Peter Goedhart

How to evaluate the microcirculation: report of a round table conference

IntroductionMicrovascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis.MethodsThe participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology.ResultsThe participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 μm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future.ConclusionWe proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index.

Blood transfusions recruit the microcirculation during cardiac surgery.

BACKGROUND: Perioperative red blood cell transfusions are commonly used in patients undergoing cardiac surgery to correct anemia caused by blood loss and hemodilution associated with cardiopulmonary bypass circulation. The aim of this investigation was to test the hypothesis that blood transfusion has beneficial effects on sublingual microcirculatory density, perfusion, and oxygenation. To this end, sidestream dark field (SDF) imaging and spectrophotometry were applied sublingually before and after blood transfusion during cardiac surgery.

Assessment of tissue oxygen saturation during a vascular occlusion test using near-infrared spectroscopy: the role of probe spacing and measurement site studied in healthy volunteers

IntroductionTo assess potential metabolic and microcirculatory alterations in critically ill patients, near-infrared spectroscopy (NIRS) has been used, in combination with a vascular occlusion test (VOT), for the non-invasive measurement of tissue oxygen saturation (StO2), oxygen consumption, and microvascular reperfusion and reactivity. The methodologies for assessing StO2 during a VOT, however, are very inconsistent in the literature and, consequently, results vary from study to study, making data comparison difficult and potentially inadequate. Two major aspects concerning the inconsistent methodology are measurement site and probe spacing. To address these issues, we investigated the effects of probe spacing and measurement site using 15 mm and 25 mm probe spacings on the thenar and the forearm in healthy volunteers and quantified baseline, ischemic, reperfusion, and hyperemic VOT-derived StO2 variables.MethodsStO2 was non-invasively measured in the forearm and thenar in eight healthy volunteers during 3-minute VOTs using two InSpectra tissue spectrometers equipped with a 15 mm probe or a 25 mm probe. VOT-derived StO2 traces were analyzed for base-line, ischemic, reperfusion, and hyperemic parameters. Data were categorized into four groups: 15 mm probe on the forearm (F15 mm), 25 mm probe on the forearm (F25 mm), 15 mm probe on the thenar (T15 mm), and 25 mm probe on the thenar (T25 mm).ResultsAlthough not apparent at baseline, probe spacing and measurement site significantly influenced VOT-derived StO2 variables. For F15 mm, F25 mm, T15 mm, and T25 mm, StO2 ownslope was -6.4 ± 1.7%/minute, -10.0 ± 3.2%/minute, -12.5 ± 3.0%/minute, and -36.7 ± 4.6%/minute, respectively. StO2 upslope was 105 ± 34%/minute, 158 ± 55%/minute, 226 ± 41%/minute, and 713 ± 101%/minute, and the area under the hyperemic curve was 7.4 ± 3.8%·minute, 10.1 ± 4.9%·minute, 12.6 ± 4.4%·minute, and 21.2 ± 2.7%·minute in these groups, respectively. Furthermore, the StO2 parameters of the hyperemic phase of the VOT, such as the area under the curve, significantly correlated to the minimum StO2 during ischemia.ConclusionsNIRS measurements in combination with a VOT are measurement site-dependent and probe-dependent. Whether this dependence is anatomy-, physiology-, or perhaps technology-related remains to be elucidated. Our study also indicated that reactive hyperemia depends on the extent of ischemic insult.

Distinct alterations in sublingual microcirculatory blood flow and hemoglobin oxygenation in on-pump and off-pump coronary artery bypass graft surgery

OBJECTIVE The authors hypothesized that cardiopulmonary bypass (CPB) (on-pump) is associated with more severe changes in the microcirculatory blood flow and tissue oxygenation as compared with off-pump coronary artery bypass surgery. DESIGN An observational study. SETTING A university hospital and teaching hospital. PARTICIPANTS Patients undergoing on-pump (n = 24) or off-pump (n = 24) cardiac surgery. INTERVENTIONS Microcirculatory measurements were performed before CPB and 10 minutes after the switch to CPB or before and during cardiac luxation in off-pump patients. MEASUREMENTS AND MAIN RESULTS Sublingual microcirculatory perfusion was investigated using side-stream dark field imaging, and sublingual microcirculatory oxygenation was measured using reflectance spectrophotometry. Conversion to CPB resulted in an increase in cardiac output from 4.0 ± 0.2 to 4.8 ± 0.3 L/min (p < 0.01) and a 40% reduction in arterial hemoglobin concentration. Cardiopulmonary bypass was associated with an increase in venular blood velocity from 349 ± 201 μm/s to 563 ± 227 μm/s (p < 0.05), a reduction in functional capillary density of 43%, and an increase in hemoglobin oxygenation of the red blood cells in the remaining filled capillaries from 47.2% ± 6.1% to 59.7% ± 5.2% (p < 0.001). The decrease in cardiac output during cardiac luxation from 4.5 ± 1.7 to 1.8 ± 0.8 L/min (p < 0.01) without hemoglobin changes was associated with a complete halt of capillary blood flow and a reduction in maximum capillary blood velocity from 895 ± 209 to 396 ± 178 μm/s (p < 0.01). The functional capillary density remained unchanged, whereas the hemoglobin oxygenation declined from 64.2% ± 9.1% to 48.6% ± 8.7% (p < 0.01). CONCLUSIONS On-pump and off-pump cardiac surgery are associated with distinct alterations in sublingual microcirculatory perfusion and hemoglobin oxygenation. Although on-pump surgery results in a fall out of capillaries resulting in decreased oxygen extraction, off-pump surgery results in a cessation of flow during luxation resulting in decreased convection of oxygen transport.

Changes in sublingual microcirculatory flow index and vessel density on ascent to altitude

We hypothesized that ascent to altitude would result in reduced sublingual microcirculatory flow index (MFI) and increased vessel density. Twenty‐four subjects were studied using sidestream dark‐field imaging, as they ascended to 5300 m; one cohort remained at this altitude (n= 10), while another ascended higher (maximum 8848 m; n= 14). The MFI, vessel density and grid crossings (GX; an alternative density measure) were calculated. Total study length was 71 days; images were recorded at sea level (SL), Namche Bazaar (3500 m), Everest base camp (5300 m), the Western Cwm (6400 m), South Col (7950 m) and departure from Everest base camp (5300 m; 5300 m‐b). Peripheral oxygen saturation  , heart rate and blood pressure were also recorded. Compared with SL, altitude resulted in reduced sublingual MFI in small (<25 μm; P < 0.0001) and medium vessels (26–50 μm; P= 0.006). The greatest reduction in MFI from SL was seen at 5300 m‐b; from 2.8 to 2.5 in small vessels and from 2.9 to 2.4 in medium‐sized vessels. The density of vessels <25 μm did not change during ascent, but those >25 μm rose from 1.68 (± 0.43) mm mm−2 at SL to 2.27 (± 0.57) mm mm−2 at 5300 m‐b (P= 0.005); GX increased at all altitudes (P < 0.001). The reduction in MFI was greater in climbers than in those who remained at 5300 m in small and medium‐sized vessels (P= 0.017 and P= 0.002, respectively). At 7950 m, administration of supplemental oxygen resulted in a further reduction of MFI and increase in vessel density. Thus, MFI was reduced whilst GX increased in the sublingual mucosa with prolonged exposure to hypoxia and was exaggerated in those exposed to extreme altitude.

Direct observation of human microcirculation during decompressive craniectomy after stroke.

Objectives:Most knowledge related to the pathophysiology of microcirculation in ischemic stroke comes from experimental research. Unfortunately, data on microcirculation in the human brain are limited, partially as a result of the lack of appropriate investigational techniques. The objective of our study was to test the hypothesis that cortical microcirculatory alterations in the brain, in terms of blood flow and vessel density, occur in patients with stroke who require surgical decompression compared with a control group. Design:Prospective and observational study. Setting:Third-level university hospital. Patients:Six patients who had undergone decompressive surgery as a result of a space-occupying hemispheric infarction. These patients were compared with five patients who had undergone craniotomy for a disease not affecting the cortex. Interventions:Cortical microcirculation in the brain was directly observed using sidestream dark-field imaging. All images were analyzed offline. Measurements and Main Results:In patients with stroke with a space-occupying hemispheric infarction, 18 good-quality movie images were compared with 25 control group images. In the control group, cortical vessels showed a continuous flow in small, medium, and large vessels compared with patients with stroke who presented intermittent or no flow in all vessels. The proportion of perfused vessels was near 100% in control subjects and 63.44% in patients with stroke. The perfused vessel density index was also higher in control subjects (6.16 1/mm; interquartile range, 5.65–7.56) than in patients with stroke (2.77 1/mm; interquartile range, 1.75–3.86). Conclusion:Sidestream dark-field imaging allowed direct visualization of cerebral microcirculatory alterations in the operating room. This technique allowed the documentation of a significant blood flow reduction in the cortical microvascular and a decreased vascular density in patients with stroke compared with control subjects.

Effects of 1400W and/or nitroglycerin on renal oxygenation and kidney function during endotoxaemia in anaesthetized rats

1 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. 2 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 Po2 (µPo2) were recorded continuously. Furthermore, creatinine clearance, plasma NOx (nitrate + nitrite + S‐nitrosothiols) levels and the expression of iNOS mRNA were measured. 3 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 µPo2 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 µPo2 or creatinine clearance over standard fluid resuscitation. The application of 1400W+NTG significantly reduced plasma NOx levels compared with fluid resuscitation and NTG alone. 4 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.

Clinically Relevant Differences in Accuracy of Enteral Nutrition Feeding Pump Systems

BACKGROUND There are clinically relevant discrepancies between prescribed volumes and delivered volumes of enteral nutrition (EN) in intensive care unit (ICU) patients. Next to EN-protocol violations due to insufficient care, we hypothesized technical factors to be responsible for this deficit. The aim of this study was to determine the accuracy of EN feeding pump systems frequently used in the ICU. METHODS Thirteen commercially available EN feeding pumps with their own delivery systems were tested in 12 sessions with different EN feeding tubes and EN formulas in a laboratory setting. The reproducibility of the measurements was determined for the 8 best performing EN feeding pump systems. RESULTS There were clinically important differences between prescribed volumes and delivered volumes of EN in the tested EN feeding pump systems. The deficit in volume ranged from +66 mL (surplus of 66 mL) to -271 mL (deficit of 271 mL) per 24 hours (14% of prescribed volume). Viscosity of test fluids (water/EN feeding formulas) and resistance of test tubes had no influence on the delivered volume by the tested EN feeding pump systems, because differences between prescribed volumes and delivered volumes were consistently found for each system while varying these test settings. CONCLUSIONS Differences between prescribed and delivered EN volumes are caused by the function and construction of EN feeding pump systems. To improve nutrition therapy, the flow rate has to be adjusted or the best-performing EN feeding pump has to be purchased.

Cardiac displacement during off-pump coronary artery bypass grafting surgery: effect on sublingual microcirculation and cerebral oxygenation

Cardiac displacement during off-pump coronary artery bypass (OPCAB) surgery causes a fall in cardiac output. Here, we investigate how this drop in systemic perfusion is transferred to the oxygenation of sublingual and cerebral tissue. Sublingual microcirculatory perfusion or microcirculatory hemoglobin oxygen saturation (μHbSO(2)) measurements were performed using sidestream dark-field imaging and reflectance spectrophotometry, respectively (both n = 12). The cerebral tissue oxygenation index was measured by near-infrared spectrophotometry (n = 12). Cardiac output was calculated by pulse contour analysis of arterial pressure. Cardiac displacement reduced the cardiac output from 4.3 ± 0.8 to 1.2 ± 0.3 l/min (P < 0.05), paralleled by a decrease in μHbSO(2) from 64.2 ± 9.1 to 48.6 ± 8.7% (P < 0.01). Cardiac displacement did not change functional capillary density, while red blood cell velocity decreased from 895 ± 209 to 396 ± 178 μm/s (P<0.01). Cerebral tissue oxygenation index decreased from 69.5 ± 4.0 to 57.4 ± 8.5% (P<0.01) during cardiac displacement. After repositioning of the heart, all the values returned to baseline. Our data suggest that systemic hemodynamic alterations during cardiac displacement in OPCAB surgery reduce sublingual and cerebral tissue oxygenation. These findings are particularly important for patients at risk for the consequences of cerebral ischemia.

Red blood cell storage increases hypoxia-induced nitric oxide bioavailability and methemoglobin formation in vitro and in vivo

In this study we investigated whether storage of red blood cells (RBCs) leads to alterations in nitrite reductase activity, hence in altered hypoxia‐induced nitric oxide (NO) bioavailability and methemoglobin formation.