Ince, C.

Microcirculation (Article)

2012-11-01T00:00:00Z

Transfusion of banked red blood cells and the effects on hemorrheology and microvascular hemodynamics in anemic hematology outpatients (Article)

2012-09-26T00:00:00Z

BACKGROUND: The aim of this study was to investigate the effects of red blood cell (RBC) transfusion on the hemorrheologic properties and microcirculatory hemodynamics in anemic hematology outpatients receiving 2 to 4 RBC units of either "fresh" (leukoreduced storage for less than 1week) or "aged" (leukoreduced storage for 3-4 weeks) RBCs. STUDY DESIGN AND METHODS: Measurements were performed before and 30 minutes after RBC transfusion in hematology outpatients. Leukoreduced RBC suspensions were stored in saline-adenine-glucose-mannitol (SAGM) additive solution. Whole blood viscosity was measured using Couette low-shear viscometry, RBC deformability and aggregability were measured using laser-assisted optical rotational cell analysis, and microcirculatory density and perfusion were assessed using sidestream dark field imaging. RESULTS: One group of patients (n=10) received a median (interquartile range) of 3 (2-3) RBC bags that were stored for 7 (5-7) days (fresh) and the other group of patients (n=10) received 3 (3-3) RBC bags that were stored for 23 (22-28) days (aged). After transfusion of fresh versus aged RBCs, hematocrit increased to 32±3% versus 31±2% (p<0.363), whole blood viscosity increased to 4.2±0.4Pa/sec versus 4.2±0.6Pa/sec (p<0.912), RBC deformability index remained unaffected, RBC aggregability index increased to 55±10 versus 55±13 (p=0.967), microcirculatory flow remained unaffected, and microcirculatory density increased to 19.3±2.5mm/mm2versus 18.7±1.9mm/mm2(p=0.595), respectively. CONCLUSION: Storing leukoreduced SAGM-suspended RBCs for 3 to 4 weeks did not affect their ability to improve hemorrheologic properties and microcirculatory hemodynamics in our small group of anemic hematology outpatients. Larger studies are needed to confirm this finding.

Study design of the microcirculatory shock occurrence in acutely Ill patients (microSOAP): An international multicenter observational study of sublingual microcirculatory alterations in intensive care patients (Article)

2012-09-19T00:00:00Z

Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill.

Comparison of different methods for the calculation of the microvascular flow index (Article)

2012-09-19T00:00:00Z

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.

The microcirculation is unchanged in neonates with severe respiratory failure after the initiation of ECMO treatment (Article)

2012-09-19T00:00:00Z

Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcirculation in neonates with severe respiratory failure. Methods. This single-center prospective observational pilot study took place in an intensive care unit of a level III university children's hospital. Twenty-one-term neonates, who received VA-ECMO treatment, were included. The microcirculation was assessed in the buccal mucosa, using Orthogonal Polarization Spectral imaging, within 24 hours before (T1) and within the first 24 hours after initiation of ECMO treatment (T2). Data were compared to data of a ventilated control group (N=7). Results. At baseline (T1), median functional capillary density (FCD), microvascular flow index (MFI), and heterogeneity index (HI) did not differ between the ECMO group and the control group. At T2 the median FCD was lower in the control group (median [range]: 2.4 [1.4-4.2] versus 4.3 [2.8-7.4] cm/cm2; P value <0.001). For MFI and HI there were no differences at T2 between the two groups. Conclusion. The perfusion of the microcirculation does not change after initiation of VA-ECMO treatment in neonates with severe respiratory failure.

The Microcirculation Is Unchanged in Neonates with Severe Respiratory Failure after the Initiation of ECMO Treatment (Article)

2012-01-01T00:00:00Z

Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcircu- lation in neonates with severe respiratory failure. Methods. This single-center prospective observational pilot study took place in an intensive care unit of a level III university children’s hospital. Twenty-one-term neonates, who received VA-ECMO treatment, were included. The microcirculation was assessed in the buccal mucosa, using Orthogonal Polarization Spectral imaging, within 24 hours before (T1) and within the first 24 hours after initiation of ECMO treatment (T2). Data were compared to data of a ventilated control group (N = 7). Results. At baseline (T1), median functional capillary density (FCD), microvascular flow index (MFI), and heterogeneity index (HI) did not differ between the ECMO group and the control group. At T2 the median FCD was lower in the control group (median [range]: 2.4 [1.4–4.2] versus 4.3 [2.8–7.4] cm/cm2 ; P value <0.001). For MFI and HI there were no differences at T2 between the two groups. Conclusion. The perfusion of the microcirculation does not change after initiation of VA-ECMO treatment in neonates with severe respiratory failure.

Inhaled nitric oxide improves systemic microcirculation in infants with hypoxemic respiratory failure (Article)

2011-11-01T00:00:00Z

Objectives: To investigate the effect of inhaled nitric oxide on the systemic microcirculation. We hypothesized that inhaled nitric oxide improves the systemic microcirculation. Inhaled nitric oxide improves outcome in infants with persistent pulmonary hypertension of the newborn diagnosed by improving pulmonary blood flow and oxygenation. It reduces pulmonary vascular resistance without decline in systemic blood pressure. Inhaled nitric oxide is also utilized in the treatment of acute hypoxemic respiratory failure in children and adults. It is thought to improve regional ventilation perfusion by regional selective pulmonary vasodilation. Design: Pilot study. Setting: Intensive care unit of a level III university children's hospital. Patients: Consecutive ventilated patients who were treated with inhaled nitric oxide (20 ppm) were enrolled in this study. Eight patients (five boys, three girls) were included; five had congenital diaphragmatic hernia diagnosed, one had persistent pulmonary hypertension of the newborn diagnosed, one had acute respiratory distress syndrome diagnosed, and one had bronchiolitis diagnosed. The median age was 0 months (range, 0-38 months). Interventions: Inhaled nitric oxide administration. Measurements and Main Results: The microcirculation was assessed in the buccal mucosa within 1 hr before and within 1 hr after the start of inhaled nitric oxide using orthogonal polarization spectral imaging. The median functional capillary density before the inhaled nitric oxide was started was 4.0 cm/cm (range, 1.8-5.6 cm/cm) and improved to 4.9 cm/cm (range, 2.8-6.6 cm/cm; p = .017) after the start of inhaled nitric oxide. Conclusions: Inhaled nitric oxide improves the systemic microcirculation in children with hypoxemic respiratory failure.

The microcirculatory response to compensated hypovolemia in a lower body negative pressure model (Article)

2011-11-01T00:00:00Z

The objective of the present study was to test the hypothesis that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation would be associated with decreased peripheral microcirculatory diffusion and convection properties and, consequently, decreased tissue oxygen carrying capacity and tissue oxygenation. Furthermore, we evaluated the impact of hypovolemia-induced microcirculatory alterations on resting tissue oxygen consumption. To this end, 24 subjects were subjected to a progressive lower body negative pressure (LBNP) protocol of which 14 reached the end of the protocol. At baseline and at LBNP = - 60. mm. Hg, sidestream dark field (SDF) images of the sublingual microcirculation were acquired to measure microvascular density and perfusion; thenar and forearm tissue hemoglobin content (THI) and tissue oxygenation (StO2) were recorded using near-infrared spectroscopy (NIRS); and a vascular occlusion test (VOT) was performed to assess resting tissue oxygen consumption rate. SDF images were analyzed for total vessel density (TVD), perfused vessel density (PVD), the microvascular flow index (MFI), and flow heterogeneity (MFIhetero). We found that application of LBNP resulted in: 1) a significantly decreased microvascular density (PVD) and perfusion (MFI and MFIhetero); 2) a significantly decreased THI and StO2; and 3) an unaltered resting tissue oxygen consumption rate. In conclusion, using SDF imaging in combination with NIRS we showed that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation is associated with decreased microcirculatory diffusion (PVD) and convection (MFI and MFIhetero) properties and, consequently, decreased tissue oxygen carrying capacity (THI) and tissue oxygenation (StO2). Furthermore, using a VOT we found that resting tissue oxygen consumption was maintained under conditions of adequately compensated central hypovolemia.

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

2011-10-19T00:00:00Z

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 microcirculation. Copyright

Noninvasive cardiac output monitoring during exercise testing: Nexfin pulse contour analysis compared to an inert gas rebreathing method and respired gas analysis (Article)

2011-10-01T00:00:00Z

Purpose. Exercise testing is often used to assess cardiac function during physical exertion to obtain diagnostic information. However, this procedure is limited to measuring the electrical activity of the heart using electrocardiography and intermittent blood pressure (BP) measurements and does not involve the continuous assessment of heart functioning. In this study, we compared continuous beat-to-beat pulse contour analysis to monitor noninvasive cardiac output (CO) during exercise with inert gas rebreathing and respired gas analysis. Methods. Nineteen healthy male volunteers were subjected to bicycle ergometry testing with increasing workloads. Cardiac output was determined noninvasively by continuous beat-to-beat pulse contour analysis (Nexfin) and by inert gas rebreathing, and estimated using the respired gas analysis method. The effects of the rebreathing maneuver on heart rate (HR), stroke volume (SV), and CO were evaluated. Results. The CO values derived from the Nexfinand inert gas rebreathing methods were well correlated (r = 0.88, P<0.01) and the limits of agreement were 30.3% with a measurement bias of 0.4±1.8 L/min. Nexfin- and respired gas analysis-derived CO values correlated even better (r = 0.94, P<0.01) and the limits of agreement were 21.5% with a measurement bias of -0.70±1.6 L/min. At rest, the rebreathing maneuver increased HR by 13 beats/min (P<0.01), SV remained unaffected (P = 0.7), while CO increased by 1.0 L/min (P<0.01). Rebreathing did not affect these parameters during exercise. Conclusions. Nexfin continuous beat-to-beat pulse contour analysis is an appropriate method for noninvasive assessment of CO during exercise.

Red blood cell transfusions and tissue oxygenation in anemic hematology outpatients (Article)

2011-08-31T00:00:00Z

Background: There is little clinical evidence that red blood cell (RBC) transfusions improve oxygen availability at the microcirculatory level. We tested the hypotheses that anemia in chronically anemic patients with relatively healthy microcirculation would be associated with low tissue hemoglobin (Hb) and tissue oxygenation levels and that these conditions would be improved after RBC transfusions. STUDY DESIGN AND METHODS: Near-infrared spectroscopy (NIRS) was used to determine tissue oxygen saturation (StO2) and tissue Hb index (THI; an index of the amount of Hb in the NIRS measurement volume) in the thenar eminence and sublingual tissue before and 30 minutes after RBC transfusions in 20 chronically anemic hematology outpatients. Data are presented as median (25%-75%). RESULTS: The patients received three (two to three) bags of RBCs in saline-adenine-glucose-mannitol with an age of 21 (7-21) days, which was infused intravenously at the rate of 0.7 bag/hr. RBC transfusions significantly increased hematocrit level from 26% (24%-28%) to 32% (30%-34%; p<0.0001), Hb level from 8.2 (7.6-8.9) g/dL to 11.0 (9.9-11.8) g/dL (p<0.0001), whole blood viscosity from 3.4 (3.1-3.5) mPa/sec to 4.2 (4.0-4.5) mPa/sec (p<0.0001), thenar StO2from 81% (80%-84%) to 86% (81%-89%; p=0.002), thenar THI from 11.2 (9.3-13.3) AU to 13.7 (9.7-15.3) AU (p=0.024), sublingual StO2from 86% (81%-89%) to 91% (86%-92%; p<0.0001), and sublingual THI from 15.2 (13.0-17.4) AU to 17.2 (13.5-19.7) AU (p=0.040). CONCLUSION: Although anemia in chronically anemic hematology outpatients was not associated with low StO2and THI levels, RBC transfusions were successful in improving these variables.

The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients (Article)

2011-07-01T00:00:00Z

Objective: We conducted this observational study to investigate tissue oxygen saturation during a vascular occlusion test in relationship with the condition of peripheral circulation and outcome in critically ill patients. Design: Prospective observational study. Setting: Multidisciplinary intensive care unit in a university hospital. Patients: Seventy-three critically ill adult patients admitted to the intensive care unit. Interventions: None. Measurements and Main Results: Patients were followed every 24 hrs until day 3 after intensive care admission. Near-infrared spectroscopy was used to measure thenar tissue oxygen saturation, tissue oxygen saturation deoxygenation rate, and tissue oxygen saturation recovery rate after the vascular occlusion test. Measurements included heart rate, mean arterial pressure, forearm-to-fingertip skin-temperature gradient, and physical examination of peripheral perfusion with capillary refill time. Patients were stratified according to the condition of peripheral circulation (abnormal: forearm-to-fingertip skin-temperature gradient ≥4 and capillary refill time >4.5 secs). The outcome was defined based on the daily Sequential Organ Failure Assessment score and blood lactate levels. Upon intensive care unit admission, 35 (47.9%) patients had abnormal peripheral perfusion (forearm-to-fingertip skin-temperature gradient >4 or capillary refill time >4.5 secs). With the exception of the tissue oxygen saturation deoxygenation rate, tissue oxygen saturation baseline and tissue oxygen saturation recovery rate were statistically lower in patients who exhibited abnormal peripheral perfusion than in those with normal peripheral perfusion: 72 ± 9 vs. 81 ± 9; p = .001 and 1.9 ± 0.7 vs. 3.2 ± 0.9; p = .001, respectively. When a mixed-model analysis was performed over time for estimate (s) calculation, adjusted to the condition of disease, we did not find a significant clinical effect between vascular occlusion test-derived tissue oxygen saturation measurements (as response variables) and mean systemic hemodynamic variables (as independent variables): tissue oxygen saturation vs. heart rate: s (95% confidence interval) = 0.007 (-0.08; 0.09); tissue oxygen saturation vs. mean arterial pressure: s (95% confidence interval) = -0.02 (-0.12; 0.08); tissue oxygen saturation deoxygenation rate vs. heart rate: s (95% confidence interval) = 0.002 (-0.0004; 0.006); tissue oxygen saturation deoxygenation rate vs. mean arterial pressure: s (95% confidence interval) - 0.0007 (-0.003; 0.004); tissue oxygen saturation recovery rate vs. heart rate: s (95% confidence interval) = -0.009 (-0.02; -0.0015); tissue oxygen saturation recovery rate vs. mean arterial pressure: s (95% confidence interval) = 0.01 (0.002; 0.018). However, there was a strong association between tissue oxygen saturation baseline and tissue oxygen saturation recovery rate with abnormal peripheral perfusion: tissue oxygen saturation vs. abnormal peripheral perfusion: s (95% confidence interval) = -10.1 (-13.9; -6.2); tissue oxygen saturation recovery rate vs. abnormal peripheral perfusion: s (95% confidence interval) =-10.1 (-13.9; -6.2); tissue oxygen saturation recovery rate vs. abnormal peripheral perfusion: s (95% confidence interval) = -1.1 (-1.4; -0.81). Poor outcome was more closely related to abnormalities in peripheral perfusion than to tissue oxygen saturation-derived parameters. Conclusions: We found that the condition of peripheral circulation in critically ill patients strongly influences tissue oxygen saturation resting values and the tissue oxygen saturation reoxygenation rate but not the tissue oxygen saturation deoxygenation rate. In addition, changes in near-infrared spectroscopy-derived variables were independent of condition of disease and were not accompanied by any major differences in systemic hemodynamic variables. Copyright

Multi-site and multi-depth near-infrared spectroscopy in a model of simulated (central) hypovolemia: Lower body negative pressure (Article)

2011-04-01T00:00:00Z

Purpose: To test the hypothesis that the sensitivity of near-infrared spectroscopy (NIRS) in reflecting the degree of (compensated) hypovolemia would be affected by the application site and probing depth. We simultaneously applied multi-site (thenar and forearm) and multi-depth (15-2.5 and 25-2.5 mm probe distance) NIRS in a model of simulated hypovolemia: lower body negative pressure (LBNP). Methods: The study group comprised 24 healthy male volunteers who were subjected to an LBNP protocol in which a baseline period of 30 min was followed by a step-wise manipulation of negative pressure in the following steps: 0, -20, -40, -60, -80 and -100 mmHg. Stroke volume and heart rate were measured using volume-clamp finger plethysmography. Two multi-depth NIRS devices were used to measure tissue oxygen saturation (StO2) and tissue hemoglobin index (THI) continuously in the thenar and the forearm. To monitor the shift of blood volume towards the lower extremities, calf THI was measured by single-depth NIRS. Results: The main findings were that the application of LBNP resulted in a significant reduction in stroke volume which was accompanied by a reduction in forearm StO2 and THI. Conclusions: NIRS can be used to detect changes in StO2 and THI consequent upon central hypovolemia. Forearm NIRS measurements reflect hypovolemia more sensitively than thenar NIRS measurements. The sensitivity of these NIRS measurements does not depend on NIRS probing depth. The LBNP-induced shift in blood volume is reflected by a decreased THI in the forearm and an increased THI in the calf.

The microcirculation of the critically ill pediatric patient (Article)

2011-03-22T00:00:00Z

Persistent low microcirculatory vessel density in nonsurvivors of sepsis in pediatric intensive care (Article)

2011-01-01T00:00:00Z

Objective: To investigate the time course and predictive value of microvascular alterations in children with severe sepsis. Design: Single-center, prospective observational study. Setting: Intensive care unit of a level III university children's hospital. Patients: Patients with septic shock, requiring the administration of fluid and vasopressor agents and/or inotropes after the correction of hypovolemia, who were intubated and ventilated, were included. Interventions: None. Measurements and main results: The microcirculation was assessed in the buccal mucosa, using orthogonal polarization spectral imaging, within 24 hrs after admission. Subsequent measurements were performed every 24 hrs for 3 days. The measurements were discontinued when the patient was extubated. There were no significant differences in the functional capillary density or microvascular flow index for all vessel types between survivors and nonsurvivors on day 1. In the survival group, the functional capillary density increased significantly between day 1 and day 2 from 1.7 cm/cm2(0.8-3.4) to 4.3 cm/cm2(2.1-6.9) (p = .001). Functional capillary density values in nonsurvivors did not change (day 1: 3.2 cm/cm2[0.8-3.8]; day 2: 1.9 cm/cm2[1.0-2.1]). The median functional capillary density on days 2 and 3 were significantly lower in nonsurvivors (day 2: 1.9 cm/cm2[1.0 -2.1] vs. 4.3 cm/cm2[2.1-6.9], p = .009; day 3: 1.8 cm/cm2[1.0-2.0] vs. 4.7 cm/cm2[2.1-8.6], p = .01). The microvascular flow index for all vessel types improved in survivors and did not change in nonsurvivors. Differences in microvascular flow index values between survivors and nonsurvivors were not significant. Conclusion: Persistent microcirculatory alterations can be prognostic for survival in children with septic shock. Copyright

Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study (Article)

2010-12-23T00:00:00Z

Introduction: The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups.Methods: The study was designed as a prospective, randomized, double-blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 μg·kg-1·min-1(n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test.Results: Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group (24 hrs: MFIm 3.0 (3.0; 3.0) vs. 2.9 (2.8; 3.0); P = .02; MFIs 2.9 (2.9; 3.0) vs. 2.7 (2.3; 2.8); P < .001). The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group (dMFIm 10 (3; 23)% vs. 0 (-1; 9)%; P = .007; dMFIs 47 (26; 83)% vs. 10 (-3; 27); P < .001). In addition, the heterogeneity index decreased only in the levosimendan group (dHI -93 (-100; -84)% vs. 0 (-78; 57)%; P < .001). There was no statistically significant correlation between systemic and microcirculatory flow variables within each group (each P > .05). Conclusions: Compared to a standard dose of 5 μg·kg-1·min-1of dobutamine, levosimendan at 0.2 μg·kg-1·min-1improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels.Trial registration: NCT00800306.

Functional capillary density decreases after the first week of life in term neonates (Article)

2010-12-01T00:00:00Z

Background: Changes in the microcirculation have been recognized to play a crucial role in many disease processes. In premature neonates, functional capillary density (FCD) decreases during the first months of life. Objectives: The aims of this study were to obtain microcirculatory parameters in term neonates and older children who did not present with compromised respiration or circulation and to determine developmental changes in the microcirculation in young children. Methods: This single-center prospective observational study was performed at a level III university children's hospital. Subjects eligible for inclusion were children up to the age of 3 years who did not have any respiratory compromise, circulatory compromise or signs of dehydration. The buccal mucosa of 45 children was assessed, using orthogonal polarization spectral imaging. Results: We found a significantly higher FCD in neonates younger than 1 week compared with older children. The median FCD was 8.1 cm/cm2(range 7.3-9.4) for 0- to 7-day-old neonates (n = 12), 6.9 cm/cm2(range 4.7-8.7) for 8- to 28-day-olds (n = 10), 7.3 cm/cm2(range 6.1-8.8) for 1- to 6-month-olds (n = 19) and 6.7 cm/cm2(range 6.5-9.2) for 3-year-olds (n = 4). After the first week, there was no significant correlation between age and FCD. Conclusion: FCD of the buccal mucosa decreases after the first week of life. Copyright

Aortic cross-clamping and reperfusion in pigs reduces microvascular oxygenation by altered systemic and regional blood flow distribution (Article)

2010-08-01T00:00:00Z

Background: In this study, we tested the hypothesis that aortic cross-clamping (ACC) and reperfusion cause distributive alterations of oxygenation and perfusion in the microcirculation of the gut and kidneys despite normal systemic hemodynamics and oxygenation. Methods: Fifteen anesthetized pigs were randomized between an ACC group (n = 10), undergoing 45 minutes of aortic clamping above the superior mesenteric artery, and a time-matched sham surgery control group (n = 5). Systemic, intestinal, and renal hemodynamics and oxygenation variables were monitored during 4 hours of reperfusion. Microvascular oxygen partial pressure (μPO2) was measured in the intestinal serosa and mucosa and the renal cortex, using the Pd-porphyrin phosphorescence technique. Intestinal luminal PCO2was determined by air tonometry and the serosal microvascular flow by orthogonal polarization spectral imaging. Results: Organ blood flow and renal and intestinal μPO2decreased significantly during ACC, whereas the intestinal oxygen extraction and PCO2gap increased. The intestinal response to reperfusion after ACC was a sustained reactive hyperemia but no such effect was seen in the kidney. Despite a sustained high intestinal O2delivery, serosal μPO2(median [range], 49 mm Hg [41-67 mm Hg] versus 37 mm Hg [27-41 mm Hg]; P < 0.05 baseline versus 4 hours reperfusion) and the absolute number of perfused microvessels decreased along with an increased intestinal PCO2gap (17 mm Hg [10-19 mm Hg] versus 23 mm Hg [19-30 mm Hg]; P < 0.05). In contrast, the kidney showed a progressive O2delivery decrease accompanied by a decrease in renal cortex oxygenation (70 mm Hg [52-93 mm Hg] versus 57 mm Hg [33-64 mm Hg]; P < 0.05). Conclusion: Increased systemic and regional blood flow and oxygen supply after ACC does not ensure adequate regional blood flow and microcirculatory oxygenation in all organs.

The impact of fluid therapy on microcirculation and tissue oxygenation in hypovolemic patients: A review (Article)

2010-08-01T00:00:00Z

Purpose: An optimal volume replacement strategy aims to restore systemic hemodynamics with the ultimate goals of improving organ perfusion and microcirculation for sustaining adequate tissue oxygenation. This review presents the (patho)physiological basis of hypovolemia, microcirculation, and tissue oxygenation and presents a literature review on the effects of plasma substitutes on microperfusion and oxygenation in the clinical setting. Methods: Literature review of the effects of fluid therapy on microcirculation and tissue oxygenation using PubMed search including original papers in English from 1988 to 2009. Results: We identified a total of 14 articles dealing with the effects of different crystalloids and colloids on organ perfusion, microcirculation, and tissue oxygenation in patients. The results are divergent, but there is a general trend that colloids are superior to crystalloids in improving organ perfusion, microcirculation, and tissue oxygenation. Due to the limited number of studies and different study conditions, a metaanalysis on the effects of the volume replacement strategies on microcirculation is not possible. Conclusions: Improving the microcirculation by volume replacement appears to be a promising issue when treating the critically ill. The growing insights from animal experiments have to be translated into the clinical setting to identify the optimal fluid regimen for correcting hypovolemia. New techniques for monitoring microcirculation at the bedside might provide such endpoints, although these have to be validated also in the clinical setting. Whether improved microperfusion and tissue oxygenation by fluid therapy will also improve patient outcomes will have to be proven by future studies.

Improvement of Sidestream Dark Field Imaging with an Image Acquisition Stabilizer (Article)

2010-07-01T00:00:00Z

Background: In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging.Methods: The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared.Results: Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 ± 0.15 N without vs. 0.62 ± 0.05 N with the IAS, p < 0.001). The IAS ensured an increased duration of a stable image sequence (8 ± 2 s without vs. 42 ± 8 s with the IAS, p < 0.001). The time required to obtain a stable image sequence was similar with and without the IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 ± 5 s without vs. 67 ± 14 s with the IAS, p = 0.006).Conclusions: The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the microscopic field of view. The IAS improved both axial and lateral SDF image stability and thereby increased the critical force required to induce pressure artifacts. The IAS ensured a significantly increased duration of maintaining a stable image sequence.

Validation of near-infrared laser speckle imaging for assessing microvascular (re)perfusion (Article)

2010-03-01T00:00:00Z

The present study was conducted to compare laser speckle imaging (LSI) with sidestream dark field (SDF) imaging (i.e., capillary microscopy) so as to validate the use of LSI for assessing microvascular (re)perfusion. For this purpose, LSI and SDF measurements were performed on the human nail fold during gradual occlusion of the upperarm circulation to modify nail fold perfusion under controlled circumstances. Additionally, a vascular occlusion test was performed to test the ability of LSI to detect rapid changes in tissue perfusion during reactive hyperemia and a hyperthermic challenge was performed to measure LSI perfusion at maximum functional capillary density. Normalized LSI measurements (i.e., normalized to baseline is 100%) were shown to correlate positively with normalized SDF measurements (Pearson's r = 0.92). This was supported by linear regression analysis (slope of 1.01, R2 = 0.85, p < 0.001). During the vascular occlusion test, LSI perfusion decreased from 307 ± 90 AU (baseline) to 42 ± 8 AU (ischemia). Peak perfusion during reperfusion was 651 ± 93 AU (212% of baseline), which had returned to baseline after 2 min. Hyperthermia increased LSI perfusion from 332 ± 90 AU to 1067 ± 256 AU (321% of baseline). The main finding was that changes in perfusion as measured by LSI correlated well with changes in capillary red blood cell velocities as measured by SDF imaging during controlled reduction of the (micro)vascular perfusion. It was further shown that LSI is capable of measuring tissue perfusion at high temporal and spatial resolution. In conclusion, LSI can be employed to accurately quantitate microvascular reactivity following ischemic and hyperthermic challenges.

Gastrointestinal complications and its predictors after cardiac surgery (Article)

2010-03-01T00:00:00Z

The response of the host microcirculation to bacterial sepsis: Does the pathogen matter? (Article)

2010-02-01T00:00:00Z

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte-endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis.

The effect of perfusion pressure on gastric tissue blood flow in an experimental gastric tube model (Article)

2010-02-01T00:00:00Z

Background: Anastomotic leakage and stricture formation remain an important surgical challenge after esophagectomy with gastric tube reconstruction for cancer of the esophagus. The perfusion of the anastomotic site at the proximal site of the gastric tube depends exclusively on the microcirculation, making it susceptible to hypoperfusion. We hypothesized that increasing the perfusion pressure would improve blood flow at the anastomotic site of the gastric tube. Methods: A gastric tube was reconstructed in 9 pigs. Laser speckle imaging and thermographic imaging were used to measure blood flow and temperature, respectively, at the base, medial part, future anastomotic site, and top of the gastric tube. Measurements were repeated at every stepwise increase of mean arterial blood pressure (MAP) from 50 to 110 mm Hg. Results: Besides MAP, global hemodynamics did not change throughout the experiment. The blood flow in the top of the gastric tube was significantly lower than the flow in the base and medial part of the gastric tube at all levels of MAP. Increasing MAP did not have a significant effect on blood flow at any location in the gastric tube. Distribution of temperature was similar to distribution of flow for the different locations. Increases in MAP did not change temperature values at any location of the gastric tube. CONCLUSION: Blood flow in the upper part of the gastric tube is decreased compared with more proximal sites. Gastric tissue blood flow does not increase with increased perfusion pressure. Therefore, it is not recommended to increase MAP to supranormal levels to increase anastomotic tissue blood flow and reduce postoperative complications.

Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study (Article)

2010-01-01T00:00:00Z

Fluid resuscitation does not improve renal oxygenation during hemorrhagic shock in rats (Article)

2010-01-01T00:00:00Z

Background: The resuscitation strategy for hemorrhagic shock remains controversial, with the kidney being especially prone to hypoxia. Methods: The authors used a three-phase hemorrhagic shock model to investigate the effects of fluid resuscitation on renal oxygenation. After a 1-h shock phase, rats were randomized into four groups to receive either normal saline or hypertonic saline targeting a mean arterial pressure (MAP) of either 40 or 80 mmHg. After such resuscitation, rats were transfused with the shed blood. Renal macro-and microcirculation were monitored with cortical and outer-medullary microvascular oxygen pressure, renal oxygen delivery, and renal oxygen consumption measured using oxygen-dependent quenching of phosphorescence. Results: Hemorrhagic shock was characterized by a drop of aortic blood flow, MAP, renal blood flow, renal oxygen delivery, renal oxygen consumption, and renal microvascular PO2. During the fluid resuscitation phase, normal saline targeting a MAP = 80 mmHg was the sole strategy able to restore aortic blood flow, renal blood flow, and renal oxygen consumption, although without improving renal oxygen delivery. However, none of the strategies using either normal saline or hypertonic saline or targeting a high MAP could restore the renal microvascular Po2. Blood transfusion increased microvascular Po2 but was unable to totally restore renal microvascular oxygenation to baseline values. Conclusions: This experimental rat study shows that (1) high MAP-directed fluid resuscitation (80 mmHg) does not lead to higher renal microvascular Po2 compared with fluid resuscitation targeted to MAP (40 mmHg); (2) hypertonic saline is not superior to normal saline regarding renal oxygenation; and (3) decreased renal oxygenation persists after blood transfusion.

Effects of 1400w and/or nitroglycerin on renal oxygenation and kidney function during endotoxaemia in anaesthetized rats (Article)

2009-09-01T00:00:00Z

The pathogenesis of acute renal failure (ARF) in sepsis is multifactorial. The role of nitric oxide (NO) in septic ARF has been a source of controversy. We hypothesized that endotoxaemia-induced exacerbation of inducible nitric oxide synthase (iNOS)-related NO release impairs renal oxygenation and contributes to ARF in anaesthetized rats. In the present study, rats received lipopolysaccharide (2.5 mg/kg) for 30 min. Two hours later, fluid resuscitation was started (HES130; 5 mL/kg per h after a 5 mL/kg bolus) supplemented either by the NO donor nitroglycerin (NTG; 0.5 μg/kg per min after a 2 μg/kg bolus), the selective iNOS inhibitor 1400W (3 mg/kg per h after a 3 mg/kg bolus) or both. Systemic haemodynamics and renal microvascular P o2 (μP o2) were recorded continuously. Furthermore, creatinine clearance, plasma NOx (nitrate + nitrite + S-nitrosothiols) levels and the expression of iNOS mRNA were measured. Endotoxaemia reduced renal blood flow, decreased mean arterial pressure, resulted in anuria and was associated with an increase in plasma NOx levels and renal iNOS expression. Renal μP o2 deteriorated gradually during endotoxaemia and there was a significant decrease in renal O2 delivery and consumption. Manipulation of NO levels had no beneficial effect on systemic haemodynamics, renal μP o2 or creatinine clearance over standard fluid resuscitation. The application of 1400W+NTG significantly reduced plasma NO x levels compared with fluid resuscitation and NTG alone. Neither iNOS inhibition, NO donation nor a combination of both showed beneficial effects on systemic haemodynamics, renal oxygenation and renal function compared with fluid resuscitation alone. Our results question the proposed key role of NO in the pathogenesis of septic ARF in rats.

Mitochondrial oxygen tension within the heart (Article)

2009-06-01T00:00:00Z

By using a newly developed optical technique which enables non-invasive measurement of mitochondrial oxygenation (mitoPO2) in the intact heart, we addressed three long-standing oxygenation questions in cardiac physiology: 1) what is mitoPO2 within the in vivo heart?, 2) is mitoPO2 heterogeneously distributed?, and 3) how does mitoPO2 of the isolated Langendorff-perfused heart compare with that in the in vivo working heart? Following calibration and validation studies of the optical technique in isolated cardiomyocytes, mitochondria and intact hearts, we show that in the in vivo condition mean mitoPO2 was 35 ± 5 mm Hg. The mitoPO2 was highly heterogeneous, with the largest fraction (26%) of mitochondria having a mitoPO2 between 10 and 20 mm Hg, and 10% between 0 and 10 mm Hg. Hypoxic ventilation (10% oxygen) increased the fraction of mitochondria in the 0-10 mm Hg range to 45%, whereas hyperoxic ventilation (100% oxygen) had no major effect on mitoPO2. For Langendorff-perfused rat hearts, mean mitoPO2 was 29 ± 5 mm Hg with the largest fraction of mitochondria (30%) having a mitoPO2 between 0 and 10 mm Hg. Only in the maximally vasodilated condition, did the isolated heart compare with the in vivo heart (11% of mitochondria between 0 and 10 mm Hg). These data indicate 1) that the mean oxygen tension at the level of the mitochondria within the heart in vivo is higher than generally considered, 2) that mitoPO2 is considerably heterogeneous, and 3) that mitoPO2 of the classic buffer-perfused Langendorff heart is shifted to lower values as compared to the in vivo heart.

L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats (Article)

2009-05-01T00:00:00Z

Even though renal hypoxia is believed to play a pivotal role in the development of acute kidney injury, no study has specifically addressed the alterations in renal oxygenation in the early onset of renal ischemia-reperfusion (I/R). Renal oxygenation depends on a balance between oxygen supply and consumption, with the nitric oxide (NO) as a major regulator of microvascular oxygen supply and oxygen consumption. The aim of this study was to investigate whether I/R induces inducible NO synthase (iNOS)-dependent early changes in renal oxygenation and the potential benefit of iNOS inhibitors on such alterations. Anesthetized Sprague-Dawley rats underwent a 30-min suprarenal aortic clamping with or without either the nonselective NO synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) or the selective iNOS inhibitor L-N6-(1-iminoethyl)lysine hydrochloride (L-NIL). Cortical (CμPO2) and outer medullary (MμPO2) microvascular oxygen pressure (μPO2), renal oxygen delivery (DO2ren), renal oxygen consumption (V̇O2ren), and renal oxygen extraction (O2ER) were measured by oxygen-dependent quenching phosphorescence techniques throughout 2 h of reperfusion. During reperfusion renal arterial resistance and oxygen shunting increased, whereas renal blood flow, CμPO 2, and MμPO2 (-70, -42, and -42%, respectively, P < 0.05), V̇O2ren, and DO2ren (-70%, P < 0.0001, and -28%, P < 0.05) dropped. Whereas L-NAME further decreased DO2ren, V̇O2ren, CμPO2, and MμPO2 and deteriorated renal function, L-NIL partially prevented the drop of DO 2ren and μPO2, increased O2ER, restored V̇O2ren and metabolic efficiency, and prevented deterioration of renal function. Our results demonstrate that renal I/R induces early iNOS-dependent microvascular hypoxia in disrupting the balance between microvascular oxygen supply and V̇O2ren, whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxia.

Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia (Article)

2009-05-01T00:00:00Z

There is growing evidence that impairment in intrarenal oxygenation and hypoxic injury might contribute to the pathogenesis of septic renal failure. An important molecule known to act on the renal microvascular tone and therefore consequently being involved in the regulation of intrarenal oxygen supply is NO. The main production of NO under septic conditions derives from iNOS, an enzyme that can be blocked by dexamethasone (DEX). In an animal model of endotoxin-induced renal failure, we tested the hypothesis that inhibition of iNOS by low-dose DEX would improve an impaired intrarenal oxygenation and kidney function. Twenty-two male Wistar rats received a 30-min intravenous infusion of LPS (2.5 mg/kg) and consecutively developed endotoxemic shock. Two hours later, in 12 animals, fluid resuscitation was initiated. Six rats did not receive resuscitation; four animals served as time control. In addition to the fluid, six animals received a bolus of low-dose DEX (0.1 mg/kg). In these animals, the renal iNOS mRNA expression was significantly suppressed 3 h later. Dexamethasone prevented the appearance of cortical microcirculatory hypoxic areas, improved renal oxygen delivery, and significantly restored oxygen consumption. Besides a significant increase in MAP and renal blood flow, DEX restored kidney function and tubular sodium reabsorption to baseline values. In conclusion, treatment with low-dose DEX in addition to fluid resuscitation reversed endotoxin-induced renal failure associated by an improvement in intrarenal microvascular oxygenation. Therefore, low-dose DEX might have potential application in the prevention of septic acute renal failure.

Low-dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure (Article)

2009-04-01T00:00:00Z

AimsImpaired tissue perfusion is often observed in patients with acute heart failure. We tested whether low-dose nitroglycerin (NTG) improves microcirculatory perfusion in patients admitted for acute heart failure.Methods and resultsIn 20 acute heart failure patients, NTG was given as intravenous infusion at a fixed dose of 33 g/min. Using Sidestream Dark Field (SDF) imaging, sublingual microvascular perfusion was evaluated before (T0, average of two baseline measurements) and 15 min after initiation of NTG (T1). In a subgroup of seven patients, SDF measurements were repeated after NTG had been stopped for 20 min. Capillaries were defined as microvessels with a diameter of <20 m. Perfused capillary density (PCD) was determined as the parameter of tissue perfusion. Values are expressed as median and interquartile range (P25; P75). The median age of the subjects was 60 (52; 73) years, and 65 were male. Patients were stable before starting NTG. Nitroglycerin decreased central venous pressure [17 (13; 19) mmHg at T0 vs. 16 (13; 17) mmHg at T1, P = 0.03] and pulmonary capillary wedge pressure [23 (18; 31) mmHg at T0 vs. 19 (16; 25) mmHg at T1, P = 0.03]. It increased PCD [10.7 (9.9; 12.5) mm mm-2at T0 vs. 12.4 (11.4; 13.6) mm mm-2at T1, P = 0.01]. After cessation of NTG, PCD returned to baseline values (P = 0.04).ConclusionLow-dose NTG significantly reduces cardiac filling pressures and improves microvascular perfusion in patients admitted for acute heart failure.

Iloprost preserves renal oxygenation and restores kidney function in endotoxemia-related acute renal failure in the rat (Article)

2009-04-01T00:00:00Z

OBJECTIVE: To investigate that exogenous prostacyclin would counterbalance an endotoxemia-induced intrarenal vasoconstriction and would therefore have beneficial effects on kidney function. DESIGN: Prospective, randomized, controlled study. SETTING: University medical center research laboratory. SUBJECTS: Eighteen male Wistar rats. INTERVENTIONS: In anesthetized and ventilated animals, arterial blood pressure (mean arterial blood pressure [MAP]) and renal blood flow (RBF) were recorded. Renal microvascular Po2 (μPo2) and renal venous Po2 were continuously measured by phosphorescence lifetime technique. All animals received a 30-minute infusion of lipopolysaccharide (LPS) (2.5 mg/kg) to induce endotoxemia. One group of rats was not resuscitated. A second group received fluid resuscitation 90 minutes after stop of LPS infusion. In a third group of rats, the prostacyclin analogue iloprost (100 ng/kg/min) was continuously infused in addition to fluid resuscitation. Furthermore, in all the animals, plasma NOx levels, renal inducible nitric-oxide synthase (iNOS) messenger RNA (mRNA) expression, and creatinine clearance were determined. MEASUREMENTS AND MAIN RESULTS: During LPS infusion, MAP and RBF progressively dropped to 50% of baseline at 120 minutes. After an initial increase in MAP and RBF, start of fluid resuscitation with iloprost resulted in the stabilization of both parameters. All animals became anuric during endotoxemia. Only in animals receiving iloprost was creatinine clearance totally restored at the end of the experiment. Iloprost had no significant effects on average μPo2, but prevented the occurrence of cortical microcirculatory hypoxic areas. NOx levels and iNOS mRNA expression were significantly increased in all animals receiving LPS after 5 hours. There was no difference in NOx concentration between the different groups. In animals receiving iloprost, iNOS mRNA expression was significantly suppressed in the inner medulla. CONCLUSIONS: Iloprost significantly restored kidney function of endotoxemic rats to baseline values. This beneficial effect of iloprost on renal function might be addressed to an improvement in intrarenal oxygenation.

The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients (Article)

2009-03-01T00:00:00Z

OBJECTIVE:: The physical examination of peripheral perfusion based on touching the skin or measuring capillary refill time has been related to the prognosis of patients with circulatory shock. It is unclear, however, whether monitoring peripheral perfusion after initial resuscitation still provides information on morbidity in critically ill patients. Therefore, we investigated whether subjective assessment of peripheral perfusion could help identify critically ill patients with a more severe organ or metabolic dysfunction using the Sequential Organ Failure Assessment (SOFA) score and lactate levels. DESIGN:: Prospective observational study. SETTING:: Multidisciplinary intensive care unit in a university hospital. PATIENTS:: Fifty consecutive adult patients admitted to the intensive care unit. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Patients were considered to have abnormal peripheral perfusion if the examined extremity had an increase in capillary refill time (>4.5 seconds) or it was cool to the examiner hands. To address reliability of subjective inspection and palpation of peripheral perfusion, we also measured forearm-to-fingertip skin-temperature gradient (Tskin-diff), central-to-toe temperature difference (Tc-toe), and peripheral flow index. The measurements were taken within 24 hours of admission to the intensive care after hemodynamic stability was obtained (mean arterial pressure >65 mm Hg). Changes in SOFA score during the first 48 hours were analyzed (δ-SOFA). Individual SOFA score was significantly higher in patients with abnormal peripheral perfusion than in those with normal peripheral perfusion (9 ± 3 vs. 7 ± 2, p < 0.05). Tskin-diff, Tc-toe, and peripheral flow index were congruent with the subjective assessment of peripheral perfusion. The proportion of patients with δ-SOFA score >0 was significantly higher in patients with abnormal peripheral perfusion (77% vs. 23%, p < 0.05). The logistic regression analysis showed that the odds of unfavorable evolution are 7.4 (95% confidence interval 2-19; p < 0.05) times higher for a patient with abnormal peripheral perfusion. The proportion of hyperlactatemia was significantly different between patients with abnormal and normal peripheral perfusion (67% vs. 33%, p < 0.05). The odds of hyperlactatemia by logistic regression analysis are 4.6 (95% confidence interval 1.4-15; p < 0.05) times higher for a patient with abnormal peripheral perfusion. CONCLUSIONS:: Subjective assessment of peripheral perfusion with physical examination following initial hemodynamic resuscitation in the first 24 hours of admission could identify hemodynamically stable patients with a more severe organ dysfunction and higher lactate levels. Patients with abnormal peripheral perfusion had significantly higher odds of worsening organ failure than did patients with normal peripheral perfusion following initial resuscitation.

Changes in buccal microcirculation following extracorporeal membrane oxygenation in term neonates with severe respiratory failure (Article)

2009-03-01T00:00:00Z

OBJECTIVES:: Extracorporeal membrane oxygenation (ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. In this study, we tested two hypotheses: 1) neonates with severe respiratory failure exhibit alterations of the microcirculation and 2) after ECMO therapy these microcirculatory alterations are improved. DESIGN:: Single-center prospective observational study. SETTING:: Intensive care unit of a level III university children's hospital. PATIENTS:: Term neonates receiving venoarterial ECMO. Control patients with and without respiratory failure. MEASUREMENTS AND MAIN RESULTS:: The microcirculation was assessed in the buccal mucosa, using orthogonal polarization spectral imaging, before and after ECMO. Functional capillary density was lower in patients with severe respiratory failure before ECMO (n = 14) compared with control patients (n = 10; p < 0.01). Functional capillary density had increased significantly after ECMO (p < 0.01). CONCLUSION:: Microcirculatory parameters are depressed in neonates with severe respiratory failure and improve significantly following ECMO treatment.

Nonresuscitated endotoxemia induces microcirculatory hypoxic areas in the renal cortex in the rat (Article)

2009-01-01T00:00:00Z

The pathophysiology of acute renal failure (ARF) in sepsis is only partly understood. In several animal models of septic ARF, no profound tissue hypoxia or decrease in microcirculatory Po2(μPo2) can be seen. We hypothesized that heterogeneity of microcirculatory oxygen supply to demand in the kidney is obscured when looking at the average 7mu;Po2during endotoxemia. In 20 anesthetized and ventilated rats, MAP, renal blood flow (RBF), and creatinine clearance (CLcrea) were recorded. Renal μPo2was measured by phosphorescence quenching, allowing measurement of nPo2distributions. Five animals received a 1-h LPS infusion (10 mg kg-1h-11). In 5 rats, RBF was mechanically reduced to 2.1 ± 0.2 mL min-1. Five animals served as time control. LPS infusion significantly reduced RBF to 2.1 ± 0.2 mL min-1and induced anuria. Average cortical μPo2decreased from 68 ± 4 to 52 ± 6 mmHg, with a significant left shift in the cortical oxygen histogram toward hypoxia. This shift could not be observed in animals receiving mechanical RBF reduction. In these animals, CLcreawas reduced to 50%. An additional group of rats (n = 5) received fluid resuscitation. In these animals, RBF was restored to baseline, CLcreaincreased approximately 50%, and the cortical microcirculatory hypoxic areas disappeared after resuscitation. In conclusion, endotoxemia was associated with the occurrence of cortical microcirculatory hypoxic areas that are not detected in the average Po2measurement, proving the hypothesis of our study. These observations suggest the involvement of hypoxia in the pathogenesis of endotoxemia-induced ARF. Copyright

Near infrared spectroscopy (Article)

2009-01-01T00:00:00Z

The Heterogeneity of the Microcirculation in Critical Illness (Article)

2008-12-01T00:00:00Z

Microcirculation, a complex and specialized facet of organ architecture, has characteristics that vary according to the function of the tissue it supplies. Bedside technology that can directly observe microcirculation in patients, such as orthogonal polarization spectral imaging and sidestream dark field imaging, has opened the way to investigating this network and its components, especially in critical illness and surgery. These investigations have underscored the central role of microcirculation in perioperative disease states. They have also highlighted variations in the nature of microcirculation, both among organ systems and within specific organs. Supported by experimental studies, current investigations are better defining the nature of microcirculatory alterations in critical illness and how these alterations respond to therapy. This review focuses on studies conducted to date on the microcirculatory beds of critically ill patients. The functional anatomy of microcirculation networks and the role of these networks in the pathogenesis of critical illness are discussed. The morphology of microvascular beds that have been visualized during surgery and intensive care at the bedside are also described, including those of the brain, sublingual region, skin, intestine, and eyes.

In vivo mitochondrial oxygen tension measured by a delayed fluorescence lifetime technique (Article)

2008-10-15T00:00:00Z

Mitochondrial oxygen tension (mitoPO2) is a key parameter for cellular function, which is considered to be affected under various pathophysiological circumstances. Although many techniques for assessing in vivo oxygenation are available, no technique for measuring mitoPO2in vivo exists. Here we report in vivo measurement of mitoPO2and the recovery of mitoPO2histograms in rat liver by a novel optical technique under normal and pathological circumstances. The technique is based on oxygen-dependent quenching of the delayed fluorescence lifetime of protoporphyrin IX. Application of 5-aminolevulinic acid enhanced mitochondrial protoporphyrin IX levels and induced oxygen-dependent delayed fluorescence in various tissues, without affecting mitochondrial respiration. Using fluorescence microscopy, we demonstrate in isolated hepatocytes that the signal is of mitochondrial origin. The delayed fluorescence lifetime was calibrated in isolated hepatocytes and isolated perfused livers. Ultimately, the technique was applied to measure mitoPO2in rat liver in vivo. The results demonstrate mitoPO2values of ∼30-40 mmHg. mitoPO2was highly sensitive to small changes in inspired oxygen concentration around atmospheric oxygen level. Ischemia-reperfusion interventions showed altered mitoPO2distribution, which flattened overall compared to baseline conditions. The reported technology is scalable from microscopic to macroscopic applications, and its reliance on an endogenous compound greatly enhances its potential field of applications.

The elusive microcirculation (Article)

2008-10-01T00:00:00Z

The Microcirculation in Health and Critical Disease (Article)

2008-09-01T00:00:00Z

The microcirculation is a complex system, which regulates the balance between oxygen demand and supply of parenchymal cells. In addition, the peripheral microcirculation has an important role in regulating the hemodynamics of the human body because it warrants arterial blood pressure as well as venous return to the heart. Novel techniques have made it possible that the microcirculation can be observed directly at the bedside in patients. Currently, research using these new techniques is focusing at the central role of the microcirculation in critical diseases. Experimental studies have demonstrated differences in microvascular alterations between models of septic and hypovolemic shock. In human studies, the microcirculation has most extensively been investigated in septic syndromes and has revealed highly heterogeneous alterations with clear evidence of arteriolar-venular shunting. Until now, the microcirculation in acute heart failure syndromes such as cardiogenic shock has scarcely been investigated. This review concerns the physiologic properties of the microcirculation as well as its role in pathophysiologic states such as sepsis, hypovolemic shock, and acute heart failure.

Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock (Article)

2008-06-01T00:00:00Z

OBJECTIVE:: To determine the effects of norepinephrine and levosimendan on microvascular perfusion and oxygenation in a rat model of septic shock. DESIGN:: Controlled laboratory animal study. SETTING:: Research laboratory in a university hospital. SUBJECTS:: Forty Sprague-Dawley rats. INTERVENTIONS:: Sepsis was induced in 32 animals by cecal ligation and puncture. Eight animals served as sham controls. Animals were randomly assigned to five groups: 1) fluid resuscitation (25 ml•kg•h), 2) fluid resuscitation plus norepinephrine (0.5 μg•kg•min), 3) fluid resuscitation plus levosimendan (0.3 μg•kg•min), 4) no treatment and 5) sham control. MEASUREMENTS AND MAIN RESULTS:: Microvascular perfusion was quantitated using sidestream darkfield imaging and microvascular oxygenation (μPO2) was assessed by oxygen-dependent quenching of phosphorescence. Measurements were obtained on the buccal mucosa at baseline and at hourly intervals thereafter. In parallel, cardiac output (CO) was recorded. After induction of sepsis microvascular perfusion and μPO2 were impaired early followed by significant decreases in CO. Although levosimendan and norepinephrine were equally effective in restoring CO, only treatment with levosimendan significantly improved μPO2 after 1 and 2 hours of treatment (9.7 ± 2.0 vs. 15.1 ± 2.6 and 16.0 ± 3.7 mmHg; p < 0.05). Microvascular perfusion was not significantly influenced by any of the treatment strategies. CONCLUSIONS:: In this model, treatment with levosimendan and norepinephrine showed comparable effects in restoring CO and had no significant influence on microvascular perfusion. However, only levosimendan significantly improved μPO2, suggesting that a mechanism relatively independent of macrocirculatory hemodynamics and overall microvascular perfusion might account for these observations.

Monitoring of renal venous PO2 and kidney oxygen consumption in rats by a near-infrared phosphorescence lifetime technique (Article)

2008-03-01T00:00:00Z

Renal oxygen consumption (V̇O2,ren) is an important parameter that has been shown to be influenced by various pathophysiological circumstances. VV̇O2,renhas to be repeatedly measured during an experiment to gain insight in the dynamics of (dys)regulation of oxygen metabolism. In small animals, the classical approach of blood gas analysis of arterial and venous blood samples is only limitedly applicable due to fragile vessels and a low circulating blood volume. We present a phosphorescence lifetime technique that allows nearcontinuous measurement of renal venous PO2(vPO2) and VV̇O2,renin rats. The technique does not rely on penetration of the blood vessel, but uses a small reflection probe. This probe is placed in close proximity to the renal vein for detection of the oxygen-dependent phosphorescence of the injected water-soluble near-infrared phosphor Oxyphor G2. The technique was calibrated in vitro and the calibration constants were validated in vivo in anesthetized and mechanically ventilated male Wistar rats. The hemoglobin saturation curve and its pH dependency were determined for calculation of renal venous oxygen content. The phosphorescence technique was in good agreement with blood gas analysis of renal venous blood samples, for both PO2and hemoglobin saturation. To demonstrate its feasibility in practice, the technique was used in four rats during endotoxin infusion (10 mg·kg-1·h-1during 1 h). Renal vPO2reduced by 40% upon reduction in oxygen delivery to 30% of baseline, but V̇O2remained unchanged. This study documents the feasibility of near-continuous, nondestructive measurement of renal vPO2and V̇O2by oxygen-dependent quenching of phosphorescence. Copyright

Heart, kidney, and intestine have different tolerances for anemia (Article)

2008-02-01T00:00:00Z

Organ systems do not respond uniformly to changes in systemic oxygen delivery because of global and local redistributive mechanisms. We hypothesized that progressive hemodilution would evoke a different response in the microvascular oxygenation of the heart compared with kidney and gut. To evaluate this hypothesis, we studied the effect of stepwise isovolemic hemodilution on systemic hemodynamic and oxygenation parameters as well as the relation between systemic hematocrit (Ht) and microvascular PO2(μPO2) in heart, kidney, and intestines in an anesthetized and mechanically ventilated rat model. Baseline conditions were similar in the hemodilution group and in the control group. In the hemodilution group, Ht was diminished from 46.6 ± 3.8% to 7.0 ± 1.8% [mean ± standard deviation (SD)]. This group had no effect on measured hemodynamics; only when Ht fell below 10% did blood pressure start to decrease. The μPO2values in heart, kidney, and intestines did not respond uniformly. Renal μPO2(56 ± 10 mm Hg at baseline) started to decrease at a Ht of 38.5 ± 8.6%, whereas intestinal μPO2(59 ± 6 mm Hg at baseline) did not start to decrease until Ht reached 17.4 ± 7.1%. Finally, cardiac μPO2(40 ± 6 mm Hg at baseline) decreased only in the ultimate stage of the experiment at Ht of 8.7 ± 3.5%. Based on these observations, we conclude that the regulation of microvascular oxygenation during progressive anemia is specific for each organ system. The relation between these observations and organ function and damage needs to be determined.

The NO donor SIN-1 improves intestinal-arterial Pco2 gap in experimental endotoxemia: An animal study (Article)

2007-07-01T00:00:00Z

Background: Dysfunction of the microcirculation is a prominent feature of sepsis and endotoxemia. Recently, it has been shown that microcirculatory alterations are completely reversed by local or systemic application of vasodilators in severely septic patients. Therefore, we investigated the influence of vasodilator therapy on microcirculatory dysfunction of the ileum during endotoxic shock in a prospective, controlled animal study. Methods: After baseline measurements, shock was induced in 12 domestic pigs by lipopolysaccharide via the mesenteric vein until the mean arterial pressure fell below 60 mmHg. After 30 min in shock, six animals were resuscitated with either fluid alone (control) or fluid and 2 μg/kg/min of the vasodilator 3-morpholino-sydnonimine (SIN-1). The systemic and regional hemodynamics and oxygenation parameters, tonometric ileal Pco2and microvascular oxygen pressures (μPo2) (by oxygen-dependent Pd-porphyrin phosphorescence) were measured simultaneously. Results: The ileal-arterial Pco2gap increased during shock and the ileal mucosal and serosal μPo2decreased concurrently. SIN-1 in addition to fluid resuscitation significantly improved the ileal-arterial Pco2gap, whereas fluid alone failed to decrease the Pco2gap. The SIN-1-induced improvement in the Pco2gap was accompanied by an increase in serosal μPo2above shock levels. Mucosal μPo2was resuscitated to baseline levels in both groups. Conclusion: The application of the vasodilator SIN-1 in addition to fluid resuscitation improves the ileal-arterial Pco2gap and mucosal μPo2, together with a moderate increase in serosal μPo2, after endotoxic shock. This finding is consistent with the concept that vasodilators may correct pathologic flow distribution within the intestinal wall.

Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution (Article)

2007-02-01T00:00:00Z

Large differences in the tolerance of organ systems to conditions of decreased O2delivery such as hemodilution exist. The kidney receives ∼25% of the cardiac output and O2delivery is in excess of the oxygen demand under normal circumstances. In a rat model of acute normovolemic hemodilution (ANH), we studied the effect of reduced hematocrit on renal regional and microvascular oxygenation. Experiments were performed in 12 anesthetized male Wistar rats. Six animals underwent four steps of ANH (hematocrit 25, 15, 10, and <10%). Six animals served as time-matched controls. Systemic and renal hemodynamic and oxygenation parameters were monitored. Renal cortical (c) and outer medullary (m) microvascular PO2(μPO2) and the renal venous PO2(PrvO2) were continuously measured by oxygen-dependent quenching of phosphorescence. Despite a significant increase in renal blood flow in the first two steps of ANH, cμPO2and mμPO2dropped immediately. From the first step onward oxygen consumption (V̇O2ren) became dependent on oxygen delivery (DO2ren). With a progressive decrease in hematocrit, a significant correlation between μPO2and V̇O2rencould be observed, as well as a PO2gap between μPO2and PrvO2. Furthermore, there was a high correlation between V̇O2renand RBF over a wide range of flows. In conclusion, the oxygen supply to the renal tissue is becoming critical already in an early stage of ANH due to the combination of increased V̇O2ren, decreased DO2ren, and intrarenal O2shunt. This has clinical relevance as recent publications reporting that hemodilution during surgery forms a risk factor for postoperative renal dysfunction. Copyright

Regional ischemia in hypertrophic Langendorff-perfused rat hearts (Article)

1999-01-01T00:00:00Z

Myocardial hypertrophy decreases the muscle mass-to-vascularization ratio, thereby changing myocardial perfusion. The effect of these changes on myocardial oxygenation in hypertrophic Langendorff-perfused rat hearts was measured using epimyocardial NADH videofluorimetry, whereby ischemic myocardium displays a high fluorescence intensity. Hypertrophic hearts, in contrast to control hearts, developed ischemic areas during oxygen-saturated Langendorff perfusion. Reoxygenation of control hearts after a hypoxic episode resulted in a swift decrease of fluorescence in a heterogeneous pattern of small, evenly dispersed, highly fluorescent patches. Identical patterns could be evoked by occluding capillaries with microspheres 5.9 micrometer in diameter. Ten seconds after reoxygenation there were no more dysoxic areas, whereas reoxygenation in hypertrophic hearts showed larger ischemic areas that took significantly longer to return to normoxic fluorescence intensities. Hypothesizing that the larger areas originate at a vascular level proximal to the capillary network, we induced hypoxic patterns by embolizing control hearts with microspheres 9.8 and 15 micrometer in diameter. The frequency distribution histograms of these dysoxic surface areas matched those of hypertrophic hearts and differed significantly from those of hearts embolized with 5.9-micrometer microspheres. These results suggest the existence of areas in hypertrophic Langendorff-perfused hearts with suboptimal vascularization originating at the arteriolar and/or arterial level.

(Semi-)quantitative analysis of reduced nicotinamide adenine dinucleotide fluorescence images of blood-perfused rat heart (Article)

1997-01-01T00:00:00Z

In vivo analysis of the metabolic state of tissue by means of reduced nicotinamide adenine dinucleotide (NADH) fluorimetry is disturbed by tissue movements and by hemodynamic and oximetric effects. These factors cause changes in the absorption of ultraviolet (UV) excitation light by the tissue. Many different methods have been used in the literature to compensate measured NADH fluorescence intensities for these effects. In this paper we show on theoretical grounds that the ratio of NADH fluorescence intensity and UV diffuse reflectance intensity provides a (semi-)quantitative measure of tissue NADH concentrations. This result is corroborated by experiments with tissue phantoms in which absorption and back-scattering properties were varied. Furthermore, we have verified the validity of this compensation method in isolated Langendorff-perfused rat heart preparations. In this preparation oximetric effects (of blood and tissue) are the major determinants of the metabolism-dependent UV diffuse reflectance change. Hemodynamic effects accompanying compensatory vasodilation are negligible. Movement artifacts were eliminated by simultaneously recording fluorescence and reflectance images, using a CCD camera with a biprism configuration. The results show that the NADH fluorescence/UV reflectance ratio can be used to monitor the mitochondrial redox state of the surface of intact blood-perfused myocardium.