The results of this study can be summarized as follows: 1) in critically ill patients with hyperlactatemia, elevated PvaCO2/CavO2 is not associated with decreases in blood-lactate levels after FB and cannot be used to predict them, 2) increases in oxygen consumption observed only in patients with elevated baseline PvaCO2/CavO2 were not associated with blood lactate decreases after FB and 3) in patients with hyperlactatemia, blood-lactate levels and changes during FB were not corelated with PvaCO2/CavO2 values and changes.
Previous studies have suggested using the PvaCO2/CavO2 ratio measured after the end of resuscitation for predicting failure for decreasing blood-lactate levels in patients with hyperlactatemia [15–17]. Similar to these studies, we found that decreasing blood-lactate levels are less likely in patients with elevated PvaCO2/CavO2 before FB. Thus, the results of our study extend the knowledge about the effects of FB on blood lactate in critically ill patients with elevated PvaCO2/CavO2 .
Herein, PvaCO2/CavO2 was used as an alternative of respiratory quotient. As such, in theory, the failure of PvaCO2/CavO2 to predict decreases in blood-lactate levels could be explained by the fact that the ratio does not reliably illustrate anaerobic metabolism in this mixed population of critically ill patients [18]. Factors that can affect PvaCO2/CavO2 such as hemoglobin concentrations mixed venous saturation and oxygen delivery were not different across the studied patients [19, 20]. Furthermore, similar to previous studies [8, 9] patients with hyperlactatemia and high PvaCO2/CavO2 increased VO2 after FB, which implies oxygen delivery dependence observed in patients with severe global anaerobic metabolism. Nevertheless, other parameters that can affect the amount PvaCO2 such as temperature, metabolic acidosis, and Haldane effect were not assessed in this study. Therefore, we conclude that in our cohort of non-selected critically ill patients with hyperlactatemia, elevated PvaCO2/CavO2 was associated with sever anaerobic metabolism not excluding, however, the possibility that some patients had an increased PvaCO2/CavO2 without anaerobic metabolism and vice versa.
Significant decreases in blood lactate after FB were observed in patients with PvaCO2/CavO2 < 1.4 mmHg/mL. PvaCO2/CavO2 ≥ 1.4 mmHg/mL was defined abnormal based on the previous studies that have demonstrated that this cut-off can predict persistent hyperlactatemia in critically ill patients [6, 15]. Incidentally, other authors have suggested higher cut-off values to predict increases in VO2 after FB [8, 9, 21]. Almost all the patients with FB induced decreases in blood lactate levels had a PvaCO2/CavO2 higher than 1 mmHg/mL, which in previous study was found as best cut-off value for predicting mortality [17]. Hence, our results suggest that the anaerobic threshold of critically ill patients with hyperlactatemia may vary across the patients [22]. Nevertheless, a value of PvaCO2/CavO2 < 1 mmHg/mL may be used to exclude anaerobic metabolism and decreasing blood lactate levels after FB.
Increases in oxygen consumption after FB were not associated with a decrease in blood-lactate levels. Notably, we found that the patients who had an increase oxygen consumption after FB were less likely to present a significant decrease in blood-lactate levels. Different factors can explain this phenomenon. Calculation of VO2 based on the reverse Fick principle may not be accurate[23, 24]. Inadequate hemodynamic resuscitation can be an additional explanation, even though a sufficient dose of fluid at high rate was administrated [25]. Furthermore, increased tissue perfusion during FB may cause a paradoxical elevation in blood lactate levels due to ‘washout’ phenomenon [26–29] or accelerated aerobic glycolysis [30, 31]. Of note, a weak correlation between VO2 and blood lactate changes was observed. Thus, based on our results, high PvaCO2/CavO2 before FB is associated with VO2 dependency on DO2, similar to previous studies[8, 9], but also with failure of FB to decrease blood lactate. In these patients, whether no change or even increase in blood lactate levels indicates FB failure to improve peripheral perfusion should be further evaluated in future studies.
Not surprisingly, the majority of the patients with hyperlactatemia had an elevated PvaCO2/CavO2 since either of these variables increases due to anaerobic metabolism. Nevertheless, there was no correlation between PvaCO2/CavO2 and blood-lactate levels. Hence, our results suggest that PvaCO2/CavO2 can be used as a complementary marker for the evaluation of patients with hyperlactatemia and the effects of FB. For instance, we observed a negative correlation of changes in blood lactate and PvaCO2/CavO2 during FB. A plausible explanation for this phenomenon could be that decreases in blood lactate illustrate an improvement in tissue oxygenation, and PvaCO2/CavO2 illustrates oxygen debt repayment after perfusion improvement [32, 33].
The strength of this study was that we evaluated the predictive value of PvaCO2/CavO2 in a non-selected critically ill population with mild hyperlactatemia treated with FB. Patients in this cohort presented a high range of PvaCO2/CavO2, and a significant number of patients had low PvaCO2/CavO2. We evaluated changes in blood lactate close to the time of the FB in stable conditions, and non-major variation in metabolism was expected.
Nevertheless, this study has several limitations. First, no formal sample power calculation was done and not predictive test were performed. However, the results are in the opposite direction of our hypothesis, and the possibility of finding different results with a higher sample size is low. Additionaly, based on our findings we conclude that PvaCO2/CavO2 cannot have clinical relevant predictive value for decreasing blood lactate levels after FB. Second, therapeutic interventions that can affect lactate levels before and after FB were not standardized. However, all the patients were treated under standard local therapeutic strategies. Third, only central venous and not mixed venous-to-arterial carbon dioxide tension differences were evaluated.