Sustained inflation with 21% versus 100% oxygen during cardiopulmonary resuscitation of asphyxiated newborn piglets - A randomized controlled animal study.

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.

Incidence of Newborn Stabilization and Resuscitation Measures and Guideline Compliance during the First Minutes of Life in Norway.

BACKGROUND: Most newborns manage the transition from intra- to extrauterine life without interventions, yet neonatal morbidity caused by failure of transition remains an important health problem. OBJECTIVE: To determine the incidence of neonatal stabilization and resuscitation measures and guideline compliance during the first minutes after birth. METHODS: This is a prospective, observational study of all births in three Norwegian hospitals. All interventions performed, including suctioning, use of pulse oximetry, continuous positive airway pressure (CPAP), positive pressure ventilation (PPV), supplemental oxygen, intubation, and administration of drugs, were registered at every on-call team shift during the study period. RESULTS: A total of 1,507 live-born infants were included, of whom 264 (18%) were brought to the resuscitation crib. Oropharyngeal suctioning was performed in 77 (5%), deep blind suctioning was carried out in 10 (1%) and 84 (6%) were monitored using pulse oximetry. PPV was provided in 58 cases (4%) - 8 (21%) of <34 weeks and 50 (3%) of ≥34 weeks of gestation. Sustained inflation is not routinely used in these departments. CPAP (without PPV) was provided in 17 cases (1%) - 4 (0.3%) were intubated and ventilated through the endotracheal tube. Supplemental oxygen was given to 39 infants (3%) - 9 without pulse oximetry monitoring. The median (interquartile range) birth weight and gestational age of the newborns requiring PPV and/or CPAP were 3,220 g (2,643-3,858) and 39 weeks (37-41), respectively. CONCLUSION: In this study, the need for resuscitation and/or stabilization measures was commonly considered, and 4% of all newborns received PPV. Despite strong guideline emphasis on the use of pulse oximetry to guide oxygen administration, many infants received oxygen treatment without pulse oximetry monitoring.

Pulse oximetry performance in mechanically ventilated newborn infants.

Pulse oximetry is widely used to target oxygenation in newborn infants. In a retrospective chart review of 138 mechanically ventilated infants, pulse oximetry overestimated blood oxygen saturation compared to arterial blood gas analyses. Despite improvements in pulse oximeter technology, pulse oximetry performance in sick newborns should still be under scrutiny.

How doctors learn and perform sustained inflations with a self-inflating bag: a manikin study with a newborn lung simulator.

AIM: Sustained inflations during initial resuscitation may help a depressed infant make a more efficient transition to air-filled lungs. This study examined whether doctors could perform sustained inflations with a self-inflating bag in high and low compliance settings and with an open or blocked pressure-relief valve. METHODS: We asked 43 doctors to carry out sustained inflations for more than 5-sec in a manikin connected to a newborn lung simulator with randomised compliance settings. Tidal volume, inflation time, peak and mean inflating pressure were measured, and 34 were retested 3 months later. RESULTS: The majority of the doctors - 72% in the initial study and 62% in the retest - managed sustained inflations within three ventilation attempts, irrespective of lung compliance setting and years of work experience. Using a blocked pressure-relief valve produced higher tidal volume (27.8 versus 22.6 mL, p < 0.001), inflation time (8.9 versus 8.1 sec, p = 0.025), peak inflating pressure (34.0 versus 28.0 cmH2O; p = 0.012) and mean inflating pressure (28.1 versus 22.8 cmH2O; p < 0.001). CONCLUSION: The majority of doctors could deliver sustained inflation with a self-inflating bag in a newborn lung simulator for more than 5-sec. Using a blocked pressure-relief valve resulted in higher inflation time, tidal volume and inflation pressure.

Use of a modified pediatric early warning score in a department of pediatric and adolescent medicine.

BACKGROUND: Several versions of the Pediatric Early Warning Score (PEWS) exist, but there is limited information available on the use of such systems in different contexts. In the present study, we aimed to examine the relationship between a modified version of The Brighton Paediatric Early Warning Score (PEWS) and patient characteristics in a Norwegian department of pediatric and adolescent medicine. In addition, we sought to establish guidelines for escalation in patient care based on the PEWS in our patient population. METHODS: The medical records of patients referred for acute care from March to May 2011 were retrospectively reviewed. Children with a PEWS ≥3 were compared to children with a PEWS 0-2 with regard to age, diagnostic group and indicators of severe disease. RESULTS: A total of 761 patients (0-18 years of age) were included in the analysis. A younger age and diagnostic groups such as lower airway and cardiovascular disease were associated with PEWS ≥3. Upper airway disease and minor injury were more frequent in patients with PEWS 0-2. Children with PEWS ≥3 received fluid resuscitation, intravenous antibiotics, and oxygen supplementation, and were transferred to a higher level of care more often than children with PEWS 0-2. CONCLUSIONS: A PEWS ≥3 was associated with severe illnesses and surrogate markers of cardio-respiratory compromise. Patients with PEWS ≥3 should be carefully monitored to prevent further deterioration.

Lung Injury in Asphyxiated Newborn Pigs Resuscitated from Cardiac Arrest - The Impact of Supplementary Oxygen, Longer Ventilation Intervals and Chest Compressions at Different Compression-to-Ventilation Ratios.

INTRODUCTION: Non-specific lung inflammatory events caused by severe asphyxia may be intensified by the way we resuscitate the newly born. Assessing lung injury is potentially important because if alternative resuscitation approaches induces similar inflammatory responses or less lung injury. then we may choose the resuscitation approach that is most gentle, and easiest to perform and learn. We investigated the levels of lung inflammatory markers by comparing different ventilation, chest compression and inhaled oxygen fraction strategies in resuscitation of newly born pigs at cardiac arrest. MATERIALS AND METHODOLOGY: Progressive asphyxia in newborn pigs was induced until asystole occurred. With current resuscitation guidelines as a reference group, pigs were randomized to receive initial ventilation before chest compressions for 30s, 60s or 90s, or to compression-to-ventilation ratios 3:1or 9:3, or to resuscitation using pure oxygen or air. We analysed inflammatory markers in bronchoalveolar lavage fluid (BAL), IL8 and TNFα, and lung tissue qPCR for genes matrix metalloproteinases (MMP)2, MMP9, TNFα and ICAM-1. RESULTS: BAL-levels of TNFα and IL8 tended to be higher in the 30s group compared to 60s group (p = 0.028 and p = 0.023, respectively) as was gene expression in lung tissue of ICAM-1 and MMP2 (p=0.012 and p=0.043, respectively). MMP2 expression was slightly higher in the 30s group compared to 90s group (p = 0.020). No differences were found between pigs resuscitated with C:V ratio 9:3 and 3:1 or pure oxygen versus air. CONCLUSION: Compared to current guidelines, with respect to lung injury, resuscitation with longer initial ventilation should be considered. Longer series of chest compressions did not change the lung inflammatory response, neither did the use of air instead of pure oxygen in severely asphyxiated pigs resuscitated from asystole.

Minute ventilation at different compression to ventilation ratios, different ventilation rates, and continuous chest compressions with asynchronous ventilation in a newborn manikin.

BACKGROUND: In newborn resuscitation the recommended rate of chest compressions should be 90 per minute and 30 ventilations should be delivered each minute, aiming at achieving a total of 120 events per minute. However, this recommendation is based on physiological plausibility and consensus rather than scientific evidence. With focus on minute ventilation (Mv), we aimed to compare today's standard to alternative chest compression to ventilation (C:V) ratios and different ventilation rates, as well as to continuous chest compressions with asynchronous ventilation. METHODS: Two investigators performed cardiopulmonary resuscitation on a newborn manikin with a T-piece resuscitator and manual chest compressions. The C:V ratios 3:1, 9:3 and 15:2, as well as continuous chest compressions with asynchronous ventilation (120 compressions and 40 ventilations per minute) were performed in a randomised fashion in series of 10 × 2 minutes. In addition, ventilation only was performed at three different rates (40, 60 and 120 ventilations per minute, respectively). A respiratory function monitor measured inspiration time, tidal volume and ventilation rate. Mv was calculated for the different interventions and the Mann-Whitney test was used for comparisons between groups. RESULTS: Median Mv per kg in ml (interquartile range) was significantly lower at the C:V ratios of 9:3 (140 (134-144)) and 15:2 (77 (74-83)) as compared to 3:1 (191(183-199)). With ventilation only, there was a correlation between ventilation rate and Mv despite a negative correlation between ventilation rate and tidal volumes. Continuous chest compressions with asynchronous ventilation gave higher Mv as compared to coordinated compressions and ventilations at a C:V ratio of 3:1. CONCLUSIONS: In this study, higher C:V ratios than 3:1 compromised ventilation dynamics in a newborn manikin. However, higher ventilation rates, as well as continuous chest compressions with asynchronous ventilation gave higher Mv than coordinated compressions and ventilations with 90 compressions and 30 ventilations per minute.

Return of spontaneous circulation with a compression:ventilation ratio of 15:2 versus 3:1 in newborn pigs with cardiac arrest due to asphyxia.

OBJECTIVE: International guidelines recommend a compression to ventilation (C:V) ratio of 3:1 in neonates, and 15:2 for other paediatric age groups. The authors aimed to compare these two C:V ratios in a neonatal swine model of cardiac arrest following asphyxia. DESIGN: Experimental animal study. SETTING: Facility for animal research. SUBJECTS: 22 newborn pigs (age 12-36 h, weight 2.0-2.7 kg). INTERVENTIONS: Progressive asphyxia until asystole. Animals were randomised to receive C:V 3:1 (n=11) or 15:2 (n=11). MAIN OUTCOME MEASURES: Return of spontaneous circulation (ROSC) was defined as a heart rate ≥ 100 bpm. Also of interest were haemodynamic parameters, cerebral and systemic oxygen saturation and the proinflammatory cytokine interleukin-1ß (IL-1ß). RESULTS: Two animals in each group did not achieve ROSC. Mean (SD) increase in diastolic blood pressure (DBP; mm Hg) during compression cycles was significantly higher at a C:V ratio of 15:2 than 3:1 (7.1 (2.8) vs 4.8 (2.6)). Median time (IQR) to ROSC for the 3:1 group was 150 (140-180) s, and 195 (145-358) s for the 15:2 group. There were no significant differences in the temporal changes in haemodynamic parameters or oxygen saturation indices between the groups. IL-1ß levels in cerebrospinal and bronchoalveolar lavage fluid was comparable between the groups. CONCLUSION: In neonatal pigs with asphyxia-induced cardiac arrest, the response to a C:V ratio of 15:2 is not better than the response to a C:V ratio of 3:1 despite better generation of DBP during resuscitation.

Delayed onset of cardiac compressions in cardiopulmonary resuscitation of newborn pigs with asphyctic cardiac arrest.

BACKGROUND: When 30 s of initial positive pressure ventilation fails to stabilize the heart rate (HR) of newborns in the delivery room, the International Liaison Committee on Resuscitation guidelines recommend initiation of cardiac compressions. However, it may take longer than 30 s to establish effective pulmonary gas exchange. Whether a longer period of initial ventilation to reverse asphyxia would result in less need for cardiac compressions is unknown. OBJECTIVES: Our purpose was to investigate the effect of three different initial ventilation intervals prior to initiation of cardiac compressions on hemodynamic parameters, arterial blood gases, oxygen saturations and markers of inflammation and hypoxic damage in a piglet model of asystole due to asphyxia. METHODS: Noroc piglets were anesthetized and mechanically ventilated. Progressive asphyxia was induced until asystole occurred. Randomization was made to ventilation with 21% O(2) for (1) 30 s (n = 16), (2) 1 min (n = 16), or (3) 1.5 min (n = 8) before initiation of cardiac compressions. Return of spontaneous circulation (ROSC) was defined as HR ≥100 min(-1). RESULTS: Piglets initially ventilated for 30 s and 1 and 1.5 min achieved ROSC in a median of 150 (interquartile range 115-180),163 (124-177) and 282 (199-364) s, respectively. p value for group 1 versus group 2 was 0.51 and <0.001 for group 1 versus group 3. There were no differences in temporal changes in oxygen saturations, mean arterial blood pressure, HR, pH, pCO(2), interleukin-1ß or lactate/pyruvate ratios between groups. CONCLUSION: Although an additional 30 s to ensure effective ventilation does not impair the speed or success in achieving ROSC, delaying circulatory support for as long as 1.5 min of initial ventilation may be harmful.

Extended series of cardiac compressions during CPR in a swine model of perinatal asphyxia.

BACKGROUND: The rationale for a compression to ventilation ratio of 3:1 in neonates with primary hypoxic, hypercapnic cardiac arrest is to emphasize the importance of ventilation; however, there are no published studies testing this approach against alternative methods. An extended series of cardiac compressions offers the theoretical advantage of improving coronary perfusion pressures and hence, we aimed to explore the impact of compression cycles of two different durations. MATERIALS AND METHODS: Newborn swine (n = 32, age 12-36 h, weight 2.0-2.7 kg) were progressively asphyxiated until asystole occurred. Animals were randomized to receive compressions:ventilations 3:1 (n=16) or 9:3 (n=16). Return of spontaneous circulation (ROSC) was defined as a heart rate ≥ 100 beats min⁻¹. RESULTS: All animals except one in the 9:3 group achieved ROSC. One animal in the 3:1 group suffered bradycardia at baseline, and was excluded, leaving us with 15 animals in each group surviving to completion of protocol. Time to ROSC (median and interquartile range) was 150 s (115-180) vs. 148 s (116-195) for 3:1 and 9:3, respectively (P = 0.74). There were no differences in diastolic blood pressure during compression cycles or in markers of hypoxia and inflammation. The temporal changes in mean arterial blood pressure, heart rate, arterial blood gas parameters, and systemic and regional oxygen saturation were comparable between groups. CONCLUSION: Neonatal pigs with asphyxia-induced cardiac arrest did not respond to a compression:ventilation ratio of 9:3 better than to 3:1. Future research should address if alternative compression:ventilation ratios offer advantages over the current gold standard of 3:1.

Resuscitation of severely asphyctic newborn pigs with cardiac arrest by using 21% or 100% oxygen.

BACKGROUND: In spite of evidence suggesting that resuscitation with 100% O(2) is detrimental, international guidelines still recommend its use. Clinical studies comparing 21% and 100% O(2) included many infants with only mild and moderate asphyxia. OBJECTIVES: We aimed to investigate the effect of these oxygen fractions on haemodynamic parameters, arterial blood gases, oxygen saturation indices and markers of inflammation and hypoxic damage when resuscitating asystolic newborn pigs following asphyxia. METHODS: Newborn swine (n = 32, age 12-36 h, weight 2.0-2.7 kg) were progressively asphyxiated until asystole occurred. Cardiopulmonary resuscitation was initiated with ventilation with either 21% (n = 16) or 100% O(2) (n = 16). Return of spontaneous circulation (ROSC) was defined as a heart rate >or= 100 min(-1). RESULTS: Mean time of hypoxia, pH, base excess and pCO(2) at asystole were comparable between the groups. All animals except 2 in the 100% group achieved ROSC. One animal in the 21% group suffered bradycardia at baseline and was excluded. For the remaining 15 animals resuscitated with 21% O(2), median time to ROSC (interquartile range) was 150 s (115-180), whereas animals in the 100% group achieved ROSC after 135 s (113-168); p = 0.80. There were no differences in the temporal changes in mean arterial blood pressure, heart rate, pH, pCO(2), interleukin-1beta or lactate/pyruvate ratios. However, systemic and regional cerebral oxygen saturations were higher in the animals resuscitated with 100% oxygen. CONCLUSION: In this animal model of severe perinatal asphyxia, resuscitation with room air seemed to be as safe and effective as the use of 100% oxygen.