Mat van Iterson

International study on microcirculatory shock occurrence in acutely ill patients

Objectives:Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. Design:Multicenter observational point prevalence study. Setting:The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. Patients:A heterogeneous ICU population consisting of 501 patients. Interventions:None. Measurements and Main Results:Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10–21), a Sequential Organ Failure Assessment score of 5 (2–8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67–4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963–0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11–3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28–3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30–8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. Conclusions:In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

Microcirculatory Imaging in Cardiac Anesthesia: Ketanserin Reduces Blood Pressure But Not Perfused Capillary Density

OBJECTIVES It has become possible to image the human microcirculation at the bedside using sidestream dark field (SDF) imaging. This may help the clinician when correlation between global and microvascular hemodynamics may not be straightforward. Ketanserin, a serotonin and alpha-1 adrenoceptor antagonist, is used in some countries to treat elevated blood pressure after extracorporeal circulation. This might hamper microcirculatory perfusion. Conversely, it is also conceivable that microcirculatory flow is maintained or improved as a result of flow redistribution. In order to introduce SDF imaging in cardiac anesthesia, the authors set out to directly observe the sublingual microcirculation in this setting. DESIGN An observational study. SETTING A large teaching hospital. PARTICIPANTS Mechanically ventilated patients with elevated arterial blood pressure immediately after extracorporeal circulation (ECC). INTERVENTION An intravenous bolus of ketanserin, 0.15 mg/kg. MEASUREMENTS AND MAIN RESULTS Five minutes before and 10 minutes after ketanserin administration, global hemodynamic variables were recorded. In addition, the authors used SDF imaging to record video clips of the microcirculation. Analysis of these allowed for quantification of microvascular hemodynamics including determination of perfused vessel density (PVD) and microcirculatory flow index (MFI). After ketanserin administration, there was a significant reduction in systolic arterial blood pressure (129 +/- 9 to 100 +/- 15 mmHg, p = 0.0001). At the level of the microcirculation, the mean MFI did not change significantly for small (diameter <20 microm, 2.79 [interquartile range, 1.38-3] to 2.38 [1.88-2.75], p = 0.62) or large (diameter >20 microm, 2.83 [1.4-3] to 2.67 [0.35-2.84] p = 1.0) vessels. There was a significant increase in mean PVD for large vessels (1.23 +/- 0.63 to 1.70 +/- 79 mm(-1), p = 0.017) but not for small vessels (5.59 +/- 2.60 to 5.87 +/- 1.22 mm(-1), p = 0.72) where red blood cell flow was maintained. CONCLUSIONS SDF imaging clearly showed a discrepancy between global and microvascular hemodynamics after the administration of ketanserin for elevated blood pressure after ECC. Ketanserin effectively lowers arterial blood pressure. However, capillary perfusion is maintained at a steady value. Both effects may be explained by an increase in shunting in the larger vessels of the microcirculation.

Withdrawing intra-aortic balloon pump support paradoxically improves microvascular flow

IntroductionThe Intra-Aortic Balloon Pump (IABP) is frequently used to mechanically support the heart. There is evidence that IABP improves microvascular flow during cardiogenic shock but its influence on the human microcirculation in patients deemed ready for discontinuing IABP support has not yet been studied. Therefore we used sidestream dark field imaging (SDF) to test our hypothesis that human microcirculation remains unaltered with or without IABP support in patients clinically ready for discontinuation of mechanical support.MethodsWe studied 15 ICU patients on IABP therapy. Measurements were performed after the clinical decision was made to remove the balloon catheter. We recorded global hemodynamic parameters and performed venous oximetry during maximal IABP support (1:1) and 10 minutes after temporarily stopping the IABP therapy. At both time points, we also recorded video clips of the sublingual microcirculation. From these we determined indices of microvascular perfusion including perfused vessel density (PVD) and microvascular flow index (MFI).ResultsCeasing IABP support lowered mean arterial pressure (74 ± 8 to 71 ± 10 mmHg; P = 0.048) and increased diastolic pressure (43 ± 10 to 53 ± 9 mmHg; P = 0.0002). However, at the level of the microcirculation we found an increase of PVD of small vessels <20 μm (5.47 ± 1.76 to 6.63 ± 1.90; P = 0.0039). PVD for vessels >20 μm and MFI for both small and large vessels were unaltered. During the procedure global oxygenation parameters (ScvO2/SvO2) remained unchanged.ConclusionsIn patients deemed ready for discontinuing IABP support according to current practice, SDF imaging showed an increase of microcirculatory flow of small vessels after ceasing IABP therapy. This observation may indicate that IABP impairs microvascular perfusion in recovered patients, although this warrants confirmation.

Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine

Using palladium-porphyrin quenching of phosphorescence, we investigated the influence of diaspirin cross-linked hemoglobin (DCLHb) on gut microvascular oxygen pressure (microPO2) in anesthetized pigs. Values of gut microPO2 were studied in correlation with regional intestinal as well as global metabolic and circulatory parameters. A controlled hemorrhagic shock (blood withdrawal of 40 mL/kg) was followed by resuscitation with either a combination of lactated Ringers solution (75 mL/kg) and modified gelatin (15 mL/kg)(lactR/Gel) or 10% DCLHb (5 mL/kg). After resuscitation, gut microPO2 was similarly improved in the lactR/Gel group (from 25 +/- 10 mm Hg to 53 +/- 8 mm Hg) and the DCLHb group (from 23 +/- 9 mm Hg to 46 +/- 6 mm Hg), which was associated with increased gut oxygen delivery. However, the improvement after resuscitation with DCLHb was sustained for longer periods of time (75 vs 30 min). Mesenteric venous PO2 was increased after resuscitation with lactated Ringers solution and modified gelatin but not with DCLHb, which was associated with an increased gut oxygen consumption in the latter group. We conclude that measurement of microPO2 by the palladium-porphyrin phosphorescence technique revealed DCLHb to be an effective carrier of oxygen to the microcirculation of the gut. Also, this effect can be achieved with a lower volume than is currently used in resuscitation procedures.

Microcirculation follows macrocirculation in heart and gut in the acute phase of hemorrhagic shock and isovolemic autologous whole blood resuscitation in pigs.

BACKGROUND: Disparity between the macro‐ and microcirculation is thought to occur as a result of (micro)vascular dysfunction in some types of shock. Whether this occurs during hemorrhagic shock, however, is unknown. We therefore investigated both macro‐ and microcirculatory variables in the heart as a vital organ and the gut as a nonvital organ. We hypothesized that the microcirculation in the gut would follow the macrocirculation in the acute phase of hemorrhagic shock and isovolemic autologous whole blood resuscitation, but that the microcirculation in the heart would be preserved even under conditions of macrocirculatory depression.

Hemoglobin-based oxygen carrier provides heterogeneous microvascular oxygenation in heart and gut after hemorrhage in pigs

BACKGROUND In this study, the hypothesis was tested that resuscitation with hemoglobin-based oxygen carriers (HBOCs) affects the oxygenation of the microcirculation differently between and within organs. To this end, we tested the influence of the volume of an HBOC on the microcirculatory oxygenation of the heart and the gut serosa and mucosa in a porcine model of hemorrhage. METHODS In anesthetized open-chested pigs (n = 24), a controlled hemorrhage (30 mL/kg over 1 hour) was followed by resuscitation with 10, 20, or 30 mL/kg diaspirin-crosslinked hemoglobin (DCLHb) or isovolemic resuscitation with 30 mL/kg of a 6% hydroxyethyl starch solution (HAES). Measurements included systemic and regional hemodynamic and oxygenation parameters. Microvascular oxygen pressures (microPO2) of the epicardium and the serosa and mucosa of the ileum were measured simultaneously by the palladium-porphyrin phosphorescence technique. Measurements were obtained up to 120 minutes after resuscitation. RESULTS After hemorrhage, a low volume of DCLHb restored both cardiac and intestinal microPO2. Resuscitation of gut microPO2 with a low volume of DCLHb was as effective as isovolemic resuscitation with HAES. Higher volumes of DCLHb did not restore cardiac microPO2, as did isovolemic resuscitation with HAES, but increased gut microPO2 to hyperoxic values, dose-dependently. Effects were similar for the serosal and mucosal microPo2. In contrast to a sustained hypertensive effect after resuscitation with DCLHb, effects of DCLHb on regional oxygenation and hemodynamics were transient. CONCLUSION This study showed that a low volume of DCLHb was effective in resuscitation of the microcirculatory oxygenation of the heart and gut back to control levels. Increasing the volume of DCLHb did not cause an additional increase in heart microPO2, but caused hyperoxic microvascular values in the gut to be attained. It is concluded that microcirculatory monitoring in this way elucidates the regional behavior of oxygen transport to the tissue by HBOCs, whereas systemic variables were ineffective in describing their response.

Direct observation of the human microcirculation during cardiopulmonary bypass: effects of pulsatile perfusion.

OBJECTIVES Possible benefits of pulsatile perfusion during cardiopulmonary bypass often are attributed to enhanced microvascular flow. However, there is no evidence to support this in humans. Therefore, the authors assessed whether pulsatile perfusion alters human microvascular flow. DESIGN A prospective, randomized observational crossover study. SETTING A tertiary cardiothoracic surgery referral center. PARTICIPANTS Sixteen patients undergoing routine cardiopulmonary bypass for cardiac surgery. INTERVENTIONS All patients underwent both pulsatile and nonpulsatile perfusion in random order. MEASUREMENTS AND MAIN RESULTS The authors used sidestream dark-field imaging to record video clips of the sublingual human microcirculation. Perfusion was started either in the pulsatile (n = 8) or the nonpulsatile mode. After 10 minutes, microvascular recordings were made. The perfusion mode was then switched, and after 10 minutes, new microvascular recordings were taken. The authors quantified pulsatile perfusion-generated surplus hemodynamic energy by calculating pulse pressure and energy-equivalent pressure. Microvascular analysis included determination of the perfused vessel density (mean ± standard deviation). This did not differ between nonpulsatile and pulsatile perfusion (6.65 ± 1.39 v 6.83 ± 1.23 mm(-1), p = 0.58, and 2.16 ± 0.64 v 1.96 ± 0.48 mm(-1), p = 0.20 for small and large microvessels, respectively, cutoff diameter = 20 μm). Pulse pressure and energy-equivalent pressure was higher during pulsatile perfusion. However, there was no correlation between the difference in energy-equivalent pressure or pulse pressure and perfused vessel density (r = -0.43, p = 0.13, and r = -0.09, p = 0.76, respectively). CONCLUSION Pulsatile perfusion does not alter human microvascular perfusion using standard equipment in routine cardiac surgery. Changes in pulse pressure or energy-equivalent pressure bear no obvious relationship with microcirculatory parameters.

Microvascular hemodynamics in human hypothermic circulatory arrest and selective antegrade cerebral perfusion.

Objective:The behavior of the human microcirculation in the setting of cardiac arrest is largely unknown. Animal experiments have consistently revealed that global hemodynamics do not necessarily reflect microvascular perfusion. In addition, the time it takes for capillary blood flow to stop after the heart arrests is debated. Estimations range from 50 seconds to 5 mins, but data in humans are lacking. Aortic arch surgery frequently necessitates deep hypothermic circulatory arrest and subsequent selective antegrade cerebral perfusion. To elucidate microvascular behavior surrounding cessation of human circulation, we used sublingual microvascular imaging in this setting. Design:Prospective, observational study. Setting:Operating room of a large tertiary referral center for cardiac surgery. Patients:Seven patients undergoing elective aortic arch repair. Interventions:We used sidestream dark field imaging to study the sublingual microcirculation immediately before circulatory arrest, during circulatory arrest, and immediately after selective antegrade cerebral perfusion. Measurements and Main Results:Results are reported as mean (sd) unless indicated otherwise. Before circulatory arrest, perfused vessel density was 6.41 (1.18) for small (<20 &mgr;m) and 1.57 (0.88) mm−1 for large (>20 &mgr;m) microvessels. Microvascular flow index was a median of 3.0 (interquartile range 3.0–3.0) for both vessel sizes. After circulatory arrest, there was no equilibration of arterial and venous blood pressure before onset of selective antegrade cerebral perfusion after 59 (17) secs (range, 40–80 secs). Flow in small microvessels came to a complete stop after 45 (9) secs (range, 34–57 secs) after transition to circulatory arrest. However, flow in larger microvessels did not completely stop before selective antegrade cerebral perfusion started. Selective antegrade cerebral perfusion restored microvascular flow, reaching precirculatory arrest levels after 45 (27) secs (range, 20–85 secs). Conclusions:In a controlled surgical setting, circulatory arrest in humans induces a complete sublingual small microvessel shutdown within 1 min. However, flow in larger microvessels persists. Selective antegrade cerebral perfusion was able to restore microvascular flow to precirculatory arrest levels within a similar timeframe.

Aortic Cross-Clamping and Reperfusion in Pigs Reduces Microvascular Oxygenation by Altered Systemic and Regional Blood Flow Distribution

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 (&mgr;PO2) was measured in the intestinal serosa and mucosa and the renal cortex, using the Pd-porphyrin phosphorescence technique. Intestinal luminal PCO2 was determined by air tonometry and the serosal microvascular flow by orthogonal polarization spectral imaging. RESULTS: Organ blood flow and renal and intestinal &mgr;PO2 decreased significantly during ACC, whereas the intestinal oxygen extraction and PCO2 gap 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 O2 delivery, serosal &mgr;PO2 (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 PCO2 gap (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 O2 delivery 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.

Electrical Cardioversion for Atrial Fibrillation Improves Microvascular Flow Independent of Blood Pressure Changes

OBJECTIVE This study tested the hypothesis that there is a discrepancy between global hemodynamic parameters and microvascular flow in patients before and after successful elective electrical cardioversion (ECV) for atrial fibrillation (AF). DESIGN Prospective observational study. SETTING Preanesthesia holding area in a teaching hospital. PARTICIPANTS Adult patients who underwent successful elective ECV for AF. INTERVENTIONS ECV. MEASUREMENTS AND MAIN RESULTS Routine measurements of heart rate and noninvasive blood pressure were recorded and the sublingual microcirculation was visualized by sidestream darkfield imaging before and after the conversion of AF to sinus rhythm by elective ECV. The conversion to sinus rhythm significantly improved the microvascular flow index for smaller and larger microvessels. For smaller microvessels, perfused vessel density did not reach significance after conversion to sinus rhythm, whereas the proportion of perfused vessels was significantly larger and indices of heterogeneity for microvascular flow index decreased significantly. No correlation could be identified for the changes in mean blood pressure, perfused vessel density, and microvascular flow index for smaller microvessels. CONCLUSIONS Successful ECV in patients with AF improves indices of sublingual microvascular perfusion. This change has no clear relation to the change in blood pressure and cannot be predicted from it. It may be prudent not to rely solely on global hemodynamic parameters to assess end-organ perfusion in this setting.