RESUMEN
OBJECTIVE: 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.
Asunto(s)
Microcirculación/fisiología , Choque Séptico/fisiopatología , Adulto , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Capilares/fisiología , Capilares/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Suelo de la Boca/irrigación sanguínea , Estudios Prospectivos , Choque Séptico/mortalidadRESUMEN
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/Ca-vO2 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.
RESUMEN
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 (912 ± 291, 968 ± 204, and 1303 ± 120 µm/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 shock.
Asunto(s)
Hemodinámica/fisiología , Microcirculación/fisiología , Suelo de la Boca/irrigación sanguínea , Choque Séptico/fisiopatología , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Microscopía Intravital , Masculino , Microscopía por Video , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
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 DeltaPCO2 3 +/- 3 versus 12 +/- 5, ileal DeltaPCO2 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 < 0.05 versus basal for all). After blood reinfusion, PCO2 gradients returned to basal values except for bladder DeltaPCO2, 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 PCO2 gradients occurred in gut mucosa. Moreover, the fact that ileal DeltaPCO2 was greater than the mesenteric venous-arterial PCO2 suggests that tonometrically measured PCO2 reflects mucosal rather than transmural PCO2. Ileal DeltaPCO2 appears to be the more sensitive marker of ischaemia.
Asunto(s)
Dióxido de Carbono/sangre , Hipercapnia/sangre , Choque Hemorrágico/complicaciones , Vejiga Urinaria/irrigación sanguínea , Análisis de Varianza , Animales , Biomarcadores/sangre , Manometría/métodos , Reperfusión , OvinosRESUMEN
INTRODUCTION: Increased intramucosal-arterial carbon dioxide tension (PCO2) difference (DeltaPCO2) 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 DeltaPCO2. 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 PCO2 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 microg/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 DeltaPCO2 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 DeltaPCO2 (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.
Asunto(s)
Acidosis/prevención & control , Endotoxemia/complicaciones , Infecciones por Escherichia coli/complicaciones , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/metabolismo , Equilibrio Ácido-Base , Acidosis/metabolismo , Animales , Dióxido de Carbono/sangre , Dióxido de Carbono/metabolismo , Interpretación Estadística de Datos , Modelos Animales de Enfermedad , Endotoxemia/sangre , Escherichia coli , Lipopolisacáridos/administración & dosificación , Arteria Mesentérica Superior/fisiología , Mesenterio/irrigación sanguínea , Oxígeno/sangre , Oxígeno/metabolismo , Consumo de Oxígeno , OvinosRESUMEN
OBJECTIVE: To evaluate the effects of nitroglycerin (glyceryl trinitrate) on intestinal microcirculation during endotoxaemic shock. DESIGN: Controlled experimental study. SETTING: Research laboratory. SUBJECTS: 20 anaesthetised, mechanically ventilated sheep. INTERVENTIONS: Septic shock was induced by endotoxin infusion. After 60 minutes without resuscitation, sheep received fluid resuscitation and were randomised to control or nitroglycerin groups. Nitroglycerin was infused at a rate of 0.2 µg/kg/min for 90 minutes. MAIN OUTCOME MEASURE: Improved villi microcirculation. RESULTS: Endotoxin lowered arterial blood pressure, cardiac output and intestinal blood flow, which were improved by fluid resuscitation. Mean (SD) ileal intramucosal-arterial PCO2 gradient increased during shock and remained elevated after resuscitation in control and nitroglycerin groups (8 [8], 15 [9] and 17 [9], and 6 [6], 13 [11] and 14 [9]mmHg, respectively; P < 0.05, baseline v shock and resuscitation for both groups). Villi microvascular flow index was reduced during shock and remained lower than baseline after the resuscitation in both groups (3.0 [0.0], 2.5 [0.2] and 2.7 [0.2], and 3.0 [0.0], 2.3 [0.3] and 2.6 [0.3], respectively; P < 0.05, baseline v shock and resuscitation for both groups). The red blood cell velocity behaved similarly (859 [443], 553 [236] and 670 [276], and 886 [440], 447 [124] and 606 [235] µm/s, respectively; P < 0.05, baseline v shock and resuscitation for both groups). CONCLUSIONS: In endotoxaemic sheep, low doses of nitroglycerin failed to improve the subtle but persistent villi hypoperfusion that remains present after fluid resuscitation.