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.

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.

Cardiopulmonary resuscitation with 3:1 Compression:Ventilation or continuous compression with asynchronized ventilation in infantile piglets.

BACKGROUND: To compare neonatal and pediatric resuscitation approaches to ventilation and chest compression by using either continuous chest compression with asynchronized ventilation (CCaV) or 3:1 Compression:Ventilation ration (3:1 C:V) during infant cardiopulmonary resuscitation. We hypothesized that 3:1 C:V compared to CCaV will 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 3:1 C:V or CCaV for resuscitation (n = 10/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The median time (IQR) to ROSC among survivors was 157 (113-219) vs 421 (118-660) for 3:1 C:V and CCaV, respectively (p = 0.253). The duration of resuscitation with 3:1 C:V compared to CCaV was 206 (119-660) vs 660 (212-660)sec, respectively (p = 0.171). The number of piglets achieving ROSC with 3:1 C:V and CCaV were 7/10 and 6/10, respectively (p = 1.00). There was no difference in hemodynamic and respiratory parameters between groups. CONCLUSIONS: Time to ROSC and survival was not different between 3:1 C:V and CCaV in infantile piglets. Either approach appears reasonable during infantile cardiopulmonary resuscitation. IMPACT: Similar time to return of spontaneous circulation and survival with 3:1 C:V and CCaV in infant piglets equivalent to 28-day-old children. Either approach appears reasonable during infantile cardiopulmonary resuscitation. Lack of scientific data to provide recommendations on when to switch between neonatal to pediatric resuscitation guidelines. No difference in time to return of spontaneous circulation or survival between 3:1 C:V and CCaV in infantile piglets with asphyxia-induced bradycardic cardiac arrest. Both methods are viable options during infant cardiopulmonary resuscitation.

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.

Effects of epinephrine on hemodynamic changes during cardiopulmonary resuscitation in a neonatal piglet model.

BackgroundAsphyxia is the most common reason for newborns to fail to make a successful fetal-to-neonatal transition. There is currently a lack of data evaluating hemodynamic effects of epinephrine during neonatal cardiopulmonary resuscitation.MethodsTwenty-four newborn piglets were exposed to asphyxia. Thereafter, positive pressure ventilation was commenced for 30 s, followed by chest compressions (CC). Piglets were randomized into three experimental groups: 3:1 compression:ventilation ratio; CC during sustained inflation (SI) at a rate of 90 CC per minute, or CC during SI at a rate of 120 CC per minute. Epinephrine (0.01 mg/kg per dose) was administered to a maximum of four doses. Hemodynamic parameters were measured throughout the experiment.ResultsAnimals were divided into survivors and nonsurvivors. End-diastolic and developed pressures declined after epinephrine administration in the survivor group. dp/dt min was significantly higher in the survivor group whereas dp/dt max showed no significant differences. Epinephrine had no effect on either heart rate or cardiac output in both groups. Ejection fraction increased after epinephrine with no significant difference between groups.ConclusionEpinephrine did not affect survival rates or return of spontaneous circulation in our postnatal porcine model of neonatal asphyxia.

Cardiopulmonary resuscitation with chest compressions during sustained inflations: a new technique of neonatal resuscitation that improves recovery and survival in a neonatal porcine model.

BACKGROUND: Guidelines on neonatal resuscitation recommend 90 chest compressions (CCs) and 30 manual inflations (3:1) per minute in newborns. The study aimed to determine whether CC s during sustained inflations (SIs) improves the recovery of asphyxiated newborn piglets in comparison with coordinated 3:1 resuscitation. METHODS AND RESULTS: Term newborn piglets (n=8/group) were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by asphyxia. Piglets were randomly assigned to receive either 3:1 resuscitation (3:1 group) or CCs during SIs (SI group) when the heart rate decreased to 25% of baseline. Piglets randomly assigned to the SI group received SIs with a pressure of 30 cm H2O for 30 s. During the SI, CCs at a rate of 120/min were provided. SI was interrupted after 30 s for 1 s before a further 30-s SI was provided. CCs were continued throughout SIs. CCs and SI were continued until the return of spontaneous circulation. Continuous respiratory parameters, cardiac output, mean systemic and pulmonary artery pressures, and regional blood flows were measured. Mean (standard deviation) time for return of spontaneous circulation was significantly reduced in SI group versus 3:1 group (32 [11] s versus 205 [113] s, respectively). In the SI group, administration of oxygen and epinephrine was significantly lower, whereas minute ventilation and exhaled CO2 were significantly increased. The SI group had significantly higher mean systemic and pulmonary arterial pressures during resuscitation in comparison with the 3:1 group (51 [10] versus 31 [5] mm Hg; 41[7] versus 31 [7] mm Hg, respectively; all P<0.05), with improved cardiac output and carotid blood flow. CONCLUSIONS: Combining CCs and SIs significantly improved the return of spontaneous circulation with better hemodynamic recovery in asphyxiated newborn piglets in comparison with standard coordinated 3:1 resuscitation.

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.

Intramuscular versus intravenous epinephrine administration in a pediatric porcine model of cardiopulmonary resuscitation.

Background: American Heart Association Pediatric Life Support guidelines recommend epinephrine administration via intravenous (IV) or intraosseous (IO) route, with endotracheal (ET) administration admissible in the absence of IV/IO access. Establishing IV/IO/ET access can take several minutes and may require proficient skills and/or specific equipment, which may not be readily available in all situations. Alternatively, intramuscular (IM) epinephrine could be administered immediately. At present, there is limited data on the use of IM epinephrine in pediatric resuscitation. Aim: To compare IM with IV epinephrine in a pediatric porcine model of asphyxia-induced cardiac arrest. We hypothesized that in a pediatric animal model of cardiac arrest, IM epinephrine would result in a similar time to achieve return of spontaneous circulation (ROSC) to IV epinephrine. Methods: Twenty pediatric piglets (5-10 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to IM or IV epinephrine with bradycardic or asystolic cardiac arrest (n = 5/group) and were resuscitated. Time to ROSC was recorded; blood plasma was collected throughout resuscitation for measurement of epinephrine concentration; heart rate, arterial blood pressure, carotid blood flow, cardiac function, and cerebral oxygenation were continuously recorded throughout the experiment. Results: Time to ROSC and the number of piglets that achieved ROSC were comparable between IM and IV epinephrine groups with either bradycardic or asystolic cardiac arrest. Conclusions: In a pediatric piglet model of bradycardic and asystolic cardiac arrest, administration of IM epinephrine resulted in similar resuscitative outcomes to IV epinephrine. Although immediate IM epinephrine injection may provide a first-line treatment option until subsequent IV/IO access is established, large, randomized trials are needed to confirm our finding before it can be used during pediatric resuscitation.

Pharmacokinetic and pharmacodynamic evaluation of various vasopressin doses and routes of administration in a neonatal piglet model.

Epinephrine is the only recommended vasopressor during neonatal cardiopulmonary resuscitation. However, there are concerns about the potential adverse effects of epinephrine, which might hamper efficacy during cardiopulmonary resuscitation. An alternative might be vasopressin, which has a preferable adverse effect profile, however, its optimal dose and route of administration is unknown. We aimed to compare the pharmacodynamics and pharmacokinetics of various vasopressin doses administered via intravenous (IV), intraosseous (IO), endotracheal (ETT), and intranasal (IN) routes in healthy neonatal piglets. Forty-four post-transitional piglets (1-3 days of age) were anesthetized, intubated via a tracheostomy, and randomized to receive vasopressin via intravenous (control), IO, ETT, or IN route. Heart rate (HR), arterial blood pressure, carotid blood flow, and cardiac function (e.g., stroke volume, ejection fraction) were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the observation period for pharmacodynamics and pharmacokinetic analysis. Significant changes in hemodynamic parameters were observed following IO administration of vasopressin while pharmacokinetic parameters were not different between IV and IO vasopressin. Administration of vasopressin via ETT or IN did not change hemodynamic parameters and had significantly lower maximum plasma concentrations and systemic absorption compared to piglets administered IV vasopressin (p < 0.05). The IV and IO routes appear the most effective for vasopressin administration in neonatal piglets, while the ETT and IN routes appear unsuitable for vasopressin administration.

Postresuscitation cyclosporine treatment attenuates myocardial and cardiac mitochondrial injury in newborn piglets with asphyxia-reoxygenation.

OBJECTIVES: Cardiovascular dysfunction occurs in the majority of asphyxiated neonates and has been suggested to be a major cause of neonatal morbidity and mortality. We previously demonstrated that cyclosporine A treatment during resuscitation can significantly improve cardiovascular performance in asphyxiated newborn piglets. However, the mechanisms through which cyclosporine elicits its protective effect in neonates have not yet been fully characterized. We hypothesized that cyclosporine A treatment would attenuate myocardial and cardiac mitochondrial injury during the resuscitation of asphyxiated newborn piglets. DESIGN: After acute instrumentation, piglets received normocapnic alveolar hypoxia (10% to 15% oxygen) for 2 hours followed by reoxygenation with 100% oxygen (0.5 hr) and then 21% oxygen (3.5 hr). At 4 hours of reoxygenation, plasma troponin level, left ventricle myocardial levels of lipid hydroperoxides, cytochrome-c, and mitochondrial aconitase activity were determined. SETTING: Neonatal asphyxia and reoxygenation. SUBJECTS: Twenty-four newborn (1-4 days old) piglets. INTERVENTIONS: Piglets were randomized to receive an IV bolus of cyclosporine A (10 mg/kg) or normal saline (placebo, control) at 5 minutes of reoxygenation (n=8/group). Sham-operated piglets (n=8) underwent no asphyxia-reoxygenation. MEASUREMENTS AND MAIN RESULTS: Asphyxiated piglets treated with cyclosporine had lower plasma troponin and myocardial lipid hydroperoxides levels (vs. controls, both p<0.05, analysis of variance). Cyclosporine treatment also improved mitochondrial aconitase activity and attenuated the rise in cytosol cytochrome-c level (vs. controls, all p<0.05). The improved mitochondrial function significantly correlated with cardiac output (p<0.05, Spearman rank-correlation test). CONCLUSIONS: We demonstrate that the postresuscitation administration of cyclosporine attenuates myocardial and cardiac mitochondrial injury in asphyxiated newborn piglets following resuscitation.

Pharmacokinetic characterization of intravenous cyclosporine treatment for cardioprotection during resuscitation of asphyxiated newborn piglets.

OBJECTIVES: Cyclosporine treatment, as a single intravenous bolus, during resuscitation has been shown to attenuate myocardial injury in asphyxiated newborn piglets. However, the pharmacokinetics of cyclosporine treatment for cardioprotection in newborns has not been studied. We aimed to assess the pharmacokinetics of a single intravenous cyclosporine treatment during resuscitation of asphyxiated newborn piglets and compare these parameters with healthy newborn piglets. DESIGN: Newborn piglets were acutely instrumented and normocapnic alveolar hypoxia was induced for 2 hours followed by 4 hours of reoxygenation. Piglets were block-randomized to receive a single intravenous bolus of cyclosporine (2.5-25 mg/kg) (n = 8 per group). Eight piglets underwent no hypoxia-reoxygenation and received 10 mg/kg cyclosporine at the corresponding time point. Plasma cyclosporine and troponin concentrations during reoxygenation period were determined by high-pressure liquid chromatography and enzyme-linked immunosorbent assay, respectively. Noncompartmental methods were used to calculate the pharmacokinetic parameters. Cyclosporine concentrations and pharmacokinetic parameters were analyzed by one-way analysis of variance. SETTING: University animal laboratory. SUBJECTS: Piglets (1-4 days old, weighing 1.4-2.5 kg). INTERVENTIONS: Intravenous cyclosporine (2.5, 10, or 25 mg/kg) given during resuscitation. MEASUREMENTS AND MAIN RESULTS: In the hypoxic-reoxygenated piglets, the plasma AUC(0-4 hrs) and C(max) of cyclosporine at reoxygenation were in the following rank order: 25 > 10 > 2.5 mg/kg treatment (p < 0.001 between groups, analysis of variance). Plasma AUC(0-4 hrs) and C(max) in piglets treated with cyclosporine at 25 mg/kg was associated with increased plasma troponin levels, a marker of myocardial injury, relative to piglets treated with 2.5 and 10 mg/kg. Asphyxiated newborn piglets had higher clearance and lower AUC(0-∞), but similar AUC(0-4 hrs), steady-state volume of distribution, and mean residence time compared with those of healthy newborn piglets. CONCLUSIONS: This is the first study to demonstrate the pharmacokinetics of intravenous cyclosporine treatment during resuscitation of asphyxiated newborn piglets, which did not appear to different from that of healthy piglets.

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.

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.

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.

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.

Cyclosporine treatment improves cardiac function and systemic hemodynamics during resuscitation in a newborn piglet model of asphyxia: a dose-response study.

OBJECTIVES: Asphyxiated neonates often have myocardial depression, which is a significant cause of morbidity and mortality. Cardioprotective effects of cyclosporine have been observed in adult patients and animals with myocardial infarction. However, the cardioprotective effect of cyclosporine in neonates has not yet been studied. We hypothesize that cyclosporine will improve cardiac function and reduce myocardial injury in asphyxiated newborn piglets. DESIGN: Thirty-six piglets (1-4 days old, weighing 1.4-2.5 kg) were acutely instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10% to 15% oxygen) was instituted for 2 hrs followed by reoxygenation with 100% oxygen for 0.5 hrs and then 21% for 3.5 hrs. A nonasphyxiated, sham-operated group was included (n = 4) to control for effects of the surgical model. Plasma troponin and myocardial lactate concentrations were determined as well as morphologic examinations. SETTING: Neonatal asphyxia and reoxygenation. SUBJECTS: Newborn (1-4 days old) piglets. INTERVENTIONS: Piglets were block-randomized to receive intravenous boluses of cyclosporine A (2.5, 10, or 25 mg/kg) or normal saline (control) at 5 mins of reoxygenation (n = 8/group). MEASUREMENTS AND MAIN RESULTS: Cardiac index, heart rate, systemic oxygenation, plasma troponin, and left ventricular lactate were measured. Hypoxic piglets had cardiogenic shock (cardiac output 40% to 48% of baseline), hypotension (mean arterial pressure 27-31 mm Hg), and acidosis (pH 7.04). Cyclosporine treatment caused bell-shaped improvements in cardiac output, stroke volume, and systemic oxygen delivery (p < .05 vs. controls). Plasma troponin and left ventricle lactate were higher in controls than that of 2.5 and 10 mg/kg cyclosporine-treated groups (p < .05). Although histologic features of myocardial injury were not different among groups, severe damage was observed in mitochondria of control piglets but attenuated in that of cyclosporine (10 mg/kg) treatment. CONCLUSIONS: Postresuscitation administration of cyclosporine causes preservation of cardiac function and attenuates myocardial injury in newborn piglets after asphyxia-reoxygenation.

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.

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.

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.

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.