Exhaled CO2 Parameters as a Tool to Assess Ventilation-Perfusion Mismatching during Neonatal Resuscitation in a Swine Model of Neonatal Asphyxia

Background

End-tidal CO₂ (ETCO₂), partial pressure of exhaled CO₂ (PECO₂), and volume of expired CO₂ (VCO₂) can be continuously monitored non-invasively to reflect pulmonary ventilation and perfusion status. Although ETCO₂ ≥14mmHg has been shown to be associated with return of an adequate heart rate in neonatal resuscitation and quantifying the PECO₂ has the potential to serve as an indicator of resuscitation quality, there is little information regarding capnometric measurement of PECO₂ and ETCO₂ in detecting return of spontaneous circulation (ROSC) and survivability in asphyxiated neonates receiving cardiopulmonary resuscitation (CPR).

Methods

Seventeen newborn piglets were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by apnea to induce asphyxia. Protocolized resuscitation was initiated when heart rate decreased to 25% of baseline. Respiratory and hemodynamic parameters including ETCO₂, PECO₂, VCO₂, heart rate, cardiac output, and carotid artery flow were continuously measured and analyzed.

Results

There were no differences in respiratory and hemodynamic parameters between surviving and non-surviving piglets prior to CPR. Surviving piglets had significantly higher ETCO₂, PECO₂, VCO₂, cardiac index, and carotid artery flow values during CPR compared to non-surviving piglets.

Conclusion

Surviving piglets had significantly better respiratory and hemodynamic parameters during resuscitation compared to non-surviving piglets. In addition to optimizing resuscitation efforts, capnometry can assist by predicting outcomes of newborns requiring chest compressions.     

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world’s 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials^1,2. The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (< 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.     

A Neonatal Mouse Model of Coxsackievirus A16 for Vaccine Evaluation

To evaluate vaccine efficacy in protecting against coxsackievirus A16 (CA16), which causes human hand, foot, and mouth disease (HFMD), we established the first neonatal mouse model. In this article, we report data concerning CA16-induced pathological changes, and we demonstrate that anti-CA16 antibody can protect mice against lethal challenge and that the neonatal mouse model could be used to evaluate vaccine efficacy. To establish a mouse model, a BJCA08/CA16 strain (at 260 50% lethal doses [LD₅₀]) was isolated from a patient and used to intracerebrally (i.c.) inoculate neonatal mice. The infection resulted in wasting, hind-limb paralysis, and even death. Pathological examination and immunohistochemistry (IHC) staining indicated that BJCA08 had a strong tropism to muscle and caused severe necrosis in skeletal and cardiac muscles. We then found that BJCA08 pretreated with goat anti-G10/CA16 serum could significantly lose its lethal effect in neonatal mice. When the anti-G10 serum was intraperitoneally (i.p.) injected into the neonatal mice and, within 1 h, the same mice were intracerebrally inoculated with BJCA08, there was significant passive immunization protection. In a separate experiment, female mice were immunized with formaldehyde-inactivated G10/CA16 and BJCA08/CA16 and then allowed to mate 1 h after the first immunization. We found that there was significant protection against BJCA08 for neonatal mice born to the immunized dams. These data demonstrated that anti-CA16 antibody may block virus invasion and protect mice against lethal challenge, and that the neonatal mouse model was a viable tool for evaluating vaccine efficacy.     

Development of A Neonatal Mouse Model for Coxsackievirus B1 Antiviral Evaluation

Virologica Sinica - Coxsackievirus B1 (CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis,...     

Effect of Neonatal Asphyxia on the Impairment of the Auditory Pathway by Recording Auditory Brainstem Responses in Newborn Piglets: A New Experimentation Model to Study the Perinatal Hypoxic-Ischemic Damage on the Auditory System

IntroductionHypoxia–ischemia (HI) is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets.MethodHypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs) of newborn piglets exposed to acute hypoxia/ischemia (n = 6) and a control group with no such exposure (n = 10). ABRs were recorded for both ears before the start of the experiment (baseline), after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury.ResultsAuditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant.ConclusionThe described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.