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Review

Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications

by
Vladimir L. Cousin
1,
Raphael Joye
2,
Julie Wacker
2,
Maurice Beghetti
2,* and
Angelo Polito
1
1
Réanimation Pédiatrique, Women, Child and Adolescent Department, Geneva University Hospital, 1205 Geneva, Switzerland
2
Pediatric Cardiology Unit, Women, Child and Adolescent Department, Geneva University Hospital, 1205 Geneva, Switzerland
*
Author to whom correspondence should be addressed.
J. Cardiovasc. Dev. Dis. 2023, 10(5), 208; https://doi.org/10.3390/jcdd10050208
Submission received: 14 March 2023 / Revised: 28 April 2023 / Accepted: 9 May 2023 / Published: 10 May 2023
Browse Figure
Versions Notes

Abstract

:
Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO2) are usually used as shock biomarkers to monitor the efficacy of resuscitation efforts, but they are plagued by some limitations. Carbon dioxide (CO2)-derived parameters, namely veno-arterial CO2 difference (ΔCCO2) and the VCO2/VO2 ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO2 or VCO2/VO2 ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO2-derived indices for patients’ management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO2 and VCO2/VO2 ratio while summarizing the actual state of knowledge on the use of CO2-derived indices as hemodynamical markers in CICU.

1. Introduction

Shock and low cardiac output syndrome (LCOS) are life-threatening conditions characterized by an inadequacy between oxygen delivery (DO2) and oxygen consumption (VO2), leading to cellular dysfunction and end-organ lesions [1]. Timely recognition is crucial for early and aggressive management of such dreadful conditions. Therefore, sensitive biomarkers to assess tissue perfusion and cellular oxygenation are required to guide clinical management and prognosis.
Serum lactate level and central venous oxygen saturation (ScVO2) have been used traditionally as markers of tissue perfusion and adequacy of DO2 in case of shock. Nonetheless, ScVO2 and lactate have drawbacks that need to be known in order to correctly interpret their values in the intensive care setting. Moreover, if their role as predictors of unfavorable outcomes is undeniable, resuscitation algorithms based either on lactate or ScVO2 failed to demonstrate clear clinical benefits [2,3,4,5,6,7,8].
The measurement of SvO2 (venous oxygen saturation measured in the pulmonary artery) has become a rarity, especially in pediatric patients, as a pulmonary catheter must be placed, which is a complicated and risky procedure. SvO2 and ScVO2 are closely correlated, provided that the central venous catheter tip is correctly positioned at the junction between the superior venous cava and the right atrium.
ScVO2 use is based on the comparison between the VO2 and the extraction of oxygen by the tissue, using the Fick formula:
VO2 = Cardiac Output × Oxygen Extraction
That is
VO2 = Cardiac Output × (CaO2 − CvO2)
Knowing that CaO2 = Hb × 1.34 × SpaO2 + 0.003 × PaO2 and CvO2 = Hb × 1.34 × ScVO2 + 0.003 × PaO2
And after rearrangement of the equation, the final formula:
ScVO2 = SpaO2 − VO2/[CO × Hb × 1.34]
A reduction of oxygen delivery (the denominator of the equation) will first lead to an increase in oxygen extraction to maintain the VO2. As a result, ScVO2 will decrease proportionally to the reduction of DO2, regardless of the cause that generated the DO2 reduction, thus providing a global picture of the patient’s hemodynamic status. The role of ScVO2 as a marker of both hemodynamic deterioration and clinical response to treatments has been extensively studied in both adult and pediatric ICU patients [9]. Specifically, after pediatric cardiac surgeries, ScVO2 levels have been associated with progressive hemodynamic deterioration and unfavorable clinical outcomes [10,11].
However, several limitations of ScVO2 should be mentioned, and its interpretation comes with some caveats. In fact, low ScVO2 values indicate a global imbalance between DO2 and VO2 without giving any further information regarding the individual components of these two elements, such as arterial oxygen saturation, hemoglobin, and CO. Moreover, during the early phase of resuscitation, the increase in DO2 may lead to an increase in VO2, which could result in a transitory decrease in ScvO2 levels. In a situation of shock, a mismatch between DO2 and capillary perfusion may lead to a misleadingly normal ScVO2 resulting from oxygen extraction impairment [9,12,13].
Serum lactate is a key metabolic parameter that could be related to both hypoperfusion and hypoxia [14]. It is produced in all human cells as part of intracellular glucose metabolism. In patients with shock, DO2 could be insufficient to meet cellular metabolism demands. As a consequence, the absence of aerobic mitochondrial metabolism leads to an over-production of lactate from the intracellular excess pyruvate.
As lactate level is a marker of hypoperfusion, serum lactate’s peak level, as well as lactate clearance, are strongly associated with patient outcomes in both adult and pediatric critically ill patients [1,6,15,16]. In patients admitted to the pediatric cardiac intensive care unit (CICU), increased blood lactate level has been associated with significant morbidity and mortality [17,18]. However, both the production and the clearance of lactate can be impacted by several factors, which limit its interpretation. Lactate production can be increased by alternative mechanisms frequently encountered in intensive care, such as hyperglycemia or beta-receptor stimulation [19,20,21,22]. Both hyperglycemia and the adrenergic stimulation of beta-2 receptors will lead to excess pyruvate production at the mitochondrial level [20,23,24,25]. Part of this excess pyruvate will be diverted to lactate production. Reduced lactate clearance, as well as washout phenomena’ (temporary increase in serum lactate level once sufficient capillary blood flow has been reestablished), can impact serum lactate level even in the absence of tissue hypoxia.
Given the aforementioned limitations in the interpretations of conventional tissue oxygenation markers, supplementary tools to assess the hemodynamic status of critically ill patients are needed [26,27]. Carbon dioxide (CO2)-derived parameters may represent a potentially valuable addition to serum lactate level and ScVO2 when it comes to the evaluation of tissue perfusion and hypoxia, as underlined by the recent recommendation on hemodynamic monitoring adult experts when lack of data prevented pediatric experts from giving such recommendations [28,29]. The simplicity of CO2-derived parameters measurement at the bedside makes them an attractive tool to guide resuscitation in the clinical setting.
The purpose of this review is to describe currently available CO2-derived parameters and their physiological underpinnings, as well as their potential clinical applications in CICU.

2. CO2 Metabolism

CO2 is produced by cellular metabolism (VCO2) under both aerobic and anaerobic conditions. Under aerobic metabolism, CO2 is produced by the mitochondrial metabolism as a by-product of substrate oxidation. In the case of anaerobic metabolism, CO2 is also produced by bicarbonate buffering of H+ derived from lactic acid production and ATP hydrolysis. Carbon dioxide diffuses from the intracellular to the extracellular compartment. Once in the blood, CO2 transportation occurs in three forms: dissolved, as bicarbonate after the reaction of CO2 with H2O in red blood cells, and finally, as carbamino compounds within circulating proteins, particularly hemoglobin. The dissolved fraction of CO2 is in equilibrium with the partial pressure of CO2 (PCO2) according to Henry’s law of gas solubility, depending on the gas solubility, the atmospheric pressure, and P CO2 itself. The majority of CO2 is transported in the blood as bicarbonate. As CO2 diffuses nearly freely in red blood cells, it reacts with H2O to form carbonic acid (H2CO3). In turn, H2CO3 will dissociate to form both bicarbonate (HCO3−) and H+. Eventually, H+ will be buffered by hemoglobin, and HCO3− exits the red blood cell. A small proportion of CO2 is transported as carbamino compounds that are linked to proteins, particularly to hemoglobin.
The proportion of diluted CO2, bicarbonate, and protein bounded CO2 varies between the arterial and venous compartments. In arterial blood, bicarbonate accounts for 90% of total CO2 content, while 5% is dissolved and 5% is bound to proteins. In venous blood, only 70% of the total CO2 content corresponds to bicarbonate, while 10% is dissolved, and a carbamino compound contributes 20%. The total content of CO2 (CCO2) in the blood under physiological conditions equals the dissolved CO2 + the bicarbonate (HCO3) + the CO2 linked to hemoglobin (R-NH2-CO2).
The content of CO2 (CCO2) is dependent on several variables and can be precisely calculated. According to the Douglas formula [30], the CCO2 could be determined using the content of CO2 in the plasma, the blood pH, and temperature:
Plasma CCO2 = 2.226 × S × plasma PCO2 × (1 + 10pH-pK’)
S = 0.0307 + [0.00057 × (37 − Temp)] + [0.00002 × (37 − Temp)2]
pK’ = 6.086 + [0.042 × (7.4 − pH)] + [(38 − Temp) × (0.00472 + (0.00139 × (7.4 − pH))]
For the final calculation, the hemoglobin level, the saturation in oxygenation, and the total amount of CO2 in the plasma are used:
CCO2 = Plasma CCO2 × [1 − [0.0289 × [Hb]/[[3.352 − 0.456 × SpO2] × [8.142 − pH]]]
The complete formula for the calculation of CCO2 gives the opportunity to appreciate the complexity of factors that are impacting the transport and content of CO2. However, despite its accuracy, this formula is extremely difficult to use at the bedside due to its computational complexity. Importantly, CO2 partial pressure (PCO2) is easier to obtain at the bedside, and a relationship exists between both CCO2 and PCO2 [31,32]. This relationship can be defined by the following equation PCO2 = k × CCO2, where k is a constant. This relationship follows a curvilinear curve with a near-linear relationship only in physiological PCO2 [31,32,33]. This nearly linear relation window has permitted the use of PCO2 in place of CCO2 in multiple clinical studies and expert opinion reports [26,28,34,35,36,37]. However, outside those ranges, it could be recommended to use CCO2 as the PCO2 will mostly divert significantly from the PCO2. The curvilinear relationship is directly impacted by the complex interaction of numerous variables such as the blood pH and temperature, the dissolved CO2, the CO2 bound to hemoglobin, and the CO2 as bicarbonate, as it is suggested by the multiple variables incorporated in the complete calculation of CCO2. The relationship between both CCO2 and pCO2 could be shifted by four factors: PO2, plasma pH and temperature, as well as hemoglobin levels. Those factors impact the k constant, with k increasing in case of a rise in PO2, acidosis, temperature, and hemoglobin level. Of special importance is the impact of oxygen on the content of CO2 through the Haldane effect. The Haldane effect describes the ability of hemoglobin to carry, at any PCO2, increased amounts of CO2 in the deoxygenated state compared to the oxygenated state [38]. Consequently, as blood enters the systemic microcirculation and releases O2, the CO2-carrying capacity increases so that the blood may remove the excess CO2. On the contrary, as blood enters the pulmonary circulation and binds O2, the CO2-carrying capacity decreases, thus facilitating CO2 removal from the lungs. In light of all the factors impacting the relationship between CCO2 and PCO2, we would argue for preferentially using CCO2 or, in case the PCO2 is used, it seems crucial that the clinicians understand the limitations of such approximation [38,39,40].

3. Relation between CO2 and Cardiac Output

3.1. Macrocirculation and Cardiac Output

Circulating CO2 is slightly higher in the venous compartment as a result of aerobic production of CO2 in tissues and alveolar elimination, thus creating a CO2 gradient between the venous and the arterial compartments. This difference will also be present under anaerobic circumstances due to the non-aerobic production of CO2. The increase in CO2 on the venous side will create an obligatory difference between the arterial and the venous blood, which could be estimated using the Fick equation.
In accordance with the Fick principle, the production of CO2 (VCO2) could be described as follows:
VCO2 = Cardiac Output (CO) × ΔCCO2
where ΔCCO2 is the difference in CCO2 between the venous and arterial compartments (CvCO2-CaCO2).
As mentioned above, PCO2 and CCO2 show a near-linear relationship at physiological ranges. Consequently, PCO2 values may be regarded as surrogate measures for CCO2 at the bedside.
A modified Fick equation can be obtained by substituting PCO2 with CCO2:
ΔPCO2 = (k × VCO2)/CO
This equation shows the inversely proportional relationship between CO and ΔPCO2 (Figure 1).
The ability of ΔCCO2 and ΔPCO2 to monitor CO is unique and of primary importance. In shocked patients, the measurement of CO is a key element in the evaluation of the hemodynamic status of the patient as well as for the assessment of the appropriateness of the implementation of therapeutic measures. Although measuring CO in PICU patients is theoretically possible, the methods currently available are burdened by some limitations, which make their use in clinical practice sometimes difficult [41].
The gold standard of CO estimation is cardiac echocardiography through the measurement of the left ventricular outflow tract (LVOT) diameter and the aortic velocity time integral [42]. Nonetheless, the correct implementation of cardiac echography and its interpretation requires highly specialized training, and it may be difficult to perform in patients with congenital cardiac malformations. Other methods using Doppler technologies are available, such as Ultrasound Cardiac Output Monitor (USCOM™, Sydney, NSW, Australia) or transesophageal Doppler [43,44,45]. These devices have some drawbacks as they use pre-established LVOT diameters, and the comparison of CO values with thermodilution methods has yielded conflicting results [45]. Thermodilution methods use the change in temperature of the circulating blood after a cold saline bolus to estimate blood flow. Using either a pulmonary catheter or a femoral catheter, CO could be precisely monitored. Some catheters, such as the PICCO™ device, can continuously monitor CO. However, despite very promising data on the applicability and validity of the CO measure devices, the invasiveness and relative difficulties of use probably limit their use in the setting of clinical trials [46,47,48,49]. A more recent tool for CO measurement is represented by electrical bioimpedance. This technology is based on the detection of electrical resistance changes in electrical resistance at the level of the thorax skin caused by cardiac stroke volume. The reliability of this method is still under scrutiny [50]. Again, the presence of a congenital cardiac anomaly and intracardiac shunts further complicate the interpretation of CO measurements and represents an important limitation of the aforementioned techniques.
The fact that ΔPCO2 and ΔCCO2 only depend on CO under stable VO2 conditions makes its use in the ICU setting a reliable way to estimate the adequacy of CO with respect to tissue metabolic demand [51]. The relationship between ΔPCO2 and CO has been studied in previous reports. A progressive decrease in ΔPCO2 in parallel to an increase in CO in patients receiving escalating doses of dobutamine has been described [52,53]. Moreover, experimental models show that ΔPCO2 remains stable under hypoxic conditions, and low DO2 provides a normal and stable CO [54]. It is important to underline that, despite previous reports, ΔPCO2 does not change in the case of cellular hypoxia [55,56,57]. In fact, the stagnation of CO2 in tissues caused by the absence of sufficient blood flow but not hypoxia was responsible for the increase in ΔPCO2 in patients after cardiac arrest [58]. Clinicians might therefore disentangle low CO (low ScVO2 and elevated ΔPCO2) from cellular hypoxia in the presence of normal CO (low ScVO2 and normal ΔPCO2) [31,59]. Thus, unlike ScVO2, ΔPCO2 might play an important role as a further easy-to-use bedside tool to monitor CO regardless of the presence of hypoxemia.

3.2. Microcirculation and the Microhemodynamic

If ScVO2 can be helpful in assessing global hemodynamics with some caveats, it is not suitable for the evaluation of microcirculatory imbalances. Indeed, ScVO2 may exert normal values in case of microcirculation derangements because of a lower oxygen extraction [9,12,13]. In a state of shock, the increased heterogeneity of blood flow (that is, well-perfused vessels in close vicinity to non-perfused capillaries) along with a reduction in the functional capillary density may lead to an increase in ΔCCO2 regardless of CO [60].
Hypo-perfused areas will accumulate CO2 under anaerobic circumstances. The excess CO2 will then diffuse across well-perfused capillaries, and the ΔCCO2 will increase. The association between abnormal ΔPCO2 with altered microcirculatory blood flow has been demonstrated in septic shock patients [61,62,63,64]. ΔPCO2 should be regarded as a potential tool for the evaluation of microcirculatory perfusion abnormalities, even in the absence of low CO. Under such circumstances, the increase in CO might improve tissue perfusion [36,65,66,67].

3.3. Clinical Use of ΔCCO2 and ΔPCO2

In adult patients with septic shock, both ΔCCO2 and ΔPCO2 are associated with patient mortality [36,65,66,68]. The correlation between ΔCCO2 and ΔPCO2 with CO, along with the detection of microcirculation anomalies, could be the main reasons for such findings. Higher ΔPCO2 levels are also associated with both post-operative complications after cardiac surgery and mortality in general ICU patients [69,70,71,72]. Moreover, higher ΔPCO2 might indicate microcirculatory derangements and predict patient mortality in adult patients on ECMO [73]. A recent meta-analysis confirmed the association between higher ΔPCO2 and increased mortality in shocked ICU patients [74]. Importantly, ΔPCO2 plays no role as a marker of tissular hypoxia but rather as a marker of adequacy between CO2 production and CO. In fact, high-flow shocks should result in a decrease rather than an increase in ΔPCO2.
Several treatment algorithms based on the combined use of serum lactate, ScVO2, and ΔPCO2 as a marker of insufficient CO have been proposed [26,31,32]. Most of those algorithms suggest the use of ΔPCO2 with a cut-off value of 6 mmHg (0.8 kPa). Higher values will mostly indicate that CO is not able to meet global metabolic demands. In case of shock, a high ΔPCO2 could prompt clinicians to increase CO (fluid bolus and/or inotropes). In the absence of shock, a high ΔPCO2 might indicate a state of high oxygen demand and CO2 production. A normal ΔPCO2 might also indicate that CO is correct, while other determinants of oxygen delivery (SpO2, hemoglobin) should possibly be improved in the presence of anaerobic metabolism (increased lactate and/or VCO2/VO2 ratio). Many of the available algorithms propose the use of both ScVO2 and ΔPCO2 to help clinicians to identify anemia, hypoxemia, or low CO as possible causes of tissue hypoxia. To our knowledge, though, none of those algorithms have been clinically validated.
Studies in the pediatric population are scarce and showed promising but conflicting results. A recent pediatric study in children with septic shock failed to detect a clear association between higher ΔPCO2 and CO measures [75].
Most of the studies on ΔPCO2 have been conducted in the CICU setting. A study from Furqan et al. suggests a possible association between higher ΔPCO2 and low ScVO2 after pediatric cardiac surgeries [76]. In this study, normal ScVO2 was sometimes accompanied by increased ΔPCO2. Unfortunately, the association of normal ScVO2 and low ΔPCO2 with clinical outcomes was not explored.
We found three studies looking at the possible association between increased ΔPCO2 and unfavorable outcomes in the immediate post-operative period in children after cardiac surgery has been recently studied (Table 1) [35,77,78]. Two articles reported an association between higher ΔPCO2 and poor outcome, defined as a composite variable including death, cardiac arrest, ECMO requirement, unplanned surgical reinterventions, and elevated inotropic score [35,78]. On the contrary, Akamatsu et al. could not find such an association [77]. Differences in the study population, as well as the use of the PCO2 variable used in the analysis (continuous vs. dichotomous), might explain these conflicting results. Although encouraging, current literature on the relation between CO2-derived parameters and clinical outcomes in ICU is not yet conclusive. As ΔPCO2 is directly linked to the CO, a more immediate and precise outcome, such as the duration of inotrope/vasopressor support or the need for mechanical circulatory support, may be more suited.

3.4. Production of CO2 and O2 Consumption (VCO2/VO2 Ratio)

Oxygen consumption (VO2) and CO2 production (VCO2) are directly proportional to CO. Under aerobic steady-state conditions, the ratio between VO2 and VCO2 (VCO2/VO2 ratio) varies between 0.7 and 1, depending on the main metabolic substrate used for oxidative metabolism [79,80]. Under aerobic conditions, VCO2 should not exceed O2 availability; therefore, the ratio should not exceed one. However, under anaerobic conditions, during circulatory shock, both VO2 and VCO2 are globally reduced. However, due to buffering of cations (H+) by bicarbonate, a small production of CO2 remains [81]. This “anaerobic CO2 production” would result in a relative rise of VCO2 in comparison to VO2. As a result, under anaerobic metabolism and dysoxia, the VCO2/VO2 ratio will be higher than one [33].
The VCO2/VO2 ratio can be calculated at the bedside.
According to the Fick principle:
VO2 = CO × (CaO2 − CvO2)
and
VCO2 = CO × (CvCO2 − CaCO2)
The ratio is, therefore, equal to CvCO2 − CaCO2/CaO2 − CvO2. As mentioned above, at usual physiologic ranges, CvCO2 − CaCO2 can be replaced by ΔPCO2.
It gives the final equation:
VCO2/VO2 = ΔPCO2/CaO2 − CvO2
ΔPCO2, CaO2, and CvO2 are either directly accessible or easily calculated at bedside (CaO2 and CvO2 only need hemoglobin and oxygen saturation for their calculation).
The VCO2/VO2 ratio can identify anaerobic metabolism, and it has shown to be closely correlated with lactate levels, the usual dysoxia marker [33,39]. Moreover, the use of the VCO2/VO2 ratio might represent a possible alternative to lactate levels in specific situations that are frequently encountered in the ICU setting, such as hyperglycemia or catecholamine-induced hyperlactatemia.

3.5. Clinical Use of VCO2/VO2 Ratio

The VCO2/VO2 ratio has been less studied than ΔCO2. The princeps study by Mekontso-Dessap et al., carried out nearly 20 years ago, showed the role of the VCO2/VO2 ratio as a mortality marker in adult septic shock [66]. More recently, Ospina-Tascon also described the same relation, again in patients with septic shock [39]. Interestingly, even in patients with a normal lactate level, increased VCO2/VO2 ratio was strongly associated with a worse outcome. Other reports described the link between the VCO2/VO2 ratio and patients’ outcome both in septic shock and after cardiac surgery. Interestingly, both Ospina-Tascon et al. and He et al. showed an association between the VCO2/VO2 ratio and outcome in shocked patients with normal ScVO2 [39,82]. These findings underline the role of more advanced indices of tissue hypoxia when ScVO2 levels are within normal ranges, possibly signaling low O2 extraction and/or capillary perfusion disturbances [64,83]. This ratio might provide important prognostic information, especially in case of persistent high values and normalization of lactate levels after initial resuscitation.
The VCO2/VO2 ratio has also been described as a possible tool for the prediction of fluid responsiveness. In patients with a hypotensive episode, only those with an elevated VCO2/VO2 ratio showed a rapid increase in VO2 after the fluid challenge [65,84].
As with the ΔCO2, several algorithms propose the use VCO2/VO2 ratio in the initial patient assessment as a sign of tissue dysoxia. As for lactates, an elevated VCO2/VO2 ratio > one indicates anaerobic metabolism and should prompt a complete hemodynamic assessment of the patient and the possible implementation of rapid therapeutic measures to restore aerobic metabolism. On the other hand, a VCO2/VO2 ratio < one could also point to hyperglycemia or adrenergic stimulation as possible alternative causes of elevated lactate levels. Several cut-off values have been proposed to predict unfavorable outcomes, varying from 1.2 to 1.6 [31,37,85]. Unfortunately, as for the ΔPCO2, none of those algorithms has been validated in the clinical setting.
To the best of our knowledge, only one study looked at the VCO2/VO2 ratio in the pediatric population. Xu et al. studied the impact of elevated increased VCO2/VO2 ratio on acute kidney injury after pediatric cardiac surgery [86]. As blood is diverted from the kidneys in the case of shock, the authors suggest that an increased VCO2/VO2 ratio might represent a sign of anaerobic metabolism at the kidney level and indicate a possible kidney injury in CICU patients [87]. Despite the lack of clear evidence at the moment, these results suggest that VCO2/VO2 ratio may possibly help detect patients at risk of end-organ lesions in the context of anaerobic metabolism.

4. Implications for Research

Future studies are warranted to establish reference values of ΔPCO2 in CICU and PICU. Currently, reference values are derived from adult patients with septic shock. However, those values may differ significantly in children, especially in the cardiac population after a cardio-pulmonary bypass, where alterations of microcirculation may increase the ΔPCO2 value without macrohemodynamic disturbances. Our experience confirms current pediatric literature describing large ΔPCO2 regardless of clinical outcomes. Multicenter prospective cohort studies are also needed to better define the relationship between ΔPCO2.and cardiac output in the case of LCOS. The description and validation of the impact of CO2-derived parameters in patient management, both adult and pediatric patients, are highly needed. Whether the introduction of CO2-derived parameters into clinical algorithms may improve patients’ outcomes is unknown.

5. Conclusions

Despite the many limitations and the lack of robust data, CO2-derived parameters such as ΔPCO2 and VCO2/VO2 ratio represent valuable markers of hemodynamic derangements from macrocirculation to microcirculation. Moreover, unlike traditional markers of cardiac output, they seem to be reliable in specific situations commonly encountered in the post-cardiac surgery setting, such as hyperglycemia and catecholamine use. Their integration with classical markers of hypoperfusion into treatment algorithms holds the promise of adding substantial information that might help refine the management of patients suffering from shock in the adult and in the pediatric population alike. Further studies are needed to clearly define the role of those attractive tools in guiding resuscitation in the clinical setting.

Author Contributions

Conceptualization, V.L.C.; writing-original draft preparation V.L.C. and R.J.; writing-review and editing V.L.C., R.J. and A.P.; final review of the manuscript V.L.C., R.J., J.W., M.B. and AP. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest in relation to the subject of this review.

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Jcdd 10 00208 g001 550
Figure 1. Relation between cardiac output and ΔPCO2. Inverse relation between cardiac output and ΔPCO2. Reduction of cardiac output is associated with an increase in ΔPCO2, initially slow, which become exponential at very low cardiac output. Modification of CO2 production (VCO2) shift the curves to the right and upward.
Figure 1. Relation between cardiac output and ΔPCO2. Inverse relation between cardiac output and ΔPCO2. Reduction of cardiac output is associated with an increase in ΔPCO2, initially slow, which become exponential at very low cardiac output. Modification of CO2 production (VCO2) shift the curves to the right and upward.
Jcdd 10 00208 g001
Table
Table 1. Pediatric study looking ΔCO2 as a tool in resuscitation.
Table 1. Pediatric study looking ΔCO2 as a tool in resuscitation.
Insom et al. [78]
Cardiol Young 2021		Rhodes et al. [35]
PCCM 2017		Akamatsu et al. [77]
PCCM 2017
N patients40 patients139 patients114 patients
Age (days/months)Median 215 days
(range 3–5600)		Median 12 days
(IQR 6–38)		Median 15.5 months
(IQR 7–34)
PopulationCICUCICUCICU
Outcome measuredComposite outcome
−
VIS > 15
−
CICU LOS > 5 days
Composite outcome:
−
IS > 15
−
Mortality
−
Cardiac arrest
−
ECMO within 48 h
−
Reintervention
−
Mecanical ventilation duration
−
Mortality
∆PCO2 measured (mmHg)Median 9 mmHg (range 1–25)Median 5.9 mmHg
(IQR 3.8–9.2)		Not reported
∆PCO2 analyzed as a dichotomous variable >6 mmHg or <6 mmHg
Association ∆PCO2-outcomeSignificant association
OR 1.13 (95% CI 1.01–1.35)		Significant association
−
composite outcome OR 1.3 (95% CI 1.1–1.45)
−
Mortality OR 1.2 (95% CI 1.07–1.31)
No significant association
CommentaryHigher values of ∆PCO2 are associated with more complex clinical course.Underline role for ∆PCO2 monitoring in CICU
Suggest an association between ∆PCO2 and outcome.		Population separated into 2 groups: ∆PCO2 > 6 mmHg or <6 mmHg and no difference between both groups.
CICU, cardiac intensive care unit.
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Cousin, V.L.; Joye, R.; Wacker, J.; Beghetti, M.; Polito, A. Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications. J. Cardiovasc. Dev. Dis. 2023, 10, 208. https://doi.org/10.3390/jcdd10050208

AMA Style

Cousin VL, Joye R, Wacker J, Beghetti M, Polito A. Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications. Journal of Cardiovascular Development and Disease. 2023; 10(5):208. https://doi.org/10.3390/jcdd10050208

Chicago/Turabian Style

Cousin, Vladimir L., Raphael Joye, Julie Wacker, Maurice Beghetti, and Angelo Polito. 2023. "Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications" Journal of Cardiovascular Development and Disease 10, no. 5: 208. https://doi.org/10.3390/jcdd10050208

APA Style

Cousin, V. L., Joye, R., Wacker, J., Beghetti, M., & Polito, A. (2023). Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications. Journal of Cardiovascular Development and Disease, 10(5), 208. https://doi.org/10.3390/jcdd10050208

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