Venoarterial PCO₂-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO2 (Pv–aCO2) to arteriovenous oxygen content difference (Ca–vO2) might be a good surrogate for respiratory quotient (RQ). Yet Pv–aCO2/Ca–vO2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between Pv–aCO2/Ca–vO2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented Pv–aCO2 and decreased Ca–vO2, our hypothesis was that Pv–aCO2/Ca–vO2 might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in Pv–aCO2/Ca–vO2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in Pv–aCO2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO2 content difference and Ca–vO2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, Pv–aCO2/Ca–vO2 increased before the fall in oxygen consumption and the increase in RQ. Pv–aCO2/Ca–vO2 was strongly correlated with Hb (R2 = 0.79, P < 0.00001) and moderately with RQ (R2 = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO2 as Pv–aCO2/Ca–vO2 determinants (adjusted R2 = 0.86, P < 0.000001). Conclusions: In hemodilution, Pv–aCO2/Ca–vO2 was considerably increased, irrespective of the presence of anaerobic metabolism. Pv–aCO2/Ca–vO2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.Facultad de Ciencias Médica

Venoarterial PCO₂-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO2 (Pv–aCO2) to arteriovenous oxygen content difference (Ca–vO2) might be a good surrogate for respiratory quotient (RQ). Yet Pv–aCO2/Ca–vO2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between Pv–aCO2/Ca–vO2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented Pv–aCO2 and decreased Ca–vO2, our hypothesis was that Pv–aCO2/Ca–vO2 might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in Pv–aCO2/Ca–vO2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in Pv–aCO2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO2 content difference and Ca–vO2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, Pv–aCO2/Ca–vO2 increased before the fall in oxygen consumption and the increase in RQ. Pv–aCO2/Ca–vO2 was strongly correlated with Hb (R2 = 0.79, P < 0.00001) and moderately with RQ (R2 = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO2 as Pv–aCO2/Ca–vO2 determinants (adjusted R2 = 0.86, P < 0.000001). Conclusions: In hemodilution, Pv–aCO2/Ca–vO2 was considerably increased, irrespective of the presence of anaerobic metabolism. Pv–aCO2/Ca–vO2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.Facultad de Ciencias Médica

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

INTRODUCTION: Continuous monitoring of bladder partial carbon dioxide tension (PCO(2)) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO(2). Our hypothesis was that bladder PCO(2), measured using saline tonometry, will be similar to ileal PCO(2 )during ischaemia and reperfusion. METHOD: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO(2 )gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO(2 )were measured using saline tonometry. RESULTS: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO(2 )gradients when compared with baseline values (all values in mmHg; bladder ΔPCO(2 )3 ± 3 versus 12 ± 5, ileal ΔPCO(2 )9 ± 5 versus 29 ± 16, mixed venous–arterial PCO(2 )5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO(2 )4 ± 2 versus 14 ± 4; P < 0.05 versus basal for all). After blood reinfusion, PCO(2 )gradients returned to basal values except for bladder ΔPCO(2), which remained at ischaemic levels (13 ± 7 mmHg). CONCLUSION: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO(2 )might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO(2 )gradients occurred in gut mucosa. Moreover, the fact that ileal ΔPCO(2 )was greater than the mesenteric venous–arterial PCO(2 )suggests that tonometrically measured PCO(2 )reflects mucosal rather than transmural PCO(2). Ileal ΔPCO(2 )appears to be the more sensitive marker of ischaemia

0588. Effects of norepinephrine on tissue perfusion in a sheep model of intraabdominal hypertension

Intraabdominal hypertension (IAH) produces detrimental effects on tissue perfusion. A putative underlying mechanism is the decrease in abdominal perfusion pressure (APP = mean arterial pressure-intraabdominal pressure). Nevertheless, the benefits of increasing blood pressure on tissue perfusion are controversial.Facultad de Ciencias Médica

Venoarterial PCO₂-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO2 (Pv–aCO2) to arteriovenous oxygen content difference (Ca–vO2) might be a good surrogate for respiratory quotient (RQ). Yet Pv–aCO2/Ca–vO2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between Pv–aCO2/Ca–vO2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented Pv–aCO2 and decreased Ca–vO2, our hypothesis was that Pv–aCO2/Ca–vO2 might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in Pv–aCO2/Ca–vO2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in Pv–aCO2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO2 content difference and Ca–vO2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, Pv–aCO2/Ca–vO2 increased before the fall in oxygen consumption and the increase in RQ. Pv–aCO2/Ca–vO2 was strongly correlated with Hb (R2 = 0.79, P < 0.00001) and moderately with RQ (R2 = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO2 as Pv–aCO2/Ca–vO2 determinants (adjusted R2 = 0.86, P < 0.000001). Conclusions: In hemodilution, Pv–aCO2/Ca–vO2 was considerably increased, irrespective of the presence of anaerobic metabolism. Pv–aCO2/Ca–vO2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.Facultad de Ciencias Médica

Microcirculatory alterations are more severe in anemic than in ischemic hypoxia

The intestinal mucosal-arterial PCO2 (ΔPCO2) remains remarkably stable in anemic hypoxia suggesting that the villi perfusion is well-maintained. The microcirculation, however, has been insufficiently studied in extreme hemodilution.Facultad de Ciencias Médica

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

Introduction: Continuous monitoring of bladder partial carbon dioxide tension (PCO₂) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO₂. Our hypothesis was that bladder PCO₂, measured using saline tonometry, will be similar to ileal PCO₂ during ischaemia and reperfusion. Method: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO₂ gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO2 were measured using saline tonometry. Results: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO₂ gradients when compared with baseline values (all values in mmHg; bladder ∆PCO₂ 3 ± 3 versus 12 ± 5, ileal ∆PCO₂ 9 ± 5 versus 29 ± 16, mixed venous–arterial PCO₂ 5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO₂ 4 ± 2 versus 14 ± 4; P &lt; 0.05 versus basal for all). After blood reinfusion, PCO₂ gradients returned to basal values except for bladder ∆PCO₂, which remained at ischaemic levels (13 ± 7 mmHg). Conclusion: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO₂ might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO₂gradients occurred in gut mucosa. Moreover, the fact that ileal ∆PCO₂ was greater than the mesenteric venous–arterial PCO₂ suggests that tonometrically measured PCO₂ reflects mucosal rather than transmural PCO₂. Ileal ∆PCO₂ appears to be the more sensitive marker of ischaemia.Facultad de Ciencias Médica

Intestinal and sublingual microcirculation are more severely compromised in hemodilution than in hemorrhage

The alterations in O₂ extraction in hemodilution have been linked to fast red blood cell (RBC) velocity, which might affect the complete release of O₂ from Hb. Fast RBC velocity might also explain the normal mucosal-arterial Pco2 (ΔPco₂). Yet sublingual and intestinal microcirculation have not been completely characterized in extreme hemodilution. Our hypothesis was that the unchanged ΔPco₂ in hemodilution depends on the preservation of villi microcirculation. For this purpose, pentobarbital-anesthetized and mechanically ventilated sheep were submitted to stepwise hemodilution (n = 8), hemorrhage (n = 8), or no intervention (sham, n = 8). In both hypoxic groups, equivalent reductions in O₂ consumption (Vo₂) were targeted. Microcirculation was assessed by videomicroscopy, intestinal ΔPco₂ by air tonometry, and Vo₂ by expired gases analysis. Although cardiac output and superior mesenteric flow increased in hemodilution, from the very first step (Hb = 5.0 g/dl), villi functional vascular density and RBC velocity decreased (21.7 ± 0.9 vs. 15.9 ± 1.0 mm/mm² and 1,033 ± 75 vs. 850 ± 79 μm/s, P < 0.01). In the last stage (Hb = 1.2 g/dl), these variables were lower in hemodiution than in hemorrhage (11.1 ± 0.5 vs. 15.4 ± 0.9 mm/mm² and 544 ± 26 vs. 686 ± 70 μm/s, P < 0.01), and were associated with lower intestinal fractional O₂ extraction (0.61 ± 0.04 vs. 0.79 ± 0.02, P < 0.01) but preserved ΔPco₂ (5 ± 2 vs. 25 ± 4 mmHg, P < 0.01). Therefore, alterations in O₂ extraction in hemodilution seemed related to microvascular shunting, not to fast RBC velocity. The severe microvascular abnormalities suggest that normal ΔPco₂ was not dependent on CO₂ washout by the villi microcirculation. Increased perfusion in deeper intestinal layers might be an alternative explanation.Facultad de Ciencias Médica

Systemic and microcirculatory responses to progressive hemorrhage

Objective: To compare systemic hemodynamics with microcirculatory changes at different vascular beds during progressive hemorrhage. Setting: Universitybased research laboratory. Subjects: Twelve anesthetized, mechanically ventilated sheep. Interventions: Sheep were randomly assigned to HEMORRHAGE or CONTROL group. In the HEMORRHAGE group (n = 8), three stepwise bleedings of 5 ml/kg at 30- min intervals were performed to add up 15 ml/kg. In the CONTROL group (n = 4), sheep had the same surgical preparation but were not bled. Measurements and main results: Progressive bleeding decreased cardiac output, and superior mesenteric artery blood flow, and systemic and intestinal oxygen transports from the first step of bleeding whereas systemic and intestinal oxygen consumption remained unchanged. Mean arterial blood pressure, arterial pH and base excess, and intramucosal-arterial PCO2 were only significantly modified in the last step of bleeding. Arterial lactate increased and sublingual, and intestinal serosal and mucosal capillary microvascular flow indexes and red blood cell velocities progressively decreased after the first step of bleeding (3.0 ± 0.1 vs. 2.3 ± 0.4, 3.2 ± 0.2 vs. 2.4 ± 0.6, 3.0 ± 0.0 vs. 2.0 ± 0.2, and 1,082 ± 29 vs. 977 ± 79, 1,042 ± 24 vs. 953 ± 60, 287 ± 65 vs. 262 ± 16 μm/s; P\0.05 for all). Conclusions: Alterations in sublingual, intestinal microcirculation, and arterial lactate simultaneously arose from the first step of bleeding. The microcirculatory changes were identified either by semi-quantitative flow index or by quantitative red blood cell velocity measurements.Facultad de Ciencias Médica

Systemic and microcirculatory effects of blood transfusion in experimental hemorrhagic shock

Background: The microvascular reperfusion injury after retransfusion has not been completely characterized. Specifically, the question of heterogeneity among different microvascular beds needs to be addressed. In addition, the identification of anaerobic metabolism is elusive. The venoarterial PCO2 to arteriovenous oxygen content difference ratio (Pv-aCO2/Ca-vO2) might be a surrogate for respiratory quotient, but this has not been validated. Therefore, our goal was to characterize sublingual and intestinal (mucosal and serosal) microvascular injury after blood resuscitation in hemorrhagic shock and its relation with O2 and CO2 metabolism. Methods: Anesthetized and mechanically ventilated sheep were assigned to stepwise bleeding and blood retransfusion (n = 10) and sham (n = 7) groups. We performed analysis of expired gases, arterial and mixed venous blood gases, and intestinal and sublingual videomicroscopy. Results: In the bleeding group during the last step of hemorrhage, and compared to the sham group, there were decreases in oxygen consumption (3.7 [2.8–4.6] vs. 6.8 [5.8–8.0] mL min−1 kg−1 , P < 0.001) and increases in respiratory quotient (0.96 [0.91–1.06] vs. 0.72 [0.69–0.77], P < 0.001). Retransfusion normalized these variables. The Pv-aCO2/CavO2 increased in the last step of bleeding (2.4 [2.0–2.8] vs. 1.1 [1.0–1.3], P < 0.001) and remained elevated after retransfusion, compared to the sham group (1.8 [1.5–2.0] vs. 1.1 [0.9–1.3], P < 0.001). Pv-aCO2/Ca-vO2 had a weak correlation with respiratory quotient (Spearman R = 0.42, P < 0.001). All the intestinal and sublingual microcirculatory variables were affected during hemorrhage and improved after retransfusion. The recovery was only complete for intestinal red blood cell velocity and sublingual total and perfused vascular densities. Conclusions: Although there were some minor differences, intestinal and sublingual microcirculation behaved similarly. Therefore, sublingual mucosa might be an adequate window to track intestinal microvascular reperfusion injury. Additionally, Pv-aCO2/Ca-vO2 was poorly correlated with respiratory quotient, and its physiologic behavior was different. Thus, it might be a misleading surrogate for anaerobic metabolism.Facultad de Ciencias Médica