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Revista Brasileira de Terapia Intensiva

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OFFICIAL JOURNAL OF THE ASSOCIAÇÃO BRASILEIRA DE MEDICINA INTENSIVA AND THE SOCIEDADE PORTUGUESA DE CUIDADOS INTENSIVOS

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Online ISSN: 1982-4335

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Dubin A, Pozo MO, Hurtado J. Proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo arterial menos venoso central de oxigênio como indicador de oxigenação tissular: uma revisão narrativa. Rev Bras Ter Intensiva. 2020;32(1):115-122

 

 

2020 2020;32(1):115-122
REVIEW ARTICLE

10.5935/0103-507X.20200017

Central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio as an indicator of tissue oxygenation: a narrative review

Proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo arterial menos venoso central de oxigênio como indicador de oxigenação tissular: uma revisão narrativa

Arnaldo Dubin1,2, Mario Omar Pozo3, Javier Hurtado4,5

1 Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata - La Plata, Argentina.
2 Servicio de Terapia Intensiva, Sanatorio Otamendi - Buenos Aires, Argentina.
3 Servicio de Terapia Intensiva, Hospital Británico - Buenos Aires, Argentina.
4 Servicio de Terapia Intensiva, Hospital Español-ASSE - Montevideo, Uruguay.
5 Departamento de Fisiopatología, Facultad de Medicina, Universidad de la República - Montevideo, Uruguay.

Conflicts of interest: None.

Responsible editor: Luciano César Pontes de Azevedo

Submitted on April 28, 2019
Accepted on June 09, 2019

Corresponding author: Arnaldo Dubin, Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 42 Nº 577 (1900) La Plata, Argentina. E-mail: [email protected]

 

Abstract

The central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) has been proposed as a surrogate for respiratory quotient and an indicator of tissue oxygenation. Some small observational studies have found that a Pcv-aCO2/Ca-cvO2 > 1.4 was associated with hyperlactatemia, oxygen supply dependency, and increased mortality. Moreover, Pcv-aCO2/Ca-cvO2 has been incorporated into algorithms for tissue oxygenation evaluation and resuscitation. However, the evidence for these recommendations is quite limited and of low quality. The goal of this narrative review was to analyze the methodological bases, the pathophysiologic foundations, and the experimental and clinical evidence supporting the use of Pcv-aCO2/Ca-cvO2 as a surrogate for respiratory quotient. Physiologically, the increase in respiratory quotient secondary to critical reductions in oxygen transport is a life-threatening and dramatic event. Nevertheless, this event is easily noticeable and probably does not require further monitoring. Since the beginning of anaerobic metabolism is indicated by the sudden increase in respiratory quotient and the normal range of respiratory quotient is wide, the use of a defined cutoff of 1.4 for Pcv-aCO2/Ca-cvO2 is meaningless. Experimental studies have shown that Pcv-aCO2/Ca-cvO2 is more dependent on factors that modify the dissociation of carbon dioxide from hemoglobin than on respiratory quotient and that respiratory quotient and Pcv-aCO2/Ca-cvO2 may have distinct behaviors. Studies performed in critically ill patients have shown controversial results regarding the ability of Pcv-aCO2/Ca-cvO2 to predict outcome, hyperlactatemia, microvascular abnormalities, and oxygen supply dependency. A randomized controlled trial also showed that Pcv-aCO2/Ca-cvO2 is useless as a goal of resuscitation. Pcv-aCO2/Ca-cvO2 should be carefully interpreted in critically ill patients.

Keywords: Anaerobiosis; Respiration; Oxygenation; Carbon dioxide; Respiratory quotient; Critical illness.

 

INTRODUCTION

In critically ill patients, tissue hypoxia is a leading mechanism of multiple organ failure and death. Therefore, the detection and correction of anaerobic metabolism are crucial tasks. Unfortunately, gold standards for the assessment of tissue oxygenation are lacking. Some variables, which are commonly used in the monitoring of critically ill patients, might be misleading indicators of anaerobic metabolism. Lactate is an excellent predictor of outcome,(1,2) but it is an unreliable marker of tissue hypoxia.(3) Clinical monitoring of peripheral perfusion is an attractive and feasible approach but also has limitations.(4) Although central venous oxygen saturation (ScvO2) and central venous minus arterial partial pressures of carbon dioxide (PCO2) difference (Pcv-aCO2) can track changes in cardiac output, their role in the evaluation of the adequacy of tissue oxygenation is controversial.(5,6) Regrettably, the evaluation of tissue PCO2 is no longer feasible, and the monitoring of microcirculation is still restricted to research.(7) Hence, the search for new approaches is warranted.

In the physiology of exercise, the analysis of expired gases allows the identification of anaerobic metabolism. Increasing workloads are associated with parallel increases in carbon dioxide (CO2) production (VCO2) and O2 consumption (VO2). The slope of this relationship is the respiratory quotient (RQ = VCO2/VO2). The RQ remains initially constant under aerobic conditions. At some point, however, the increases in VCO2 exceed those in VO2, and the RQ increases. This inflection point corresponds with the development of hyperlactatemia and is known as the anaerobic threshold.(8) In the context of the other physiological extreme, during oxygen supply dependency, the reductions in VO2 are higher than those in VCO2. Consequently, sharp elevations in RQ ensue(9-11) (Figure 1). In both situations, anaerobic exercise and critical decreases in oxygen transport, the underlying phenomenon is the appearance of anaerobic VCO2 secondary to bicarbonate buffering of anaerobically generated protons. Thus, the increase in RQ indicates ongoing anaerobic metabolism.

Figure 1 - Oxygen consumption, carbon dioxide production, and respiratory quotient as function of oxygen transport. (A) Relationship of oxygen consumption and carbon dioxide production with oxygen transport. (B) Relationship of respiratory quotient with oxygen transport. Critical reductions in oxygen transport are associated with progressive decreases in oxygen consumption and carbon dioxide production. The reductions in carbon dioxide production are lower than those in oxygen consumption because of the beginning of anaerobic carbon dioxide production secondary to bicarbonate buffering of anaerobically generated protons. Consequently, sharp increases in respiratory quotient ensue. O2 - oxygen; CO2 - carbon dioxide.

Consequently, the measurement of RQ arises as an appealing approach for the identification of global tissue hypoxia. Nevertheless, metabolic carts are not usually available in the setting of the intensive care unit. In addition, the use of a high inspired oxygen fraction can interfere with the measurements.(12) To solve this problem, some researchers have proposed a simplification of Fick’s equation adapted to CO2, the Pcv-aCO2 to arterial minus central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2), as a substitute for RQ. Some small observational studies have found that a Pcv-aCO2/Ca-cvO2 higher than 1.4 was associated with hyperlactatemia,(13) oxygen supply dependency,(14,15) and worse outcome.(13) Moreover, Pcv-aCO2/Ca-cvO2 has been incorporated in algorithms for tissue oxygenation evaluation and resuscitation.(16-18) However, the evidence for these recommendations is quite limited and of low quality.

The goal of this narrative review was to analyze the methodological bases, the pathophysiologic foundations, and the experimental and clinical evidence supporting the use of Pcv-aCO2/Ca-cvO2 as a surrogate for RQ. We comprehensively assessed the existing evidence for the association between Pcv-aCO2/Ca-cvO2 and outcomes in critically ill patients. We aimed to determine whether, in critically ill patients, increased Pcv-aCO2/Ca-cvO2 is associated with higher mortality and is a better predictor of outcome than arterial lactate. We also reviewed the role of Pcv-aCO2/Ca-cvO2 as a predictor of oxygen supply dependency and its use as a goal of resuscitation.

METHODOLOGICAL CONCERNS

The use of Pcv-aCO2/Ca-cvO2 as a surrogate for RQ and tissue oxygenation relies on some assumptions. First, RQ is the ratio between VCO2 and VO2:

RQ = VCO2/VO2 (Equation 1)

Formula 6
RQ = VCO 2 / VO 2

According to Fick’s equation, this calculation can be rearranged as:

RQ = Q x Cmv-aCO2/Q x Ca-mvO2 (Equation 2)

Formula 7
RQ = Q x C mv a CO 2 / Q x C a mv O 2

where Q = cardiac output, Cmv-aCO2 = mixed venous - arterial CO2 content difference, and Ca-mvO2 = arterial - mixed venous oxygen content difference.

Next, an equivalence between mixed and central samples is assumed:

RQ = Q x Ccv-aCO2/Q x Ca-cvO2 (Equation 3)

Formula 8
RQ = Q x C cv a CO 2 / Q x C a cv O 2

where Ccv-aCO2 = central venous - arterial CO2 content difference, and Ca-cvO2 = arterial - central venous O2 content difference.

Then, the common factor (Q) is simplified in the numerator and denominator:

RQ = Ccv-aCO2/Ca-cvO2 (Equation 4)

Formula 9
RQ = C cv a CO 2 / C a cv O 2

Finally, since the calculation of CO2 content is not straightforward, CO2 content is replaced by CO2 pressure. This assumption is based on the fact that CO2 content and pressure are linearly correlated over the physiological range of CO2 content:

RQ = Pcv-aCO2/Ca-cvO2 (Equation 5)

Formula 10
RQ = P cv a CO 2 / C a cv O 2

Unfortunately, some of these assumptions are problematic, such as the use of CO2 pressure instead of content(19,20) and the lack of interchangeability between central and mixed venous samples.(21) In addition, the use of a defined cutoff of Pcv-aCO2/Ca-cvO2 for the identification of tissue hypoxia is also questionable.(9-11) In the following paragraphs, we reviewed these and other methodological issues.

The use of carbon dioxide pressure instead of content in the calculation of the ratio

The relationship between CO2 content and pressure is complex. In general terms, the relationship is curvilinear. This implies that for the highest range of CO2 content, the relationship becomes flatter. In this way, further increases in CO2 content induce a larger increase in PCO2. The CO2 dissociation curve can be modified by changes in base excess, hemoglobin levels, and oxygen saturation (Haldane effect) (Figure 2). These factors can significantly modify Pcv-aCO2/Ca-cvO2, even in the absence of alterations in RQ and tissue oxygenation.(19)

Figure 2 - Relationship between carbon dioxide content and pressure (carbon dioxide dissociation curve). For the same partial pressure of carbon dioxide, anemia, metabolic acidosis, and elevated oxygen saturation (Haldane effect) are associated with decreased carbon dioxide content. CO2 - carbon dioxide; O2 - oxygen; PCO2 - partial pressure of carbon dioxide.

Theoretically, these drawbacks of Pcv-aCO2/Ca-cvO2 might be overcome by the use of equation 3. Nevertheless, any algorithm for the calculation of CO2 content can be misleading. For example, the most commonly used method results in 95% limits of agreement between calculated and manometrically measured CO2 content of 4.66mL/100mL.(22) This value is unacceptably high, especially taking into account the error propagation related to the additional calculation of venous - arterial CO2 content difference. Consequently, the method frequently produces unreliable negative values of Cmv-aCO2.(23)

An experimental study addressed the methodological pitfalls associated with Pmv-aCO2/Ca-mvO2 as a surrogate for RQ.(19) In this study, Pmv-aCO2/Ca-mvO2, RQ, and their determinants were measured during stepwise reductions of oxygen transport (DO2) induced by hemorrhage or hemodilution. The correlation between Pmv-aCO2/Ca-mvO2 and RQ was significant but poor. Moreover, in the context of hemodilution, Pmv-aCO2/Ca-mvO2 increased even before the decrease in VO2 and the increase in RQ (Figure 3). This finding was related to the opposite effects of hemoglobin reduction on Pmv-aCO2 and Ca-mvO2. Pmv-aCO2 increased as a consequence of the effects of anemia on the CO2 dissociation curve, while Ca-mvO2 decreased as a result of the increase in the oxygen extraction ratio (Figure 4). In addition, in the last step of DO2 reduction and despite similar degrees of tissue hypoxia and elevations in RQ, Pmv-aCO2/Ca-mvO2 disproportionally increased in the context of hemodilution compared to the hemorrhage condition because of the aforementioned factors. Moreover, a multiple linear regression model identified hemoglobin, metabolic acidosis, the Haldane effect, the position in the flattened portion of the CO2 dissociation curve, and RQ as independent determinants of Pmv-aCO2/Ca-mvO2. Although Pmv-aCO2/Ca-mvO2 was found to be dependent on RQ, this was its weakest determinant.

Figure 3 - Oxygen consumption, respiratory quotient, and venoarterial partial pressure of carbon dioxide difference with arteriovenous oxygen content difference ratio as functions of oxygen transport . Relationship of oxygen transport with oxygen consumption (A), respiratory quotient (B), and venoarterial partial pressure of carbon dioxide difference with arteriovenous oxygen content difference ratio (Pv-aCO2/Ca-vO2). Oxygen consumption decreased and respiratory quotient increased only in the last step of hemodilution and hemorrhage. In the context of hemodilution, the increase in Pv-aCO2/Ca-vO2 was higher than in the hemorrhage condition and appeared before the development of oxygen supply dependency.

Figure 4 - Oxygen consumption, respiratory quotient, and venoarterial partial pressure of carbon dioxide difference with arteriovenous oxygen content difference ratio as functions of oxygen transport. Relationship of oxygen transport with venoarterial partial pressure of carbon dioxide difference (Pv-aCO2) (A), venoarterial carbon dioxide content difference (Cv-aCO2) (B), and arteriovenous oxygen content difference (Ca-vO2). Hemodilution produced opposite effects on Pv-aCO2 and Cv-aCO2. Cv-aCO2 decreased in the context of hemodilution and increased in the hemorrhage condition. These changes are the underlying explanation for the different behavior of Pv-aCO2/Ca-vO2 in both groups. CO2 - carbon dioxide. Source: reproduced with permission of Dubin et al.(19)

Given that metabolic acidosis is a key determinant of Pmv-aCO2/Ca-mvO2, the relationship between this variable and lactate is complicated. Both variables can be increased as an expression of anaerobic metabolism. On the other hand, hyperlactatemia that results from the activation of aerobic glycolysis can increase Pmv-aCO2/Ca-mvO2, even in the absence of tissue hypoxia. For example, after blood retransfusion in experimental hemorrhagic shock, VO2 and RQ normalize, but Pmv-aCO2/Ca-mvO2 remain high as a probable consequence of persistent hyperlactatemia.(20) Although Pmv-aCO2/Ca-mvO2 has been suggested as a tool to assert the source of lactate,(18) the results of this experimental study suggest that this approach might be misleading.

The poor agreement between central and mixed venous samples

Another methodological concern is the lack of interchangeability between central and mixed venous samples for the different calculations. The issue of the agreement between mixed venous and central O2 saturation has been extensively addressed. Although the agreement is poor, a small study advocated that both variables have similar behavior.(24) In contrast, a multicenter study comprehensively showed that both variables not only have poor agreement but also might differ in the direction of their changes.(25) Furthermore, a recent study showed that the problem is even worse for CO2-derived variables: 95% limits of agreement for venous-arterial PCO2 and its ratio to arterial-venous O2 content were 8mmHg and 1.48, respectively, which are unacceptably high.(21)

The use of a particular cutoff of Pcv-a CO2/Ca-cv O2 for the diagnosis of anaerobic metabolism

In addition, the identification of anaerobic metabolism based on a cutoff value of Pcv-aCO2/Ca-cvO2 is arguable. Since the beginning of anaerobic metabolism is indicated by sharp increases in RQ, not by a particular threshold,(9-11) similar criteria should be considered for Pcv-aCO2/Ca-cvO2. This is especially relevant taking into account the fact that a normal RQ ranges from 0.67 to 1.30.(26) The wide normal limits of RQ are mainly dependent on energetic oil. Diets based only on carbohydrates and overfeeding consistently increased RQ, while fat-based diets and fasting decreased RQ.

Accordingly, a clinical study showed that the ability of the absolute value of RQ to predict death or low cardiac output syndrome was lower than that of lactate in cardiac surgery patients.(27) Although RQ was higher in nonsurvivors (0.83 ± 0.08 versus 0.75 ± 0.08; p = 0.02), values were in the normal range. Therefore, defined cutoffs of Pcv-aCO2/Ca-cvO2 or RQ should not be used for the detection of anaerobic metabolism; sudden increases in these parameters should be used instead.

The use of calculated instead of measured oxygen saturation for Pcv-a CO2/Ca-cv O2

Another relevant limitation of some studies was that the computation of Pcv-aCO2/Ca-cvO2 was based on values of oxygen saturation calculated from blood gases and oxyhemoglobin dissociation curves instead of measurements performed by co-oximetry.(23,28-30) The calculated O2 saturation does not agree with the measured values. In addition, the measurement error is propagated in the calculation of Pcv-aCO2/Ca-cvO2. Additionally, paired measurements of Pcv-aCO2/Ca-cvO2 in the same analyzer had poor reproducibility with 95% limits of agreement of 1.22.(31)

The physiological feasibility of increased Pcv-a CO2/Ca-cv O2 as a reflection of tissue hypoxia in critically ill patients

In experimental models, the increase in RQ is a dramatic event associated with impending death. For example, during progressive hemodilution, RQ increases only when hemoglobin reaches 1.2g%. Likewise, during progressive bleeding, RQ increases when the mean arterial pressure is lower than 30mmHg.(11) These are extreme and obvious conditions that do not require additional monitoring or sensitive assessment of tissue oxygenation to be identified. Accordingly, high values of Pcv-aCO2/Ca-cvO2 in patients with otherwise stable conditions might seldom reflect global anaerobic metabolism but rather the presence of factors that modify the dissociation of CO2 from hemoglobin. This has been shown in experimental models, in which RQ and Pmv-aCO2/Ca-mvO2 are poorly correlated. In these cases, the presence of anemia, metabolic acidosis, or the Haldane effect explained the findings of increased Pmv-aCO2/Ca-mvO2, even when VO2 and RQ were normal.(19) In addition, at higher levels of CO2 content, the linear relationship between CO2 content and pressure is progressively lost, and minor changes in CO2 content may be associated with larger changes in PCO2. In patients, a direct comparison between Pmv-aCO2/Ca-mvO2 or Pcv-aCO2/Ca-cvO2 and RQ has not yet been performed. Therefore, values of Pcv-aCO2/Ca-cvO2 should be interpreted cautiously in clinically stable patients.

The clinical usefulness of Pcv-a CO2/Ca-cv O2

Although Pcv-aCO2/Ca-cvO2 might fail to reflect the actual value of RQ, it might still reflect the severity of the critical illness because it is a compound variable, which is partially dependent on hemoglobin and base excess. Consequently, anemia and metabolic acidosis can produce high Pcv-aCO2/Ca-cvO2 by themselves and can be indicators of a severe condition or predictors of worse outcome. Thus, the presence of anemia and metabolic acidosis might be responsible for the predictive ability of Pcv-aCO2/Ca-cvO2. Next, we discuss the controversies about Pcv-aCO2/Ca-cvO2 as a predictor of outcome, oxygen supply dependency and microcirculatory alterations and as a goal of resuscitation.

Pcv-a CO2/Ca-cv O2 as a predictor of outcome and hyperlactatemia

Several years ago, a retrospective study of 89 patients monitored with a pulmonary catheter found that Pmv-aCO2/Ca-mvO2 was a sensitive predictor of hyperlactatemia, with an area under receiving operating characteristic (AUROC) curve of 0.85.(13) Pmv-aCO2/Ca-mvO2 was also higher in hyperlactatemic patients than in normolactatemic patients (2.0 ± 0.9 versus 1.1 ± 0.6). Additionally, 30-day survival was higher for patients with Pmv-aCO2/Ca-mvO2 < 1.4 than for patients with a ratio ≥ 1.4 (38 versus 20%). Despite these findings, Pmv-aCO2/Ca-mvO2 was not significantly different between nonsurvivors and survivors (1.7 ± 1.0 versus 1.3 ± 0.5). On the other hand, lactate was lower in survivors (2.0 ± 1.5 versus 5.4 ± 6.1mmol/L). Although lactate and Pmv-aCO2/Ca-mvO2 were correlated and Pmv-aCO2/Ca-mvO2 showed some association with outcome, lactate was a better predictor of outcome in this study.(13) Similarly, in 135 patients with septic shock, Pmv-aCO2/Ca-mvO2 and lactate had a distinct time course in survivors and nonsurvivors, but only Cmv-aCO2/Ca-mvO2 and lactate, but not Pmv-aCO2/Ca-mvO2, were related to the outcome.(28)

In another study performed with 50 patients with shock, Pcv-aCO2/Ca-cvO2 and lactate at the beginning of the study were lower in survivors than in nonsurvivors. Lactate, however, showed a better prognostic ability (AUROC curve of 0.73 and 0.81).(29) A retrospective series of 144 patients with septic shock found that Pcv-aCO2/Ca-cvO2 and lactate showed a similar ability to predict mortality and organ failure, but their combination was superior.(30) In another observational study in 35 patients with septic shock, Pcv-aCO2/Ca-cvO2 was a strong predictor of lactate behavior, and both variables were associated with outcome.(32)

In contrast, other studies have shown that Pcv-aCO2/Ca-cvO2 has a poor association with either lactate or mortality. In a prospective multicenter cohort study that recruited 363 patients with septic shock, Pcv-aCO2/Ca-cvO2 could not distinguish patients with high lactate levels or poor lactate clearance from patients with low lactate levels or proper lactate clearance.(33) In another observational study of 23 septic patients, neither Pcv-aCO2/Ca-cvO2 nor Pmv-aCO2/Ca-mvO2 distinguished survivors from nonsurvivors.(21)

In brief, there are conflicting results about the relationship between Pcv-aCO2/Ca-cvO2 and mortality. It appears that a high Pcv-aCO2/Ca-cvO2 has some prognostic implications that seem similar to those of lactate. There are also conflicting reports about the relationship between Pcv-aCO2/Ca-cvO2 and lactate. Nevertheless, there is great heterogeneity among the studies.

Pcv-a CO2/Ca-cv O2 as a predictor of oxygen supply dependency

The increase in VO2 in response to elevated DO2 is characterized as oxygen supply dependency. Although the oxygen supply dependency might reveal the presence of an oxygen debt, its actual meaning is controversial. Since both VO2 and DO2 are usually calculated from a shared variable (cardiac output) and the magnitude of change of the calculated variables is also small, there is a considerable risk of mathematical coupling of data. Therefore, oxygen supply dependency is sometimes not a real fact but an artifact. Nevertheless, different studies have aimed to show that Pcv-aCO2/Ca-cvO2 is a predictor of oxygen supply dependency.

In 25 patients with shock, in whom cardiac output was increased in response to 500mL of saline solution, VO2 increased in 14 patients and remained unchanged in 11 patients.(14) Lactate (5.5 ± 4.0 versus 2.3 ± 1.1mmol/L) and Pcv-aCO2/Ca-cvO2 (2.3 ± 0.8 versus 1.3 ± 0.5) were higher in patients with oxygen supply dependency. Both variables, lactate and Pcv-aCO2/Ca-cvO2, showed high areas under the receiving operating characteristic (AUROC) curves to predict the increase in VO2 (0.94 ± 0.05 and 0.91 ± 0.06, respectively). Another study, performed with 51 fluid-responsive patients with septic shock, also showed increased levels of lactate and Pcv-aCO2/Ca-cvO2 in patients with oxygen supply dependency, but lactate had a lower AUROC (0.745 versus 0.965).(15) In contrast, in 92 fluid responders admitted to a cardiothoracic ICU, Pcv-aCO2/Ca-cvO2 failed to predict the increase in VO2 (AUROC = 0.52).(34) In another small study, in 17 cardiac surgery patients, Pcv-aCO2/Ca-cvO2 was also unable to predict oxygen supply dependency (AUROC = 0.64).(35)

Therefore, the results are inconclusive. Furthermore, in these studies, VO2 was calculated from central instead of mixed venous samples, which generates further methodological uncertainties about the interpretation of the results.

Pcv-a CO2/Ca-cv O2 as a predictor of microcirculatory alterations

An observational study described a correlation between Cmv-aCO2/Ca-mvO2 and the sublingual proportion of perfused vessels in patients with septic shock.(23) Another clinical study, however, did not find any correlation of Pcv-aCO2/Ca-cvO2 or Pmv-aCO2/Ca-mvO2 with sublingual microcirculation.(21)

Pcv-a CO2/Ca-cv O2 as a goal of resuscitation

Only one study has assessed the usefulness of Pcv-aCO2/Ca-cvO2 as a goal of resuscitation.(36) In a randomized controlled trial, 228 patients were assigned to Pcv-aCO2/Ca-cvO2- or ScvO2-targeted resuscitation. There were no differences in mortality, organ failure, length of stay, or other secondary outcomes.

CONCLUSIONS

The clinical use of Pcv-aCO2/Ca-cvO2 as a surrogate for RQ is controversial. First, the increase in respiratory quotient secondary to critical reductions in oxygen transport is a life-threatening and dramatic but easily noticeable event that probably does not require further monitoring. Since the beginning of anaerobic metabolism is indicated by the sudden increase in respiratory quotient and the normal range of respiratory quotient is wide, the use of a defined cutoff of 1.4 for Pcv-aCO2/Ca-cvO2 is meaningless. Pcv-aCO2/Ca-cvO2 is more dependent on factors that modify the dissociation of carbon dioxide from hemoglobin than on respiratory quotient. Experimental studies have shown that RQ and Pcv-aCO2/Ca-cvO2 might display distinct behaviors in different models. Clinical studies in critically ill patients have shown controversial results regarding the ability of Pcv-aCO2/Ca-cvO2 to predict outcomes, hyperlactatemia, microvascular abnormalities, and oxygen supply dependency. A randomized controlled trial also showed that Pcv-aCO2/Ca-cvO2 is useless as a goal of resuscitation. Consequently, Pcv-aCO2/Ca-cvO2 should be carefully interpreted in critically ill patients.

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