The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: Protective effect of caffeic acid phenethyl ester

The aim of this experimental study was to investigate the possible role of nitric oxide (NO) levels and activity of adenosine deaminase (ADA) in the pathogenesis of methotrexate (MTX)-induced neurotoxicity, to demonstrate the effect of caffeic acid phenethyl ester (CAPE), the potent antioxidant, in decreasing the toxicity. A total of 19 adult male rats were divided into three experimental groups, as follows: group I, control group; group II, MTX-treatcd group; group III, MTX+CAPE-treated group. In the second day of experiment, MTX was administered intraperitoneally (i.p.) with a single dose of 20 mg/kg to group II and group III. CAPE was administered i.p. with a dose of 10 mu mol/kg once daily for 7 days to group III. Histopathological findings of the inflammatory reaction were observed in spinal cord of MTX administered rats, compared with control rats. All parameters of: inflammatory reaction were significantly decreased in MTX plus CAPE administered rats, compared with MTX administered rats. The injection of MTX caused significant increase in the activity of ADA and in levels NO levels in spinal cord of rats (p = 0.007 and p = 0.0001, respectively). Co-treatment with CAPE caused a significant decrease in activity of ADA and the levels of NO in spinal cord (p = 0.024 and p=0.0001, respectively). Study indicate that NO and ADA may play ail important role in the pathogenesis of MTX-induced oxidative spinal cord damage. CAPE may have protective aspects in this process by antioxidant and anti-inflammatory effect and it will become a promising drug in the prevention Of undesired side effect of MTX. (C) 2005 Elsevier Ireland Ltd. All rights reserved

Recruitment of sublingual microcirculation using handheld incident dark field imaging as a routine measurement tool during the postoperative de-escalation phase—a pilot study in post ICU cardiac surgery patients

Abstract Background Management of tissue perfusion following cardiac surgery is a challenging task where common clinical parameters do not reflect microcirculatory dysfunction. Heterogeneity in blood flow perfusion and abnormalities in capillary density characterize microcirculatory dysfunction. The restoration of a normal microcirculation may become a novel target for therapy in the future in addition to macrocirculatory parameters. The aim of this study is to determine how the sublingual microcirculatory parameters vary at the bedside in post-cardiac surgery patients which underwent diuretic therapy to correct fluid overload. Methods In this prospective observational pilot study, video clips of sublingual microcirculation in post-cardiac surgery patients receiving furosemide and/or spironolactone to achieve normal fluid balance were recorded using Cytocam-IDF imaging. Data was obtained on the first (T0), second (T1), and third (T2) day after the patients left the intensive care unit (ICU). Measurements were analyzed off-line to obtain the following microcirculatory parameters: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), and perfused vessel density (PVD). Macrocirculatory parameters and body weight were also collected at these time points. Results Ninety measurements were performed in ten post ICU cardiac surgery patients. Thirteen measurements were excluded due to quality reasons; these excluded measurements were spread across the patients and time points, and there was no loss of patients or time points. An increase in TVD was observed from T0 to T1 (20 ± 2.7 to 24 ± 3.2 mm/mm2; p = 0.0410) and from T0 to T2 (20 ± 2.7 to 26 ± 3.3 mm/mm2; p = 0.0005). An increase in PVD was present from T0 to T1 (19 ± 2.3 to 24 ± 3.5 mm/mm2; p = 0.0072) and from T0 to T2 (19 ± 2.3 to 26 ± 3.4 mm/mm2, p = 0.0008). Fluid overload was assessed through a positive cumulative fluid balance on the day of ICU discharge. Conclusions Cytocam-IDF imaging to monitor microcirculation as a daily parameter is feasible and could become a valuable tool to non-invasively assess the tissue oxygenation at the bedside. An increase in TVD and PVD (functional capillary density) indicated the recruitment of the sublingual microcirculation in patients with diuretic therapy. Future research is needed to prove the correlation between the recruitment of the sublingual microcirculation and the de-escalation phase of the fluid management

Identification and quantification of human microcirculatory leukocytes using handheld video microscopes at the bedside

Leukocyte recruitment and adhesion to the endothelium are hallmarks of systemic inflammation that manifest in a wide range of diseases. At present, no method is available to directly measure leukocyte kinetics at the bedside. In this study, we validate a new method to identify and quantify microcirculatory leukocytes observed by handheld vital microscopy (HVM) using space-time diagram (STD) analysis. Video clips (n 59) containing one capillary-postcapillary venule unit where leukocytes could be observed emanating from a capillary into a venule in cardiac surgery patients (n 20) were included. STD analysis and manual counting were used to quantify the number of leukocytes (total, rolling, and nonrolling). Pearson’s correlation and Bland-Altman analysis were used to determine agreement between the STDs and manual counting. For reproducibility, intra- and interobserver coefficients of variation (CVs) were assessed. Leukocyte (rolling and nonrolling) and red blood cell velocities were assessed. The STDs and manual counting procedures for the quantification of rolling leukocytes showed good agreement (r 0.8197, P 0.0001), with a Bland-Altman analysis mean difference of 0.0 (6.56; 6.56). The overall intraobserver CV for the STD method was 1.5%. The overall interobserver CVs for the STD and the manual method were 5.6% and 9.4%, respectively. The nonrolling velocity was significantly higher than the rolling velocity (812 519 m/s vs. 201 149 m/s, P 0.001). STD results agreed with the manual counting procedure results, had a better reproducibility, and could assess the leukocyte velocity. STD analysis using bedside HVM imaging presented a new methodology for quantifying leukocyte kinetics and functions in the microcirculation. NEW & NOTEWORTHY In this study, we introduce space-time diagram analysis of sublingual microcirculation imaging using handheld vital microscopy to identify and quantify the presence and kinetics of human microcirculatory leukocytes. We validated the methodology by choosing anatomical units consisting of a capillary connected to a venule, which allowed precise identification of leukocytes

Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study

The demographic development suggests a dramatic growth in the number of elderly patients undergoing surgery in Europe. Most red blood cell transfusions (RBCT) are administered to older people, but little is known about perioperative transfusion practices in this population. In this secondary analysis of the prospective observational multicentre European Transfusion Practice and Outcome Study (ETPOS), we specifically evaluated intraoperative transfusion practices and the related outcomes of 3149 patients aged 65 years and older. Enrolled patients underwent elective surgery in 123 European hospitals, received at least one RBCT intraoperatively and were followed up for 30 days maximum. The mean haemoglobin value at the beginning of surgery was 108 (21) g/l, 84 (15) g/l before transfusion and 101 (16) g/l at the end of surgery. A median of 2 [1–2] units of RBCT were administered. Mostly, more than one transfusion trigger was present, with physiological triggers being preeminent. We revealed a descriptive association between each intraoperatively administered RBCT and mortality and discharge respectively, within the first 10 postoperative days but not thereafter. In our unadjusted model the hazard ratio (HR) for mortality was 1.11 (95% CI: 1.08–1.15) and the HR for discharge was 0.78 (95% CI: 0.74–0.83). After adjustment for several variables, such as age, preoperative haemoglobin and blood loss, the HR for mortality was 1.10 (95% CI: 1.05–1.15) and HR for discharge was 0.82 (95% CI: 0.78–0.87). Preoperative anaemia in European elderly surgical patients is undertreated. Various triggers seem to support the decision for RBCT. A closer monitoring of elderly patients receiving intraoperative RBCT for the first 10 postoperative days might be justifiable. Further research on the causal relationship between RBCT and outcomes and on optimal transfusion strategies in the elderly population is warranted. A thorough analysis of different time periods within the first 30 postoperative days is recommended

Intraoperative transfusion practices in Europe

© 2016 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.Background: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl-1 and increased to 9.8 (1.8) g dl-1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusions: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl-1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold