Effects of Thoracic Epidural Anaesthesia on the Serosal Microcirculation of the Human Small Intestine.

BACKGROUND: The effect of thoracic epidural analgesia (TEA) on splanchnic blood flow during abdominal surgery remains unclear. The purpose of this study was to examine whether the hemodynamic effects of TEA resulted in microcirculatory alterations to the intestinal serosa, which was visualized using incident dark-field (IDF) videomicroscopy. METHODS: An observational cohort study was performed. In 18 patients, the microcirculation of the intestinal serosa was visualized with IDF. Microcirculatory and hemodynamic measurements were performed prior to (T1) and after administering a bolus of levobupivacaine (T2). If correction of blood pressure was indicated, a third measurement was performed (T3). The following microcirculatory parameters were calculated: microvascular flow index, proportion of perfused vessels, perfused vessel density and total vessel density. Data are presented as median [IQR]. RESULTS: Mean arterial pressure decreased from 73 mmHg (68-83) at T1 to 63 mmHg (±11) at T2 (p = 0.001) with a systolic blood pressure of 114 mmHg (98-128) and 87 (81-97), respectively (p = 0.001). The microcirculatory parameters of the bowel serosa, however, were unaltered. In seven patients, blood pressure was corrected to baseline values from a MAP of 56 mmHg (55-57), while microcirculatory parameters remained constant. CONCLUSION: We examined the effects of TEA on the intestinal serosal microcirculation during abdominal surgery using IDF imaging for the first time in patients. Regardless of a marked decrease in hemodynamics, microcirculatory parameters of the bowel serosa were not significantly affected. TRIAL REGISTRY NUMBER: ClinicalTrials.gov identifier NCT02688946.

Can sidestream dark field (SDF) imaging identify subtle microvascular changes of the bowel during colorectal surgery?

BACKGROUND: Recognition of a non-viable bowel during colorectal surgery is a challenging task for surgeons. Identifying the turning point in serosal microcirculatory deterioration leading up to a non-viable bowel is crucial. The aim of the present study was to determine whether sidestream darkfield (SDF) imaging can detect subtle changes in serosal microcirculation of the sigmoid after vascular transection during colorectal surgery. METHODS: A prospective observational clinical study was performed at a single medical centre. All eligible participants underwent laparoscopic sigmoid resection and measurements were taken during the extra-abdominal phase. Microcirculation was measured at the transected bowel and 20 cm proximal to this point. Microcirculatory parameters such as Microvascular Flow Index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD), total vessel density (TVD) and the Heterogeneity Index were determined. Data are presented as median (interquartile range) or mean ± standard deviation. RESULTS: A total of 60 SDF images were acquired for 10 patients. Perfusion parameters and perfused vessel density were significantly lower at the transected bowel compared with the non-transected measurements [MFI 2.29 (1.96-2.63) vs 2.96 (2.73-3.00), p = 0.007; PPV 74% (55-83) vs 94% (86-97), p = 0.007; and PVD 7.61 ± 2.99 mm/mm2 versus 10.67 ± 1.48 mm/mm2, p = 0.009]. Total vessel density was similar between the measurement locations. CONCLUSIONS: SDF imaging can identify changes of the bowel serosal microcirculation. Significantly lower serosal microcirculatory parameters of the vascular transected bowel was seen compared with the non-transected bowel. The ability of SDF imaging to detect subtle differences holds promise for future research on microvascular cut-off values leading to a non-viable bowel.

Sidestream dark field imaging of the serosal microcirculation during gastrointestinal surgery.

AIM: The study aimed to describe the serosal microcirculation of the human bowel using sidestream dark field imaging, a microscopic technique using polarized light to visualize erythrocytes through capillaries. We also compared its feasibility to the current practice of sublingual microcirculatory assessment. METHOD: In 17 patients sidestream dark field measurements were performed during gastrointestinal surgery. Microcirculatory parameters like microvascular flow index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD) and total vessel density (TVD) were determined for every patient, sublingually and on the bowel serosa. RESULTS: Sixty measurements were done on the bowel of which eight (13%) were excluded, five owing to too much bowel peristalsis and three because of pressure artefacts. Image stability was in favour of sublingual measurements [pixel loss per image, bowel 145 (95% CI 126-164) vs sublingual 55 (95% CI 41-68); P < 0.001] and time to acquire a stable image [bowel 96 s (95% CI 63-129) vs. sublingual 46 s (95% CI 29-64); P = 0.013]. No difference in the MFI was observed [bowel 2.9 (interquartile range 2.87-2.95) vs sublingual 3.0 (interquartile range 2.91-3.0); P = 0.081]. There was a difference in the PPV [bowel 95% (95% CI 94-96) vs sublingual 97% (95% CI 97-99); P < 0.001], PVD [bowel 12.9 mm/mm2 (95% CI 11.1-14.8) vs sublingual 17.4 mm/mm2 (95% CI 15.6-19.1); P = 0.003] and the TVD [bowel 13.6 mm/mm2 (95% CI 11.6-15.6) vs sublingual 17.7 mm/mm2 (95% CI 16.0-19.4); P = 0.008]. CONCLUSION: Sidestream dark field imaging is a very promising technique for bowel microcirculatory visualization and assessment. It is comparable to sublingual assessment and the analysis produces a similar outcome with slightly differing anatomical features.

Decontamination of the digestive tract and oropharynx in ICU patients.

BACKGROUND: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting. METHODS: We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in The Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance. RESULTS: A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively. CONCLUSIONS: In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.)

[Wasp and bee stings with serious consequences]. / Wespen- en bijensteken met ernstige gevolgen.

Wasp and bee stings can lead to allergic reactions, anaphylaxis, Kounis syndrome, toxicity, organ failure and, in rare cases, cardiac arrest. In the Netherlands, fatal complications as a result of wasp or bee stings are rare; here we describe three recent severe cases. We diagnosed two patients with anaphylactic shock due to multiple wasp stings, resulting in cardiac arrest and death. Taking the number of stings (> 100) in one of these cases into account, a differential diagnostic consideration was 'exogenic toxic shock'. Considering the severe reaction with fatal outcome in both patients we cannot rule out the existence of indolent mastocytosis. The third patient developed grade 1 anaphylaxis and severe facial swelling, but survived. In this article we describe the pathophysiological background, treatment, diagnostics and desensitisation therapy.

Relative power and sample size analysis on gene expression profiling data.

BACKGROUND: With the increasing number of expression profiling technologies, researchers today are confronted with choosing the technology that has sufficient power with minimal sample size, in order to reduce cost and time. These depend on data variability, partly determined by sample type, preparation and processing. Objective measures that help experimental design, given own pilot data, are thus fundamental. RESULTS: Relative power and sample size analysis were performed on two distinct data sets. The first set consisted of Affymetrix array data derived from a nutrigenomics experiment in which weak, intermediate and strong PPARalpha agonists were administered to wild-type and PPARalpha-null mice. Our analysis confirms the hierarchy of PPARalpha-activating compounds previously reported and the general idea that larger effect sizes positively contribute to the average power of the experiment. A simulation experiment was performed that mimicked the effect sizes seen in the first data set. The relative power was predicted but the estimates were slightly conservative. The second, more challenging, data set describes a microarray platform comparison study using hippocampal deltaC-doublecortin-like kinase transgenic mice that were compared to wild-type mice, which was combined with results from Solexa/Illumina deep sequencing runs. As expected, the choice of technology greatly influences the performance of the experiment. Solexa/Illumina deep sequencing has the highest overall power followed by the microarray platforms Agilent and Affymetrix. Interestingly, Solexa/Illumina deep sequencing displays comparable power across all intensity ranges, in contrast with microarray platforms that have decreased power in the low intensity range due to background noise. This means that deep sequencing technology is especially more powerful in detecting differences in the low intensity range, compared to microarray platforms. CONCLUSION: Power and sample size analysis based on pilot data give valuable information on the performance of the experiment and can thereby guide further decisions on experimental design. Solexa/Illumina deep sequencing is the technology of choice if interest lies in genes expressed in the low-intensity range. Researchers can get guidance on experimental design using our approach on their own pilot data implemented as a BioConductor package, SSPA http://bioconductor.org/packages/release/bioc/html/SSPA.html.

Functional heterogeneity of oxygen supply-consumption ratio in the heart.

In this review, the regional heterogeneity of the oxygen supply-consumption ratio within the heart is discussed. This is an important functional parameter because it determines whether regions within the heart are normoxic or dysoxic. Although the heterogeneity of the supply side of oxygen has been primarily described by flow heterogeneity, the diffusional component of oxygen supply should not be ignored, especially at high resolution (tissue regions << 1 g). Such oxygen diffusion does not seem to take place from arterioles or venules within the heart, but seems to occur between capillaries, in contrast to data recently obtained from other tissues. Oxygen diffusion may even become the primary determinant of oxygen supply during obstructed flow conditions. Studies aimed at modelling regional blood flow and oxygen consumption have demonstrated marked regional heterogeneity of oxygen consumption matched by flow heterogeneity Direct, non-invasive indicators of the balance between oxygen supply and consumption include NADH videofluorimetry (mitochondrial energy state) and microvascular PO2 measurement by the Pd-porphyrin phosphorescence technique. These indicators have shown a relatively homogeneous distribution during physiological conditions supporting the notion of regional matching of oxygen supply with oxygen consumption. NADH videofluorimetry, however, has demonstrated large increases in functional heterogeneity of this ratio in compromised hearts (ischemia, hypoxia, hypertrophy and endotoxemia) with specific areas, referred to as microcirculatory weak units, predisposed to showing the first signs of dysoxia. It has been suggested that these weak units show the largest relative reduction in flow (independent of absolute flow levels) during compromising conditions, with dysoxia initially developing at the venous end of the capillary.

Microvascular oxygen pressure in the pig intestine during haemorrhagic shock and resuscitation.

1. The aim of this study was to investigate the relation between microvascular and venous oxygen pressures during haemorrhagic shock and resuscitation in the pig intestine. To this end microvascular PO2 (microPO2) was measured by quenching of Pd-porphyrin phosphorescence by oxygen and validated for the intestines. In addition, mesenteric venous blood gasses, blood flow, ilial CO2 production and global haemodynamics were also measured. 2. In one group (n = 11), moderate shock was induced by withdrawal of 40% of the circulating blood volume. Seven of these animals were resuscitated with a crystalloid solution and four with the withdrawn blood. In a second group of three animals, a more severe shock was induced by withdrawal of 50% of the circulating blood volume; these animals were not resuscitated. 3. Baseline mesenteric venous PO2 and microPO2 values were similar (60 +/- 9 and 60 +/- 11 mmHg, respectively). During moderate shock, microPO2 dropped significantly below mesenteric venous PO2 (26 +/- 10 versus 35 +/- 8 mmHg). After resuscitation with crystalloid solution, microPO2 and mesenteric venous PO2 rose to 44 +/- 9 and 44 +/- 6 mmHg, respectively. In the group that received the withdrawn blood, values were 41 +/- 9 and 53 +/- 12 mmHg, respectively. Severe shock resulted in a drop in the mesenteric venous PO2 (n = 3) to a value similar to that seen in the moderate shock group, but the gut microPO2 dropped to a much lower value than that of the moderate shock group (15 +/- 5 versus 26 +/- 10 mmHg). 4. The results indicate that the oxygenation of the microcirculation of the gut can become lower than the venous PO2 under conditions of haemorrhagic shock.

Systemic haemodynamics and oxygenation during haemodilution in children.

Transfusion of homologous blood should be avoided when possible, and one technique that diminishes perioperative requirement for donor blood is haemodilution. In children its effects on systemic haemodynamics and systemic oxygenation have not been reported. Six children aged 4-12 yr were anaesthetised for major surgery and blood was withdrawn to reduce packed cell volume to 25%. Cardiac index increased from 3.1 (SD 0.5) L min-1 m-2 at baseline to 4.4 (0.5) L min-1 m-2 at the end of surgery, when packed cell volume was 16 (1)%; this change, compensating for the decline in oxygen carrying capacity, was associated with a fall in systemic vascular resistance and a rise in stroke volume. Oxygen extraction from haemoglobin rose from 0.22 (0.05) to 0.33 (0.06). Perioperative blood loss was 40% of circulating blood volume; however, owing to reinfusion of autologous blood (and use of a cell saver in three patients), the haemoglobin one day after operation was only 19% lower than preoperatively (9.9 [1.5] vs 12.5 [2.5] g/dL). In this study, children seemed at least as able as adults to compensate for the effects of haemodilution, which allowed major surgery without transfusion of homologous blood.

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 Ringer's 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 Ringer's 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.