Detection of respiratory activity in newborn infants using a noncontact vision-based monitor.

OBJECTIVE: To examine the effectiveness of a noncontact vision-based infrared respiratory monitor (IRM) in the detection of authentic respiratory motion in newborn infants. STUDY DESIGN: Observational study in a neonatal intensive care unit. METHODS: Eligible infants lay supine with torso exposed under the IRM's infrared depth-map camera and torso images were recorded at 30 frames/s. Respiratory motion waveforms were subsequently derived from upper (IRMupper ) and lower (IRMlower ) torso region images and compared with contemporaneous impedance pneumography (IP) and capsule pneumography (CP). Waveforms, in 15 s investigative epochs, were scanned with an 8 s sliding window for authentic respiratory waveform (spectral purity index [SPI] ≥ 0.75, minimum five complete breaths). Maximum SPI and frequency of occurrence of authentic respiratory waveform in 15 s epochs were compared between monitoring modalities in pooled and per patient data (Friedman ANOVA). RESULTS: Recordings comprised 532 min of images from 35 infants, yielding 2131 investigative epochs, with authentic respiratory motion detected in all infants. For CP, IP, IRMupper , and IRMlower , the proportion of epochs containing authentic respiratory motion in pooled data were 65%, 50%, 36%, and 48%, with median SPImax of 0.79, 0.75, 0.70, and 0.74, respectively. Per-patient average SPImax was 0.79, 0.75, 0.69, and 0.74 for CP, IP, IRMupper , and IRMlower with proportion of authentic respiratory motion being 64%, 50%, 29%, and 49%, respectively. CONCLUSION: An IRM focused on the lower torso detected authentic respiratory motion with comparable performance to IP in newborn infants in intensive care and deserves further investigation.

Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome.

BACKGROUND: Non-invasive respiratory support is increasingly used for the management of respiratory dysfunction in preterm infants. This approach runs the risk of under-treating those with respiratory distress syndrome (RDS), for whom surfactant administration is of paramount importance. Several techniques of minimally invasive surfactant therapy have been described. This review focuses on surfactant administration to spontaneously breathing infants via a thin catheter briefly inserted into the trachea. OBJECTIVES: Primary objectives In non-intubated preterm infants with established RDS or at risk of developing RDS to compare surfactant administration via thin catheter with: 1. intubation and surfactant administration through an endotracheal tube (ETT); or 2. continuation of non-invasive respiratory support without surfactant administration or intubation. Secondary objective 1. To compare different methods of surfactant administration via thin catheter Planned subgroup analyses included gestational age, timing of intervention, and use of sedating pre-medication during the intervention. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. SELECTION CRITERIA: We included randomised trials comparing surfactant administration via thin catheter (S-TC) with (1) surfactant administration through an ETT (S-ETT), or (2) continuation of non-invasive respiratory support without surfactant administration or intubation. We also included trials comparing different methods/strategies of surfactant administration via thin catheter. We included preterm infants (at < 37 weeks' gestation) with or at risk of RDS. DATA COLLECTION AND ANALYSIS: Review authors independently assessed study quality and risk of bias and extracted data. Authors of all studies were contacted regarding study design and/or missing or unpublished data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 studies (18 publications; 2164 neonates) in this review. These studies compared surfactant administration via thin catheter with surfactant administration through an ETT with early extubation (Intubate, Surfactant, Extubate technique - InSurE) (12 studies) or with delayed extubation (2 studies), or with continuation of continuous positive airway pressure (CPAP) and rescue surfactant administration at pre-specified criteria (1 study), or compared different strategies of surfactant administration via thin catheter (1 study). Two trials reported neurosensory outcomes of of surviving participants at two years of age. Eight studies were of moderate certainty with low risk of bias, and eight studies were of lower certainty with unclear risk of bias. S-TC versus S-ETT in preterm infants with or at risk of RDS Meta-analyses of 14 studies in which S-TC was compared with S-ETT as a control demonstrated a significant decrease in risk of the composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.48 to 0.73; risk difference (RD) -0.11, 95% CI -0.15 to -0.07; number needed to treat for an additional beneficial outcome (NNTB) 9, 95% CI 7 to 16; 10 studies; 1324 infants; moderate-certainty evidence); the need for intubation within 72 hours (RR 0.63, 95% CI 0.54 to 0.74; RD -0.14, 95% CI -0.18 to -0.09; NNTB 8, 95% CI; 6 to 12; 12 studies, 1422 infants; moderate-certainty evidence); severe intraventricular haemorrhage (RR 0.63, 95% CI 0.42 to 0.96; RD -0.04, 95% CI -0.08 to -0.00; NNTB 22, 95% CI 12 to 193; 5 studies, 857 infants; low-certainty evidence); death during first hospitalisation (RR 0.63, 95% CI 0.47 to 0.84; RD -0.02, 95% CI -0.10 to 0.06; NNTB 20, 95% CI 12 to 58; 11 studies, 1424 infants; low-certainty evidence); and BPD among survivors (RR 0.57, 95% CI 0.45 to 0.74; RD -0.08, 95% CI -0.11 to -0.04; NNTB 13, 95% CI 9 to 24; 11 studies, 1567 infants; moderate-certainty evidence). There was no significant difference in risk of air leak requiring drainage (RR 0.58, 95% CI 0.33 to 1.02; RD -0.03, 95% CI -0.05 to 0.00; 6 studies, 1036 infants; low-certainty evidence). None of the studies reported on the outcome of death or survival with neurosensory disability. Only one trial compared surfactant delivery via thin catheter with continuation of CPAP, and one trial compared different strategies of surfactant delivery via thin catheter, precluding meta-analysis. AUTHORS' CONCLUSIONS: Administration of surfactant via thin catheter compared with administration via an ETT is associated with reduced risk of death or BPD, less intubation in the first 72 hours, and reduced incidence of major complications and in-hospital mortality. This procedure had a similar rate of adverse effects as surfactant administration through an ETT. Data suggest that treatment with surfactant via thin catheter may be preferable to surfactant therapy by ETT. Further well-designed studies of adequate size and power, as well as ongoing studies, will help confirm and refine these findings, clarify whether surfactant therapy via thin tracheal catheter provides benefits over continuation of non-invasive respiratory support without surfactant, address uncertainties within important subgroups, and clarify the role of sedation.

Volume-targeted versus pressure-limited ventilation in neonates.

BACKGROUND: Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO2). OBJECTIVES: To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes. DATA COLLECTION AND ANALYSIS: We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes. STATISTICS: for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis. MAIN RESULTS: Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes. AUTHORS' CONCLUSIONS: Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

Development and preclinical testing of an adaptive algorithm for automated control of inspired oxygen in the preterm infant.

OBJECTIVE: To assess the performance of a novel algorithm for automated oxygen control using a simulation of oxygenation founded on in vivo data from preterm infants. METHODS: A proportional-integral-derivative (PID) control algorithm was enhanced by (i) compensation for the non-linear SpO2-PaO2 relationship, (ii) adaptation to the severity of lung dysfunction and (iii) error attenuation within the target range. Algorithm function with and without enhancements was evaluated by iterative linking with a computerised simulation of oxygenation. Data for this simulation (FiO2 and SpO2 at 1 Hz) were sourced from extant recordings from preterm infants (n=16), and converted to a datastream of values for ventilation:perfusion ratio and shunt. Combination of this datastream second by second with the FiO2 values from the algorithm under test produced a sequence of novel SpO2 values, allowing time in the SpO2 target range (91%-95%) and in various degrees of hypoxaemia and hyperoxaemia to be determined. A PID algorithm with 30 s lockout after each FiO2 adjustment, and a proportional-derivative (PD) algorithm were also evaluated. RESULTS: Separate addition of each enhancing feature to the PID algorithm showed a benefit, but not with uniformly positive effects. The fully enhanced algorithm was optimal for the combination of targeting the desired SpO2 range and avoiding time in, and episodes of, hypoxaemia and hyperoxaemia. This algorithm performed better than one with a 30 s lockout, and considerably better than PD control. CONCLUSIONS: An enhanced PID algorithm was very effective for automated oxygen control in a simulation of oxygenation, and deserves clinical evaluation.

Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support.

OBJECTIVE: To evaluate the performance of a novel rapidly responsive proportional-integral-derivative (PID) algorithm for automated oxygen control in preterm infants with respiratory insufficiency. DESIGN: Interventional study of a 4-hour period of automated oxygen control compared with combined data from two flanking periods of manual control (4 hours each). SETTING: Neonatal intensive care unit. PARTICIPANTS: Preterm infants (n=20) on non-invasive respiratory support and supplemental oxygen, with oxygen saturation (SpO2) target range 90%-94% (manual control) and 91%-95% (automated control). Median gestation at birth 27.5 weeks (IQR 26-30 weeks), postnatal age 8.0 (1.8-34) days. INTERVENTION: Automated oxygen control using a standalone device, receiving SpO2 input from a standard oximeter and computing alterations to oxygen concentration that were actuated with a modified blender. The PID algorithm was enhanced to avoid iatrogenic hyperoxaemia and adapt to the severity of lung dysfunction. MAIN OUTCOME MEASURE: Proportion of time in the SpO2 target range, or above target range when in air. RESULTS: Automated oxygen control resulted in more time in the target range or above in air (manual 56 (48-63)% vs automated 81 (76-90)%, p<0.001) and less time at both extremes of oxygenation. Prolonged episodes of hypoxaemia and hyperoxaemia were virtually eliminated. The control algorithm showed benefit in every infant. Manual changes to oxygen therapy were infrequent during automated control (0.24/hour vs 2.3/hour during manual control), and oxygen requirements were unchanged (automated control period 27%, manual 27% and 26%, p>0.05). CONCLUSIONS: The novel PID algorithm was very effective for automated oxygen control in preterm infants, and deserves further investigation.

Characterisation of the Oxygenation Response to Inspired Oxygen Adjustments in Preterm Infants.

BACKGROUND: Oxygen saturation (SpO2) targeting in the preterm infant may be improved with a better understanding of the SpO2 responses to changes in inspired oxygen (FiO2). OBJECTIVE: We investigated the first-order FiO2-SpO2 relationship, aiming to quantify the parameters governing that relationship, the influences on these parameters and their variability. METHODS: In recordings of FiO2 and SpO2 from preterm infants on continuous positive airway pressure and supplemental oxygen, we identified unique FiO2 adjustments and mapped the subsequent SpO2 responses. For responses identified as first-order, the delay, time constant and gain parameters were determined. Clinical and physiological predictors of these parameters were sought in regression analysis, and intra- and inter-subject variability was evaluated. RESULTS: In 3,788 h of available data from 47 infants at 31 (28-33) post-menstrual weeks [median (interquartile range)], we identified 993 unique FiO2 adjustments followed by a first-order SpO2 response. All response parameters differed between FiO2 increments and decrements, with increments having a shorter delay, longer time constant and higher gain [2.9 (1.7-4.8) vs. 1.3 (0.58-2.6), p < 0.05]. Gain was also higher in less mature infants and in the setting of recent SpO2 instability, and was diminished with increasing severity of lung dysfunction. Intra-subject variability in all parameters was prominent. CONCLUSIONS: First-order SpO2 responses show variable gain, influenced by the direction of FiO2 adjustment and the severity of lung disease, as well as substantial intra-subject parameter variability. These findings should be taken into account in adjustment of FiO2 for SpO2 targeting in preterm infants.

Lost without trace: oximetry signal dropout in preterm infants.

Oxygen saturation (SpO2) signal dropout leaves caregivers without a reliable measure to guide oxygen therapy. We studied SpO2 dropout in preterm infants on continuous positive airway pressure, noting the SpO2 values at signal loss and recovery and thus the resultant change in SpO2, and the factors influencing this parameter. In 32 infants of median gestation 26 weeks, a total of 3932 SpO2 dropout episodes were identified (1.1 episodes/h). In the episodes overall, SpO2 decreased by 1.1%, with the SpO2 change influenced by starting SpO2 (negative correlation), but not dropout duration. For episodes starting in hypoxia (SpO2 <85%), SpO2 recovered at a median of 3.2% higher than at SpO2 dropout, with a downward trajectory in a quarter of cases. We conclude that after signal dropout SpO2 generally recovers in a relative normoxic range. Blind FiO2 adjustments are thus unlikely to be of benefit during most SpO2 dropout episodes.

Ventilation/perfusion mismatch during lung aeration at birth.

At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Within the 6th intercostal space, the mean gray level (relative measure of iodine level) increased from 68.3 ± 11.6 and 70.3 ± 7.5%·s to 136.3 ± 22.6 and 136.3 ± 23.7%·s in the left and right PAs, respectively. No differences were observed between vessels in the left and right lungs, despite the left lung not initially being ventilated. The increase in PBF at birth is not spatially related to lung aeration allowing a large ventilation/perfusion mismatch, or pulmonary shunting, to occur in the partially aerated lung at birth.

Oxygen saturation targeting in preterm infants receiving continuous positive airway pressure.

OBJECTIVE: The precision of oxygen saturation (SpO2) targeting in preterm infants on continuous positive airway pressure (CPAP) is incompletely characterized. We therefore evaluated SpO2 targeting in infants solely receiving CPAP, aiming to describe their SpO2 profile, to document the frequency of prolonged hyperoxia and hypoxia episodes and of fraction of inspired oxygen (FiO2) adjustments, and to explore the relationships with neonatal intensive care unit operational factors. STUDY DESIGN: Preterm infants <37 weeks' gestation in 2 neonatal intensive care units were studied if they were receiving CPAP and in supplemental oxygen at the beginning of each 24-hour recording. SpO2, heart rate, and FiO2 were recorded (sampling interval 1-2 seconds). We measured the proportion of time spent in predefined SpO2 ranges, the frequency of prolonged episodes (≥30 seconds) of SpO2 deviation, and the effect of operational factors including nurse-patient ratio. RESULTS: A total of 4034 usable hours of data were recorded from 45 infants of gestation 30 (27-32) weeks (median [IQR]). When requiring supplemental oxygen, infants were in the target SpO2 range (88%-92%) for only 31% (19%-39%) of total recording time, with 48 (6.9-90) episodes per 24 hours of severe hyperoxia (SpO2 ≥98%), and 9.0 (1.6-21) episodes per 24 hours of hypoxia (SpO2 <80%). An increased frequency of prolonged hyperoxia in supplemental oxygen was noted when nurses were each caring for more patients. Adjustments to FiO2 were made 25 (16-41) times per day. CONCLUSION: SpO2 targeting is challenging in preterm infants receiving CPAP support, with a high proportion of time spent outside the target range and frequent prolonged hypoxic and hyperoxic episodes.

Volume-targeted versus pressure-limited ventilation for preterm infants: a systematic review and meta-analysis.

BACKGROUND: The causes of bronchopulmonary dysplasia (BPD) are multifactorial. Overdistension of the lung (volutrauma) is considered an important contribution. As an alternative to traditional pressure-limited ventilation (PLV), modern neonatal ventilators offer modes which can target a set tidal volume. OBJECTIVES: To determine whether volume-targeted neonatal ventilation, compared with PLV, reduces death or BPD. METHODS: We performed a systematic review and meta-analysis using the methodology of the Neonatal Review Group of the Cochrane Collaboration. A comprehensive literature search was undertaken, and data for prespecified outcomes were combined where appropriate using the fixed effects model. RESULTS: Nine trials were eligible. Volume-targeted ventilation resulted in a reduction in: the combined outcome of death or BPD [typical relative risk, RR, 0.73 (95% confidence interval, 0.57-0.93), numbers needed to treat, NNT, 8 (95% CI 5-33)], the incidence of pneumothorax [typical RR 0.46 (95% CI 0.25-0.84), NNT 17 (95% CI 10-100)], days of ventilation [weighted mean difference 0.8 days (log-transformed data, p = 0.05)], hypocarbia (pCO(2) <35 mm Hg/4.7 kPa); [typical RR 0.56 (95% CI 0.33-0.96), NNT 4 (95% CI 2-25)], and the combined outcome of periventricular leukomalacia or grade 3-4 intraventricular hemorrhage [typical RR 0.48 (95% CI 0.28-0.84), NNT 11 (95% CI 7-50)]. CONCLUSIONS: Compared with PLV, infants ventilated using volume-targeted ventilation had reduced death/BPD, duration of ventilation, pneumothoraces, hypocarbia and periventricular leukomalacia/severe intraventricular hemorrhage. Further studies are needed to assess neurodevelopmental outcomes.

Comparison of two ventilator circuits for Dräger Babylog high-frequency ventilation.

AIM: The Dräger Babylog 8000plus ventilator (Dräger Medical Systems, Lübeck, Germany) can provide both conventional and high-frequency ventilation (HFV). Dräger recommends specific circuits for each of these modes. We investigated the performance of the Babylog ventilator in HFV mode when used with the recommended circuits for both conventional and HFV. METHODS: The Fisher and Paykel RT235 (conventional; Fisher and Paykel Healthcare, Auckland, New Zealand) and Hytrel (HFV; Fisher and Paykel Healthcare) circuits were studied using a 50-mL test lung. Tidal volume, high-frequency minute volume and ventilator alarms were compared at 100 combinations of mean airway pressures (10-16 cm H2O), frequencies (6-14 Hz) and amplitudes (20-60%). RESULTS: Tidal volume with the two circuits differed by < 5% for tidal volumes ≤ 2.5 mL. Above this, tidal volumes delivered with the HFV circuit were up to 15% more than that obtained with the conventional ventilation circuit, and high-frequency minute volume differed by up to 30%. With the exception of the highest tidal/minute volumes, the tidal volume delivered using the HFV circuit could also be achieved with adjusted frequency or amplitude when using the conventional circuit. More 'pressure measurement out of range' alarms were noted with the conventional ventilation circuit, particularly at mean airway pressure ≥ 14 cm H2O and frequency ≤ 10 Hz. CONCLUSIONS: The conventional ventilation circuit may allow delivery of adequate tidal volume for some infants. Where requirements are higher, the HFV circuit allows the Babylog to deliver higher tidal volumes and higher minute volume, and reduce alarms.

An international survey of volume-targeted neonatal ventilation.

OBJECTIVE: To evaluate clinical practice of volume-targeted ventilation (VTV). DESIGN: Internet-based survey of all 50 tertiary neonatal units in Australia, New Zealand, Sweden, Denmark, Finland and Norway. RESULTS: Response rate was 100%. VTV was routinely used in 25 (50%) units; 15/25 (60%) in Australasia and 10/25 (40%) in the Nordic countries. The most common reason given for using VTV was that it reduces bronchopulmonary dysplasia (13/25; 52%). The median (IQR) of upper limits of target tidal volume were (1) for initial ventilation of preterm infants with respiratory distress syndrome 5.0 (4.6-6.0) ml/kg and (2) for infants with ventilator-dependent bronchopulmonary dysplasia 6.0 (5.0-8.0) ml/kg. The median (IQR) maximum peak inspiratory pressure limit units were prepared to use in VTV-mode was 35 (30-42.5) cm H(2)O. CONCLUSION: Half of the units used VTV routinely, but with a considerable variation in VTV practice. More studies are required to establish best VTV practice.