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the cardiotomy reservoir, which circulates through the membrane oxygenator via the arterial shunt line. During DHCA, the blood contained in the reservoir is not in contact with live tissues( except blood cells), therefore its CO 2 content will decrease as it passes through the oxygenator. Only blood cells, such as platelets and leukocytes, will produce CO 2 through oxidative phosphorylation [ 10 ]. In two patients, when the gas sweep flow was set up below 0.5 L / min( at 0.2 L / min in both cases), the pH decreased at the end of the DHCA, suggesting that the production of CO 2 by blood cells was higher than its removal. A sweep gas flow ranging between 0.5 and 1.0 L / min allowed for maintaining a post-DHCA PaCO 2 above 20 mmHg and pH below 7.6( alpha-stat), in most cases( Figure 1). The use of continuous, inline blood gas monitoring on the arterial shunt may help to monitor the variation of pH and PaCO 2 during DHCA. The clinical implication of such high pH observed at the end of DHCA is unknown. However, brutal variations of PaCO 2 and pH could negatively affect cerebral blood flow( CBF) and be associated with worse outcomes as has already been described following ECMO initiation [ 11 ]. The sensitivity of the cerebral vascular bed to pH-related dissolved CO 2 variation is preserved in hypothermia, even though it seems to be decreased at 18 ° C [ 4, 6, 7, 12, 13 ]. This is on the basis of the pH-stat strategy that PaCO 2 is maintained at 40 mmHg, at temperature-corrected values, on a blood gas analyzer. pH-stat increases cerebral blood flow, the rate, and homogeneity of brain cooling during induction of hypothermia. It also decreases cerebral metabolism and allows for a better unloading of O 2 by the hemoglobin [ 14 ]. In contrast, it could lead to an uncoupling between cerebral blood flow and metabolism, and luxury perfusion as the cerebral VO 2 decreases by more than half of its baseline values at 18 ° C [ 12,15 ]. The perfusion of very“ alkaline” blood into the patient at the end of the DHCA could potentially lead to a decrease in CBF and subsequent risk of ischemic injury. The effect of such extreme values of pH on the blood flow of other organs, such as the kidneys or liver, is poorly known. In the kidneys, some studies suggest that blood pH plays an important role in renal blood flow. Respiratory alkalosis was associated with increased vascular resistance through contraction of vascular smooth muscle and a decrease in renal blood flow [ 16, 17 ]. On the contrary, other studies found that a low blood pH and hyperchloremia were associated with decreased renal blood flow [ 18, 19 ]. Also, the Bohr effect seems to play an important role in O 2 delivery to the kidney’ s medulla, meaning that a higher pH could compromise the O 2 supply to the kidneys [ 20 ]. Given that acute kidney injuries following PAE are frequent( up to 30--40 %), limiting acid-base disorders during DHCA could have a significant impact on organ perfusion [ 21 ].
Two acid-base disturbances coexist during the period of DHCA, as a decrease of the SID was observed, in addition to the respiratory alkalosis. It could be linked to an adaptive response to counteract the rise in pH, resulting from strong ion exchange( mostly sodium) between blood cells and plasma and the accumulation of lactate. However, the change in SID in response to a change in pH is slow and limited within the red blood cells and plasma, so it cannot have a significant effect throughout the DHCA [ 22 ]. The presence of a non-respiratory acidosis has probably little effect on CBF: human and animal studies showed that changes in CSF pH in response to nonrespiratory acidosis or alkalosis are very small because of effective regulatory mechanisms [ 23, 24 ]. However, there is no data on the effectiveness of these mechanisms in deep hypothermic conditions.
The main limitation of our study was that we were not able to determine the potential clinically detrimental effect linked to the reperfusion of alkaline blood after DHCA. However, the study was not designed for this purpose, the goal was to explore the change of blood pH during DHCA. Further study monitoring the blood flow of different organs following reperfusion, according to the value of blood pH contained in the cardiotomy reservoir, could be interesting. Additionally, the blood that remains in the patient’ s capillaries during the DHCA becomes progressively loaded with dissolved CO 2 and lactate because the metabolic production continues, whereas the perfusion is stopped, and this should lead to a decrease in the pH of the capillary blood. At the end of the DHCA, the alkaline blood from the reservoir and the remaining blood in the patient mix together, but the resulting pH, PaCO 2, and effect on CBF remained unknown. We were also not able to determine the effect of the high concentration of O 2 observed in our cohort during the reperfusion period. As far as we know, there is no specific recommendation on how to set up F m O 2 during DHCA. According to our practices, the F m O 2 is increased during the cooling and DHCA period to increase dissolved O 2 and prevent potential hypoxia linked to the impaired capacity of hemoglobin to unload O 2 in hypothermia [ 15, 25, 26 ]. Such high concentrations could increase the reperfusion injuries after DHCA. Further studies are needed to determine the optimal management of F m O 2 during DHCA.
Conclusion
A significant change in pH and PaCO 2 of the blood approval for this study( Ethical Committee IRB N ° 00012157) wascontained in the cardiotomy reservoir was observed during the period of DHCA, which was correlated to the rate of sweep gas inflow. The clinical effect of such a change is not yet established. In the meantime, we suggest setting up the sweep gas inflow between 0.5 and 1.0 L / min during DHCA, to limit the variation of pH and PaCO 2.
Funding
Financial / Non-financial disclosure: Support was provided solely from institutional and / or departmental sources.
Conflicts of interest None of the authors has any conflicts of interest to disclose.
Data availability statement
The dataset used and / or analyzed during the current study is available from the corresponding authors on reasonable request.
Author contribution statement
SD designed the study. SD, MN, JT, and HG collected the data, SD, JT, and MCK wrote the paper. MN, EF, and II reviewed the draft.