Skin-to-skin stabilisation and uninterrupted respiratory support for preterm infants after birth: feasibility of a new and simplified rPAP system.

BACKGROUND: The rPAP respiratory support system, used for delivery room stabilisation with nasal prongs, has been shown to reduce the need for intubation in extremely preterm infants. A simplified version of the system has been developed. The purpose of this study was to determine the feasibility of providing uninterrupted respiratory support with the simplified rPAP from birth up to 4 hours of life and to assess ease of use for skin-to skin stabilisation. METHODS: This was a non-randomised feasibility study conducted at Karolinska University Hospital, Sweden. Respiratory support with continuous positive airway pressure (CPAP) and positive pressure ventilation if needed was given with the simplified rPAP using heated humidified gases. Respiratory support was provided in the delivery room, during transportation and in the neonatal unit, for a maximum of 4 hours. RESULTS: 32 preterm infants with a mean (SD) gestational age of 33.4 weeks (±1.2) were included. Of 17 infants born vaginally, 13 were stabilised skin-to-skin. The remaining infants were stabilised on a resuscitation table. All infants received CPAP and nine received positive pressure ventilation. 31 infants received continued support during transport and after arrival in the neonatal unit. Minor interruptions in CPAP support occurred in all infants. The study did not reveal problems with usability of the system. CONCLUSION: It is feasible to stabilise preterm infants with the simplified respiratory support system both skin-to-skin and on a resuscitation table, and to provide continued respiratory support with the same system during transportation and in the neonatal unit. TRIAL REGISTRATION NUMBER: NCT04244890.

Respiratory outcomes after delivery room stabilisation with a new respiratory support system using nasal prongs.

AIM: To study if stabilisation using a new respiratory support system with nasal prongs compared to T-piece with a face mask is associated with less need for mechanical ventilation and bronchopulmonary dysplasia. METHODS: A single-centre follow-up study of neonates born <28 weeks gestation at Karolinska University Hospital, Stockholm included in the multicentre Comparison of Respiratory Support after Delivery (CORSAD) trial and randomised to initial respiratory support with the new system versus T-piece. Data on respiratory support, neonatal morbidities and mortality were collected up to 36 weeks post-menstrual age. RESULTS: Ninety-four infants, 51 female, with a median (range) gestational age of 25 + 2 (23 + 0, 27 + 6) weeks and days, were included. Significantly fewer infants in the new system group received mechanical ventilation during the first 72 h, 24 (52.2%) compared with 35 (72.9%) (p = 0.034) and during the first 7 days, 29 (63.0%) compared with 39 (81.3%) (p = 0.045) in the T-piece group. At 36 weeks post-menstrual age, 13 (28.3%) in the new system and 13 (27.1%) in the T-piece group were diagnosed with bronchopulmonary dysplasia. CONCLUSION: Stabilisation with the new system was associated with less need for mechanical ventilation during the first week of life. No significant difference was seen in the outcome of bronchopulmonary dysplasia.

Transition of Extremely Preterm Infants from Birth to Stable Breathing: A Secondary Analysis of the CORSAD Trial.

OBJECTIVE: Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period. METHODS: This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups. RESULTS: Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD -16.5, 95% CI [-31.7 to -1.1], p 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD -15.6, 95% CI [-30.7 to -0.8], p 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups. CONCLUSION: In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation.

Do newborn infants exhale through the CPAP system? Secondary analysis of a randomised cross-over trial.

BACKGROUND: During nasal continuous positive airway pressure (nCPAP) treatment in neonates, leakage is inevitable and can lead to reduced distending pressure in the lungs of the infant. In current practice, neither leakage nor expiratory flow is measured, which makes it difficult to assess if exhalation is through the device or entirely through leakages. OBJECTIVE: To examine if infants treated with nCPAP exhale through the CPAP system. DESIGN AND SETTING: Secondary data analyses from the ToNIL trial on leakages during nCPAP treatment. We retrospectively examined respiratory curves for the 50 infants included in the trial, using NI LabVIEW 2015. Each infant was measured with both prongs and nasal masks. A flow recording was classified as exhalation through the system if more than 50% of all expirations showed reverse flow, each for a minimum duration of 0.1 s. PATIENTS: 50 infants were included, born with a mean gestational age (GA) of 34 weeks, median birth weight of 1948 g and mean age at measurement 6.5 days. Inclusion criteria were CPAP treatment and a postmenstrual age (PMA) of 28-42 weeks. RESULTS: In our measurements, 32/50 infants exhaled through the CPAP system in at least one recording with either nasal mask or prongs. Leakages exceeding 0.3 L/min were seen in 97/100 recordings. CONCLUSIONS: During nCPAP treatment, infants can exhale through the CPAP system and leakage was common. Measuring expiratory flows and leakages in clinical settings could be valuable in optimising CPAP treatment of infants. TRIAL REGISTRATION NUMBER: NCT03586856.

Neonatal Resuscitation With T-Piece Systems: Risk of Inadvertent PEEP Related to Mechanical Properties.

Background: Resuscitation of infants using T-piece resuscitators (TPR) allow positive pressure ventilation with positive end-expiratory pressure (PEEP). The adjustable PEEP valve adds resistance to expiration and could contribute to inadvertent PEEP. The study indirectly investigated risk of inadvertent peep by determining expiratory time constants. The aim was to measure system expiratory time constants for a TPR device in a passive mechanical model with infant lung properties. Methods: We used adiabatic bottles to generate four levels of compliance (0.5-3.4 mL/cm H2O). Expiratory time constants were recorded for combinations of fresh gas flow (8, 10, 15 L/min), PEEP (5, 8, 10 cm H2O), airway resistance (50, 200 cm H2O/L/sec and none), endotracheal tube (none, size 2.5, 3.0, 3.5) with a peak inflation pressure of 15 cm H2O above PEEP. Results: Low compliances resulted in time constants below 0.17 s contrasting to higher compliances where the expiratory time constants were 0.25-0.81 s. Time constants increased with increased resistance, lower fresh gas flows, higher set PEEP levels and with an added airway resistance or endotracheal tube. Conclusions: The risk of inadvertent PEEP increases with a shorter time for expiration in combination with a higher compliance or resistance. The TPR resistance can be reduced by increasing the fresh gas flow or reducing PEEP. The expiratory time constants indicate that this may be clinically important. The risk of inadvertent PEEP would be highest in intubated term infants with highly compliant lungs. These results are useful for interpreting clinical events and recordings.

Comparison of Respiratory Support After Delivery in Infants Born Before 28 Weeks' Gestational Age: The CORSAD Randomized Clinical Trial.

Importance: Establishing stable breathing is a key event for preterm infants after birth. Delivery of pressure-stable continuous positive airway pressure and avoiding face mask use could be of importance in the delivery room. Objective: To determine whether using a new respiratory support system with low imposed work of breathing and short binasal prongs decreases delivery room intubations or death compared with a standard T-piece system with a face mask. Design, Setting, and Participants: In this unblinded randomized clinical trial, mothers threatening preterm delivery before week 28 of gestation were screened. A total of 365 mothers were enrolled, and 250 infants were randomized before birth and 246 liveborn infants were treated. The trial was conducted in 7 neonatal intensive care units in 5 European countries from March 2016 to May 2020. The follow-up period was 72 hours after intervention. Interventions: Infants were randomized to either the new respiratory support system with short binasal prongs (n = 124 infants) or the standard T-piece system with face mask (n = 122 infants). The intervention was providing continuous positive airway pressure for 10 to 30 minutes and positive pressure ventilation, if needed, with the randomized system. Main Outcomes and Measures: The primary outcome was delivery room intubation or death within 30 minutes of birth. Secondary outcomes included respiratory and safety variables. Results: Of 246 liveborn infants treated, the mean (SD) gestational age was 25.9 (1.3) weeks, and 127 (51.6%) were female. A total of 41 infants (33.1%) receiving the new respiratory support system were intubated or died in the delivery room compared with 55 infants (45.1%) receiving standard care. The adjusted odds ratio was statistically significant after adjusting for stratification variables (adjusted odds ratio, 0.53; 95% CI, 0.30-0.94; P = .03). No significant differences were seen in secondary outcomes or safety variables. Conclusions and Relevance: In this study, using the new respiratory support system reduced delivery room intubation in extremely preterm infants. Stabilizing preterm infants with a system that has low imposed work of breathing and binasal prongs as interface is safe and feasible. Trial Registration: ClinicalTrials.gov Identifier: NCT02563717.

Interface leakage during neonatal CPAP treatment: a randomised, cross-over trial.

OBJECTIVE: To determine leakage for two neonatal continuous positive airway pressure (CPAP) interfaces and evaluate leak-corrective manoeuvres. DESIGN: The ToNIL (Trial of NCPAP Interface Leakage) study was a randomised, clinical, cross-over trial with data collection between August 2018 and October 2019. The primary outcome was blinded to the treating staff. SETTING: One secondary, 8-bed neonatal intensive care unit (NICU) and three larger (>15 beds), academic NICU referral centres. PATIENTS: Newborn infants with CPAP were screened (n=73), and those with stable spontaneous breathing, low oxygen requirement, postmenstrual age (PMA) over 28 weeks and no comorbidities were eligible. In total, 50 infants were included (median PMA 33 completed weeks). INTERVENTIONS: Leakage was measured for both prongs and nasal mask, before and after leak-corrective manoeuvres. Interface application was performed in a randomised order by a nurse, blinded to the measured leakage. MAIN OUTCOME MEASURES: 30 s average leakage, measured in litres per minute (LPM). RESULTS: Analyses showed a significantly lower leakage (mean difference 0.86 LPM, 95% CI 0.07 to 1.65) with prongs (median 2.01 LPM, IQR 1.00-2.80) than nasal mask (median 2.45 LPM, IQR 0.99-5.11). Leak-corrective manoeuvres reduced leakage significantly for both prongs (median 1.22 LPM, IQR 0.54-1.87) and nasal mask (median 2.35 LPM, IQR 0.76-4.75). CONCLUSIONS: Large leakages were common for both interfaces, less with prongs. Simple care manoeuvres reduced leakage for both interfaces. This is the first report of absolute leakage for nasal interfaces and should encourage further studies on leakage during CPAP treatment.

T-piece resuscitators: can they provide safe ventilation in a low compliant newborn lung?

BACKGROUND: T-piece resuscitators (TPRs) are used for primary newborn resuscitation in birthing and emergency rooms worldwide. A recent study has shown spikes in peak inflation pressure (PIP) over set values with two brands of TPRs inbuilt into infant warmer/resuscitation platforms. We aimed to compare delivered ventilation between two TPR drivers with inflation pressure spikes to a standard handheld TPR in a low test lung compliance (Crs), leak-free bench test model. METHODS: A single operator provided positive pressure ventilation to a low compliance test lung model (Crs 0.2-1 mL/cmH2O) at set PIP of 15, 25, 35 and 40 cmH2O. Two TPR devices with known spikes (Draeger Resuscitaire, GE Panda) were compared with handheld Neopuff (NP). Recommended settings for positive end-expiratory pressure (5 cmH2O), inflation rate of 60/min and gas flow rate 10 L/min were used. RESULTS: 2293 inflations were analysed. Draeger and GE TPR drivers delivered higher mean PIP (Panda 18.9-49.5 cmH2O; Draeger 21.2-49.2 cmH2O and NP 14.8-39.9 cmH2O) compared with set PIP and tidal volumes (TVs) compared with the NP (Panda 2.9-7.8 mL; Draeger 3.8-8.1 mL; compared with NP 2.2-6.0 mL), outside the prespecified acceptable range (±10% of set PIP and ±10% TV compared with NP). CONCLUSION: The observed spike in PIP over set values with Draeger and GE Panda systems resulted in significantly higher delivered volumes compared with the NP with identical settings. Manufacturers need to address these differences. The effect on patient outcomes is unknown.

COVID-19: minimising contaminated aerosol spreading during CPAP treatment.

BACKGROUND: The COVID-19 pandemic has raised concern for healthcare workers getting infected via aerosol from non-invasive respiratory support of infants. Attaching filters that remove viral particles in air from the expiratory limb of continuous positive airway pressure (CPAP) devices should theoretically decrease the risk. However, adding filters to the expiratory limb could add to expiratory resistance and thereby increase the imposed work of breathing (WOB). OBJECTIVE: To evaluate the effects on imposed WOB when attaching filters to the expiratory limb of CPAP devices. METHODS: Two filters were tested on three CPAP systems at two levels of CPAP in a mechanical lung model. Main outcome was imposed WOB. RESULTS: There was a minor increase in imposed WOB when attaching the filters. The differences between the two filters were small. CONCLUSION: To minimise contaminated aerosol generation during CPAP treatment, filters can be attached to expiratory tubing with only a minimal increase in imposed WOB in a non-humidified environment. Care has to be taken to avoid filter obstruction and replace filters as recommended.

Basic principles of neonatal bubble CPAP: effects on CPAP delivery and imposed work of breathing when altering the original design.

BACKGROUND: The original bubble continuous positive airway pressure (bCPAP) design has wide-bore tubing and a low-resistance interface. This creates a stable airway pressure that is reflected by the submersion depth of the expiratory tubing. Several systems with alterations to the original bCPAP design are now available. Most of these are aimed for use in low-income and middle-income countries and have not been compared with the original design. OBJECTIVE: We identified three major alterations to the original bCPAP design: (1) resistance of nasal interface, (2) volume of dead space and (3) diameter of expiratory tubing. Our aim was to study the effect of these alterations on CPAP delivery and work of breathing in a mechanical lung model. Dead space should always be avoided and was not further tested. METHODS: The effect of nasal interface resistance and expiratory tubing diameter was evaluated with simulated breathing in a mechanical lung model without interface leakage. The main outcome was delivered CPAP and imposed work of breathing. RESULTS: High-resistance interfaces and narrow expiratory tubing increased the work of breathing. Additionally, narrow expiratory tubing resulted in higher CPAP levels than indicated by the submersion depth. CONCLUSION: Our study shows the significant effect on CPAP delivery and imposed work of breathing when using high-resistance interfaces and narrow expiratory tubing in bCPAP systems. New systems should include low-resistance interfaces and wide-bore tubing and be compared with the original bCPAP. Referring to all systems that bubble as bCPAP is misleading and potentially hazardous.

Correction: Infant CPAP for low-income countries: An experimental comparison of standard bubble CPAP and the Pumani system.

[This corrects the article DOI: 10.1371/journal.pone.0196683.].

Infant CPAP for low-income countries: An experimental comparison of standard bubble CPAP and the Pumani system.

INTRODUCTION: Access to inexpensive respiratory support to newborn infants improves survival in low-income countries. Standard bubble continuous positive airway pressure (CPAP) has been extensively used worldwide for more than 30 years. One project aimed at providing affordable CPAP is the Pumani system developed by Rice 360°. Compared to standard bubble CPAP the system has an unconventional design. The aim was to compare the Pumani system with two traditional bubble CPAP systems, focusing on in-vitro performance and safety. METHODS: The Pumani system was compared to traditional bubble CPAP from Fisher & Paykel (Auckland, New Zealand) and Diamedica (Devon, United Kingdom). The systems were tested using static flow resistance and simulated breathing for a range of fresh gas flows and submersion levels. RESULTS: There were large differences between the Pumani CPAP and the conventional bubble CPAP systems. The Pumani system was not pressure stable, had high resistance and high imposed work of breathing. It was not possible to use submersion depth to adjust CPAP without accounting for fresh gas flow. DISCUSSION: The Pumani design is novel and not similar to any previously described CPAP system. The main mechanism for CPAP generation was resistance, not submersion depth. The system should therefore not be referred to as bubble CPAP. The clinical consequences of its pressure instability and high imposed work of breathing are not known and trials on outcome and safety are needed.

Return of neonatal CPAP resistance - the Medijet device family examined using in vitro flow simulations.

AIM: Medijet nasal continuous positive airway pressure (CPAP) generators are a family of devices developed from the Benveniste valve. Previous studies have shown that the in vitro performance of the Medijet disposable generator was similar to the Neopuff resistor system. We hypothesised that resistance would be the main mechanism of CPAP generation in the Medijet disposable generator. METHODS: The in vitro performance of the Medijet reusable and disposable systems, the Neopuff resistor system and the Benveniste and Infant Flow nonresistor systems were investigated using static and dynamic bench tests. RESULTS: Large differences in performance were found between the different systems. The disposable Medijet demonstrated high resistance, low pressure stability and high imposed work of breathing. The results also showed that encapsulating the Benveniste valve changed it into a resistor system. CONCLUSION: The main mechanism of CPAP generation for the disposable Medijet generator was resistance. The Medijet device family showed increasing resistance with each design generation. The high resistance of the Medijet disposable generator could be of great value when examining the clinical importance of pressure stability. Our results suggest that this device should be used cautiously in patients where pressure-stable CPAP is believed to be clinically important.

Initial stabilisation of preterm infants: a new resuscitation system with low imposed work of breathing for use with face mask or nasal prongs.

OBJECTIVE: T-piece resuscitation systems are pressure unstable and have high imposed work of breathing (iWOB). Pressure stable respiratory support with low iWOB might improve outcome. We have developed a new resuscitation system that can be used with nasal prongs or face mask. The aim of the study was to describe the in vitro performance of the new system and to perform a clinical feasibility trial of initial stabilisation of preterm infants. METHOD: A mechanical lung model was used to determine iWOB at increasing levels of continuous positive airway pressure (CPAP). The feasibility trial included 36 infants (27-34 weeks of gestation), who were randomised into three groups (T-piece, new system with face mask or new system with prongs). Collected data included problems with usage, safety, time to stable breathing, need for positive pressure ventilation and intubation. RESULTS: In the mechanical lung model, the new system reduced iWOB with 91.5% (mask) and 86.6% (medium prongs) compared with Neopuff (4 cm CPAP, p<0.001). Informed consent was obtained from 45 patients, 39 were randomised and 36 needed support. Randomisation resulted in an imbalance: The group of new system infants had lower gestational age compared with the T-piece group. Thirteen patients needed positive pressure ventilation (median 20 cm H2O). One infant was intubated. The study did not reveal problems with the equipment or safety. CONCLUSIONS: Compared with T-piece systems, the new system had a marked reduction in iWOB in bench tests. The feasibility trial did not reveal problems with usability or safety.

Imposed Work of Breathing for Flow Meters with In-Line versus Flow-Through Technique during Simulated Neonatal Breathing.

BACKGROUND: The ability to determine airflow during nasal CPAP (NCPAP) treatment without adding dead space or resistance would be useful when investigating the physiologic effects of different NCPAP systems on breathing. The aim of this study was to investigate the effect on pressure stability of different flow measuring devices at the in-line and flow-through position, using simulated neonatal breathing. METHODS: Six different flow measure devices were evaluated by recording pressure changes and imposed work of breathing for breaths with 16 and 32 ml tidal volumes. The tests were performed initially with the devices in an in line position and with 5 and 10 L/min using flow through technique, without CPAP. The flow meters were then subsequently tested with an Infant Flow CPAP system at 3, 5 and 8 cm H2O pressure using flow through technique. The quality of the recorded signals was compared graphically. RESULTS: The resistance of the measuring devices generated pressure swings and imposed work of breathing. With bias flow, the resistance also generated CPAP pressure. Three of the devices had low resistance and generated no changes in pressure stability or CPAP pressure. The two devices intended for neonatal use had the highest measured resistance. CONCLUSION: The importance of pressure stability and increased work of breathing during non-invasive respiratory support are insufficiently studied. Clinical trials using flow-through technique have not focused on pressure stability. Our results indicate that a flow-through technique might be a way forward in obtaining a sufficiently high signal quality without the added effects of rebreathing and increased work of breathing. The results should stimulate further research and the development of equipment for dynamic flow measurements in neonates.

[Respiratory dysfunction in infants born by elective cesarean section without labor]. / Ondunarördugleikar hjá nýburum sem faedast med valkeisaraskurdi.

OBJECTIVE: To evaluate the effects of gestational age at the timing of elective caesarean section (ECS) on the incidence of respiratory dysfunction in the newborn. STUDY GROUP AND METHODS: This was a retrospective study. All infants born by ECS at the Landspitali-University Hospital Iceland over a 10 years period (1996-2005) at >or=37 weeks gestation and diagnosed with transient tachypnoea of the newborn (TTN) or respiratory distress syndrome (RDS) were included in the study. RESULTS: Of the 1486 infants delivered by ECS over the study period 57 (3.8%) developed TTN (50 infants) or RDS (7 infants). The incidence of respiratory dysfunction was inversely related to gestational age, 13.8% at 37 weeks gestation and 2.5% at 40 weeks gestation. A statistically significant reduction in the incidence of TTN or RDS was observed from 38 weeks to 39 weeks gestation (6.6% and 2.3% respectively; p<0.001). There has been a reduction in the incidence of ECS before 39 weeks gestation since 2001, when guidelines regarding optimal timing of ECS were set at our hospital. CONCLUSION: The incidence of respiratory dysfunction in neonates born by ECS is inversely related to gestational age, even in the term infant. It is important to delay ECS until 39 weeks gestation whenever possible, in order to minimize the risk of respiratory dysfunction in the newborn infant.