Microcirculatory effects of rewarming in experimental hemorrhagic shock.

BACKGROUND: Rewarming is a recommended therapy during the resuscitation of hypothermic patients with hemorrhagic shock. In experimental models, however, it increases inflammatory response and mortality. Although microcirculation is potential target of inflammation, the microvascular effects of rewarming during the resuscitation of hemorrhagic shock have not been studied. Our goal was to assess the systemic and microcirculatory effects of an increase in core temperature (T°) during the retransfusion of hemorrhagic shock in sheep. Our hypothesis was that rewarming could hamper microcirculation. METHODS: In anesthetized and mechanically ventilated sheep, we measured systemic, intestinal, and renal hemodynamics and oxygen transport. O2 consumption (VO2) and respiratory quotient were measured by indirect calorimetry. Cortical renal, intestinal villi and sublingual microcirculation were assessed by IDF-videomicroscopy. After basal measurements, hemorrhagic shock was induced and T° was reduced to ~33 °C. After 1 h of shock and hypothermia, blood was retransfused and Ringer lactate solution was administered to prevent arterial hypotension. In the control group (n = 12), T° was not modified, while in the intervention (rewarming) group, it was elevated ~3 °C. Measurements were repeated after 1 h. RESULTS: During shock, both groups showed similar systemic and microvascular derangements. After retransfusion, VO2 remained decreased compared to baseline in both groups, but was lower in the control compared to the rewarming group. Perfused vascular density has a similar behavior in both groups. Compared to baseline, it remained reduced in peritubular (control vs. rewarming group, 13.8 [8.7-17.5] vs. 15.7 [10.1-17.9] mm/mm2, PNS) and villi capillaries (14.7 [13.6-16.8] vs. 16.3 [14.2-16.9] mm/mm2, PNS), and normalized in sublingual mucosa (19.1 [16.0-20.3] vs. 16.6 [14.7-17.2] mm/mm2, PNS). CONCLUSIONS: This is the first experimental study assessing the effect of rewarming on systemic, regional, and microcirculatory perfusion in hypothermic hemorrhagic shock. We found that a 3 °C increase in T° neither improved nor impaired the microvascular alterations that persisted after retransfusion. In addition, sublingual mucosa was less susceptible to reperfusion injury than villi and renal microcirculation.

Effects of Systemic Hypothermia on Microcirculation in Conditions of Hemodynamic Stability and in Hemorrhagic Shock.

INTRODUCTION: Although hypothermia is independently associated with an increased mortality in trauma patients, it might be an effective therapeutic approach for otherwise lethal hemorrhage. The effect of hypothermia on microcirculation, however, has been poorly studied in this setting. Our goal was to characterize the effects of hypothermia on microcirculation in normal conditions and in severe hemorrhagic shock. METHODS: In anesthetized and mechanically ventilated sheep, we measured cardiac output (CO), renal blood flow (RBF), and systemic and renal O2 consumption (VO2). Cortical renal, intestinal villi, and sublingual microcirculation was assessed by IDF-videomicroscopy. After basal measurements, sheep were assigned to hypothermia (n = 12) and normothermia (n = 12) groups. Central temperature was reduced to ∼34°C and maintained at baseline in each group, respectively. Measurements were repeated after 1 h of hemodynamic stable conditions and 1 h of severe hemorrhagic shock. RESULTS: In conditions of hemodynamic stability, the hypothermia group showed lower CO, RBF, and systemic and renal VO2 than the normothermia group. Red blood cell velocity was also lower in renal, villi, and sublingual microvascular beds (836 ±â€Š195 vs. 1,066 ±â€Š162, 916 ±â€Š105 vs. 1051 ±â€Š41, and 970 ±â€Š182 vs. 1,102 ±â€Š49 µm/s, respectively; P < 0.0001 for all). In hemorrhagic shock, most of the microvascular variables were similarly compromised in both the groups. In hypo- and normothermia groups, the percentage of reduction in perfused vascular density was higher in renal than in intestinal and sublingual microcirculation (66 ±â€Š31 vs. 31 ±â€Š23 and 15 ±â€Š15%, and 78 ±â€Š26 vs. 32 ±â€Š37 and 18 ±â€Š21%, P < 0.01 for both). CONCLUSIONS: This is the first experimental study assessing the effect of systemic hypothermia on microcirculation in severe hemorrhagic shock. The main finding was that hypothermia did not hamper additionally the microcirculatory derangements induced by hemorrhagic shock. In addition, renal microcirculation was more susceptible to hemorrhagic shock than villi and sublingual microcirculation.

Microcirculation alterations in severe COVID-19 pneumonia.

PURPOSE: To assess the presence of sublingual microcirculatory and skin perfusion alterations in COVID-19 pneumonia. MATERIALS AND METHODS: This is a preliminary report of a prospective observational study performed in four teaching intensive care units. We studied 27 mechanically ventilated patients with acute respiratory distress syndrome secondary to COVID-19. Sublingual microcirculation was assessed by hand-held videomicroscopy. A software-assisted analysis of videos was performed. We also measured capillary refill time. RESULTS: Patients were hemodynamically stable with normal lactate (1.8 [1.6-2.5] mmol/L) and high D-dimer (1.30 [0.58-2.93] µg/mL). Capillary refill time was prolonged (3.5 [3.0-5.0] s). Compared to previously reported normal values, total and perfused vascular density (21.9 ± 3.9 and 21.0 ± 3.5 mm/mm2) and heterogeneity flow index (0.91 ± 0.24) were high; and the proportion of perfused vessels (0.96 ± 0.03), microvascular flow index (2.79 ± 0.10), and red blood cell velocity (1124 ± 161 µm/s) were reduced. The proportion of perfused vessels was inversely correlated with total vascular density (Pearson r = -0.41, P = 0.03). CONCLUSIONS: COVID-19 patients showed an altered tissue perfusion. Sublingual microcirculation was characterized by decreases in the proportion of perfused vessel and flow velocity along with high vascular densities. This last finding might be related to enhanced angiogenesis or hypoxia-induced capillary recruitment.

Monitoring Microcirculation: Utility and Barriers - A Point-of-View Review.

Microcirculation is a particular organ of the cardiovascular system. The goal of this narrative review is a critical reappraisal of the present knowledge of microcirculation monitoring, mainly focused on the videomicroscopic evaluation of sublingual microcirculation in critically ill patients. We discuss the technological developments in handheld videomicroscopy, which have resulted in adequate tools for the bedside monitoring of microcirculation. By means of these techniques, a large body of evidence has been acquired about the role of microcirculation in the pathophysiological mechanisms of shock, especially septic shock. We review the characteristics of sublingual microcirculation in septic shock, which mainly consist in a decrease in the perfused vascular density secondary to a reduction in the proportion of perfused vessels along with a high heterogeneity in perfusion. Even in patients with high cardiac output, red blood cell velocity is decreased. Thus, hyperdynamic flow is absent in the septic microcirculation. We also discuss the dissociation between microcirculation and systemic hemodynamics, particularly after shock resuscitation, and the different behavior among microvascular beds. In addition, we briefly comment the effects of some treatments on microcirculation. Despite the fact that sublingual microcirculation arises as a valuable goal for the resuscitation in critically ill patients, significant barriers remain present for its clinical application. Most of them are related to difficulties in video acquisition and analysis. We comprehensively analyzed these shortcomings. Unfortunately, a simpler approach, such as the central venous minus arterial PCO2 difference, is a misleading surrogate for sublingual microcirculation. As conclusion, the monitoring of sublingual microcirculation is an appealing method for monitoring critically ill patients. Nevertheless, the lack of controlled studies showing benefits in terms of outcome, as well as technical limitations for its clinical implementation, render this technique mainly as a research tool.

Effects of fluid and norepinephrine resuscitation in a sheep model of endotoxin shock and acute kidney injury.

The pathophysiology of renal failure in septic shock is complex. Although microvascular dysfunction has been proposed as a mechanism, there are controversial findings about the characteristics of microvascular redistribution and the effects of resuscitation. Our hypothesis was that the normalization of systemic hemodynamics with fluids and norepinephrine fails to improve acute kidney injury. To test this hypothesis, we assessed systemic and renal hemodynamics and oxygen metabolism in 24 anesthetized and mechanically ventilated sheep. Renal cortical microcirculation was evaluated by SDF-videomicroscopy. Shock (n = 12) was induced by intravenous administration of endotoxin. After 60 min of shock, 30 mL/kg of saline solution was infused and norepinephrine was titrated to reach a mean blood pressure of 70 mmHg for 2 h. These animals were compared with a sham group (n = 12). After endotoxin administration, mean blood pressure, cardiac index, and systemic O2 transport and consumption decreased (P < 0.05 for all). Resuscitation improved these variables. Endotoxin shock also reduced renal blood flow and O2 transport and consumption (205[157-293] vs. 131 [99-185], 28.4[19.0-38.2] vs. 15.8[13.5-23.2], and 5.4[4.0-8.8] vs. 3.7[3.3-4.5] mL·min-1·100 g-1, respectively); cortical perfused capillary density (23.8[23.5-25.9] vs. 17.5[15.1-19.0] mm/mm2); and creatinine clearance (62.4[39.2-99.4] vs. 10.7[4.4-23.5] mL/min). After 2 h of resuscitation, these variables did not improve (174[91-186], 20.5[10.8-22.7], and 3.8[1.9-4.8] mL·min-1·100 g-1, 19.9[18.6-22.1] mm/mm2, and 5.9[1.0-11.9] mL/min). In conclusion, endotoxin shock induced severe renal failure associated with decreased renal flow, O2 transport and consumption, and cortical microcirculation. Normalization of systemic hemodynamics with fluids and norepinephrine failed to improve renal perfusion, oxygenation, and function.NEW & NOTEWORTHY This experimental model of endotoxin shock induced severe renal failure, which was associated with abnormalities in renal regional blood flow, microcirculation, and oxygenation. Derangements included the compromise of peritubular microvascular perfusion. Improvements in systemic hemodynamics through fluids and norepinephrine were unable to correct these abnormalities.

Effects of short-term hyperoxia on sytemic hemodynamics, oxygen transport, and microcirculation: An observational study in patients with septic shock and healthy volunteers.

PURPOSE: To characterize the microvascular effects of a brief period of hyperoxia, in patients with septic shock and in healthy volunteers. MATERIALS AND METHODS: In 20 patients with septic shock, we assessed systemic hemodynamics, sublingual microcirculation by SDF-videomicroscopy, and skin perfusion by capillary refill time (CRT), central-peripheral temperature (ΔT°), and perfusion index. Measurements were performed at baseline and after 5 min of inspired oxygen fraction of 1.00. Additionally, we studied 8 healthy volunteers, in whom hyperoxia was prolonged to 30 min. RESULTS: In septic patients, hyperoxia increased mean arterial pressure and systemic vascular resistance, but cardiac output remained unchanged. The only significant change in sublingual microcirculation was a decreased heterogeneity flow index (1.03 [1.01-1.07] vs 1.01 [0.34-1.05], P = .002). Perfused vascular density (13.1 [12.0-15.0] vs 14.0 [12.2-14.8] mm/mm2, P = .21) and the other sublingual microvascular variables were unmodified. CRT and ΔT° did not change but perfusion index slightly decreased. In healthy volunteers, sublingual microcirculation and skin perfusion were stable. CONCLUSIONS: Short-term hyperoxia induced systemic cardiovascular changes but was not associated with noticeable derangement in sublingual microcirculation and skin perfusion. Nevertheless, longer exposures to hyperoxia might have produced different results.

Sublingual microcirculatory alterations in cirrhotic patients.

OBJECTIVE: To assess sublingual microcirculation in cirrhotic patients and its relationship to spider angiomas, complications, and outcome. METHODS: Thirty-one cirrhotic patients were prospectively compared to 31 matched controls. Sublingual microcirculation was evaluated by videomicroscopy. We specifically looked for capillaries with increased RBCV, which was defined as a velocity higher than the percentile 100th of controls. RESULTS: Compared to controls, cirrhotic patients showed decreased total and PVD (14.4 ± 2.2 vs 16.0 ± 1.3 and 14.1 ± 2.3 vs 15.9 ± 1.6 mm/mm2 , respectively, P < .001 for both) and increased HFI (0.64 ± 0.39 vs 0.36 ± 0.21, P = .001). They also exhibited high RBCV in 2% of the microvessels (P < .0001). Patients with MELD score ≥10 had higher RBCV than patients with score <10 (1414 ± 290 vs 1206 ± 239 µm/s, P < .05). Patients with spider angiomas showed lower vascular densities. Microcirculation did not differ between survivors and nonsurvivors. CONCLUSIONS: Cirrhosis is associated with microcirculatory alterations that can be easily monitored in the sublingual mucosa. Alterations included decreased density and PPV and hyperdynamic microvessels. The most striking finding, however, was the microvascular heterogeneity. Patients with spider angiomas had more severe alterations. Larger studies should clarify the relationship between microcirculatory abnormalities and outcome.

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 (R 2 = 0.79, P < 0.00001) and moderately with RQ (R 2 = 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 R 2 = 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.

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 (V̇o2) were targeted. Microcirculation was assessed by videomicroscopy, intestinal ΔPco2 by air tonometry, and V̇o2 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/mm(2) 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/mm(2) 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.

Systemic and microcirculatory responses to progressive hemorrhage.

OBJECTIVE: To compare systemic hemodynamics with microcirculatory changes at different vascular beds during progressive hemorrhage. SETTING: University-based 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 PCO(2) 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 mum/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.