The main results of the present study could be summarized as follows:
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1.
In the present series of capnograms, intrathoracic airway closure, thoracic distension and regular pattern concerned, respectively, 35%, 22% and 43% of 202 OHCA patients after intubation.
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The capnogram indicating thoracic distension was associated with higher tidal volumes on Thiel cadavers. Capnogram indicating thoracic distension on a CPR bench model was also more likely to occur with higher insufflated volumes or longer time constants (R × C).
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In the animal experiment, the distension ratio calculated from the capnogram to quantify thoracic distension was inversely correlated with cerebral perfusion and arterial blood pressure, while no correlation was found with tidal volume.
Theoretical optimal thoracic volume for effective chest compressions
The application of continuous chest compressions during CPR complicates CO2 waveform interpretation and generates specific CO2 patterns [4,5,6,7]. Both compression and decompression are needed to generate and sustain effective circulation. The increase in intrathoracic pressure during compression has been shown to generate circulation, thus introducing the concept of thoracic pump theory [11]. Venous return is facilitated by recoil of the chest creating a negative intrathoracic pressure if lung is placed below the functional residual capacity (FRC) when decompression starts. CPR close to the FRC with effective venous return could be identified by the regular CO2 pattern with fully oscillating capnogram. Interestingly, non-oscillating capnograms reported by Grieco et al. [7] reflect intrathoracic airway closure that affects ventilation and occurs when thorax is pushed far below the FRC along the course of CPR.
“Thoracic distension” pattern of the capnogram
We hypothesized that the specific capnogram called “thoracic distension” may indicate the risk associated with excessive ventilation inflating the thorax above FRC. It may jeopardize circulation (venous return) by limiting negative intrathoracic pressure during decompression [12, 13]. Expired CO2 oscillations which result from the combination of compression and decompression may transiently disappear when the time during which thoracic volume above FRC is prolonged, indicating this risk (see Fig. 6 and Additional file 2).
This is also markedly visible in the pig model (test animal), where we observed that the stepwise increase of Vt from 6 to 20 ml/kg magnified coronary and cerebral circulation oscillations related to ventilation and modified capnogram from regular to thoracic distension in parallel (Fig. 4).
Is the CO2 pattern associated with thoracic distension more informative than the Vt to detect any impact on circulation?
Thoracic distension CO2 pattern was reproduced on cadaver, bench and porcine models. This phenomenon was associated on average with higher insufflated volumes compared to intrathoracic airway closure or regular patterns. We found in the pig model that thoracic distension assessed by distension ratio was significantly and negatively correlated with mean arterial blood pressure and cerebral perfusion pressure, suggesting its potential negative impact on circulation during resuscitation.
Unlike the capnogram, Vt absolute values were not significantly associated with a negative effect on blood pressure, coronary perfusion and cerebral perfusion. Those results may suggest that the capnogram may be more relevant than Vt per se to predict a circulatory impact induced by ventilation.
The bench study provides a possible explanation for the previous observed result. Indeed, prolonged time constant that characterizes the time required to return to FRC may favor thoracic distension even with low Vt, as we observed in some animals.
Occurrence of thoracic distension, intrathoracic airway closure and regular capnogram
In our series of 202 OHCA patients, thoracic distension and intrathoracic airway closure concerned 22% and 35% of patients, respectively. Interestingly, very similar capnograms have been reported during CPR, without specifically identifying the phenomenon of thoracic distension [4, 5].
An important methodological point is that capnograms from the present study were captured soon after intubation with a respiratory rate of 10/min and a protective pressure mode of ventilation limiting Vt. One cannot exclude that thoracic distension may be much more frequently observed with manual bag ventilation during which Vt and respiratory rate are poorly controlled, thus favoring the risk of hyperventilation. In addition, a moderate level of PEEP was used in our series, which could have minimized the occurrence of intrathoracic airway closure, favored by low airway pressures. Although our brief periods of recordings with one to ten cycles displayed similar patterns for all breaths, it is likely that CO2 patterns evolve along the course of CPR, and that the classification could change depending on the time of intervention, thus precluding any interpretation of its significance in terms of outcome.
Of note, intrathoracic airway closure was not observed during the animal experiment. It is possible that the pig thorax anatomy may limit the reduction of lung volumes we observe in humans during resuscitation and thus occurrence of intrathoracic airway closure. Besides, pig bronchial tree presents lateral connections that may also limit occurrence of distal airway closure [14]. In addition, the mechanical chest compression device used in the swine study was operated with a mild active decompression due to the suction cup, which may limit the reduction of lung volume below the FRC potentially responsible for intrathoracic airway closure.
Clinical perspectives
Excessive ventilation during cardiac arrest has already been shown to be associated with poor outcomes [15, 16]. Nevertheless, it is definitively challenging to control and monitor Vt delivered during manual bag ventilation [17].
Based on these observations, a capnogram-based ventilation strategy may permit to optimize ventilation during CPR, using real-time identification of capnograms (intrathoracic airway closure, thoracic distension or regular pattern). As previously shown, PEEP increase may be considered in case of intrathoracic airway closure to open the airways, while Vt reduction could be proposed in case of thoracic distension. Further evidence is needed before developing such ventilatory approach on a ventilator, but these findings may be of potential additional value for bag valve mask ventilation during which hyperventilation is likely to occur.
Study limitations
First, the capnogram analysis proposed in the present study is based on continuous chest compression, and whether it is generalizable to an interrupted chest compression strategy ideally needs further assessment. But thoracic distension may also be present during interrupted chest compressions.
Second, capnogram from one ventilatory cycle recorded soon after intubation (according to the local routine procedure) was analyzed for each patient. This relatively limits the possibility to generalize CO2 pattern distribution to different CPR strategies (chest compression frequency, depth or other) and renders hazardous outcomes’ interpretation.
Third, the specific setup in cadavers experiment to administer CO2 via a catheter placed in the endotracheal tube resulted in significant additional resistance that favored early occurrence of thoracic distension as suggested by the observations obtained on the bench.
In the animal study, since each animal was its own control,
several time-related factors might have also impacted circulation. Further studies comparing animals with different ventilation strategies are needed to confirm our observations.