In this neonatal model of asphyxia-induced asystole, increasing ETCO2 values appear to correlate with ROSC and an audible HR greater than 60 bpm. Given the consistent threshold above 14 mmHg at which ETCO2 correlates with return of an adequate HR, it may be useful to guide uninterrupted neonatal CPR. An ETCO2 cut off higher than 14 mmHg appears most useful for determining when to interrupt CPR to auscultate for a HR by providing the lowest combination of false positives and false negatives and the best fit with optimal calculated distance to an ideal curve using ROC analysis with a sensitivity of 93%, 81% specificity, and a positive likelihood ratio of 5.
The current NRP recommendation to interrupt cardiac compressions every 30 seconds for a 6 second auscultation pause to check for ROSC (13
) may not be optimal. “In an adult animal model, such breaks in cardiac compressions” further delay reestablishment of adequate coronary perfusion pressure which is very dependent on ongoing uninterrupted compressions (23
). NRP also recommends checking for the presence or absence of a palpable pulse during the resuscitative effort to assess the adequacy of artificial perfusion during cardiac compressions (13
); however, coronary perfusion pressure (which is calculated as the aortic diastolic blood pressure – the right atrial diastolic blood pressure) is not impacted by the difference in systolic and diastolic pressures represented by a palpable pulse but rather by the aortic diastolic pressure itself (24
). Thus, monitoring ETCO2
trends during CPR would allow uninterrupted cardiac compressions and might provide a better indicator of the effectiveness of perfusion during compression administration.
is a measure of the partial pressure of carbon dioxide at the end of an exhaled breath and is mainly determined by alveolar ventilation, pulmonary perfusion (right cardiac output) and CO2
production due to metabolism. During acutely low cardiac output states as in cardiac arrest, decreased pulmonary blood flow becomes the primary determinant of ETCO2
resulting in low values (25
). The concept of change in ETCO2
reflecting the changes in pulmonary blood flow in the presence of constant cardiac compressions and ventilation has been utilized to assess circulatory status during cardiac arrest and resuscitation in adults (17
). In experimental models of ventricular fibrillation induced cardiac arrest, ETCO2
concentration during ongoing CPR correlates with cardiac output, coronary perfusion pressure, and successful resuscitation from cardiac arrest (27
Experimental animal adult studies of atraumatic cardiac arrest have reported increasing ETCO2
to be also associated with ROSC (21
). In such models an ETCO2
threshold of 15 mmHg predicted ROSC with a positive predictive value 91% and negative predictive value of 91% (25
). In contrast to adult models of ventricular fibrillation, animal models of brief asphyxial pediatric cardiac arrest reported initially elevated ETCO2
levels reflective of the high alveolar PCO2
present at the time of asphyxial arrest. This was followed by a subsequent decrease in PCO2
once ventilation was initiated (22
) as the PCO2
present in the lung at the time of arrest was ventilated off and no further CO2
was brought to the lung due to arrested perfusion. In our neonatal model of asphyxia-induced asystole we observed similar findings with high initial ETCO2
at the time of asystole that decreased following 30 seconds of adequate PPV. This pattern of ETCO2
changes is different from that observed in ventricular fibrillation arrest because PCO2
levels are typically normal at the time of cardiac arrest from ventricular fibrillation as opposed to very elevated at the time of asphyxial cardiac arrest. No prior study of asphyxial cardiac arrest has determined ETCO2
values that correlate with return of an audible HR >60 bpm which is the current clinical goal for stopping cardiac compressions following asphyxia-induced asystole in neonates.
A strength of this translational study is the use of a piglet asphyxia model that closely mimics delivery room events with gradual onset of severe asphyxia leading to asystole. The presence of a dedicated focused clinical resuscitation team with current NRP training, along with designated roles during the resuscitation, a supervisor leading the code and a recorder for accuracy of documentation makes this piglet asphyxia model an ideally controlled mega code environment. We attempted to control for depth of compressions and compressor fatigue by real-time assessment and adjustment of the pulse pressures generated by the compressor. This controlled setting allowed us to generate an ROC curve related to the predictive values of ETCO2, with minimum confounding variables.
The following limitations should be considered before general application of ETCO2
guidance in future clinical neonatal resuscitation trials. The current model is one where the animals have already undergone fetal to neonatal transition and in addition are sedated/anesthetized. The findings are still relevant despite this limitation, because the distribution of cardiac output in the fetus and post-transitional neonate during asphyxial episodes are qualitatively similar (30
). In addition, responsiveness and reactivity of the cerebral circulation to factors that modulate cerebral blood flow such as hypoxia qualitatively remain intact under barbiturate anesthesia (33
). Another limitation is that manual ventilation and chest compressions could cause ETCO2
to fluctuate with the effort of compression and rate of ventilation (20
), so uniform compressions need to be delivered for ETCO2
to be used as a predictor of ROSC. In addition, acute and chronic illness with co-morbidities can result in a ventilation/perfusion mismatch, which can limit the accuracy of ETCO2
). This is unlikely to be a problem in the post transitional neonatal piglet model currently utilized in this study. The effect of resuscitation medications such as epinephrine needs to be carefully recorded and should also be taken into consideration. According to adult studies, NaHCO3
can transiently increase ETCO2
, while epinephrine can lead to decreased levels (37
). Lastly, this model is based on heart rate assessment in term animals and does not include evaluation for pseudo-pulseless electrical activity where there is no clinically palpable pulses but presence of blood flow. The model does not address issues of prematurity or low birth weight.
In conclusion, our study using this piglet model of asystole due to asphyxia demonstrates that capnometry can be used as a predictor of ROSC, and may be a useful substitute for frequent pauses in cardiac compressions in order to auscultate HR during neonatal CPR. Further investigation is needed to determine if uninterrupted ETCO2-guided CPR can improve time to return of spontaneous circulation and short and long-term outcomes following neonatal resuscitation.