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 (MFIby quadrants), (2) the direct assessment during the bedside video acquisition (MFIpoint of care), and (3) the mean value of the MFIs determined in each individual vessel (MFIvessel by vessel). We hypothesized that the agreement between the MFIs is poor and that the MFIvessel 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 MFIby quadrants and MFIpoint of care (1.46), between MFIby quadrants and MFIvessel by vessel (2.85), and between MFIby point of care and MFIvessel by vessel (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFIvessel by vessel showed the best R2. Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFIvessel by vessel might be better

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

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

INTRODUCTION: Increased intramucosal–arterial carbon dioxide tension (PCO(2)) difference (ΔPCO(2)) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ΔPCO(2). METHODS: In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO(2 )by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 μg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. RESULTS: In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ΔPCO(2 )increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ΔPCO(2 )(5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both). CONCLUSIONS: In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations

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 (Delta PCO2). 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 Delta PCO2 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/mm(2), 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 (R-2 = 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 patient

What is microcirculatory shock?

Microcirculatory shock is a condition defined by the presence of tissue hypoperfusion despite the normalization of systemic and regional blood flow. In this article, we discuss the characteristics of the microcirculation in septic shock, the main form of microcirculatory shock, along with its interaction with systemic hemodynamics, and the response to different therapies. In septic shock, microcirculatory abnormalities are common, and more severe in nonsurvivors. In addition, the microcirculation shows a behavior that is frequently dissociated from that of systemic hemodynamics. Therefore, microcirculatory alterations may persist despite correction of systemic hemodynamic variables. Sublingual and intestinal microcirculation might also display divergent behaviors. Moreover, microvascular alterations may improve in response to hemodynamic resuscitation, but the response might depend on the underlying microcirculatory alterations. Particularly, the response to fluids seems to be related to both its basal state and the magnitude of the increase in cardiac output. The optimal treatment of microcirculatory shock might require monitoring and therapeutic goals targeted on the microcirculation, more than in systemic variables. The clinical benefits of this approach should be demonstrated in clinical trial

The microcirculation as a therapeutic target in the treatment of sepsis and shock

Largely ignored throughout the history of clinical medicine, the microcirculation has recently been recognized at the bedside as the center of several pathophysiological processes. Normal microcirculatory function is critical for adequate tissue oxygenation and organ function, but it has a poorly understood and highly heterogeneous structure that is related to the diversity of functions that it accomplishes. The most important function of the microcirculation is the regulation and distribution of oxygen carrying red blood cells within the different organs. The determinants of oxygen delivery, blood flow regulation, tissue oxygen tension, and mitochondrial well-being are not fully understood; however, it is clear that insight into the function of the microcirculation is key in this respect. In fact, it is clear that the origin of circulatory failure in critical illness unresponsive to therapy is not represented in systemic hemodynamic variables but rather in the dysfunction of the microcirculation. The introduction of bedside techniques into clinical practice that allow the evaluation of the microcirculation has opened up a new field of functional hemodynamic monitoring, identified the microcirculatory failure as the most sensitive indicator of circulatory failure associated with adverse outcome, and has provided the promise of identifying new therapeutic targets. Clinical research has identified various conventional and new therapeutic approaches that are successful in modifying the microcirculation. Current research must determine whether some of these approaches are successful in improving the outcome of critically ill patients by recruiting the microcirculatio

Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock.

International audienceOBJECTIVE: The microcirculation of septic patients has been characterized only semiquantitatively. Our goal was to characterize the sublingual microcirculation in healthy volunteers and patients with septic shock quantitatively. Our hypotheses were that 1) hyperdynamic blood flow is absent in septic shock; 2) nonsurvivors show more severe alterations than survivors; and 3) quantitative and semiquantitative microcirculatory parameters have a similar performance. DESIGN: Prospective, observational study. SETTING: Teaching intensive care unit in a university-affiliated hospital. SUBJECTS: Twenty-five normal volunteers and 25 patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The sublingual microcirculation was evaluated by means of sidestream dark field imaging. Semiquantitative and quantitative microcirculatory parameters were determined through the use of applied software. Septic patients showed decreased perfused capillary density (13.2±4.4 mm/mm² vs. 16.6±1.6 mm/mm²), proportion of perfused capillaries (0.78±0.23 vs. 1.00±0.01), microvascular flow index (2.15±0.61 vs. 2.97±0.03), and red blood cell velocity (830±183 µm/sec vs. 1332±187 µm/sec) along with increased heterogeneity flow index (1.64±1.14 vs. 0.25±0.19) compared with controls. No differences were found in total capillary density (16.9±2.2 vs. 16.7±1.6). Only 4% of capillaries analyzed showed red blood cell velocities>75th percentile of the velocities of the normal volunteers. The nonsurvivors exhibited decreased perfused capillary density, proportion of perfused capillaries, and microvascular flow index along with increased heterogeneity flow index compared with the survivors. The correlations between microvascular flow index and proportion of perfused capillaries, total capillary density and number of grid-crossing capillaries, and red blood cell velocities and microvascular flow index gave high R values (0.92, 0.65, and 0.52, respectively; p<.0001 for all). CONCLUSIONS: The main characteristics of sublingual microcirculation in patients with septic shock are hypoperfusion and increased flow heterogeneity. Hyperdynamic microvascular blood flow was not found. Nonsurvivors showed more severe alterations than survivors. Quantitative and semiquantitative microcirculatory variables displayed similar behaviors

The Effects of Arterial Hypertension and Age on the Sublingual Microcirculation of Healthy Volunteers and Outpatients with Cardiovascular Risk Factors

To quantitatively assess the effects of age, blood pressure, chronic arterial hypertension, and physical activity on sublingual microcirculation in ambulatory volunteers. Sublingual microcirculation was assessed in 61 volunteers with or without chronic arterial hypertension. Volunteers with chronic arterial hypertension had lower TVD all vessels, and TVD small vessels and PVD small vessels than those without this condition (16.0 ± 1.4 vs. 17.2 ± 1.6 mm/mm(2), p < 0.01, 15.1 ± 1.3 vs. 16.1 ± 1.7 mm/mm(2), p < 0.04, and 15.1 ± 1.3 vs. 16.1 ± 1.7 mm/mm(2), p < 0.04, respectively). Mean blood pressure correlated with TVD all vessels (r = -0.34, p < 0.01), TVD small vessels (r = -0.31, p < 0.02), and PVD small vessels (r = -0.27, p < 0.04) but not with other microvascular variables. Age was not correlated with any microcirculatory variables. Physical activity correlated with TVDall vessels and RBCV small vessels (r = 0.30, p < 0.02 and r = -0.47, p < 0.001, respectively). Chronic arterial hypertension was the only independent determinant of PVD small vessels . Preexistent chronic arterial hypertension was associated with lower vascular densities. In contrast, age showed no effect on sublingual microcirculatio

Similar Microcirculatory Alterations in Patients with Normodynamic and Hyperdynamic Septic Shock

Rationale: In normodynamic septic shock, the quantitative assessment of sublingual microcirculation has shown decreases in perfused vascular density and red blood cell velocity. However, no studies have been performed in hyperdynamic septic shock. Objectives: To characterize the microcirculatory patterns and rule out the presence of fast red blood cell velocity in patients with hyperdynamic septic shock. Methods: We prospectively evaluated the sublingual microcirculation in healthy volunteers (n = 20) and in patients with hyperdynamic (n = 20) and normodynamic (n = 20) septic shock. Hyperdynamic septic shock was defined by a cardiac index >4.0 L/min/m(2). The microcirculation was assessed with sidestream dark field imaging and AVA 3.0 software. Measurements and Main Results: There were no differences in perfused vascular density, proportion of perfused vessels, or microvascular flow index between patients with hyperdynamic and normodynamic septic shock, but these variables were reduced compared with those of healthy volunteers, A similar pattern was observed in red blood cell velocity (9126291, 9686204, and 13036 120 mm/s, respectively; P <0.0001) and its coefficient of variation. In both types of septic shock, no microvessel had a red blood cell velocity higher than the 100th percentile value for healthy volunteers. Conclusions: Patients with hyperdynamic septic shock showed microcirculatory alterations similar to those of patients with normal cardiac output. Both groups of patients had reduced perfused vascular density and red blood cell velocity and increased flow heterogeneity compared with that of healthy subjects. Fast red blood cell velocity was not found, even in patients with high cardiac output. These results support the conclusion that microcirculatory function is frequently dissociated from systemic hemodynamic derangements in septic shoc

Systemic and microcirculatory effects of dobutamine in patients with septic shock

Purpose: The aim of this study was to characterize the cardiovascular responses to dobutamine and their predictors. Our hypotheses were that dobutamine mainly produces tachycardia and vasodilation and fails to improve the microcirculation of patients with septic shock. Materials and Methods: Systemic hemodynamics and sublingual microcirculation were evaluated with dobutamine (0, 2.5, 5.0, and 10.0 mu g kg(-1) min(-1)) in 23 patients with septic shock. Results: Dobutamine increased heart rate, cardiac index, and stroke volume index (SVI). Mean blood pressure was unchanged, and systemic vascular resistance decreased. Individual responses were heterogeneous. Stroke volume index increased in 52% of the patients. These patients showed lower changes in mean blood pressure (3 +/- 16 mm Hg vs -10 +/- 6 mm Hg, P <.05) and higher increases in cardiac index (1.47 +/- 0.93 L m(-1) m(-2) vs 0.20 +/- 0.5 L m(-1) m(-2)) than did nonresponders. Changes in SVI significantly correlated with echocardiographic left ventricular ejection fraction (r = 0.55). In the whole group, perfused capillary density remained unchanged (14.0 +/- 4.3 mm/mm(2) vs 14.8 +/- 3.7 mm/mm(2)), but improved if basal values were 12 mm/mm(2) or less (9.1 +/- 4.3 mm/mm(2) vs 12.5 +/- 4.8 mm/mm(2)). Conclusions: Dobutamine produced variable hemodynamic effects. Systolic dysfunction was the only variable associated with increases in SVI. Finally, dobutamine only improved sublingual microcirculation when severe alterations were found at baseline. (C) 2012 Elsevier Inc. All rights reserve