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AimThe study aimed to examine the optimal anterior-posterior depth which will reduce the time to return of spontaneous circulation and improve survival during chest compressions. Asphyxiated neonatal piglets receiving chest compression resuscitated with a 40% anterior-posterior chest depth compared with 33%, 25% or 12.5% will have reduced time to return of spontaneous circulation and improved survival.MethodsNewborn piglets (n=8 per group) were anaesthetised, intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to four intervention groups (‘anterior-posterior 12.5% depth’, ‘anterior-posterior 25% depth’, ‘anterior-posterior 33% depth’ or ‘anterior-posterior 40% depth’). Chest compressions were performed using an automated chest compression machine with a rate of 90 per minute. Haemodynamic and respiratory parameters, applied compression force, and chest compression depth were continuously measured.ResultsThe median (IQR) time to return of spontaneous circulation was 600 (600–600) s, 135 (90–589) s, 85 (71–158)* s and 116 (63–173)* s for the 12.5%, 25%, 33% and 40% depth groups, respectively (*pConclusionsTime to return of spontaneous circulation and survival were similar between 25%, 33% and 40% anterior-posterior depths, while 12.5% anterior-posterior depth did not result in return of spontaneous circulation or survival. Haemodynamic and respiratory parameters improved with increasing anterior-posterior depth, suggesting improved organ perfusion and oxygen delivery with 33%–40% anterior-posterior depth.Trial registration numberPTCE0000193.

Background Chest compression (CC) during sustained inflations (CC+SI) compared with CC with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation in asphyxiated pediatric piglets will reduce time to return of spontaneous circulation (ROSC). Methods and Results Piglets (20–23 days of age, weighing 6.2–10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure P =0.0292). There was a 100% higher rate of ROSC in the CC+SI group versus CCaV group, with 10 (83%) versus 5 (42%) achieving ROSC ( P =0.089), respectively. Piglets in the CC+SI and CCaV groups received intravenous epinephrine boluses to achieve ROSC (8/12 versus 10/12 P =0.639). There was a significantly higher minute ventilation in the CC+SI group, which was secondary to a 5‐fold increase in the number of inflations per minute and a 1.5‐fold increase in tidal volume. Conclusions CC+SI reduced time to ROSC and improved survival compared with using CCaV. CC+SI allowed passive ventilation of the lung while providing chest compressions. This technique warrants further studies to examine the potential to improve outcomes in pediatric patients with cardiac arrest. Registration URL: https://www.preclinicaltrials.eu ; Unique identifier: PCTE0000152.

Background: Male newborns have a greater risk of poor cardiovascular and respiratory outcomes compared to females. The mechanisms associated with the “male disadvantage” remains unclear. We have previously shown no difference between male and female newborn piglets during hypoxia, asphyxia, resuscitation, and post-resuscitation recovery. However, it is unknown if there are differences in resuscitation outcomes between males and females during different cardiopulmonary resuscitation techniques.Intervention and Measurements: Secondary analysis of 184 term newborn mixed breed duroc piglets (1–3 days of age, weighing 2.0 (0.2) kg) from seven different studies, which were exposed to 30–50 min of normocapnic hypoxia followed by asphyxia until asystole. This was followed by cardiopulmonary resuscitation. For the analysis, piglets were divided into male and female groups, as well as resuscitation technique groups (sustained inflation, 3:1 compression-to-ventilation ratio, or asynchronous ventilations during chest compressions). Cardiac function, carotid blood flow, and cerebral oxygenation were continuously recorded throughout the experiment.Main results: Regardless of resuscitation technique, there was no significant difference between males and females in the number achieving return of spontaneous circulation (ROSC) [95/123 (77%) vs. 48/61 (79%)], the time to achieve ROSC [112 (80–185) s vs. 110 (77–186) s], and the 4-h survival rate [81/95 (85%) vs. 40/48 (83%)]. Levels of the injury markers interleukin (IL)−1ß, IL-6, IL-8, and tumor necrosis factor-α in frontoparietal cortex tissue homogenates were similar between males and females.Conclusions: Regardless of resuscitation technique, there was no significant effect of sex on resuscitation outcome, survival, and hemodynamic recovery in asphyxiated newborn piglets.

Introduction: Neonatal chest compression (CC) should be performed to a 1/3 anterior-posterior (AP) chest diameter depth, however, the optimal AP depth is unknown. Hypothesis: We hypothesized that in asphyxiated neonatal piglets a 40% AP depth compared to 1/3, or 1/4 AP depth will reduce time to achieve return of spontaneously circulation and improve survival. Methods: Newborn piglets (n=8/group) were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to four intervention groups (“AP 12.5% depth”, “AP 1/4 depth”, “AP 1/3 depth” or “AP 40% depth“). CCs were performed using an automated CC machine with a rate of 90/min. Hemodynamic and respiratory parameters were continuously measured. Results: Median (IQR) time to return of spontaneously circulation was 70 (60-117), 85 (72-90), 90 (90-130), and 600 (600-600) sec with AP 40% depth, AP 1/3 depth, AP 1/4 depth, AP 12.5% depth, respectively. No piglet in the AP 12.5% depth group achieved ROSC while the short-term survival (1h) in the other groups was 100%. Systolic and diastolic blood pressure, central venous pressure, carotid blood flow, tidal volume, and minute ventilation increased with increasing AP depth. Conclusions: Time to return of spontaneously circulation and survival was similar between 1/4, 1/3, and 40% AP depth, while 12.5% AP depth did not result in return of spontaneously circulation. Hemodynamic and respiratory parameters improved with increasing AP depth suggesting that 40% AP depth might provide improved organ perfusion and oxygen delivery.

ObjectiveSustained inflation (SI) during chest compression (CC = CC+SI) significantly reduces time to return of spontaneous circulation (ROSC) compared to 3:1 compression-to-ventilation ratio during neonatal resuscitation. However, the optimal peak inflation pressure (PIP) of SI during CC+SI to improve ROSC and hemodynamic recovery in severely asphyxiated piglets is unknown.AimTo examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets.Intervention and measurementsTwenty-nine newborn piglets (1-3 days old) were anesthetized, intubated, instrumented and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into four groups: CC+SI with a PIP of 10 cmH2O (CC+SI_PIP_10, n=8), a PIP of 20 cmH2O (CC+SI_PIP_20, n=8), a PIP of 30 cmH2O (CC+SI_PIP_30, n=8), and a sham-operated control group (n=5). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment.Main resultsBaseline parameters were similar between all groups. There was no difference in asphyxiation (duration and degree) between intervention groups. PIP correlated positively with tidal volume and inversely with exhaled CO2 during cardiopulmonary resuscitation. Time to ROSC and rate of ROSC were similar between piglets resuscitated with CC+SI_PIP_10, CC+SI_PIP_20, and CC+SI_PIP_30 cmH2O: median (IQR) 75 (63-193) sec, 94 (78-210) sec, and 85 (70-90) sec; 5/8 (63%), 7/8 (88%), and 3/8 (38%) (p=0.56 and p=0.12, respectively). All piglets that achieved ROSC survived to four hours post-resuscitation. Piglets resuscitated with CC+SI_PIP_30 cmH2O exhibited increased concentrations of pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α in the frontoparietal cerebral cortex (both pConclusionsIn asphyxiated term newborn piglets resuscitated by CC+SI, the use of different PIPs resulted in similar time to ROSC, but PIP at 30 cmH2O showed a larger VT delivery, lower exhaled CO2 and increased tissue inflammatory markers in the brain.

Background Current neonatal resuscitation guidelines recommend using 100% oxygen during chest compressions (CC), however the most effective oxygen concentration during cardiopulmonary resuscitation remains controversial. Aim In term newborn piglets with asphyxia-induced cardiac arrest does 21% oxygen compared to 100% oxygen during resuscitation using CC during sustained inflation (SI; CC + SI) will have a reduced time to return of spontaneous circulation (ROSC). Intervention and measurements Twenty-two mixed breed piglets (1–3 days old, 1.7–2.4 kg), were obtained on the day of the experiment and anesthetized, intubated, instrumented, and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were resuscitated using CC + SI and randomized to 21% oxygen (n = 8) or 100% oxygen (n = 8). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. Main results Baseline parameters were similar between 21% and 100% oxygen groups. There was no difference in asphyxiation (duration and degree) between groups. Time to ROSC was similar between 21% and 100% oxygen groups: median (interquartile range - IQR) 80 (70−190)sec vs. 90 (70−324)sec, (p = 0.56). There was no significant difference in the rate of ROSC between 21% and 100% oxygen groups: 7/8 (88%) vs. 5/8 (63%), (p = 0.569). All piglets that achieved ROSC survived to four hours post-resuscitation. Hemodynamics and regional perfusion were not significantly different between groups. Conclusions In term newborn piglets resuscitated by CC + SI, the use of 21% oxygen resulted in a similar time to ROSC, short-term survival, and hemodynamic recovery compared to 100% oxygen.

Approximately 0.1% for term and 10–15% of preterm infants receive chest compression (CC) in the delivery room, with high incidence of mortality and neurologic impairment. The poor prognosis associated with receiving CC in the delivery room has raised concerns as to whether specifically-tailored cardiopulmonary resuscitation methods are needed. The current neonatal resuscitation guidelines recommend a 3:1 compression:ventilation ratio; however, the most effective approach to deliver chest compression is unknown. We recently demonstrated that providing continuous chest compression superimposed with a high distending pressure or sustained inflation significantly reduced time to return of spontaneous circulation and mortality while improving respiratory and cardiovascular parameters in asphyxiated piglet and newborn infants. This review summarizes the current available evidence of continuous chest compression superimposed with a sustained inflation.

BackgroundSustained inflation (SI) during chest compression (CC = CC+SI) has been recently shown as an alternative method during cardiopulmonary resuscitation in neonates. However, the optimal peak inflation pressure (PIP) of SI during CC+SI to improve ROSC and hemodynamic recovery is unknown.ObjectiveTo examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets.MethodsTwenty-nine newborn piglets (1-3 days old) were anesthetized, intubated, instrumented and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into four groups: CC+SI with a PIP of 10 cmH2O (CC+SI_PIP_10, n = 8), a PIP of 20 cmH2O (CC+SI_PIP_20, n = 8), a PIP of 30 cmH2O (CC+SI_PIP_30, n = 8), and a sham-operated control group (n = 5). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment.ResultsBaseline parameters were similar between all groups. There was no difference in asphyxiation (duration and degree) between intervention groups. PIP correlated positively with tidal volume (VT) and inversely with exhaled CO2 during cardiopulmonary resuscitation. Time to ROSC and rate of ROSC were similar between piglets resuscitated with CC+SI_PIP_10, CC+SI_PIP_20, and CC+SI_PIP_30 cmH2O: median (IQR) 75 (63-193) sec, 94 (78-210) sec, and 85 (70-90) sec; 5/8 (63%), 7/8 (88%), and 3/8 (38%) (p = 0.56 and p = 0.12, respectively). All piglets that achieved ROSC survived to four hours post-resuscitation. Piglets resuscitated with CC+SI_PIP_30 cmH2O exhibited increased concentrations of pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α in the frontoparietal cerebral cortex (both pConclusionIn asphyxiated term newborn piglets resuscitated by CC+SI, the use of different PIPs resulted in similar time to ROSC, but PIP at 30 cmH2O showed a larger VT delivery, lower exhaled CO2 and increased tissue inflammatory markers in the brain.

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) ('classic' BPD) and with minimal early lung disease ('atypical' BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1(st), 3(rd) and 7(th) day of life and measured the levels of leukotriene E(4) (LTE(4)) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3(rd) day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7(th) day were the independent risk factor for developing moderate/severe BPD. In 'classic' BPD, the 8-OHdG values on the 3(rd) day were higher than those of 'atypical' BPD. In 'atypical' BPD, the LTE(4) values on the 7(th) day were higher than the values in 'classic' BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in 'atypical' BPD.

To date, preterm infants with respiratory distress syndrome (RDS) after birth have been managed with a combination of endotracheal intubation, surfactant instillation, and mechanical ventilation. It is now recognized that noninvasive ventilation (NIV) such as nasal continuous positive airway pressure (CPAP) in preterm infants is a reasonable alternative to elective intubation after birth. Recently, a meta-analysis of large controlled trials comparing conventional methods and nasal CPAP suggested that CPAP decreased the risk of the combined outcome of bronchopulmonary dysplasia or death. Since then, the use of NIV as primary therapy for preterm infants has increased, but when and how to give exogenous surfactant remains unclear. Overcoming this problem, minimally invasive surfactant therapy (MIST) allows spontaneously breathing neonates to remain on CPAP in the first week after birth. MIST has included administration of exogenous surfactant by intrapharyngeal instillation, nebulization, a laryngeal mask, and a thin catheter. In recent clinical trials, surfactant delivery via a thin catheter was found to reduce the need for subsequent endotracheal intubation and mechanical ventilation, and improves short-term respiratory outcomes. There is also growing evidence for MIST as an alternative to the INSURE (intubation-surfactant-extubation) procedure in spontaneously breathing preterm infants with RDS. In conclusion, MIST is gentle, safe, feasible, and effective in preterm infants, and is widely used for surfactant administration with noninvasive respiratory support by neonatologists. However, further studies are needed to resolve uncertainties in the MIST method, including infant selection, optimal surfactant dosage and administration method, and need for sedation.

For many years preterm infants with respiratory distress syndrome have been managed with a combination of intubation and surfactant replacement therapy. It is now recognized that applying noninvasive ventilation (NIV) such as nasal continuous positive airway pressure (CPAP) in preterm infants is a reasonable alternative to early intubation after birth. Recently, nasal CPAP has shown a benefit with a small reduction in the risk of the combined outcome of death or bronchopulmonary dysplasia. There has been an upsurge in the use of NIV as primary therapy for preterm infants, bringing with it the dilemma of when and how to give exogenous surfactant. In an effort to overcome this problem, minimally invasive surfactant therapy (MIST) to spontaneously breathing infants, allows them to remain on CPAP in first days after birth. MIST has included administration of exogenous surfactant by brief tracheal catheterization, aerosolization, laryngeal mask, and intrapharyngeal instillation. In recent clinical trials, surfactant delivery via brief tracheal catheterization was found to reduce the need for subsequent intubation and mechanical ventilation and to improve short-term respiratory outcomes. In conclusion, MIST is gentle, safe, feasible and effective to perform in preterm infants and will also be used commonly in Korea.

Purpose : This study aims to describe the clinical characteristics of severe meconium aspiration syndrome (MAS) which re quired mechanical ventilation over 48 h and to delineate the progress of respiratory failure and radiographic findings in severe MAS. Methods : Twelve infants admitted to the Neonatal Intensive Care Unit (NICU) of the Seoul National University Bundang Hospital diagnosed with severe MAS from January 2004 to July 2007 were analyzed retrospectively. Results : The presence of persistent pulmonary hypertension of the newborn (PPHN) is the only independently significant risk factor for a longer hospital stay and longer duration of mechanical ventilation. Surfactant replacement therapy (SRT) was not randomized but only performed in infants with radiographic findings for respiratory distress syndrome (RDS). In the presence of radiographic findings for RDS, the duration of high-frequency oscillatory ventilation was significantly longer. PPHN developed in 8 infants (75%). The PPHN group had a significantly longer duration of mechanical ventilation. All infants who received SRT showed radiographic improvement within 12 h, but there was no significant change in the severity score during the same period. Infants without the PPHN complications showed significant decrease in the severity score within 12 h after SRT, whereas infants with PPHN complications did not. Conclusion : The clinical course of severe MAS differed significantly depending on the development of PPHN. SRT conferred radiographic improvement in infants who showed radiographic findings for RDS, but did not influence the clinical course of MAS significantly. (Korean J Pediatr 2008;51:713-721)