Determinants of Tissue PCO₂ in Shock and Sepsis: Relationship to the Microcirculation

The development of gastrointestinal tonometry was an important step in the monitoring of tissue dysoxia. It rapidly became a useful tool in basic research. In addition, and for the first time, a regional parameter could be used to detect and to treat hypoperfusion. From an experimental point of view, tonometry adequately tracks intramucosal acidosis, i.e., the increase in intramucosal-arterial PCO2 difference (ΔPCO2). Likewise, the increase in ΔPCO2 is better than other systemic and intestinal variables to show tissue hypoperfusion in normal volunteers and in experimental models. Intramucosal acidosis is a sensitive predictor of gastric and colonic mucosal ischemia. Furthermore, gastric tonometry is an insightful predictor of outcome. This usefulness has been shown in postoperative, critically ill, septic and shock patients. Gastric tonometry might also be used to assess the effect of vasoactive drugs. Finally, intramucosal pH (pHi) has been evaluated as a guide for resuscitation. Gutierrez et al. demonstrated in a randomized controlled trial that pHi-guided therapy could decrease mortality in critically ill patients.Facultad de Ciencias Médica

Comparison of different methods for the calculation of the microvascular flow index

The microvascular flow index (MFI) is commonly used to semiquantitatively characterize the velocity of microcirculatory perfusion as absent (0), intermittent (1), sluggish (2), or normal (3). There are three approaches to compute MFI: (1) the average of the predominant flow in each of the four quadrants (MFI by quadrants), (2) the direct assessment during the bedside video acquisition (MFI point of care), and (3) the mean value of the MFIs determined in each individual vessel (MFI vessel by vessel). We hypothesized that the agreement between the MFIs is poor and that the MFI vessel by vessel better reflects the microvascular perfusion. For this purpose, we analyzed 100 videos from septic patients. In 25 of them, red blood cell (RBC) velocity was also measured. There were wide 95% limits of agreement between MFI by quadrants and MFI point of care (1.46), between MFI by quadrants and MFI vessel by vessel (2.85), and between MFI by point of care and MFI vessel by vessel (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFI vessel by vessel showed the best R 2. Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFI vessel by vessel might be better.Facultad de Ciencias Médica

Comparison of different methods for the calculation of the microvascular flow index

The microvascular flow index (MFI) is commonly used to semiquantitatively characterize the velocity of microcirculatory perfusion as absent (0), intermittent (1), sluggish (2), or normal (3). There are three approaches to compute MFI: (1) the average of the predominant flow in each of the four quadrants (MFI by quadrants), (2) the direct assessment during the bedside video acquisition (MFI point of care), and (3) the mean value of the MFIs determined in each individual vessel (MFI vessel by vessel). We hypothesized that the agreement between the MFIs is poor and that the MFI vessel by vessel better reflects the microvascular perfusion. For this purpose, we analyzed 100 videos from septic patients. In 25 of them, red blood cell (RBC) velocity was also measured. There were wide 95% limits of agreement between MFI by quadrants and MFI point of care (1.46), between MFI by quadrants and MFI vessel by vessel (2.85), and between MFI by point of care and MFI vessel by vessel (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFI vessel by vessel showed the best R 2. Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFI vessel by vessel might be better.Facultad de Ciencias Médica

Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis

Results: Fluid administration increased the cardiac index (2.6 ± 0.5 vs. 3.3 ± 1.0 L/min/m2, P < 0.01) and mean arterial blood pressure (68 ± 11 vs. 82 ± 12 mm Hg, P < 0.0001). The sublingual but not the intestinal red blood cell (RBC) velocity increased (912 ± 270 vs. 1,064 ± 200 μm/s, P < 0.002 and 679 ± 379 vs. 747 ± 419 μm/s, P = 0.12, respectively). The sublingual and intestinal perfused vascular density (PVD) did not change significantly (15.2 ± 2.9 vs. 16.1 ± 1.2 mm/mm2 and 12.3 ± 6.7 vs. 13.0 ± 6.7 mm/mm2). We found no correlation between the basal sublingual and intestinal RBC velocities or between their changes in response to the fluid challenge. The individual changes in sublingual RBC velocity correlated with those in cardiac index and basal RBC velocity. Individual changes in intestinal RBC velocity did not correlate with either the cardiac index modifications or the basal RBC velocity. The same pattern was observed with the sublingual and the intestinal PVDs. The sublingual RBC velocities and PVDs were similar between survivors and nonsurvivors. But the intestinal RBC velocities and PVDs were lower in nonsurvivors.Conclusions: In this series of postoperative septic patients, we found a dissociation between sublingual and intestinal microcirculation. The improvement in the sublingual microcirculation after fluid challenge was dependent on the basal state and the increase in cardiac output. In contrast, the intestinal microcirculation behaved as an isolated territory.Methods: Twenty-two septic patients in the first postoperative day of an intestinal surgery, in which an ostomy had been constructed, were evaluated both before and 20 min after a challenge of 10 mL/kg of 6% hydroxyethylstarch 130/0.4. We measured systemic hemodynamics and sublingual and intestinal microcirculation. Correlations between variables were determined through the Pearson test.Background: This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge.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

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

Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis

Results: Fluid administration increased the cardiac index (2.6 ± 0.5 vs. 3.3 ± 1.0 L/min/m2, P < 0.01) and mean arterial blood pressure (68 ± 11 vs. 82 ± 12 mm Hg, P < 0.0001). The sublingual but not the intestinal red blood cell (RBC) velocity increased (912 ± 270 vs. 1,064 ± 200 μm/s, P < 0.002 and 679 ± 379 vs. 747 ± 419 μm/s, P = 0.12, respectively). The sublingual and intestinal perfused vascular density (PVD) did not change significantly (15.2 ± 2.9 vs. 16.1 ± 1.2 mm/mm2 and 12.3 ± 6.7 vs. 13.0 ± 6.7 mm/mm2). We found no correlation between the basal sublingual and intestinal RBC velocities or between their changes in response to the fluid challenge. The individual changes in sublingual RBC velocity correlated with those in cardiac index and basal RBC velocity. Individual changes in intestinal RBC velocity did not correlate with either the cardiac index modifications or the basal RBC velocity. The same pattern was observed with the sublingual and the intestinal PVDs. The sublingual RBC velocities and PVDs were similar between survivors and nonsurvivors. But the intestinal RBC velocities and PVDs were lower in nonsurvivors.Conclusions: In this series of postoperative septic patients, we found a dissociation between sublingual and intestinal microcirculation. The improvement in the sublingual microcirculation after fluid challenge was dependent on the basal state and the increase in cardiac output. In contrast, the intestinal microcirculation behaved as an isolated territory.Methods: Twenty-two septic patients in the first postoperative day of an intestinal surgery, in which an ostomy had been constructed, were evaluated both before and 20 min after a challenge of 10 mL/kg of 6% hydroxyethylstarch 130/0.4. We measured systemic hemodynamics and sublingual and intestinal microcirculation. Correlations between variables were determined through the Pearson test.Background: This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge.Facultad de Ciencias Médica

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: A prospective study

Introduction: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and ΔPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). Conclusions: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.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