Improved viscosity modeling in patients with type 2 diabetes mellitus by accounting for enhanced red blood cell aggregation tendency.

AIMS: Distorted wall shear stress (WSS) in patients with type 2 diabetes mellitus (T2DM) may be partly explained by an altered red blood cell aggregation tendency (RAT) on viscosity at low shear rate (SR). The present study evaluates viscosity modeling by implementation of hematocrit and RAT in patients with and without T2DM (non-T2DM). METHODS: A Couette viscometer and LORCA aggregometer provided viscosity and RAT on 6 shear rates in 55 patients (46-78 yrs, 66% male, T2DM: n = 28), following informed consent. Using a K-fold cross-validation, two linear mixed models predicted by SR and Hct and by SR, Hct and RAT were compared. RESULTS: In non-T2DM modeling was improved in relatively low RATs (48%, p = 1.0 x 10-11) and became worse in relatively high RATs (-18%, p = 0.019). In T2DM the opposite was observed, as modeling became worse in relatively low RATs (-16%, p = 0.001) but was improved in relatively high RATs (22%, p = 0.022). CONCLUSIONS: In addition to confirming previous research, major differences in modeling improvement between T2DM and non-T2DM were found. Especially patients with T2DM, a high RAT and often high viscosity at low SR benefit from a more accurate viscosity modeling. Further studies should evaluate how these findings affect WSS in these patients.

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.

INTRODUCTION: To 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. METHODS: StO2 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). RESULTS: Although 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. CONCLUSIONS: NIRS 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.

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 1400 W (3 mg/kg per h after a 3 mg/kg bolus) or both. Systemic haemodynamics and renal microvascular Po2 (µPo(2)) were recorded continuously. Furthermore, creatinine clearance, plasma NO(x) (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 NO(x) levels and renal iNOS expression. Renal µPo2 deteriorated gradually during endotoxaemia and there was a significant decrease in renal O(2) delivery and consumption. Manipulation of NO levels had no beneficial effect on systemic haemodynamics, renal µPo(2) or creatinine clearance over standard fluid resuscitation. The application of 1400 W+NTG significantly reduced plasma NO(x) 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.

Normal sublingual microcirculation during painful crisis in sickle cell disease.

Obstruction of the microcirculation is the most important cause of painful crisis in sickle cell disease (SCD). Extensive microvascular obstruction has been observed in mouse models of SCD. A technique to determine the extent of the microcirculatory obstructions in humans may be helpful in the clinical setting and for research purposes. Therefore, we measured sublingual microcirculation longitudinally in patients with SCD admitted with painful crisis. Sublingual microcirculation was recorded with side-stream darkfield (SDF) imaging and semi-quantified with a microvascular flow index (MFI) on a range from 0 to 4 (arbitrary units; from 0 (no flow) to 4 (hyperdynamic flow)). Thirteen consecutive adult sickle cell patients admitted with painful crises were included and provided 47 measurements of MFI in 14 episodes of painful crisis. Seven patients provided baseline measurements and seven healthy controls were studied. The mean (+/-standard error of the mean) MFI during painful crisis was 2.6+/-0.1 and did not change during the painful crisis. The mean MFI of patients with SCD during steady state (2.7+/-0.1) and the mean MFI of the controls (2.7+/-0.1) were not different from the mean MFI during painful crisis. During painful crisis irregular microvascular perfusion, expressed by the distribution width of the microvascular blood flow velocity, correlated negatively (r=-0.484; P=0.002) with hemoglobin concentration. We conclude that sublingual microcirculatory blood flow velocity is not disturbed in sickle cell patients during painful crisis.

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.