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

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

Cardiac Agents during Neonatal Cardiopulmonary Resuscitation.

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

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

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

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

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

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

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

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

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

Vasopressin versus epinephrine during neonatal cardiopulmonary resuscitation of asphyxiated post-transitional piglets.

Background: Epinephrine is currently the only recommended cardio-resuscitative medication for use in neonatal cardiopulmonary resuscitation (CPR), as per the consensus of science and treatment recommendations. An alternative medication, vasopressin, might be beneficial in neonatal CPR due to its combined pulmonary vasodilation and systemic vasoconstriction properties. Aim: We aimed to compare the time to return of spontaneous circulation (ROSC) with administration of vasopressin or epinephrine during CPR of asphyxiated post-transitional piglets. Methods: Newborn piglets (n = 8/group) were anesthetized, tracheotomized and intubated, instrumented, and exposed to 50 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to receive vasopressin (Vaso, 0.4 U/kg) or epinephrine (Epi, 0.02 mg/kg) during CPR. Piglets were resuscitated with chest compressions superimposed with sustained inflations, and were administered either Vaso or Epi intravenously every 3 min until ROSC (max. 3 doses). Hemodynamic and cardiac function parameters were collected. Main Results: The median (IQR) time to ROSC was 106 (93-140) s with Vaso and 128 (100-198) s with Epi (p = 0.28). The number of piglets that achieved ROSC was 8 (100%) with Vaso and 7 (88%) with Epi (p = 1.00). Vaso-treated piglets had a significantly longer post-resuscitation survival time (240 (240-240) min) than Epi-treated piglets (65 (30-240) min, p = 0.02). Vaso-treated piglets had significantly improved carotid blood flow immediately after ROSC (p < 0.05), had longer duration of post-resuscitation hypertension (p = 0.05), and had significantly improved heart rate, arterial pressure, and cerebral blood oxygen saturation 4 h after ROSC (p < 0.05). Conclusions: Vasopressin improved post-resuscitation survival and hemodynamics, and might be an alternative cardio-resuscitative medication during neonatal CPR, but further studies are warranted.

Four Different Finger Positions and Their Effects on Hemodynamic Changes during Chest Compression in Asphyxiated Neonatal Piglets.

Background: The Neonatal Life Support Consensus on Science With Treatment Recommendations states that chest compressions (CC) be performed preferably with the 2-thumb encircling technique. The aim of this study was to compare the hemodynamic effects of four different finger positions during CC in a piglet model of neonatal asphyxia. Methods: Seven asphyxiated post-transitional piglets were randomized to CC with 2-thumb-, 2-finger-, knocking-fingers-, and over-the-head 2-thumb-techniques for one minute at each technique. CC superimposed with sustained inflations were performed manually. Results: Seven newborn piglets (age 0-4 days, weight 2.0-2.1 kg) were included in the study. The mean (SD) slope rise of carotid blood flow was significantly higher with the 2-thumb-technique and over-the-head 2-thumb-technique (118 (45) mL/min/s and 121 (46) mL/min/s, respectively) compared to the 2-finger-technique and knocking-finger-technique (75 (48) mL/min/s and 71 (67) mL/min/s, respectively) (p < 0.001). The mean (SD) dp/dtmin (as an expression of left ventricular function) was significantly lower with the 2-thumb-technique, with -1052 (369) mmHg/s, compared to -568 (229) mmHg/s and -578(180) mmHg/s (both p = 0.012) with the 2-finger-technique and knocking-finger-technique, respectively. Conclusion: The 2-thumb-technique and the over-the-head 2-thumb-technique resulted in improved slope rises of carotid blood flow and dp/dtmin during chest compression.

Haemodynamic changes with varying chest compression rates in asphyxiated piglets.

BACKGROUND: Current neonatal resuscitation guidelines recommend that chest compressions (CCs) be delivered at a rate of 90/min. The aim of the study was to investigate the haemodynamic effects of different CC rates in a neonatal piglet model. METHODS: Six asphyxiated piglets were randomised to CC with rates of 60/min, 90/min, 120/min, 150/min and 180/min for 1 min at each rate. CCs superimposed with sustained inflations were performed with an automated CC machine. RESULTS: Six newborn piglets (age 0-3 days, weight 2.0-2.3 kg) were included in the study. Overall, there was a gradual increase in stroke volume, minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax), and carotid blood flow until CC rate of 150/min, with a level-off effect at a CC rate of 180/min. However, cardiac output continued to increase with the highest being at a CC rate of 180/min. CONCLUSION: Rate of CC was associated with changes in haemodynamic parameters during cardiopulmonary resuscitation. CC rate of 150-180/min during CC resulted in the highest cardiac output and arterial blood pressure. TRIAL REGISTRATION NUMBER: Preclincialtrials.eu PCTE0000249.

Chest Compression Rates of 90/min versus 180/min during Neonatal Cardiopulmonary Resuscitation: A Randomized Controlled Animal Trial.

BACKGROUND: To compare chest compression (CC) rates of 90/min with 180/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 180/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. METHODS: Newborn piglets (n = 7/group) were anesthetized, intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 180/min or 90/min. CC was performed using an automated chest compression machine using CC superimposed with sustained inflation. Hemodynamic and respiratory parameters and applied compression force were continuously measured. RESULTS: The mean (SD) time to ROSC was 91 (34) and 256 (97) s for CC rates of 180/min and 90/min, respectively (p = 0.08). The number of piglets that achieved ROSC was 7 (100%) and 5 (71%) with 180/min and 90/min CC rates, respectively (p = 0.46). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all improved with a CC rate of 180/min. CONCLUSION: Time to ROSC and hemodynamic and respiratory parameters were not statistical significant different between CC rates of 90/min and 180/min. Higher CC rates during neonatal resuscitation warrant further investigation.

A Randomized, Controlled Animal Study: 21% or 100% Oxygen during Cardiopulmonary Resuscitation in Asphyxiated Infant Piglets.

Background: During pediatric cardiopulmonary resuscitation (CPR), resuscitation guidelines recommend 100% oxygen (O2); however, the most effective O2 concentration for infants unknown. Aim: We aimed to determine if 21% O2 during CPR with either chest compression (CC) during sustained inflation (SI) (CC + SI) or continuous chest compression with asynchronized ventilation (CCaV) will reduce time to return of spontaneous circulation (ROSC) compared to 100% O2 in infant piglets with asphyxia-induced cardiac arrest. Methods: Piglets (20−23 days of age, weighing 6.2−10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure < 25 mmHg with bradycardia. After cardiac arrest, piglets were randomized to CC + SI or CCaV with either 21% or 100% O2 or the sham. Heart rate, arterial blood pressure, carotid blood flow, and respiratory parameters were continuously recorded. Main results: Baseline parameters, duration, and degree of asphyxiation were not different. Median (interquartile range) time to ROSC was 107 (90−440) and 140 (105−200) s with CC + SI 21% and 100% O2, and 600 (50−600) and 600 (95−600) s with CCaV 21% and 100% O2 (p = 0.27). Overall, six (86%) and six (86%) piglets with CC + SI 21% and 100% O2, and three (43%) and three (43%) piglets achieved ROSC with CCaV 21% and 100% O2 (p = 0.13). Conclusions: In infant piglets resuscitated with CC + SI, time to ROSC reduced and survival improved compared to CCaV. The use of 21% O2 had similar time to ROSC, short-term survival, and hemodynamic recovery compared to 100% oxygen. Clinical studies comparing 21% with 100% O2 during infant CPR are warranted.

Pulmonary and Neurologic Effects of Mesenchymal Stromal Cell Extracellular Vesicles in a Multifactorial Lung Injury Model.

Rationale: Bronchopulmonary dysplasia, a chronic respiratory condition originating from preterm birth, is associated with abnormal neurodevelopment. Currently, there is an absence of effective therapies for bronchopulmonary dysplasia and its associated brain injury. In preclinical trials, mesenchymal stromal cell therapies demonstrate promise as a therapeutic alternative for bronchopulmonary dysplasia. Objectives: To investigate whether a multifactorial neonatal mouse model of lung injury perturbs neural progenitor cell function and to assess the ability of human umbilical cord-derived mesenchymal stromal cell extracellular vesicles to mitigate pulmonary and neurologic injury. Methods: Mice at Postnatal Day 7 or 8 were injected intraperitoneally with LPS and ventilated with 40% oxygen at Postnatal Day 9 or 10 for 8 hours. Treated animals received umbilical cord-mesenchymal stromal cell-derived extracellular vesicles intratracheally preceding ventilation. Lung morphology, vascularity, and inflammation were quantified. Neural progenitor cells were isolated from the subventricular zone and hippocampus and assessed for self-renewal, in vitro differentiation ability, and transcriptional profiles. Measurements and Main Results: The multifactorial lung injury model produced alveolar and vascular rarefaction mimicking bronchopulmonary dysplasia. Neural progenitor cells from lung injury mice showed reduced neurosphere and oligodendrocyte formation, as well as inflammatory transcriptional signatures. Mice treated with mesenchymal stromal cell extracellular vesicles showed significant improvement in lung architecture, vessel formation, and inflammatory modulation. In addition, we observed significantly increased in vitro neurosphere formation and altered neural progenitor cell transcriptional signatures. Conclusions: Our multifactorial lung injury model impairs neural progenitor cell function. Observed pulmonary and neurologic alterations are mitigated by intratracheal treatment with mesenchymal stromal cell-derived extracellular vesicles.

Assessment of optimal chest compression depth during neonatal cardiopulmonary resuscitation: a randomised controlled animal trial.

AIM: The study aimed to examine the optimal anterior-posterior depth which will reduce the time to return of spontaneous circulation and improve survival during chest compressions. Asphyxiated neonatal piglets receiving chest compression resuscitated with a 40% anterior-posterior chest depth compared with 33%, 25% or 12.5% will have reduced time to return of spontaneous circulation and improved survival. METHODS: Newborn piglets (n=8 per group) were anaesthetised, intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to four intervention groups ('anterior-posterior 12.5% depth', 'anterior-posterior 25% depth', 'anterior-posterior 33% depth' or 'anterior-posterior 40% depth'). Chest compressions were performed using an automated chest compression machine with a rate of 90 per minute. Haemodynamic and respiratory parameters, applied compression force, and chest compression depth were continuously measured. RESULTS: The median (IQR) time to return of spontaneous circulation was 600 (600-600) s, 135 (90-589) s, 85 (71-158)* s and 116 (63-173)* s for the 12.5%, 25%, 33% and 40% depth groups, respectively (*p<0.001 vs 12.5%). The number of piglets that achieved return of spontaneous circulation was 0 (0%), 6 (75%), 7 (88%) and 7 (88%) in the 12.5%, 25%, 33% and 40% anterior-posterior depth groups, respectively. Arterial blood pressure, central venous pressure, carotid blood flow, applied compression force, tidal volume and minute ventilation increased with greater anterior-posterior chest depth during chest compression. CONCLUSIONS: Time to return of spontaneous circulation and survival were similar between 25%, 33% and 40% anterior-posterior depths, while 12.5% anterior-posterior depth did not result in return of spontaneous circulation or survival. Haemodynamic and respiratory parameters improved with increasing anterior-posterior depth, suggesting improved organ perfusion and oxygen delivery with 33%-40% anterior-posterior depth. TRIAL REGISTRATION NUMBER: PTCE0000193.

Sustained Inflation During Chest Compression: A New Technique of Pediatric Cardiopulmonary Resuscitation That Improves Recovery and Survival in a Pediatric Porcine Model.

Background Chest compression (CC) during sustained inflations (CC+SI) compared with CC with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation in asphyxiated pediatric piglets will reduce time to return of spontaneous circulation (ROSC). Methods and Results Piglets (20-23 days of age, weighing 6.2-10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure <25 mm Hg with bradycardia. After cardiac arrest, piglets were randomized to CC+SI (n=12) or CCaV (n=12) or sham (n=8). Sham-operated animals had no asphyxia. Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded. There were no differences in baseline parameters or the duration and degree of asphyxiation. Median (interquartile range) Time to ROSC was 248 (41-346) seconds compared with 720 (167-720) seconds in the CC+SI group and CCaV group, respectively (P=0.0292). There was a 100% higher rate of ROSC in the CC+SI group versus CCaV group, with 10 (83%) versus 5 (42%) achieving ROSC (P=0.089), respectively. Piglets in the CC+SI and CCaV groups received intravenous epinephrine boluses to achieve ROSC (8/12 versus 10/12 P=0.639). There was a significantly higher minute ventilation in the CC+SI group, which was secondary to a 5-fold increase in the number of inflations per minute and a 1.5-fold increase in tidal volume. Conclusions CC+SI reduced time to ROSC and improved survival compared with using CCaV. CC+SI allowed passive ventilation of the lung while providing chest compressions. This technique warrants further studies to examine the potential to improve outcomes in pediatric patients with cardiac arrest. Registration URL: https://www.preclinicaltrials.eu; Unique identifier: PCTE0000152.

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

Objective: 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). Design: 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 cmH2O), and oxygen concentration (18, 21, or 100%). Setting and Subjects: 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. Interventions: 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. Measurements: 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. Main Results: Piglets with PEA (n = 29) and asystole (n = 13) had a significantly longer asphyxiation time and time to ROSC vs. bradycardia (n = 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. Conclusion: This study indicates that cardiac rhythm before resuscitation influences the time to ROSC and hemodynamic recovery after ROSC.

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

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.

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

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.

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.

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

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-1ß 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.

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

Objective: To determine the incidence and risk factors associated with neonatal hypoglycemia in the premature population <33 weeks' gestation. Methods: 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. Main outcome measures: 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. Results: 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, p = 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, p = 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. Conclusions: 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.