Publications by authors named "Po-Yin Cheung"

180 Publications

Bi-Level Noninvasive Ventilation in Neonatal Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis.

Neonatology 2021 Mar 23:1-10. Epub 2021 Mar 23.

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Background: Bi-level noninvasive ventilation (NIV) has been used in respiratory distress syndrome (RDS) as primary treatment, post-extubation, and to treat apnea. This review summarizes studies on bi-level NIV in premature infants with RDS. Nonsynchronized nasal intermittent positive pressure ventilation (nsNIPPV) and synchronized NIPPV (SNIPPV) use pressure settings ≥ those used during mechanical ventilation (MV), and biphasic continuous positive airway pressure (BiPAP) use two nasal continuous positive airway pressure (NCPAP) levels ≤4 cm H2O apart.

Methods: A systematic review (Medline OVID and Pubmed) and meta-analysis of randomized controlled trials. Primary outcomes were bronchopulmonary dysplasia (BPD) and mortality. Secondary outcomes included NIV failure (intubation) and extubation failure (re-intubation). Data were pooled using a fixed-effects model to calculate the relative risk (RR) with 95% confidence interval (CI) between NIV modes (RevMan v 5.3, Copenhagen, Denmark).

Results: Twenty-four randomized controlled trials that largely did not correct for mean airway pressure (MAP) and used outdated ventilators were included. Compared with NCPAP, both nsNIPPV and SNIPPV resulted in less re-intubation (RR 0.88 with 95% CI (0.80, 0.97) and RR 0.20 (0.10, 0.38), respectively) and BPD (RR 0.69 (0.49, 0.97) and RR 0.51 (0.29, 0.88), respectively). nsNIPPV also resulted in less intubation (RR 0.57 (0.45, 0.73) versus NCPAP, with no difference in mortality. One study showed less intubation in BiPAP versus NCPAP.

Conclusions: Bi-level NIV versus NCPAP may reduce MV and BPD in premature infants with RDS. Studies comparing equivalent MAP utilizing currently available machines are needed.
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http://dx.doi.org/10.1159/000514637DOI Listing
March 2021

Family-centered care management strategies for term and near-term neonates with brief hospitalization in a level III NICU in Shenzhen, China during the time of COVID-19 pandemic.

J Matern Fetal Neonatal Med 2021 Mar 22:1-4. Epub 2021 Mar 22.

Department of Pediatrics, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Background: Adopting the family-centered care (FCC) approach in the neonatal care has been shown to improve breastfeeding rate and parental satisfaction. To minimize the transmission of COVID-19, family visit in neonatal intensive care unit (NICU) was suspended in China. In order to maintain the benefits of FCC, the Hong Kong University-Shenzhen Hospital NICU modified FCC strategies. We evaluated the effects of new strategies and aimed to share our results and experience with other NICUs during the COVID-19 pandemic.

Methods: Using prospectively collected hospital databases, we retrospectively compared the demographic and clinical data of neonates, rates of breastfeeding at discharge, nosocomial infection and parental satisfaction one month before (open group) and after (closed group) the implementation of alternative FCC management strategies when family visit was suspended during COVID-19 pandemic.

Results: During the COVID-19 pandemic, we organized a multidisciplinary task force and adopted strategies of triage and screening, management of suspected infants, and breastfeeding promotion with effective communication. The nosocomial infection rate and parental satisfaction for open and closed groups (144 and 108 term and near-term neonates with brief hospitalization, respectively) were not different (1% vs. 0%,  = 1.00; 98.6 vs. 98.8,  = .80; respectively). Breastfeeding rate at discharge decreased but the difference was not significant (74% vs. 80%,  = .29).

Conclusions: In our experience, in term and near-term neonates with brief hospitalization, the alternative FCC strategies maintained high parental satisfaction without increased nosocomial infection rate, but strong support for breastfeeding was needed. Through multidisciplinary collaboration, the continuation of "modified" FCC in a level III NICU is feasible in the context of COVID-19 pandemic with reduced family visitation and participation in the care.
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http://dx.doi.org/10.1080/14767058.2021.1902499DOI Listing
March 2021

Return of Spontaneous Circulation Depends on Cardiac Rhythm During Neonatal Cardiac Arrest in Asphyxiated Newborn Animals.

Front Pediatr 2021 12;9:641132. Epub 2021 Feb 12.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada.

Pulseless electrical activity (PEA) occurs in asphyxiated newborn piglets and infants. We aimed to examine whether different cardiac rhythms (asystole, bradycardia, PEA) affects the resuscitation outcomes during continuous chest compressions (CC) during sustained inflations (CC+SI). This study is a secondary analysis of four previous randomized controlled animal trials that compared CC+SI with different CC rate (90 or 120/min), SI duration (20 or 60 s), peak inflation pressure (10, 20, or 30 cmHO), and oxygen concentration (18, 21, or 100%). Sixty-six newborn mixed breed piglets (1-3 days of age, weight 1.7-2.4 kg) were obtained on the day of experimentation from the University Swine Research Technology Center. In all four studies, piglets were randomized into intervention or sham. Piglets randomized to "intervention" underwent both hypoxia and asphyxia, whereas, piglets randomized to "sham" received the same surgical protocol, stabilization, and equivalent experimental periods without hypoxia and asphyxia. To compare differences in asphyxiation time, time to return of spontaneous circulation (ROSC), hemodynamics, and survival rate in newborn piglets with asystole, bradycardia or PEA. Piglets with PEA ( = 29) and asystole ( = 13) had a significantly longer asphyxiation time and time to ROSC vs. bradycardia ( = 24). Survival rates were similar between all groups. Compared to their baseline, mean arterial pressure and carotid blood flow were significantly lower 4 h after resuscitation in all groups, while being significantly higher in the bradycardia group. This study indicates that cardiac rhythm before resuscitation influences the time to ROSC and hemodynamic recovery after ROSC.
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http://dx.doi.org/10.3389/fped.2021.641132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907180PMC
February 2021

Hypotension in Preterm Infants (HIP) randomised trial.

Arch Dis Child Fetal Neonatal Ed 2021 Feb 24. Epub 2021 Feb 24.

Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Objective: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation.

Design: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment.

Setting: 10 sites across Europe and Canada.

Participants: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage.

Intervention: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management).

Primary Outcome: Survival to 36 weeks of PMA without severe brain injury.

Results: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038).

Conclusion: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area.

Trial Registration Number: NCT01482559, EudraCT 2010-023988-17.
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http://dx.doi.org/10.1136/archdischild-2020-320241DOI Listing
February 2021

Hemodynamic effects of high frequency oscillatory ventilation with volume guarantee in a piglet model of respiratory distress syndrome.

PLoS One 2021 16;16(2):e0246996. Epub 2021 Feb 16.

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Respiratory failure is a common condition faced by critically ill neonates with respiratory distress syndrome (RDS). High frequency oscillatory ventilation (HFOV) is often used for neonates with refractory respiratory failure related to RDS. Volume guarantee (VG) mode has been added to some HFOV ventilators for providing consistent tidal volume. We sought to examine the impact of adding the VG mode during HFOV on systemic and cerebral hemodynamics, which has not been studied to date. A neonatal piglet model of moderate to severe RDS was induced by saline lavage. Piglets (full term, age 1-3 days, weight 1.5-2.4 kg) were randomized to have RDS induced and receive either HFOV or HFOV+VG (n = 8/group) or sham-operation (n = 6) without RDS. Cardiac function measured by a Millar® catheter placed in the left ventricle as well as systemic and carotid hemodynamic and oxygen tissue saturation parameters were collected over 240 min of ventilation. Mean airway pressure, alveolar-arterial oxygen difference and left ventricular cardiac index of piglets on HFOV vs. HFOV+VG were not significantly different during the experimental period. Right common carotid artery flow index by in-situ ultrasonic flow measurement and cerebral tissue oxygen saturation (near-infrared spectroscopy) significantly decreased in HFOV+VG at 240 min compared to HFOV (14 vs. 31 ml/kg/min, and 30% vs. 43%, respectively; p<0.05). There were no significant differences in lung, brain and heart tissue markers of oxidative stress, ischemia and inflammation. HFOV+VG compared to HFOV was associated with similar left ventricular function, however HFOV+VG had a negative effect on cerebral blood flow and oxygenation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246996PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886162PMC
February 2021

Outcomes of Preterm Infants With Congenital Heart Defects After Early Surgery: Defining Risk Factors at Different Time Points During Hospitalization.

Front Pediatr 2020 28;8:616659. Epub 2021 Jan 28.

Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

Compared with those born at term gestation, infants with complex congenital heart defects (CCHD) who were delivered before 37 weeks gestational age and received neonatal open-heart surgery (OHS) have poorer neurodevelopmental outcomes in early childhood. We aimed to describe the growth, disability, functional, and neurodevelopmental outcomes in early childhood of preterm infants with CCHD after neonatal OHS. Prediction models were evaluated at various timepoints during hospitalization which could be useful in the management of these infants. We studied all preterm infants with CCHD who received OHS within 6 weeks of corrected age between 1996 and 2016. The Western Canadian Complex Pediatric Therapies Follow-up Program completed multidisciplinary comprehensive neurodevelopmental assessments at 2-year corrected age at the referral-site follow-up clinics. We collected demographic and acute-care clinical data, standardized age-appropriate outcome measures including physical growth with calculated scores; disabilities including cerebral palsy, visual impairment, permanent hearing loss; adaptive function (Adaptive Behavior Assessment System-II); and cognitive, language, and motor skills (Bayley Scales of Infant and Toddler Development-III). Multiple variable logistic or linear regressions determined predictors displayed as Odds Ratio (OR) or Effect Size (ES) with 95% confidence intervals. Of 115 preterm infants (34 ± 2 weeks gestation, 2,339 ± 637 g, 64% males) with CCHD and OHS, there were 11(10%) deaths before first discharge and 21(18%) deaths by 2-years. Seven (6%) neonates had cerebral injuries, 7 had necrotizing enterocolitis; none had retinopathy of prematurity. Among 94 survivors, 9% had cerebral palsy and 6% had permanent hearing loss, with worse outcomes in those with syndromic diagnoses. Significant predictors of mortality included birth weight score [OR 0.28(0.11,0.72), = 0.008], single-ventricle anatomy [OR 5.92(1.31,26.80), = 0.021], post-operative ventilation days [OR 1.06(1.02,1.09), = 0.007], and cardiopulmonary resuscitation [OR 11.58 (1.97,68.24), = 0.007]; for adverse functional outcome in those without syndromic diagnoses, birth weight 2,000-2,499 g [ES -11.60(-18.67, -4.53), = 0.002], post-conceptual age [ES -0.11(-0.22,0.00), = 0.044], post-operative lowest pH [ES 6.75(1.25,12.25), = 0.017], and sepsis [ES -9.70(-17.74, -1.66), = 0.050]. Our findings suggest preterm neonates with CCHD and early OHS had significant mortality and morbidity at 2-years and were at risk for cerebral palsy and adverse neurodevelopment. This information may be important for management, parental counseling and the decision-making process.
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http://dx.doi.org/10.3389/fped.2020.616659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876369PMC
January 2021

Effects of varying chest compression depths on carotid blood flow and blood pressure in asphyxiated piglets.

Arch Dis Child Fetal Neonatal Ed 2021 Feb 4. Epub 2021 Feb 4.

Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Steiermark, Austria

Background: Current neonatal resuscitation guidelines recommend chest compressions (CCs) should be delivered to a depth of approximately 1/3 of the anterior-posterior (AP) chest diameter. The aim of the study was to investigate the haemodynamic effects of different CC depths in a neonatal piglet model.

Methods: CCs were performed with an automated CC machine with 33%, 40% and 25% AP chest diameter in all piglets in the same order for a duration of 3 min each.

Results: Eight newborn piglets (age 1-3 days, weight 1.7-2.3 kg) were included in the study. Carotid blood flow (CBF) and systolic blood pressure were the highest using a CC depth of 40% AP chest diameter (19.3±7.5 mL/min/kg and 58±32 mm Hg).

Conclusion: CC depth influences haemodynamic parameters in asphyxiated newborn piglets during cardiopulmonary resuscitation. The highest CBF and systolic blood pressure were achieved using a CC depth of 40% AP chest diameter.

Trial Registration Number: PCTE0000148.
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http://dx.doi.org/10.1136/archdischild-2020-319473DOI Listing
February 2021

Asphyxiated Female and Male Newborn Piglets Have Similar Outcomes With Different Cardiopulmonary Resuscitation Interventions.

Front Pediatr 2020 3;8:602228. Epub 2020 Dec 3.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada.

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. 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. 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. Regardless of resuscitation technique, there was no significant effect of sex on resuscitation outcome, survival, and hemodynamic recovery in asphyxiated newborn piglets.
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http://dx.doi.org/10.3389/fped.2020.602228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793777PMC
December 2020

Early Risk Factors for Retinopathy of Prematurity in Very and Extremely Preterm Chinese Neonates.

Front Pediatr 2020 15;8:553519. Epub 2020 Oct 15.

Department of Pediatrics, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

To investigate the incidence and risk factors of retinopathy of prematurity (ROP) in very and extremely preterm (28- <32, and <28 weeks gestation, respectively) neonates, and the predictive factors for ROP in the early hours after birth and during hospitalization. Using a prospective database supplemented with a retrospective chart review, we identified preterm neonates born at gestation <32 weeks at the University of Hong Kong-Shenzhen Hospital between January 2015 and August 2018. Demographic and clinical variables were studied including indicators of disease acuity in the first 24 h after birth. We also compared the difference in risk factors between survivors with ROP and survivors without ROP. During the study period, there were 529 preterm neonates admitted to our neonatal intensive care unit with 120 (23%) born at <32 weeks' gestation. Thirteen (11%) neonates died. Among the 107 survivors, 23 (21%) had ROP, of whom five (22%) received laser and/or medical therapy for severe ROP. Compared with survivors without ROP, infants with ROP had lower mean blood pressure in the first 12 and 24 h after birth, respectively. Using multivariate regression, gestation age, mean blood pressure in the first 12 h after birth, hospital length of stay, and total days of blood gases pH <7.2 were independent risk factors for ROP. In this small cohort of Chinese neonates born <32 weeks' gestation, survivors with ROP had a lower blood pressure in the early hours after birth, younger gestation, longer hospital stay, and duration of acidosis when compared to those without ROP.
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http://dx.doi.org/10.3389/fped.2020.553519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593333PMC
October 2020

Effect of COVID-19 Precautions on Neonatal Resuscitation Practice: A Balance Between Healthcare Provider Safety, Infection Control, and Effective Neonatal Care.

Front Pediatr 2020 18;8:478. Epub 2020 Aug 18.

Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada.

Adaptations have been proposed for resuscitation of infants born to women with COVID-19, to protect health care providers, maintain infection control, and limit post-natal transmission. Changes especially impact respiratory procedures, personal protective equipment (PPE) use, resuscitation environments, teamwork, and family involvement. Adding viral filters to ventilation devices and modifications to intubation procedures might hinder effective ventilation. PPE could delay resuscitation, hinder task performance, and degrade communication. Changes to resuscitation locations and team composition alter workflow and teamwork. Physical distancing measures and PPE impede family-integrated care. These disruptions need to be considered given the uncertainty of vertical transmission of SARS-CoV-2.
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http://dx.doi.org/10.3389/fped.2020.00478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461943PMC
August 2020

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

Resuscitation 2020 10 24;155:39-47. Epub 2020 Jul 24.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, T5H 3V9, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.resuscitation.2020.07.015DOI Listing
October 2020

Effects of Early Myocardial Postnatal Maturation on Tolerance to Atrial Tachycardia With Altered Loading Conditions: An Swine Model.

Front Pediatr 2020 25;8:346. Epub 2020 Jun 25.

Fetal and Neonatal Cardiology Program, University of Alberta, Edmonton, AB, Canada.

Post-natal maturation of the myocardium starts shortly after birth and could affect how clinicians should provide hemodynamic support during this transition. Our aim was to assess the impact of post-natal maturation on tolerance to tachycardia with altered loading condition in a piglet model. We report three series of experimentations. Six groups of landrace cross neonatal piglets (NP) (1-3 days) and young piglets (YP) (14-17 days) were assigned to tachycardia (NP, YP), tachycardia and hypervolemia (NPV, YPV) or tachycardia and increased afterload (NPA, YPA) groups ( = 7/group). Under anesthesia, a pressure catheter was placed in the left ventricle and pacing wire in the right atrium. NPV and YPV groups had 60 ml/kg of normal saline infused over 20 min. NPA and YPA had balloon sub-occlusion of the descending aorta. Heart rate was increased by 10 bpm increments to 300 bpm. Left ventricular output was measured by echocardiography. NP maintained left ventricular output throughout the pacing protocol but it decreased in the YP ( < 0.001). With volume loading both NPV and YPV maintained their output with tachycardia. Although increased afterload resulted in reduced output during tachycardia in NPA ( = 0.005), there was no added impact on output in YPA. Interestingly, 4 of 7 NPV had significant desaturation at 300 bpm (baseline 99.7% vs. 300 bpm 87.9%, = 0.04), associated with a right to left shunt through the patent foramen ovale which resolved immediately on cessation of pacing. Early post-natal maturation is associated with improved myocardial tolerance to increased afterload and poor tolerance of tachycardia, the latter of which may be alleviated by increasing intravascular volume. These data could translate into the development of better strategies to optimize cardiac output at these early development ages.
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http://dx.doi.org/10.3389/fped.2020.00346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330128PMC
June 2020

Effects of sustained inflation pressure during neonatal cardiopulmonary resuscitation of asphyxiated piglets.

PLoS One 2020 23;15(6):e0228693. Epub 2020 Jun 23.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada.

Background: Sustained 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.

Objective: To examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets.

Methods: Twenty-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.

Results: Baseline 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 p<0.05 vs. sham-operated controls).

Conclusion: In 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310834PMC
August 2020

Table-top exercises to prepare for neonatal resuscitation in the Era of COVID-19.

Resuscitation 2020 06 28;151:85-86. Epub 2020 Apr 28.

Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, Canada; Department of Pediatrics, University of Alberta, Edmonton, Canada.

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http://dx.doi.org/10.1016/j.resuscitation.2020.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187840PMC
June 2020

Chest Compression in Neonatal Cardiac Arrest: Cerebral Blood Flow Measurements in Experimental Models.

Healthcare (Basel) 2020 Jan 10;8(1). Epub 2020 Jan 10.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB T5H 3V9, Canada.

The main aim of this paper was to provide an overview of studies that measured cerebral blood flow (CBF), directly or indirectly, during chest compression (CC) in neonatal animals. Our main research question was: how did different ways of performing CC influence CBF. We also aimed to discuss strengths and limitations of different methods for measuring CBF. Based on a search in Medline Ovid, we identified three studies in piglets that investigated different CC:ventilation (C:V) ratios, as well as three piglet studies investigating continuous CC with asynchronous ventilation. CBF was measured indirectly in all studies by means of carotid artery (CA) flow and regional cerebral oxygenation (rcSO). The CA provides flow to the brain, but also to extracerebral structures. The relative sizes of the internal and external carotid arteries and their flow distributions are species-dependent. rcSO is a non-invasive continuous measure, but does not only reflect CBF, but also cerebral blood volume and the metabolic rate of oxygen in the brain. Continuous CC with asynchronous ventilation at a CC rate of 120/min, and combining CC with a sustained inflation (four studies in piglets and one in lambs) provided a faster CBF recovery compared with the standard 3:1 C:V approach.
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http://dx.doi.org/10.3390/healthcare8010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151419PMC
January 2020

Incidence and Risk Factors for Hypoglycemia During Fetal-to-Neonatal Transition in Premature Infants.

Front Pediatr 2020 11;8:34. Epub 2020 Feb 11.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Alberta Health Services, Edmonton, AB, Canada.

To determine the incidence and risk factors associated with neonatal hypoglycemia in the premature population <33 weeks' gestation. This was a secondary retrospective analysis from previous infants enrolled in randomized controlled trials. A total of 255 infants <33 weeks' gestation were born during the study period. Eight infants were excluded due to missing glucose or maternal data and 175 infants were analyzed. Primary outcome was hypoglycemia (blood glucose <2.6mmol/L) determined via glucose oxidase method on arterial or venous blood gas. Birth weight subgroups: small for gestational age (SGA, birth weight <10%ile for gestational age) and large for gestational age (LGA, birth weight >90%ile for gestational age). Maternal hypertension was systolic blood pressure >140mmHg. 175 infants <33 weeks' gestational age (89 male, 84 female) were analyzed. Hypoglycemia occurred in 59 infants (33.7%). Maternal hypertension (OR 3.07, 95% CI 1.51-6.30, = 0.002) was the sole risk factor for neonatal hypoglycemia. Protective factors for hypoglycemia included labor at time of delivery (OR 4.51, 95% CI 2.29-9.18, p <0.0001) and antenatal magnesium sulfate (OR 2.53, 95% CI 1.23-5.50, = 0.01). There were no significant differences between hypoglycemic and euglycemic infants in sex, gestational age, LGA infants, antenatal steroids, vaginal birth, or maternal diabetes. SGA infants were excluded from analysis due to sample size. Premature infants <33 weeks' gestation have increased risk of hypoglycemia. Maternal hypertension increases hypoglycemia risk. Antenatal magnesium sulfate administration or labor at time of delivery decrease hypoglycemia risk.
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http://dx.doi.org/10.3389/fped.2020.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026247PMC
February 2020

Doppler Ultrasound for Heart Rate Assessment in a Porcine Model of Neonatal Asphyxia.

Front Pediatr 2020 31;8:18. Epub 2020 Jan 31.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, AB, Canada.

Approximately 10% of newborn infants require resuscitation at birth. Accurate heart rate (HR) assessment guides resuscitation interventions, thereby reducing morbidities and mortality. While existing HR assessment methods have several limitations, the Doppler ultrasound (Doppler-US) might be a promising alternative. We aimed to evaluate accuracy and optimal use of Doppler-US for HR assessments during neonatal asphyxia in a pre-clinical model. HR assessments were performed in 16 term newborn piglets that were anesthetized, intubated, and instrumented. Study I evaluated optimal transducer position, Study II compared aortic (AV) and pulmonary (PV) examination modes, and Study III examined accuracy during asphyxia, for HR assessment. Experimental setting. Asphyxia-induced piglets. Study I: Doppler-US (USCOM® 1A) HR was assessed on upper (A), middle (B), and lower (C) third of the sternum; study II: Doppler-US HR was assessed using AV and PV examination modes; study III: HR was assessed during asphyxia. Comparisons were made between Doppler-US and the clinical gold standard for HR assessments, electrocardiography (ECG). Study I: Mean (SD) Doppler-US HR at position A, B, and C showed no difference when compared to ECG HR. Study II: The mean (SD) Doppler-US HR using AV and PV modes also showed no difference when compared to ECG HR. Study III: Bland-Altman analysis revealed a mean difference (95% limits of agreement) between Doppler-US and ECG HR of 1.5 (-16 to 19) bpm. Additionally, motion artifacts produced false peaks and peak size was seen to decrease as bradycardia progressed. HR assessment using Doppler-US during asphyxia is accurate but has limitations and must be further evaluated prior to clinical use. Doppler-US can be positioned along the sternum and use either AV or PV mode for accurate assessments in a piglet model of neonatal asphyxia.
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http://dx.doi.org/10.3389/fped.2020.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004956PMC
January 2020

Comparing the Quality of Cardiopulmonary Resuscitation Performed at the Over-the-Head Position and Lateral Position of Neonatal Manikin.

Front Pediatr 2019 20;7:559. Epub 2020 Jan 20.

Hong Kong University-Shenzhen Hospital, Shenzhen, China.

Recent neonatal resuscitation guidelines suggest to perform chest compression (CC) at over-the-head (OTH) position instead of lateral position when further interventions including umbilical venous access are needed. Little information is available regarding the quality of cardiopulmonary resuscitation at different positions. Our study compared the quality of CC and ventilation at OTH position vs. lateral position in simulated neonatal resuscitation. Thirty-nine neonatal practitioners who attended the NRP®-based Provider renewal course workshop participated this study. Laerdal QCPR infant model were used to collect the data (2-miutes continuous recording) on quality of CC and ventilation of all participants at OTH position and lateral position in randomized order, both coordinated with mask ventilation or endotracheal ventilation through a Neopuff T-piece system. The quality of CC and ventilation were compared. Participants also reported their demographics and opinions in anonymous questionnaires after the session. The quality of CC and ventilation was not different when CPR was performed at OTH position and lateral position, in both mask and endotracheal ventilation. When CPR was performed with endotracheal ventilation, there were small faster frequencies of CC and ventilation at OTH position, compared with those at lateral position ( = 0.004). Most participants (87%) liked the CC performed at OTH position and had no adverse feedback. Performing CC at OTH position was generally well-received in simulated resuscitation; the quality of CC and ventilation at OTH position was not significantly different from that at lateral position, irrespective of mask or endotracheal ventilation.
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http://dx.doi.org/10.3389/fped.2019.00559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984128PMC
January 2020

Ventilation with 18, 21, or 100% Oxygen during Cardiopulmonary Resuscitation of Asphyxiated Piglets: A Randomized Controlled Animal Trial.

Neonatology 2020 2;117(1):102-110. Epub 2020 Jan 2.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada.

Background: In previous piglet experiments of profound asphyxia and cardiac arrest, recovery was similar when 21 and 100% oxygen were used for positive pressure ventilation (PPV). There was no consistent reduction in inflammation and oxidative stress in piglets ventilated with 21 or 100% oxygen.

Objectives: We aimed to investigate hypoxic resuscitation, i.e., PPV with 18% oxygen, in profoundly asphyxiated piglets with cardiac arrest. We hypothesized that resuscitation with 18% oxygen would result in less inflammation and oxidative stress compared to 21 or 100% oxygen.

Method: Twenty-four piglets were exposed to 30 min of normocapnic hypoxia followed by asphyxia until asystole. The piglets were randomized to PPV with 18% oxygen (n = 8), 21% oxygen (n = 8), or 100% oxygen (n = 8), and resuscitated with chest compressions and intravenous epinephrine. Return of spontaneous circulation (ROSC) was defined as an unassisted heart rate ≥100 bpm for 15 s. Lactate, GSH (total glutathione), GSSG (oxidized glutathione), and GSSG/GSH ratio were measured in myocardial and frontoparietal cortex homogenates. Interleukin (IL)-8, IL-6, IL-1β and tumor necrosis factor α were measured in frontoparietal cortex homogenates.

Results: There was no difference in time to ROSC or inflammation and oxidative stress in the 3 oxygen groups.

Conclusions: Resuscitation with 18% oxygen did not result in differences in inflammation and oxidative stress when compared to 21 or 100% oxygen.
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http://dx.doi.org/10.1159/000504494DOI Listing
November 2020

Is Supplemental Oxygen Needed in Cardiac Compression?-The Influence of Oxygen on Cerebral Perfusion in Severely Asphyxiated Neonates With Bradycardia or Cardiac Asystole.

Front Pediatr 2019 20;7:486. Epub 2019 Nov 20.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada.

Previous studies have investigated hemodynamic recovery using 21% vs. 100% oxygen during cardiopulmonary resuscitation (CPR) with chest compression (CC) in term infants. Animal studies indicate that systemic circulatory recovery is the same whether 21 or 100% oxygen is used during neonatal CPR. One of the main goals of resuscitation is to maintain cerebral oxygen delivery and prevent cerebral hypo- and hyperoxygenation. Oxygen delivery to the brain depends on cerebral hemodynamics, concentration of inhaled oxygen and blood oxygen content. The aim of this paper was to synthesize available research about cerebral oxygen delivery during CPR using different oxygen concentrations. Our research questions included how do different oxygen concentrations during CPR with CC influence cerebral perfusion and oxygen delivery, and how do cerebral hemodynamics during CC influence outcomes. A search in Medline Ovid using the search terms hypoxia AND oxygen AND cerebrovascular circulation AND infant, newborn. Inclusion criteria included studies of hypoxia and resuscitation of term infants. Studies were excluded if no measures of cerebral blood flow (CBF), oxygenation, or perfusion were reported. The search retrieved 21 papers. None of the studies directly fulfilled our inclusion criteria. The reference lists of some of the retrieved papers provided relevant animal studies with slightly conflicting results regarding blood flow and oxygen delivery to the brain using 21 or 100% oxygen. No study in term infants was identified, but we included one study in preterm infants. Studies in asphyxiated animals indicate that 100% oxygen increases CBF and oxygenation during and after CC with a potential increase in oxidative stress. In asphyxia, cerebral autoregulation may be impaired. Pure oxygen administration during CC may result in cerebral hyperperfusion and increased cerebral oxygen delivery, which may be associated with oxidative stress-related damage to the brain tissue. As systemic circulatory recovery is the same whether 21 or 100% oxygen is used during neonatal CPR, it is important to investigate whether brain damage could be aggravated when 100% oxygen is used.
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http://dx.doi.org/10.3389/fped.2019.00486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879425PMC
November 2019

Corrigendum to "Novel technologies for heart rate assessment during neonatal resuscitation at birth - A systematic review" [Resuscitation 143 (2019) 196-207].

Resuscitation 2020 Jan 4;146:288. Epub 2019 Dec 4.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.resuscitation.2019.11.015DOI Listing
January 2020

Evaluation of a Tap-Based Smartphone App for Heart Rate Assessment During Asphyxia in a Porcine Model of Neonatal Resuscitation.

Front Pediatr 2019 5;7:453. Epub 2019 Nov 5.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, AB, Canada.

Heart rate (HR) is the most significant parameter to assess a newborn's clinical status at birth. Recently, novel technologies including smartphone applications have been suggested for HR assessment during neonatal resuscitation. The aim of this study was to evaluate the accuracy, speed, and precision of the NeoTapLifeSupport (NeoTapLS) smartphone application using a digital stethoscope (DS) for HR assessment during neonatal resuscitation. Newborn piglets ( = 20, 1-3 days, 1.7-2.4 kg) were anesthetized, intubated, mechanically ventilated, and subjected to 30 min of hypoxia, followed by asphyxia. Asphyxia was induced by clamping the endotracheal tube and disconnecting the ventilator, until asystole was confirmed by zero carotid blood flow (CBF). Experimental setting. Asphyxia-induced newborn piglets. During asphyxia, HR assessments were performed with a DS using the NeoTapLS smartphone application, and compared to 6-s method (6 s), and 10-s method (10 s). Accuracy of obtained HRs was compared to CBF and electrocardiogram and assessment time using NeoTapLS, 6 s, and 10 s were also measured. The mean(SD) HR with the NeoTapLS was 68(26), compared to CBF with 68(27) bpm, 6 s with 68(27), and 10 s with 66(26) bpm during asphyxia. Bland-Altman analysis revealed no difference between HR using the NeoTapLS, 6 s, 10 s, compared to CBF HR, with NeoTapLS showing the smallest difference between 95% limits of agreement. The median (IQR) time required to obtain a HR using the NeoTapLS was 3(2-4) s, compared to 6(6-7), and 10(10-11) s for 6 and 10 s, respectively. Our data suggests that the NeoTapLS is accurate, fast, and precise during neonatal asphyxia to assess heart rate.
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http://dx.doi.org/10.3389/fped.2019.00453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848456PMC
November 2019

Sex Differences Between Female and Male Newborn Piglets During Asphyxia, Resuscitation, and Recovery.

Front Pediatr 2019 16;7:290. Epub 2019 Jul 16.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada.

Male and female newborns have differences in their fetal development, fetal-to-neonatal transition, and postnatal morbidity. However, the cardiovascular fetal-to-neonatal adaption is similar between sexes. No study has examined sex differences in newborns during hypoxia, asphyxia, cardio-pulmonary resuscitation, or post-resuscitation recovery. Secondary analysis (two previous publications and two studies currently under peer-review) of 110 term newborn mixed breed piglets (1-3 days of age, weighing 2.0 ± 0.2 kg), which were exposed to 30 min normocapnic hypoxia followed by asphyxia until asystole, which was achieved by disconnecting the ventilator and clamping the endotracheal tube. This was followed by cardio-pulmonary resuscitation. For the analysis piglets were divided into female and male groups. Cardiac function, carotid blood flow, and cerebral and renal oxygenation were continuously recorded throughout the experiment. A total of 35/41 (85%) female and 54/69 (78%) male piglets resuscitated achieved ROSC ( = 0.881). The median (IQR) time to achieve return of spontaneous circulation in females and males was 111 (80-228) s and 106 (80-206) s ( = 0.875), respectively. The 4-h survival rate was similar between females and males with 28/35 (80%) and 49/54 (91%) piglets surviving ( = 0.241), respectively. No difference between female and male newborn piglets was observed during hypoxia, asphyxia, resuscitation, and post-resuscitation recovery.
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http://dx.doi.org/10.3389/fped.2019.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646717PMC
July 2019

Effect of monitor positioning on visual attention and situation awareness during neonatal resuscitation: a randomised simulation study.

Arch Dis Child Fetal Neonatal Ed 2020 May 2;105(3):285-291. Epub 2019 Aug 2.

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Objectives: To compare situation awareness (SA), visual attention (VA) and protocol adherence in simulated neonatal resuscitations using two different monitor positions.

Design: Randomised controlled simulation study.

Settings: Simulation lab at the Royal Alexandra Hospital, Edmonton, Canada.

Participants: Healthcare providers (HCPs) with Neonatal Resuscitation Program (NRP) certification within the last 2 years and trained in neonatal endotracheal intubations.

Intervention: HCPs were randomised to either central (eye-level on the radiant warmer) or peripheral (above eye-level, wall-mounted) monitor positions. Each led a complex resuscitation with a high-fidelity mannequin and a standardised assistant. To measure SA, situation awareness global assessment tool (SAGAT) was used, where simulations were paused at three predetermined points, with five questions asked each pause. Videos were analysed for SAGAT and adherence to a NRP checklist. Eye-tracking glasses recorded participants' VA.

Main Outcome Measure: The main outcome was SA as measured by composite SAGAT score. Secondary outcomes included VA and adherence to NRP checklist.

Results: Thirty simulations were performed; 29 were completed per protocol and analysed. Twenty-two eye-tracking recordings were of sufficient quality and analysed. Median composite SAGAT was 11.5/15 central versus 11/15 peripheral, p=0.56. Checklist scores 46/50 central versus 46/50 peripheral, p=0.75. Most VA was directed at the mannequin (30.6% central vs 34.1% peripheral, p=0.76), and the monitor (28.7% central vs 20.5% peripheral, p=0.06).

Conclusions: Simulation, SAGAT and eye-tracking can be used to evaluate human factors of neonatal resuscitation. During simulated neonatal resuscitation, monitor position did not affect SA, VA or protocol adherence.
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http://dx.doi.org/10.1136/archdischild-2019-316992DOI Listing
May 2020

Novel technologies for heart rate assessment during neonatal resuscitation at birth - A systematic review.

Resuscitation 2019 10 19;143:196-207. Epub 2019 Jul 19.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Background: 6.5-9 million newborns worldwide require resuscitation at birth annually. During neonatal resuscitation, inaccurate or slow heart rate (HR) assessments may significantly increase risk of infant mortality or morbidity. Therefore fast, accurate, and effective HR assessment tools are critical for neonatal resuscitation.

Objective: To systematically review the literature about accuracy, latency, and efficacy of technologies for HR assessment during neonatal resuscitation.

Methods: Adhering to PRISMA guidelines, PubMed, EMBASE, and Google Scholar databases were systematically searched to identify studies related to technologies for HR assessment, which could be used to guide neonatal resuscitation.

Results: Forty-six studies evaluating HR assessment technologies for neonatal resuscitation were identified. In total, 16 studies (3/16 randomized trials and 13/16 observational studies) compared two or more HR assessment technologies to measure accuracy, latency, and efficacy. Of the trials, 1/3 had a low risk of bias while 2/3 had high risks. All observational studies had high risks of bias. Most studies considered infants not requiring resuscitation, constituting indirect evidence and lower certainty in the context of neonatal resuscitation. Two trials reported faster times to HR assessment using electrocardiogram with a mean(SD) 66(20) versus 114(39) s and a median(IQR) 24(19-39) versus 48(36-69) s (both p < 0.001), compared to pulse oximetry.

Conclusion: While electrocardiography is faster to assess HR at birth and more reliable to detect HR changes compared to other recommended technologies, practice should not exclusively rely on ECG. While novel technologies could support HR assessment, no studies validate their clinical efficacy during neonatal resuscitation.
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http://dx.doi.org/10.1016/j.resuscitation.2019.07.018DOI Listing
October 2019

The Relationship Between Heart Rate and Left Ventricular Isovolumic Relaxation During Normoxia and Hypoxia-Asphyxia in Newborn Piglets.

Front Physiol 2019 7;10:525. Epub 2019 May 7.

Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

Many asphyxiated neonates have cardiac complications including arrhythmia and contractile dysfunction. Little is known about the relationship between heart rate (HR) and diastolic function in asphyxiated neonates. We aimed to study the relationship between HR and left ventricular (LV) isovolumic relaxation (IVR) in neonates with asphyxia using a swine model. Term newborn piglets were anesthetized and acutely instrumented with the placement of Millar catheter in the left ventricle. Hemodynamic parameters including HR, cardiac output, stroke volume, dP/dt and dP/dt, and IVR time constant (Tau) were continuously measured and recorded. Sixteen piglets were exposed to 50-minute normocapnic hypoxia followed by asphyxia (mean of 3.2 min) by clamping of the endotracheal tube. Sham-operated piglets ( = 11) had no hypoxia nor asphyxia. The relationship between HR and other hemodynamic parameters were analyzed using Pearson Product Moment correlation test. Asphyxiated piglets had cardiogenic shock and metabolic acidosis (vs. sham-operated piglets). There were significant correlations between HR and diastolic function as shown by Tau at baseline (sham-operated: = -0.68, = 0.02; asphyxia: = -0.55, = 0.03) and during normoxia (53 min) of sham-operated piglets ( = -0.69, = 0.02). HR and Tau was not correlated during hypoxia-asphyxia (HA) ( = -0.01, = 0.97). Cardiac output was tightly correlated with stroke volume ( < 0.001) but not HR throughout the experimental period in both groups. There was no significant correlation between HR and other hemodynamic parameters during the experimental period in both groups. We observed an uncoupling between HR and IVR Tau of the neonatal heart during HA, which deserves further studies of the relationship between HR and LV diastolic function.
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http://dx.doi.org/10.3389/fphys.2019.00525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514222PMC
May 2019

Asynchronous ventilation at 120 compared with 90 or 100 compressions per minute improves haemodynamic recovery in asphyxiated newborn piglets.

Arch Dis Child Fetal Neonatal Ed 2020 Jul 23;105(4):357-363. Epub 2019 May 23.

Neonatology, Royal Alexandra Hospital, Edmonton, Alberta, Canada.

Objective: To determine whether different chest compression (CC) rates during continuous CC with asynchronous ventilations (CCaV) reduce time to return of spontaneous circulation (ROSC) and improved haemodynamic recovery in piglets aged 24-72 hours with asphyxia-induced asystole.

Methods: Thirty piglets (aged 24-72 hours) were anaesthetised, intubated, instrumented and exposed to 30 min normocapnic hypoxia followed by asphyxia. Piglets were randomised into four groups: CCaV with CC rate of 90 (CCaV+90, n=8), 100 (CCaV+100, n=8) or 120 compressions per minute (CCaV+120, n=8), and a sham-operated group (n=6). Cardiac function, carotid blood flow, cerebral and renal oxygenation and respiratory parameters were continuously recorded. Cerebral cortical tissue was harvested and assayed for inflammatory and injury markers.

Results: All three intervention groups had a similar number of piglets achieving ROSC (6/8, 5/8 and 5/8 for CCaV+120, CCaV+100 and CCaV+90, respectively) and mean ROSC time (120, 90 and 90 s for CCaV+120, CCaV+100 and CCaV+90, respectively). The haemodynamic recovery (indicated by carotid flow, cerebral and renal perfusion) was similar between CCaV+120 and sham by the end of experiment. In comparison, CCaV+90 and CCaV+100 had significantly reduced haemodynamic recovery compared with sham operated (p≤0.05). Inflammatory (interleukin [IL]-6 and IL-1β) and injury markers (lactate) were significantly higher in the frontoparietal cortex of CCaV+90 and CCaV+100 compared with sham, whereas brain injury markers were similar between CCaV+120 and sham.

Conclusions: Although there was no difference between the groups in achieving ROSC, the haemodynamic recovery of CCaV+120 was significantly improved compared with CCaV+90 and CCaV+100, which were also associated with higher cerebral inflammatory and brain injury markers.
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http://dx.doi.org/10.1136/archdischild-2018-316610DOI Listing
July 2020

Attenuation of Acute Renal Injury After the Post-resuscitation Administration of Doxycycline in Surviving Newborn Piglets With Severe Hypoxia-Reoxygenation.

Front Pediatr 2019 22;7:75. Epub 2019 Mar 22.

Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

Asphyxiated neonates often have myocardial dysfunction and renal insufficiency. Previously we demonstrated that doxycycline improved cardio-renal function through matrix metalloproteinase (MMP)-2 inhibition in an acute swine model of neonatal hypoxia-reoxygenation. The prolonged cardio-renal protective effects of doxycycline in neonates still remained unknown. We therefore hypothesized that the protective effects of doxycycline persisted in surviving subjects. Newborn piglets were instrumented and subjected to 1 h of hypoxia followed by reoxygenation with 21-25% oxygen and observed for 4 days. Intravenous doxycycline (30 mg/kg) or normal saline (1 mL, saline-control group) was given at 5 min of reoxygenation ( = 8/group) in a randomized, blinded fashion. Sham-operated piglets ( = 5) received no hypoxia-reoxygenation. At 96 h after reoxygenation, the left ventricular function was assessed by Millar® catheter. Renal injury was investigated by measuring plasma creatinine, urinary N-acetyl-D-glucosaminidase activity, renal tissue lactate and MMP-2 activity. Both hypoxia-reoxygenation groups had similar hypoxic stress with severe lactate acidosis, and hemodynamic recovery. Doxycycline-treated piglets had higher urine output with lower urine N-acetyl-D-glucosaminidase, plasma creatinine, and renal MMP-2 activity (vs. saline-controls; all < 0.05). These markers were all negatively correlated with urine output. In newborn piglets surviving hypoxia-reoxygenation, we observed a weak but significant and persistent attenuation of renal injury and improved recovery with the post-resuscitation administration of doxycycline.
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http://dx.doi.org/10.3389/fped.2019.00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439344PMC
March 2019

Non-perfusing cardiac rhythms in asphyxiated newborn piglets.

PLoS One 2019 4;14(4):e0214506. Epub 2019 Apr 4.

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada.

Aim: We recently demonstrated that asphyxiated piglets commonly had bradycardia displayed on electrocardiography (ECG) while no carotid blood flow (CBF) or audible heart sounds could be detected. Such pulseless electrical activity (PEA) in newborn infants has not previously been thoroughly described. The aim of this study was to further investigate the occurrence of non-perfusing cardiac rhythms in asphyxiated piglets and the potential implications for the success of cardiopulmonary resuscitation (CPR) and short-term survival.

Methods: Neonatal piglets (1-4 days, 1.7-2.4kg) had their right common carotid artery exposed and enclosed with a real-time ultrasonic flow probe. Heart rate (HR) was continuously measured and recorded using ECG. This allowed simultaneous monitoring of HR via ECG and CBF. The piglets were asphyxiated until cardiac arrest, defined as no CBF and no audible beat upon precordial auscultation. CPR was performed until return of spontaneous circulation (ROSC, defined as a HR ≥100 bpm). ECG traces were retrospectively assessed.

Results: Nine out of 21 piglets (43%) had QRS-complexes on their ECG while no CBF and no audible heart sounds could be detected. Five (56%) of the piglets with PEA and 12/12 (100%) piglets with asystole at cardiac arrest obtained ROSC (p = 0.02). Thirty-three per cent of the piglets with PEA versus 58% with asystole survived to 4 hours post-ROSC (p = 0.39).

Conclusion: Cardiac arrest in the presence of a non-perfusing cardiac rhythm on ECG is common in asphyxiated piglets. Clinical arrest in the presence of a non-perfusing cardiac rhythm on ECG may reduce the success of CPR.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448889PMC
December 2019

Cardiac arrest with pulseless electrical activity rhythm in newborn infants: a case series.

Arch Dis Child Fetal Neonatal Ed 2019 Nov 22;104(6):F572-F574. Epub 2019 Feb 22.

Department of Neonatology, Royal Alexandra Hospital, Edmonoton, Alberta, Canada.

The 2015 neonatal resuscitation guidelines added ECG to assess an infant's heart rate when determining the need for resuscitation at birth. However, a recent case report raised concerns about this technique in the delivery room. We report four cases of pulseless electrical activity during neonatal cardiopulmonary resuscitation in levels II-III neonatal intensive care units in Canada (Edmonton [n=3] and Winnipeg [n=1]).Healthcare providers should be aware that pulseless electrical activity can occur in newborn infants during cardiopulmonary resuscitation. We propose an adapted neonatal resuscitation algorithm to include pulseless electrical activity. Furthermore, in compromised newborns, heart rate should be assessed using a combination of methods/techniques to ensure accurate heart rate assessment. When ECG displays a heart rate but the infant is unresponsive, pulseless electrical activity should be suspected and chest compression should be started.
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http://dx.doi.org/10.1136/archdischild-2018-316087DOI Listing
November 2019