Figure 3B shows the effect of a PEEP change from 6- to 12-PEEP before recruitment on the main variables for 18 consecutive respiratory cycles. The effects were qualitatively similar, but quantitatively different in healthy and in lavaged lungs. VTCO2,br decreased almost to zero in the first breath but recovered within 5 to 6 consecutive breaths in both healthy and lavaged lungs. This change in VTCO2,br was related to a decrease in expired VT right after the PEEP change resulting in an expansion of ΔFRC by approximately 183 mL in healthy and 154 mL in lavaged lungs. As opposed to VTCO2,br, CO was little affected by the change in PEEP.
PVCO2, PaCO2, and PETCO2 are presented in Figure 1 and Tables 1 and 2. In healthy lungs, no clinically significant changes in those variables were observed. In surfactant-depleted lungs, however, the difference between PaCO2 and PETCO2 narrowed significantly but in an inverse relation to the applied PEEP before and after lung recruitment with corresponding changes in pH. Both PVCO2 and PaCO2 decreased with lung recruitment and PEEP.
The main findings of this study can be summarized as follows:
- Lung recruitment and PEEP have different effects on CO2 elimination in healthy and surfactant-depleted lungs.
- At constant metabolism and ventilatory settings, any change in the elimination of CO2 can be explained by a combination of changes in (a) the effectiveness of lung perfusion, (b) the area for CO2 exchange, and (c) the amount of V[Combining Dot Above]A and, thus, in the global V[Combining Dot Above]/Q[Combining Dot Above] relationship of the lungs.
- In healthy and lavaged lungs, changes in PEEP altered the elimination of CO2 because of immediate effects on both expired VT values and ΔFRC for 5 to 6 consecutive breaths. Stable new values for VTCO2,br, lung perfusion, area of CO2 exchange, and V[Combining Dot Above]A were reached within 5 minutes.
- In lavaged lungs, the efficacy of CO2 elimination was directly related to the recruitment/derecruitment effect. Lung recruitment and PEEP did not retain CO2 in the blood during the study periods.
Effect of PEEP and Lung Recruitment on CO2 Elimination
Breen and Mazumdar3 and Johnson and Breen5 were the first to analyze the effect of PEEP on the non–steady-state CO2 kinetics in healthy lungs. Our main goal was to further their work and to describe the same effect in the context of a lung RM. Thus, to our knowledge, the data presented in the current study are the first to describe the effect of PEEP and lung recruitments on the elimination of CO2 in non–steady-state conditions of healthy and surfactant-depleted lungs.
The elimination of CO2 by the lungs, at constant ventilation and body metabolism, depends on its transport by the blood into the lungs, its diffusion through the alveolar-capillary membrane, and its elimination by the V[Combining Dot Above]A.3,31 Therefore, the final VTCO2,br value measured at the airway opening in response to a PEEP challenge with or without a lung RM is the result of a complex interaction of several factors. Figure 2 and Tables 1 to 3 show that these interactions differ between healthy and lavaged lungs and, sometimes, the influence on CO2 elimination of 1 factor differed from other factors.
Figure 3 shows the change in the elimination of CO2 during an increase in PEEP from 6 to 12 cm H2O without RM. The layout of this figure is similar to the ones presented in the articles by Breen and Mazumdar3 and Johnson and Breen5 to facilitate the reader's comparison of the data. According to the results shown in this figure, changes in VTCO2,br, lung perfusion, CO2 exchange, and V[Combining Dot Above]A after a PEEP challenge vary between healthy and lavaged lungs.
In healthy lungs, 12-PEEP decreased VTCO2,br because of decreased V[Combining Dot Above]A and CO despite a slight improvement in gas exchange (Fig. 3A). More than 90% of the effects on VTCO2,br induced by 12-PEEP occurred within 5 minutes. These results are similar to the findings of Breen and Mazumdar3 observed in healthy dogs and those of Johnson and Breen5 in healthy anesthetized humans. They also found that a PEEP challenge decreased VTCO2,br because of a decrement in V[Combining Dot Above]A and CO, with most of the recovery of VTCO2,br within 10 minutes. Differences in the recovery of VTCO2,br observed between these protocols could be explained by differences in the species studied, differences in the levels of PEEP applied (11 cm H2O in the study by Breen and Mazumdar and 10 cm H2O in the study by Johnson and Breen), or by differences in hemodynamic status and treatments.
In lavaged lungs, VTCO2,br increased until 12-PEEP caused by an increment in the area for CO2 exchange despite decreasing V[Combining Dot Above]A and CO (Fig. 3A). The effects of a partial alveolar recruitment induced by the increasing PEEP levels are supported by concomitant increases in PaO2 and compliance at reduced dead spaces (Table 2). Although CO was reduced by 21%, its COEPP increased by 22% because of the recruitment of shunt areas (Table 3). The final result was a better elimination of CO2 because of an improved V[Combining Dot Above]/Q[Combining Dot Above] ratio as indicated by a decrement in SIII. The different findings in lavaged and healthy lungs point toward differences in the physiological effects that PEEP and recruitment have on normally aerated and on collapsed lungs.
Figure 3B provides a zoomed view of the first breaths after a change in a PEEP step. The decrement in VTCO2,br after an increase in PEEP was caused by the trapped gas within lungs at the onset of the higher PEEP, which diluted alveolar CO2. The opposite results were observed in cases of PEEP reduction. After a PEEP change, a fast recovery in VTCO2,br was found within 5 to 6 consecutive breaths. This finding is similar to the one described by Johnson and Breen5 in anesthetized patients in which the recovery of VTCO2,br after a change of PEEP from 0 to 10 cm H2O took 8 breaths.
Does PEEP and Lung Recruitment Retain CO2 in the Blood?
A protective ventilatory management with low VT and plateau pressures is currently mandatory when treating acutely injured lungs.12,13 Arterial hypercapnia is thus a clinically tolerated negative consequence of an intentional decrease in V[Combining Dot Above]A. This hypercapnic state could become even worse if PEEP, as many authors have postulated, caused CO2 retention in the body.14–17
In healthy lungs, VTCO2,br decreased in proportion to PEEP before the recruitment but increased after it. At constant ventilation and metabolism, this decrease in CO2 elimination should lead to retention of CO2 within the body when PEEP is applied without a prior recruitment. However, PVCO2, PaCO2, and thus P[Combining Macron]V-aCO2 were not affected much during the protocol (Table 1 and Figs. 1 and 2), which must be interpreted that CO2 was not retained within the blood, at least during the study period. After recruitment, the elimination of CO2 and global lung physiology improved at PEEP levels down to 12 cm H2O (Table 1 and Figs. 1 and 2) with chances for CO2 retention even lower than before the recruitment.
Our results differ from those of Breen and Mazumdar3 and Johnson and Breen5 who found increased PVCO2 and PaCO2 in healthy lungs at 10 and 11 cm H2O of PEEP, respectively. Differences in the hemodynamic status, protocol time, and experimental models might explain these differences.
In surfactant-depleted lungs, however, results were totally different. PV-aCO2 increased whereas Pa-ETCO2 decreased with positive-pressure ventilation as long as lung collapse was low and overall lung function preserved (Table 2 and Fig. 1). The increased area of gas exchange leading to an augmented diffusion of CO2 across the alveolar-capillary membrane after a lung recruitment can explain this effect and was confirmed by parallel increments in PaO2 and Crs, 2 well-known markers of lung recruitment.32,33 COEPP increased with increasing airway pressures because of the recruitment of previously collapsed capillaries in the atelectatic areas (Table 3). Because VTCO2,br is directly proportional to lung perfusion, this increment in COEPP facilitates the transport of CO2 from the body stores toward the lungs where it is eliminated. Note that the absolute values of PVCO2 and PaCO2 decreased with both lung recruitment and PEEP, thereby confirming that CO2 was not retained within the blood but rather eliminated more efficiently.
In lavaged lungs, the highest recruitment pressures applied in pressure control ventilation resulted in a mean VT of 7.4 mL/kg (221 [202–251] mL). This small and transient increase in minute ventilation could have influenced the elimination of CO2 beyond the actual lung recruitment effect during the descending PEEP steps. However, we believe that the decreased values for PVCO2 and PaCO2 on the descending limb of the PEEP titration were mainly attributable to the recruitment of alveoli because: (1) changes in the area of gas exchange, and not in V[Combining Dot Above]A, had a dominating influence on VTCO2,br (Fig. 2), (2) variables representing the recruitment effect and which are independent of V[Combining Dot Above]A (Crs, SIII, ΔFRC, PaO2, or shunt) improved after lung recruitment, and (3) a transient and marginal increase in minute ventilation for 2 minutes only would not have had a lasting impact on VTCO2,br after a lapse of 10 minutes, the point in time when the blood samples were taken.
In contrast to continuous positive airway pressure maneuvers, cycling RMs have the following advantages: (a) they are hemodynamically better tolerated,34 (b) the step-wise and sequential increments in PEEP allow the gained volumes of air to spread progressively instead of abruptly throughout the lung parenchyma,35,36 and (c) they allow real-time monitoring of respiratory variables on a breath-by-breath basis. Today, the way to conduct and optimize RM is a topic of much debate, where the advent of volume-based capnographic monitoring may add important new arguments in favor of such an approach because of the noninvasive and real-time nature of this methodology.
Because CO2 kinetics are context sensitive and highly dependent on the sequence of steps during a cycling RM, in our protocol, the levels of PEEP were not assigned in random order. Had we randomized the protocol steps, we would not have been able to show reproducibly the sequential nature and the time dependence of CO2 elimination. For the same reason, we chose to study the CO2 kinetics during a short lapse of time because we were interested in the CO2 kinetics during the non–steady-state conditions induced by RMs and a PEEP titration process. This is crucial new information, which should contribute to a better understanding of CO2 kinetics, and we hope that it will finally have clinical implications for the monitoring of patients during mechanical ventilation.
Surfactant-depleted lungs as used in our experimental study do not adequately represent the complex nature of acute lung injury in real patients, and thus our results should be interpreted with caution.
It is well documented that healthy and sick human lungs have different opening pressures29,30and therefore we chose our recruitment pressures in health and disease assuming that this difference would be true for animals also. To achieve a complete recruitment effect in our surfactant-depleted animals, we decided to use an arbitrary and fixed opening pressure of 50 cm H2O for all animals with sick lungs based on our own previous experience33 because we did not have access to lung imaging by computed tomographic scan to determine an optimal opening pressure individually for each animal. Had we used the same pressure as we did for healthy animals, the risk of having incompletely recruited diseased lungs and thus inconclusive study results would have been high.
The results of this study show that lung recruitment and PEEP have different effects on the elimination of CO2 in healthy and lavaged lungs. These differences can be explained by a complex interaction between the key factors of lung perfusion, diffusion through the alveolar-capillary membrane, and V[Combining Dot Above]A. Our results suggest that sufficiently high levels of PEEP applied after lung recruitment may help decrease hypercapnia in patients treated with lung-protective ventilation and low VT strategies.
From the *Department of Anesthesiology, Hospital Privado de Comunidad, Mar del Plata, Argentina; †CSEM Centre Suisse d'Electronique et de Microtechnique SA, Research Centre for Nanomedicine, Landquart, Switzerland; ‡Department of Critical Care Medicine, Fundación Jiménez Díaz-UTE, Madrid, Spain; §Bioengineering Laboratory, Electronic Department, University of Mar del Plata, Mar del Plata, Argentina; and ∥Department of Medical Sciences, Clinical Physiology, University Hospital, Uppsala Sweden.
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