of 1.8 (2.2) mmHg in the liberal period. Five patients had a neutral response. CONCLUSION: This study did not show a clinically important increase in PaCO2 associated with higher SpO2 values in this specific population of obese patients after CABG. Partial pressure of carbon dioxide increased with liberal oxygen administration in almost half of the patients, but no predictive factor was identified. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02917668); registered 25 September, 2016.

Pulmonary oxygen toxicity in saturation dives with PO2 close to the lower end of the toxic range - A quantitative approach.

Pulmonary oxygen toxicity (POT) has been extensively described at partial pressures of oxygen (PO2) ≥ 1 bar, but much less so at lower PO2. We proposed the POT index [K = t2 × (PO2)4.57] as a means of evaluating the severity of POT, expressed either as reduced lung function or the incidence of POT in a group of divers. In the exponential recovery process (e - [- 0.42 + 0.384 × (PO2)ex] × tr), the time constant increases linearly from 0.0024 to 0.54 h-1 for a PO2 of 1.1 to 2.5 bar. A linear relationship was demonstrated between the incidence of POT and the POT index, given by the equation: POT incidence % = 1.85 + 0.171 × K. In saturation diving, PO2 is kept close to the lower end of the toxic limits for POT, which is approximately 0.5 bar. We suggested that at this low range of PO2, the two processes of cumulative toxicity and recovery operate simultaneously. For one example of saturation diving, we show that a recovery time constant of 0.0135 h-1 yields the measured incidence of POT. We therefore propose the formula K = t2 × PO24.57 × e-0.0135 × t for calculation of the POT index in further analyses of POT in saturation diving.

Benefits and risks of oxygen therapy during acute medical illness: Just a matter of dose!

Oxygen therapy is used to reverse hypoxemia since more than a century. Current usage is broader and includes routine oxygen administration despite normoxemia which may result in prolonged periods of hyperoxemia. While systematic oxygen therapy was expected to be of benefit in some ischemic diseases such as stroke or acute myocardial infarction, recent randomised controlled trials (RCTs) have challenged this hypothesis by showing the absence of clinical improvement. Although oxygen is known to be toxic at high inspired oxygen fractions, a recent meta-analysis of RCTs revealed the life-threatening effect of hyperoxemia, with a dose-dependent relationship. Several recommendations have therefore been updated: (i) to monitor peripheral oxygen saturation (SpO2) as a surrogate for arterial oxygen saturation (SaO2); (ii) to initiate oxygen only when the lower SpO2 threshold is crossed; (iii) to titrate the delivered oxygen fraction to maintain SpO2 within a target range; and (iv) to stop supplying oxygen when the upper limit of SpO2 is surpassed, in order to prevent hyperoxemia. The lower and upper limits of SpO2 depend on the presence of risk factors for oxygen-induced hypercapnia (Chronic obstructive pulmonary disease, asthma, and obesity-associated hypoventilation). For patients at risk, oxygen therapy should be started when SpO2 is≤88% and stopped when it is>92%. For patients without risk factors, oxygen therapy should be started when SpO2 is≤92% and stopped when it is >96%. High-flow oxygen should only be used in a few diseases such as carbon monoxide poisoning, cluster headaches, sickle cell crisis and pneumothorax.

Automatic versus Manual Oxygen Titration in Patients Requiring Supplemental Oxygen in the Hospital: A Systematic Review and Meta-Analysis.

BACKGROUND: Closed-loop oxygen titration devices have been developed to avoid periods of hypoxemia and hyperoxemia, both detrimental to patients hospitalized for respiratory failure and requiring supplemental oxygen. However, their clinical impact remains unknown. OBJECTIVE: To compare the effect of automatic versus manual oxygen titration on clinical outcomes in pediatric and adult patients requiring supplemental oxygen in the hospital. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials. We searched MEDLINE, EMBASE, and CENTRAL electronic databases (from inception to August 2018), and conference proceedings of major societies in respiratory medicine (2015-2018). Randomized controlled trials were included if they compared automatic to manual oxygen titration in hypoxemic inpatients and if they assessed at least one of the following: length of hospital stay (primary outcome), length of oxygen therapy, need and duration of mechanical ventilation, mortality, percentage of time within, above, and below the oxygen saturation target range, as well as the percentage of time spent in hypoxemia and hyperoxemia. RESULTS: We included 9 trials (354 patients, adults and preterm infants, with or without ventilatory assistance). Eight of these trials were at high risk of bias due to lack of blinding and selective reporting. Automatic titration was associated with a significant decrease in the length of hospital stay (mean difference: -2.2 days; 95% CI: -3.8 to -0.6; p = 0.009; I2 = 0%; n = 237, 2 trials), and a decrease in the length of oxygen therapy (mean difference: -1.6 days; 95% CI: -3.1 to 0.0; p = 0.05; I2 = 0%; n = 237; 2 trials). We did not observe a reduction in the need for ventilatory assistance or in mortality in the automatic titration period. An increase in the percentage of time spent within target (mean difference: 18.23%; 95% CI: 10.93-25.52; I2 = 81%; n = 351, 7 trials) and a significant reduction in the percentage of time spent in both hypoxemia and hyperoxemia with automatic compared to manual oxygen titration were, however, observed. CONCLUSIONS: In patients requiring supplemental oxygen in the hospital, automatic oxygen titration was associated with a reduction in length of both hospital stay and oxygen therapy, as well as a greater percentage of time spent within the saturation target range. However, it was not associated with a significant difference in the need for mechanical ventilation or in mortality. Results should be interpreted with caution due to the small number of included trials and their high risk of bias.