Continuous chest compression during sustained inflation versus continuous compression with asynchronized ventilation in an infantile porcine model of severe bradycardia.

Background: Recently, the American Heart Association released a statement calling for research examining the appropriate age to transition from the neonatal to pediatric cardiopulmonary resuscitation approach to resuscitation. Aim: To compare neonatal and pediatric resuscitation approach by using either continuous chest compression with asynchronized ventilation (CCaV) or continuous chest compression superimposed with sustained inflation (CC + SI) during infant cardiopulmonary resuscitation. We hypothesized that CC + SI compared to CCaV would reduce time to return of spontaneous circulation (ROSC) in infantile piglets with asphyxia-induced bradycardic cardiac arrest. Methods: Twenty infantile piglets (5-10 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 10/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, intrathoracic pressure and respiratory parameters were continuously recorded throughout the experiment. Main results: The median (IQR) time to ROSC with CC + SI compared to CCaV was 179 (104-447) vs 660 (189-660), p = 0.05. The number of piglets achieving ROSC with CC + SI and CCaV were 8/10 and 6/10, p = 0.628. Piglets resuscitated with CC + SI required less epinephrine compared to CCaV (p = 0.039). CC + SI increased the intrathoracic pressure throughout resuscitation (p = 0.025) and increased minute ventilation (p < 0.001), compared to CCaV. There was no difference in hemodynamic parameters between groups. Conclusions: CC + SI improves resuscitative efforts of infantile piglets by increasing the intrathoracic pressure and minute ventilation, and thus reducing the duration of resuscitation, compared to CCaV.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Chest compressions superimposed with sustained inflation during neonatal cardiopulmonary resuscitation: are we ready for a clinical trial?

Neonates requiring cardiopulmonary resuscitation (CPR) are at risk of mortality and neurodevelopmental injury. Poor outcomes following the need for chest compressions (CCs) in the delivery room prompt the critical need for improvements in resuscitation strategies. This article explores a technique of CPR which involves CCs with sustained inflation (CC+SI). Unique features of CC+SI include (1) improved tidal volume delivery, (2) passive ventilation during compressions, (3) uninterrupted compressions and (4) improved stability of cerebral blood flow during resuscitation. CC+SI has been shown in animal studies to have improved time to return of spontaneous circulation and reduced mortality without significant increase in markers of inflammation and injury in the lung and brain, compared with standard CPR. The mechanics of CCs, rate of compressions, ventilation strategies and compression-to-ventilation ratios are detailed here. A large randomised controlled trial comparing CC+SI versus the current 3:1 compression-to-ventilation ratio is needed, given the growing evidence of its potential benefits.

Positive Pressure Ventilation in Preterm Infants in the Delivery Room: A Review of Current Practices, Challenges, and Emerging Technologies.

BACKGROUND: A major proportion of preterm neonates require positive pressure ventilation (PPV) immediately after delivery. PPV may be administered through a face mask (FM) or nasal prongs. Current literature indicates that either of these are associated with similar outcomes. SUMMARY: Nonetheless, FM remains the most utilized and the best choice. However, most available FM sizes are too large for extremely preterm infants, which leads to mask leak and ineffective PPV. Challenges to providing effective PPV include poor respiratory drive, complaint chest wall, weak thoracic muscle, delayed liquid clearance, and surfactant deficiency in preterm infants. Mask leak, airway obstruction, poor technique, and inappropriate size are correctable causes of ineffective PPV. Visual assessment of chest rise is often used to assess the efficacy of PPV. However, its accuracy is debatable. Though end tidal CO2 may adjudge the effectiveness of PPV, clinical studies are limited. The compliance of a preterm lung is highly dynamic. The inflating pressure set on T-piece is constant throughout the resuscitation, but the lung volume and dynamics changes with every breath. This leads to huge fluctuations of tidal volume delivery and can trigger inflammatory cascade in preterm infants leading to brain and lung injury. Respiratory function monitoring in the delivery room has potential for guiding and optimizing delivery room resuscitation. This is, however, limited by high costs, complex information that is difficult to interpret during resuscitation, and absence of clinical trials. KEY MESSAGES: This review summarizes the existing literature on PPV in preterm infants, the various aspects related to it such as the pathophysiology, interfaces, devices utilized to deliver it, appropriate technique, emerging technologies, and future directions.

The Effects of a Digital Game Simulator versus a Traditional Intervention on Paramedics' Neonatal Resuscitation Performance.

Neonatal resuscitation is a skill set that comprises procedures, assessment, decision-making, communication, and teamwork. It is used in an emergency situation in the delivery room with the aim of supporting newborn infants who are not able to begin breathing on their own. Thus, healthcare providers need to refresh their neonatal resuscitation skills periodically, according to the Neonatal Resuscitation Program, to ensure that they can react quickly and effectively in emergency situations. The RETAIN digital game simulator was designed to enable healthcare providers to practice their neonatal resuscitation skills. To evaluate the effectiveness of this game in a laboratory setting, a randomized control trial sampled 42 paramedics who completed a pre-test, were randomly assigned to watch a traditional lecture video on the neonatal resuscitation procedure or to play a novel digital game simulation on the same topic, and then completed a following test. A two-way mixed ANOVA revealed a statistically significant improvement in paramedics' neonatal resuscitation performance over time, which did not differ between conditions. Thus, digital games can provide an enjoyable alternative to traditional practices in refreshing neonatal resuscitation knowledge.

Cardiac Agents during Neonatal Cardiopulmonary Resuscitation.

BACKGROUND: Epinephrine (adrenaline) is currently the only cardiac agent recommended during neonatal resuscitation. The inability to predict which newborns are at risk of requiring resuscitative efforts at birth has prevented the collection of large, high-quality human data. SUMMARY: Information on the optimal dosage and route of epinephrine administration is extrapolated from neonatal animal studies and human adult and pediatric studies. Adult resuscitation guidelines have previously recommended vasopressin use; however, neonatal studies needed to create guidelines are lacking. A review of the literature demonstrates conflicting results regarding epinephrine efficacy through various routes of access as well as vasopressin during asystolic cardiac arrest in animal models. Vasopressin appears to improve hemodynamic and post-resuscitation outcomes compared to epinephrine in asystolic cardiac arrest animal models. KEY MESSAGES: The current neonatal resuscitation guidelines recommend epinephrine be primarily given via the intravenous or intraosseous route, with the endotracheal route as an alternative if these routes are not feasible or unsuccessful. The intravenous or intraosseous dose ranges between 0.01 and 0.03 mg/kg, which should be repeated every 3-5 min during chest compressions. However, the optimal dosing and route of administration of epinephrine remain unknown. There is evidence from adult and pediatric studies that vasopressin might be an alternative to epinephrine; however, the neonatal data are scarce.

Sustained inflation and chest compression versus 3:1 chest compression to ventilation ratio during cardiopulmonary resuscitation of asphyxiated newborns (SURV1VE): A cluster randomised controlled trial.

OBJECTIVE: In newborn infants requiring chest compression (CC) in the delivery room (DR) does continuous CC superimposed by a sustained inflation (CC+SI) compared with a 3:1 compression:ventilation (3:1 C:V) ratio decreases time to return of spontaneous circulation (ROSC). DESIGN: International, multicenter, prospective, cluster cross-over randomised trial. SETTING: DR in four hospitals in Canada and Austria, PARTICIPANTS: Newborn infants >28 weeks' gestation who required CC. INTERVENTIONS: Hospitals were randomised to CC+SI or 3:1 C:V then crossed over to the other intervention. MAIN OUTCOME MEASURE: The primary outcome was time to ROSC, defined as the duration of CC until an increase in heart rate >60/min determined by auscultation of the heart, which was maintained for 60 s. Sample size of 218 infants (109/group) was sufficient to detect a clinically important 33% reduction (282 vs 420 s of CC) in time to ROSC. Analysis was intention-to-treat. RESULTS: Patient recruitment occurred between 19 October 2017 and 22 September 2022 and randomised 27 infants (CC+SI (n=12), 3:1 C:V (n=15), two (one per group) declined consent). All 11 infants in the CC+SI group and 12/14 infants in the 3:1 C:V group achieved ROSC in the DR. The median (IQR) time to ROSC was 90 (60-270) s and 615 (174-780) s (p=0.0502 (log rank), p=0.16 (cox proportional hazards regression)) with CC+SI and 3:1 C:V, respectively. Mortality was 2/11 (18.2%) with CC+SI versus 8/14 (57.1%) with 3:1 C:V (p=0.10 (Fisher's exact test), OR (95% CI) 0.17; (0.03 to 1.07)). The trial was stopped due to issues with ethics approval and securing trial insurance as well as funding reasons. CONCLUSION: The time to ROSC and mortality was not statistical different between CC+SI and 3:1 C:V. TRIAL REGISTRATION: NCT02858583.

Chest compressions superimposed with sustained inflations during cardiopulmonary resuscitation in asphyxiated pediatric piglets.

BACKGROUND: Pediatric resuscitation guidelines recommend continuous chest compression with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation. We recently described that providing a constant high distending pressure, or sustained inflation (SI) while performing continuous chest compressions (CC = CC + SI) reduces time to return of spontaneous circulation (ROSC) in neonatal and pediatric piglets with asphyxia-induced cardiac arrest. METHODS: To determine if CC + SI compared to CCaV will improve frequency of achieving ROSC and reduce time to ROSC in asphyxiated pediatric piglets. Twenty-eight pediatric piglets (21-24 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 14/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The mean(SD) duration of resuscitation was significantly reduced with CC + SI compared to CCaV with 208(190) vs. 388(258)s, p = 0.045, respectively. The number of piglets achieving ROSC with CC + SI and CCaV were 12/14 vs. 6/14, p = 0.046. Minute ventilation, end-tidal carbon dioxide, ventilation rate, and positive end expiratory pressures were also significantly improved with CC + SI. CONCLUSIONS: CC + SI improves duration of resuscitation and increases number of piglets achieving ROSC secondary to improved minute ventilation. IMPACT: Chest compressions superimposed with sustained inflation resulted in shorter duration of resuscitation Chest compressions superimposed with sustained inflation resulted in higher number of piglets achieving return of spontaneous circulation Further animal studies are needed to examine chest compressions superimposed with sustained inflation.

Comparison of hemodynamic effects of chest compression delivered via machine or human in asphyxiated piglets.

BACKGROUND: High-quality chest compressions (CC) are an important factor of neonatal resuscitation. Mechanical CC devices may provide superior CC delivery and improve resuscitation outcomes. We aimed to compare the hemodynamic effects of CC delivered by machine and human using a neonatal piglet model. METHODS: Twelve asphyxiated piglets were randomized to receive CC during resuscitation using an automated mechanical CC device ("machine") or the two-thumb encircling technique ("human"). CC was superimposed with sustained inflations. RESULTS: Twelve newborn piglets (age 0-3 days, weight 2.12 ± 0.17 kg) were included in the study. Machine-delivered CC resulted in an increase in stroke volume, and minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax) compared to human-delivered CC. CONCLUSIONS: During machine-delivered CC, stroke volume and left ventricular contractility were significantly improved. Mechanical CC devices may provide improved cardiopulmonary resuscitation outcomes in neonatal cardiac arrest induced by asphyxia. IMPACT: Machine chest compression leads to changes in hemodynamic parameters during resuscitation of asphyxiated neonatal piglets, namely greater stroke volume and left ventricular contractility, compared with standard two-thumb compression technique. Mechanical chest compression devices may provide improved cardiopulmonary resuscitation outcomes in neonatal and pediatric asphyxia-induced cardiac arrest.

Volume-targeted mask ventilation during simulated neonatal resuscitation.

OBJECTIVE: Mask positive pressure ventilation (PPV) in the delivery room is routinely delivered with set peak inflation pressures. To aid mask PPV, stand-alone respiratory function monitors (RFMs) have been used in the delivery room, while ventilator-based, volume-targeted ventilation (VTV) is routinely used in the neonatal intensive care unit (NICU). DESIGN: This is a prospective, randomised, crossover simulation study. Participants were briefly trained to use a neonatal ventilator for volume-targeted mask ventilation (VTV-PPV), then performed mask ventilation on a manikin in a randomised order using VTV-PPV, T-piece PPV or T-piece PPV with RFM visible. SETTING: In situ in a neonatal resuscitation room within a level 3 NICU. PARTICIPANTS: Healthcare professionals (HCPs) trained in neonatal resuscitation with experience as team leaders. INTERVENTIONS: Semiautomated, ventilator-based VTV-PPV using two-hand hold versus manual PPV via a T-piece device (T-piece, RFM masked) versus manual PPV with RFM visible using one-hand hold. MAIN OUTCOME MEASURES: Respiratory characteristics including % mask leak, tidal volume (VT) and peak inflation pressure (PIP). RESULTS: Thirty-two HCPs (23 (72%) female and 9 (28%) male) participated. The median mask leak was significantly lower with 'VTV-PPV' (11%, IQR 0%-14%) compared with both 'T-piece, RFM visible' (82%, IQR 30%-91%) and 'T-piece, RFM masked' (81%, IQR 47%-91%) (p<0.0001). The median delivered VT was 4.1 mL/kg (IQR 3.9-4.4) with VTV-PPV compared with 2.1 mL/kg (IQR 1.2-9) with T-piece, RFM visible and 1.8 mL/kg (IQR 1.1-5.8) with T-piece, RFM masked (p=0.0496). PIP was also significantly lower with VTV-PPV. CONCLUSION: During neonatal simulation, VTV-PPV reduced mask leak and allowed for consistent VT delivery compared with T-piece with and without RFM guidance.

2023 American Heart Association and American Academy of Pediatrics Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

2023 American Heart Association and American Academy of Pediatrics Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

Parental perspectives on a trial using waived informed consent at birth.

OBJECTIVES: To determine parental perspectives in a trial with waived consent. STUDY DESIGN: Anonymous survey of birth parents with term infants who were randomized using a waiver of consent, administered after infant discharge. RESULTS: 121 (11%) survey responses were collected. Of the 121 responding parents 111 (92%) reported that this form of consent was acceptable and 116 (96%) reported feeling comfortable having another child participate in a similar study. 110 (91%) respondents reported that they both understood the information provided in the consent process and had enough time to consider participation. Four percent had a negative opinion on the study's effect on their child's health. CONCLUSIONS: Most responding parents reported both acceptability of this study design in the neonatal period and that the study had a positive effect on their child's health. Future work should investigate additional ways to involve parents and elicit feedback on varied methods of pediatric consent.

Considerations on the Use of Neonatal and Pediatric Resuscitation Guidelines for Hospitalized Neonates and Infants: On Behalf of the American Heart Association Emergency Cardiovascular Care Committee and the American Academy of Pediatrics.

Between 0.25% and 3% of admissions to the NICU, PICU, and PCICU receive cardiopulmonary resuscitation (CPR). Most CPR events occur in patients <1 year old. The incidence of CPR is 10 times higher in the NICU than at birth. Therefore, optimizing the approach to CPR in hospitalized neonates and infants is important. At birth, the resuscitation of newborns is performed according to neonatal resuscitation guidelines. In older infants and children, resuscitation is performed according to pediatric resuscitation guidelines. Neonatal and pediatric guidelines differ in several important ways. There are no published recommendations to guide the transition from neonatal to pediatric guidelines. Therefore, hospitalized neonates and infants can be resuscitated using neonatal guidelines, pediatric guidelines, or a hybrid approach. This report summarizes the current neonatal and pediatric resuscitation guidelines, considers how to apply them to hospitalized neonates and infants, and identifies knowledge gaps and future priorities. The lack of strong scientific data makes it impossible to provide definitive recommendations on when to transition from neonatal to pediatric resuscitation guidelines. Therefore, it is up to health care teams and institutions to decide if neonatal or pediatric guidelines are the best choice in a given location or situation, considering local circumstances, health care team preferences, and resource limitations.

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets.

BACKGROUND: Current neonatal resuscitation guidelines recommend epinephrine for cardiac arrest. Vasopressin might be an alternative during asphyxial cardiac arrest. We aimed to compare vasopressin and epinephrine on incidence and time to return of spontaneous circulation (ROSC) in asphyxiated newborn piglets. DESIGN/METHODS: Newborn piglets (n = 8/group) were anesthetized, intubated, instrumented, and exposed to 30 min of normocapnic hypoxia, followed by asphyxia and asystolic cardiac arrest. Piglets were randomized to 0.2, 0.4, or 0.8IU/kg vasopressin, or 0.02 mg/kg epinephrine. Hemodynamic parameters were continuously measured. RESULTS: Median (IQR) time to ROSC was 172(103-418)s, 157(100-413)s, 122(93-289)s, and 276(117-480)s for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine groups, respectively (p = 0.59). The number of piglets that achieved ROSC was 6(75%), 6(75%), 7(88%), and 5(63%) for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine, respectively (p = 0.94). The epinephrine group had a 60% (3/5) rate of post-ROSC survival compared to 83% (5/6), 83% (5/6), and 57% (4/7) in the 0.2, 0.4, and 0.8IU/kg vasopressin groups, respectively (p = 0.61). CONCLUSION: Time to and incidence of ROSC were not different between all vasopressin dosages and epinephrine. However, non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin groups warrant further investigation. IMPACT: Time to and incidence of ROSC were not statistically different between all vasopressin dosages and epinephrine. Non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin-treated piglets. Overall poorer hemodynamic recovery following ROSC in epinephrine piglets compared to vasopressin groups. Human neonatal clinical trials examining the efficacy of vasopressin during asphyxial cardiac arrest will begin recruitment soon.

Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Virtual simulations for neonatal education.

Virtual simulation (VS) education involves the use of virtual reality, augmented reality, mixed reality and screen-based platforms, collectively referred to as extended reality, to provide education and assessment. This novel simulation modality supports experiential learning and increases access to practice opportunities, supplementing manikin-based simulation. VS has been used successfully for neonatal resuscitation training in high and low resource settings. Virtual simulators can be used to objectively assess learner performance in neonatal resuscitation knowledge and skills. When implementing VS for neonatal resuscitation training, key considerations include matching learning objectives with suitable technology, pre-session preparation, supporting learners, and debriefing. Additional research is needed to evaluate the impact of VS applications on clinical practice and patient outcomes.

Chest compression rates of 60/min versus 90/min during neonatal cardiopulmonary resuscitation: a randomized controlled animal trial.

Background: To compare chest compression (CC) rates of 60/min with 90/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 60/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. Methods: Newborn piglets (n = 7/group) were anesthetized, tracheotomized and intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 60/min or 90/min. CC was performed using an automated CC machine using CC superimposed with sustained inflation. Hemodynamic parameters, respiratory parameters, and applied compression force were continuously measured. Results: The mean (IQR) time to ROSC was 97 (65-149) s and 136 (88-395) s for CC rates of 60/min and 90/min, respectively (p = 0.31). The number of piglets that achieved ROSC was 5 (71%) and 5 (71%) with 60/min and 90/min CC rates, respectively (p = 1.00). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all similar with a CC rate of 60/min compared to 90/min. Conclusion: Time to ROSC, hemodynamic, and respiratory parameters were not significantly different between CC rates of 60/min vs. 90/min. Different CC rates during neonatal resuscitation warrant further investigation.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Exhaled CO2 monitoring to guide non-invasive ventilation at birth: a systematic review.

OBJECTIVE: Measuring exhaled carbon dioxide (ECO2) during non-invasive ventilation at birth may provide information about lung aeration. However, the International Liaison Committee on Resuscitation (ILCOR) only recommends ECO2 detection for confirming endotracheal tube placement. ILCOR has therefore prioritised a research question that needs to be urgently evaluated: 'In newborn infants receiving intermittent positive pressure ventilation by any non-invasive interface at birth, does the use of an ECO2 monitor in addition to clinical assessment, pulse oximetry and/or ECG, compared with clinical assessment, pulse oximetry and/or ECG only, decrease endotracheal intubation in the delivery room, improve response to resuscitation, improve survival or reduce morbidity?'. DESIGN: Systematic review of randomised and non-randomised studies identified by Ovid MEDLINE, Embase and Cochrane CENTRAL search until 1 August 2022. SETTING: Delivery room. PATIENTS: Newborn infants receiving non-invasive ventilation at birth. INTERVENTION: ECO2 measurement plus routine assessment compared with routine assessment alone. MAIN OUTCOME MEASURES: Endotracheal intubation in the delivery room, response to resuscitation, survival and morbidity. RESULTS: Among 2370 articles, 23 were included; however, none had a relevant control group. Although studies indicated that the absence of ECO2 may signify airway obstruction and ECO2 detection may precede a heart rate increase in adequately ventilated infants, they did not directly address the research question. CONCLUSIONS: Evidence to support the use of an ECO2 monitor to guide non-invasive positive pressure ventilation at birth is lacking. More research on the effectiveness of ECO2 measurement in addition to routine assessment during non-invasive ventilation of newborn infants at birth is needed. PROSPERO REGISTRATION NUMBER: CRD42022344849.