Prolonged use of closed-loop inspired oxygen support in preterm infants: a randomised controlled trial.

OBJECTIVE: This randomised study in preterm infants on non-invasive respiratory support investigated the effectiveness of automated oxygen control (A-FiO2) in keeping the oxygen saturation (SpO2) within a target range (TR) during a 28-day period compared with manual titration (M-FiO2). DESIGN: A single-centre randomised control trial. SETTING: A level III neonatal intensive care unit. PATIENTS: Preterm infants (<28 weeks' gestation) on non-invasive respiratory support. INTERVENTIONS: A-FiO2 versus M-FiO2 control. METHODS: Main outcomes were the proportion of time spent and median area of episodes in the TR, hyperoxaemia, hypoxaemia and the trend over 28 days using a linear random intercept model. RESULTS: 23 preterm infants (median gestation 25.7 weeks; birth weight 820 g) were randomised. Compared with M-FiO2, the time spent within TR was higher in the A-FiO2 group (68.7% vs 48.0%, p<0.001). Infants in the A-FiO2 group spent less time in hyperoxaemia (13.8% vs 37.7%, p<0.001), but no difference was found in hypoxaemia. The time-based analyses showed that the A-FiO2 efficacy may differ over time, especially for hypoxaemia. Compared with the M-FiO2 group, the A-FiO2 group had a larger intercept but with an inversed slope for the daily median area below the TR (intercept 70.1 vs 36.3; estimate/day -0.70 vs 0.69, p<0.001). CONCLUSION: A-FiO2 control was superior to manual control in keeping preterm infants on non-invasive respiratory support in a prespecified TR over a period of 28 days. This improvement may come at the expense of increased time below the TR in the first days after initiating A-FiO2 control. TRIAL REGISTRATION NUMBER: NTR6731.

Determining an Optimal Oxygen Saturation Target Range Based on Neonatal Maturity: Demonstration of a Decision Tree Analytic.

The utility of decision tree machine learning in exploring the interactions among the SpO2 target range, neonatal maturity, and oxemic-risk is demonstrated. METHODS: This observational study used 3 years of paired age-SpO2-PaO2 data from a neonatal ICU. The CHAID decision tree method was used to explore the interaction of postmenstrual age (PMA) on the risk of extreme arterial oxygen levels at six different potential SpO2 target ranges (88-92%, 89-93%, 90-94%, 91-95%, 92-96% and 93-97%). Risk was calculated using a severity-weighted average of arterial oxygen outside the normal range for neonates (50-80 mmHg). RESULTS: In total, 7500 paired data points within the potential target range envelope were analyzed. The two lowest target ranges were associated with the highest risk, and the ranges of 91-95% and 92-96% were associated with the lowest risk. There were shifts in the risk associated with PMA. All the target ranges showed the lowest risk at ≥42 weeks PMA. The lowest risk for preterm infants was within a target range of 92-96% with a PMA of ≤34 weeks. CONCLUSIONS: This study demonstrates the utility of decision tree analytics. These results suggest that SpO2 target ranges that are different from typical range might reduce morbidity and mortality. Further research, including prospective randomized trials, is warranted.

Evaluation of Leading Smartwatches for the Detection of Hypoxemia: Comparison to Reference Oximeter.

Although smartwatches are not considered medical devices, experimental validation of their accuracy in detecting hypoxemia is necessary due to their potential use in monitoring conditions manifested by a prolonged decrease in peripheral blood oxygen saturation (SpO2), such as chronic obstructive pulmonary disease, sleep apnea syndrome, and COVID-19, or at high altitudes, e.g., during sport climbing, where the use of finger-sensor-based pulse oximeters may be limited. The aim of this study was to experimentally compare the accuracy of SpO2 measurement of popular smartwatches with a clinically used pulse oximeter according to the requirements of ISO 80601-2-61. Each of the 18 young and healthy participants underwent the experimental assessment three times in randomized order-wearing Apple Watch 8, Samsung Galaxy Watch 5, or Withings ScanWatch-resulting in 54 individual experimental assessments and complete datasets. The accuracy of the SpO2 measurements was compared to that of the Radical-7 (Masimo Corporation, Irvine, CA, USA) during short-term hypoxemia induced by consecutive inhalation of three prepared gas mixtures with reduced oxygen concentrations (14%, 12%, and 10%). All three smartwatch models met the maximum acceptable root-mean-square deviation (≤4%) from the reference measurement at both normal oxygen levels and induced desaturation with SpO2 less than 90%. Apple Watch 8 reached the highest reliability due to its lowest mean bias and root-mean-square deviation, highest Pearson correlation coefficient, and accuracy in detecting hypoxemia. Our findings support the use of smartwatches to reliably detect hypoxemia in situations where the use of standard finger pulse oximeters may be limited.

Reducing the time delay of oxygen transport to the neonate on continuous positive airway pressure support: A bench study.

Background: Premature newborns often require oxygen support as part of their therapy. Systems for oxygen administration are developed to assure adequate oxygenation of newborns. Several factors were identified in the systems that contribute to the time delay between the change in the set inspiratory oxygen fraction and its actual delivery to tissues. In this study, we aimed to reduce the physical delay in oxygen delivery to newborns. Methods: We developed an O2 Flush System (O2-FS) that brings the source of oxygen as close to a patient as possible to make oxygen available for rapid delivery that compensates for the physical delay in the ventilator circuit. The O2-FS system is built around an electromechanical on/off valve. We validated the O2-FS concept in experiments with non-invasive Continuous Positive Airways Pressure (CPAP) ventilators. Results: The O2-FS accelerated oxygen delivery with all the tested systems and arrangements, typically by 5-15 s. We also observed that the application of supplemental oxygen increased the pressure in the ventilator circuit by 3-4 cmH2O which may mitigate the apneic pauses that are common in premature newborns. Conclusions: The O2-FS system may work as a universal accessory of the CPAP lung ventilator and shorten the distribution of oxygen to the patient during oxygen desaturation events, possibly eliminating or interrupting apneic pauses in neonates, for whom oxygen therapy is an essential treatment. In clinical practice, the O2-FS could help maintain normoxemic saturation values through adequate oxygen dosing in preterm neonates, thus reducing morbidity and mortality.

Commercial smartwatch with pulse oximeter detects short-time hypoxemia as well as standard medical-grade device: Validation study.

Objective: We investigated how a commercially available smartwatch that measures peripheral blood oxygen saturation (SpO2) can detect hypoxemia compared to a medical-grade pulse oximeter. Methods: We recruited 24 healthy participants. Each participant wore a smartwatch (Apple Watch Series 6) on the left wrist and a pulse oximeter sensor (Masimo Radical-7) on the left middle finger. The participants breathed via a breathing circuit with a three-way non-rebreathing valve in three phases. First, in the 2-minute initial stabilization phase, the participants inhaled the ambient air. Then in the 5-minute desaturation phase, the participants breathed the oxygen-reduced gas mixture (12% O2), which temporarily reduced their blood oxygen saturation. In the final stabilization phase, the participants inhaled the ambient air again until SpO2 returned to normal values. Measurements of SpO2 were taken from the smartwatch and the pulse oximeter simultaneously in 30-s intervals. Results: There were 642 individual pairs of SpO2 measurements. The bias in SpO2 between the smartwatch and the oximeter was 0.0% for all the data points. The bias for SpO2 less than 90% was 1.2%. The differences in individual measurements between the smartwatch and oximeter within 6% SpO2 can be expected for SpO2 readings 90%-100% and up to 8% for SpO2 readings less than 90%. Conclusions: Apple Watch Series 6 can reliably detect states of reduced blood oxygen saturation with SpO2 below 90% when compared to a medical-grade pulse oximeter. The technology used in this smartwatch is sufficiently advanced for the indicative measurement of SpO2 outside the clinic. Trial Registration: ClinicalTrials.gov NCT04780724.

Frequency and duration of extreme hypoxemic and hyperoxemic episodes during manual and automatic oxygen control in preterm infants: a retrospective cohort analysis from randomized studies.

OBJECTIVE: Neonatal exposure to episodic hypoxemia and hyperoxemia is highly relevant to outcomes. Our goal was to investigate the differences in the frequency and duration of extreme low and high SpO2 episodes between automated and manual inspired oxygen control. DESIGN: Post-hoc analysis of a cohort from prospective randomized cross-over studies. SETTING: Seven tertiary care neonatal intensive care units. PATIENTS: Fifty-eight very preterm neonates (32 or less weeks PMA) receiving respiratory support and supplemental oxygen participating in an automated versus manual oxygen control cross-over trial. MAIN MEASURES: Extreme hypoxemia was defined as a SpO2 < 80%, extreme hyperoxemia as a SpO2 > 98%. Episode duration was categorized as < 5 seconds, between 5 to < 30 seconds, 30 to < 60 seconds, 60 to < 120 seconds, and 120 seconds or longer. RESULTS: The infants were of a median postmenstrual age of 29 (28-31) weeks, receiving a median FiO2 of 0.28 (0.25-0.32) with mostly receiving non-invasive respiratory support (83%). While most of the episodes were less than 30 seconds, longer episodes had a marked effect on total time exposure to extremes. The time differences in each of the three longest durations episodes (30, 60, and 120 seconds) were significantly less during automated than during manual control (p < 0.001). Nearly two-third of the reduction of total time spent at the extremes between automated and manual control (3.8 to 2.1% for < 80% SpO2 and 3.0 to 1.6% for > 98% SpO2) was seen in the episodes of at least 60 seconds. CONCLUSIONS: This study shows that the majority of episodes preterm infants spent in SpO2 extremes are of short duration regardless of manual or automated control. However, the infrequent longer episodes not only contribute the most to the total exposure, but also their reduction in frequency to the improvement associated with automated control.

Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity.

BACKGROUND: Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited. METHODS: This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50-80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels. RESULTS: Neonates were categorized by postmenstrual age: < 33 (n = 155), 33-36 (n = 192) and > 36 (n = 1031) weeks. From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24-28) n = 2603; 34 (33-35) n = 2501; and 38 (37-39) n = 21,058. The chance of normoxemia (65, 95%-CI 64-67%) was similar across the SpO2 range of 88-95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21-29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18-33%), for infants 33-36 weeks at 97% SpO2 (24, 95%-CI 14-25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17-22%). CONCLUSIONS: The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.

Evaluation of two SpO2 alarm strategies during automated FiO2 control in the NICU: a randomized crossover study.

BACKGROUND: Changes in oxygen saturation (SpO2) exposure have been shown to have a marked impact on neonatal outcomes and therefore careful titration of inspired oxygen is essential. In routine use, however, the frequency of SpO2 alarms not requiring intervention results in alarm fatigue and its corresponding risk. SpO2 control systems that automate oxygen adjustments (Auto-FiO2) have been shown to be safe and effective. We speculated that when using Auto-FiO2, alarm settings could be refined to reduce unnecessary alarms, without compromising safety. METHODS: An unblinded randomized crossover study was conducted in a single NICU among infants routinely managed with Auto-FiO2. During the first 6 days of respiratory support a tight and a loose alarm strategy were switched each 24 h. A balanced block randomization was used. The tight strategy set the alarms at the prescribed SpO2 target range, with a 30-s delay. The loose strategy set the alarms 2 wider, with a 90-s delay. The effectiveness outcome was the frequency of SpO2 alarms, and the safety outcomes were time at SpO2 extremes (< 80, > 98%). We hypothesized that the loose strategy would result in a marked decrease in the frequency of SpO2 alarms, and no increases at SpO2 extremes with 20 subjects. Within subject differences between alarm strategies for the primary outcomes were evaluated with Wilcoxon signed-rank test. RESULTS: During a 13-month period 26 neonates were randomized. The analysis included 21 subjects with 49 days of both tight and loose intervention. The loose alarm strategy resulted in a reduction in the median rate of SpO2 alarms from 5.2 to 1.6 per hour (p <  0.001, 95%-CI difference 1.6-3.7). The incidence of hypoxemia and hyperoxemia were very low (less than 0.1%-time) with no difference associated with the alarm strategy (95%-CI difference less than 0.0-0.2%). CONCLUSIONS: In this group of infants we found a marked advantage of the looser alarm strategy. We conclude that the paradigms of alarm strategies used for manual titration of oxygen need to be reconsidered when using Auto-FiO2. We speculate that with optimal settings false positive SpO2 alarms can be minimized, with better vigilance of clinically relevant alarms. TRIAL REGISTRATION: Retrospectively registered 15 May 2018 at ISRCTN ( 49239883 ).

Hypoxemic and hyperoxemic likelihood in pulse oximetry ranges: NICU observational study.

OBJECTIVE: Describe the likelihood of hypoxemia and hyperoxemia across ranges of oxygen saturation (SpO2), during mechanical ventilation with supplemental oxygenation. DESIGN: Retrospective observational study. SETTING: University affiliated tertiary care neonatal intensive care unit. PATIENTS: Two groups of neonates based on postmenstrual age (PMA): <32 weeks (n=104) and >36 weeks (n=709). MAIN MEASURES: Hypoxemia was defined as a PaO2 <40 mm Hg, hyperoxemia as a PaO2 of >99 mm Hg and normoxemia as a PaO2 of 50-80 mm Hg. Twenty-five per cent was defined as marked likelihood of hypoxemia or hyperoxemia. RESULTS: From these infants, 18 034 SpO2-PaO2 pairs were evaluated of which 10% were preterm. The PMA (median and IQR) of the two groups were: 28 weeks (27-30) and 40 weeks (38-41). With SpO2 levels between 90% and 95%, the likelihoods of hypoxemia and hyperoxemia were low and balanced. With increasing levels of SpO2, the likelihood of hyperoxemia increased. It became marked in the preterm group when SpO2 was 99%-100% (95% CI 29% to 41%) and in the term group with SpO2 levels of 96%-98% (95% CI 29% to 32%). The likelihood of hypoxemia increased as SpO2 decreased. It became marked in both with SpO2 levels of 80%-85% (95% CI 20% to 31%, 24% to 28%, respectively). CONCLUSIONS: The likelihood of a PaO2 <40 mm Hg is marked with SpO2 below 86%. The likelihood of a PaO2 >99 mm Hg is marked in term infants with SpO2 above 95% and above 98% in preterm infants. SpO2 levels between 90% and 95% are appropriate targets for term and preterm infants.

Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome.

RATIONALE: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality. OBJECTIVES: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV. METHODS: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects. MEASUREMENTS AND MAIN RESULTS: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2 of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2 <100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with PaO2/FiO2 among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04). CONCLUSIONS: HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.

High-Frequency Oscillatory Ventilation in Pediatric Acute Lung Injury: A Multicenter International Experience.

OBJECTIVE: We aim to describe current clinical practice, the past decade of experience and factors related to improved outcomes for pediatric patients receiving high-frequency oscillatory ventilation. We have also modeled predictive factors that could help stratify mortality risk and guide future high-frequency oscillatory ventilation practice. DESIGN: Multicenter retrospective, observational questionnaire study. SETTING: Seven PICUs. PATIENTS: Demographic, disease factor, and ventilatory and outcome data were collected, and 328 patients from 2009 to 2010 were included in this analysis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients were classified into six cohorts based on underlying diagnosis. We used univariate analysis to identify factors associated with mortality risk and multivariate logistic regression to identify independent predictors of mortality risk. An oxygenation index greater than 35 and immunocompromise exhibited the greatest predictive power (p < 0.0001) for increased mortality risk, and respiratory syncytial virus was associated with lowest mortality risk (p = 0.003). Differences in mortality risk as a function of oxygenation index were highly dependent on primary underlying condition. A trend toward an increase in oscillator amplitude and frequency was observed when compared with historical data. CONCLUSIONS: Given the number of centers and subjects included in the database, these findings provide a robust description of current practice regarding the use of high-frequency oscillatory ventilation for pediatric hypoxic respiratory failure. Patients with severe hypoxic respiratory failure and immunocompromise had the highest mortality risk, and those with respiratory syncytial virus had the lowest. A means of identifying the risk of 30-day mortality for subjects can be obtained by identifying the underlying disease and oxygenation index on conventional ventilation preceding the initiation of high-frequency oscillatory ventilation.

Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants.

OBJECTIVE: To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. STUDY DESIGN: Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. RESULTS: The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2, independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. CONCLUSIONS: A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. TRIAL REGISTRATION: ISRCTN 56626482.

THE CONSEQUENCES OF FAILING ELECTIVE NONINVASIVE RESPIRATORY SUPPORT AS COMPARED TO IMMEDIATE INTUBATION: A POPULATION STUDY OF VERY LOW BIRTH WEIGHT NEONATES.

INTRODUCTION: Elective noninvasive respiratory support has become common. However, many neonates fail this procedure and they may require intubation. The aim of this study was to determine the relative outcome of very low birth weight neonates who failed noninvasive respiratory support compared to those that were initially intubated and mechanically ventilated. MATERIAL AND METHODS: We accessed the database of every neonate who received respiratory support in 18 hospitals in the central region of Poland and examined the records for a 7-year period. The evaluation encompassed 1667 neonates with very low birth weight who were potential candidates for elective noninvasive respiratory support. Three prospective primary outcome measures were assessed using logistic regression to control for differences in baseline risk. We also examined the length of respiratory support corrected for EGA. RESULTS: After controlling for significant baseline factors, we found that there was no statistically significant difference in mortality, severe retinopathy of prematurity (ROP) orsevere bronchopulmonary dysplasia (BPD) between infants failing noninvasive respiratory support and those electively intubated. However, their mortality and severe ROP were significantly higher than in those successfully treated with noninvasive respiratory support. Additionally, there was no difference in the length of mechanical ventilation or the length of all respiratory support between those that failed noninvasive support and those that were electively intubated. CONCLUSION: Our study suggests that in those preterm infants who are at a higher risk of failing noninvasive ventilation there is no compelling reason to administer elective intubation and mechanical ventilation immediately after birth. It seems that efforts should rather be made towards the implementation of the optimal non-invasive respiratory support.

Factors effecting adoption of new neonatal and pediatric respiratory technologies.

OBJECTIVE: There remains significant variation in the level and rate of adoption of new pediatric respiratory technologies, in spite of two decades of focus on "evidence-based medicine". Nearly 50 years ago Rogers introduced a rubric for understanding issues that effect the adoption of technologies that included four factors plus evidence of advantage. We sought to determine whether Rogers' factors were useful in understanding contrasts between clinical utilization of technology and evidence of advantage. DESIGN, SETTING, PARTICIPANTS: We conducted a written survey at two international neonatal/pediatric respiratory conferences. We asked about use of four specific indications for high-frequency ventilation (HFV) and nasal continuous positive airway pressure (nCPAP). RESULTS: These four specific respiratory therapies were aggressively used by most, despite significant differences in the evidence supporting their utility: elective use of HFV (57.4%); HFV to treat ARDS (62.7%); nCPAP for weaning following extubation (83.9%); and nCPAP to avoid intubation (82.1%). CONCLUSIONS: Evidence of outcomes advantage should be the key factor in assessing potentially beneficial technologies. However, we suggest that understanding the influence of observe-ability, complexity and subjectivity of relative advantage explains much of the contrast between adoption level and outcome evidence. These factors described by Rogers, that encourage adoption of mediocre technologies or that retard adoption of potentially beneficial technologies, should be understood and acknowledged. This perspective can be applied not only to national adoption patterns, but also to adoption of best practices within an individual unit.