Anne Lee Solevåg

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.

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-1β (IL-1β). 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-1β 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.

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

BackgroundIn 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.MethodsTwo 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.ResultsMedian 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.ConclusionsIn 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.

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% O2 is detrimental, international guidelines still recommend its use. Clinical studies comparing 21% and 100% O2 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% O2 (n = 16). Return of spontaneous circulation (ROSC) was defined as a heart rate ≧100 min–1. Results: Mean time of hypoxia, pH, base excess and pCO2 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% O2, 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, pCO2, interleukin-1β 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.

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.

Brain inflammation induced by severe asphyxia in newborn pigs and the impact of alternative resuscitation strategies on the newborn central nervous system

Background:We compared the current guidelines for neonatal resuscitation with alternative measures and aimed to find out whether this modulated brain inflammation.Methods:Progressive asphyxia was induced in 94 newborn pigs until asystole. With the reference being resuscitation guidelines, 30 s of initial positive-pressure ventilation before compression (C) and ventilation (V) (C:V; 3:1) in 21% oxygen, pigs were randomized to (i) ventilation for 30, 60, or 90 s before chest compressions; (ii) C:V ratios of 3:1, 9:3, or 15:2; or (iii) 21% or 100% oxygen. Concentrations of inflammatory markers in the cerebrospinal fluid (CSF) and gene expression in the hippocampus and frontal cortex were measured for different interventions.Results:In CSF, S100 was higher with 90 s than with 30 or 60 s of initial positive-pressure ventilation, whereas concentrations of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were higher with 30 than with 60 s. Matrix metalloproteinase-2 (MMP-2) and intracellular adhesion molecule 1 (ICAM-1) were higher with 30 than with 60 s. No other comparison between ratios and oxygen concentrations used yielded significant results.Conclusion:With respect to signs of brain inflammation, newly born pigs at asystole should be ventilated for longer than 30 s before chest compressions start. C:V ratios of 9:3 and 15:2 as compared with 3:1, or air instead of pure oxygen, did not modulate inflammatory markers.

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% O2 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, pCO2, interleukin-1β 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.

Chest compressions in newborn animal models: A review

OBJECTIVE Much of the knowledge about the optimal way to perform chest compressions (CC) in newborn infants is derived from animal studies. The objective of this review was to identify studies of CC in newborn term animal models and review the evidence. We also provide an overview of the different models. METHODS DATA SOURCES MEDLINE, EMBASE and CINAHL, until September 29th 2014. Study eligibility criteria and interventions: term newborn animal models where CC was performed. RESULTS Based on 419 retrieved studies from MEDLINE and 502 from EMBASE, 28 studies were included. No additional studies were identified in CINAHL. Most of the studies were performed in pigs after perinatal transition without long-term follow-up. The models differed widely in methodological aspects, which limits the possibility to compare and synthesize findings. Studies uncommonly reported the method for randomization and allocation concealment, and a limited number were blinded. Only the evidence in favour of the two-thumb encircling hands technique for performing CC, a CC to ventilation ratio of 3:1; and that air can be used for ventilation during CC; was supported by more than one study. CONCLUSIONS Animal studies should be performed and reported with the same rigor as in human randomized trials. Good transitional and survival models are needed to further increase the strength of the evidence derived from animal studies of newborn chest compressions.

A review of approaches to optimise chest compressions in the resuscitation of asphyxiated newborns.

Objective Provision of chest compressions (CCs) and/or medications in the delivery room is associated with poor outcomes. Based on the physiology of perinatal asphyxia, we aimed to provide an overview of current recommendations and explore potential determinants of effective neonatal cardiopulmonary resuscitation (CPR): balancing ventilations and CC, CC rate, depth, full chest recoil, CC technique and adrenaline. Design A search in the databases MEDLINE (Ovid) and EMBASE until 10 April 2015. Setting Delivery room. Patients Asphyxiated newborn infants. Interventions CCs. Main outcome measures Haemodynamics, recovery and survival. Results Current evidence is derived from mathematical models, manikin and animal studies, and small case series. No randomised clinical trials examining neonatal CC have been performed. There is no evidence to refute a CC to ventilation (C:V) ratio of 3:1. Raising the intrathoracic pressure, for example, by superimposing a sustained inflation on uninterrupted CC, and a CC rate >120/min may be beneficial. The optimal neonatal CC depth is unknown, but factors influencing depth and consistency include the C:V ratio. Incomplete chest wall recoil can cause less negative intrathoracic pressure between CC and reduced CPR effectiveness. CC should be performed with the two-thumb method over the lower third of the sternum. The optimal dose, route and timing of adrenaline administration remain to be determined. Conclusions Successful CPR requires the delivery of high-quality CC, encompassing optimal (A) C:V ratio (B) rate, (C) depth, (D) chest recoil between CC, (E) technique and (F) adrenaline dosage. More animal studies with high translational value and randomised clinical trials are needed.