Paul W.G. Elbers

Bench-to-bedside review: Mechanisms of critical illness – classifying microcirculatory flow abnormalities in distributive shock

Over 30 years ago Weil and Shubin proposed a re-classification of shock states and identified hypovolemic, cardiogenic, obstructive and distributive shock. The first three categories have in common that they are associated with a fall in cardiac output. Distributive shock, such as occurs during sepsis and septic shock, however, is associated with an abnormal distribution of microvascular blood flow and metabolic distress in the presence of normal or even supranormal levels of cardiac output. This Bench-to-bedside review looks at the recent insights that have been gained into the nature of distributive shock. Its pathophysiology can best be described as a microcirculatory and mitochondrial distress syndrome, where time and therapy form an integral part of the definition. The clinical introduction of new microcirculatory imaging techniques, such as orthogonal polarization spectral and side-stream dark-field imaging, have allowed direct observation of the microcirculation at the bedside. Images of the sublingual microcirculation during septic shock and resuscitation have revealed that the distributive defect of blood flow occurs at the capillary level. In this paper, we classify the different types of heterogeneous flow patterns of microcirculatory abnormalities found during different types of distributive shock. Analysis of these patterns gave a five class classification system to define the types of microcirculatory abnormalities found in different types of distributive shock and indicated that distributive shock occurs in many other clinical conditions than just sepsis and septic shock. It is likely that different mechanisms defined by pathology and treatment underlie these abnormalities observed in the different classes. Functionally, however, they all cause a distributive defect resulting in microcirculatory shunting and regional dysoxia. It is hoped that this classification system will help in the identification of mechanisms underlying these abnormalities and indicate optimal therapies for resuscitating septic and other types of distributive shock.

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.

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.

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.

Imaging the human microcirculation during cardiopulmonary resuscitation in a hypothermic victim of submersion trauma

The microcirculation is essential for delivery of oxygen and nutrients to tissue. However, the human microvascular response to cardiopulmonary resuscitation (CPR) is unknown. We report on the first use of sidestream dark field imaging to assess the human microcirculation during CPR with a mechanical chest compression/decompression device (mCPR). mCPR was able to provide microvascular perfusion. Capillary flow persisted even during brief mCPR interruption. However, indices of microvascular perfusion were low and improved vastly after return of spontaneous circulation. Microvascular perfusion was relatively independent from blood pressure. The microcirculation may be a useful monitor for determining the adequacy of CPR.

Fast-track microcirculation analysis.

The report suggests determining the microvascular flow index (MFI), the perfused vessel density (PVD) and the percentage of perfused vessels (PPV). For the MFI a grid is used dividing the screen into four quadrants, and the vessels are scored according to observed flow: 0 = none, 1 = intermittent, 2 = sluggish, 3 = continuous. For the PVD and the PPV, three equidistant horizontal and vertical lines are drawn and a different score is used: absent, intermittent, present (for details see [1]).

The Impact of a Pulmonary-Artery-Catheter-Based Protocol on Fluid and Catecholamine Administration in Early Sepsis

Objective. The pulmonary artery catheter (PAC) remains topic of debate. Despite abundant data, it is of note that many trials did not incorporate a treatment protocol. Methods. We retrospectively evaluated fluid balances and catecholamine doses in septic patients after the introduction of a PAC-based treatment protocol in comparison to historic controls. Results. 2 × 70 patients were included. The first day the PAC group had a significantly higher positive fluid balance in comparison to controls (6.1 ± 2.6 versus 3.8 ± 2.4 litre, P < 0.001). After 7 days the cumulative fluid balance in the PAC group was significantly lower than in controls (9.4 ± 7.4 versus 13 ± 7.6 litre, P = 0.001). Maximum dose of norepinephrine was significantly higher in the PAC group. Compared to controls this was associated with a significant reduction in ventilator and ICU days. Conclusions. Introduction of a PAC-based treatment protocol in sepsis changed the administration of fluid and vasopressors significantly.

Haemodialysis Impairs the Human Microcirculation Independent from Macrohemodynamic Parameters

Hemodynamic changes during haemodialysis are common. Often these changes are associated with symptoms that are thought to be the result of reduced microcirculatory blood flow and oxygen delivery. The microcirculatory effect of hemodialysis is scarcely researched, though of possible influence on patient outcome. New techniques have become available to visualise and analyse microvascular blood flow. We performed an observational study using Sidestream Dark Field imaging, a microscopic technique using polarised light to visualise erythrocytes passing through sublingual capillaries, to analyse the effect of haemodyalisis on central microvascular blood flow. We showed that there is a substantial impairment of microvascular blood flow and a discrepancy between micro- and macro-vascular parameters.