Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP): an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients

Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis

Background: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. Methods: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). Conclusions: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels.This study was supported in part by an unrestricted grant from the local hospital fund, Medical Center Leeuwarden, Leeuwarden, The Netherland

Microvascular dysfunction in the surgical patient

Purpose of review This review aims to describe recent research on perioperative microvascular alterations, with an emphasis on direct visualization of the human microcirculation. Recent findings Despite systemic haemodynamic optimization, perioperative complications are still occurring. In surgery, recent studies on both direct visualization of the microcirculation and indirect quantification of organ perfusion revealed that both the surgical procedure itself and perioperative interventions like anaesthesia, cardiopulmonary bypass, vasoactive drugs and fluid therapy may influence organ perfusion at the microvascular level. As in sepsis and heart failure, these perioperative microcirculatory abnormalities were associated with prognosis. However, whether these microcirculatory alterations are culprit or bystander in the process of developing perioperative complications remains to be established. Summary Recent research has elucidated the incidence of perioperative microvascular alterations, as well as its association with prognosis. Future research should further unravel the fascinating and complex interplay between the microcirculation and perioperative intervention

Blood urea nitrogen (BUN) independently predicts mortality in critically ill patients admitted to ICU: A multicenter study

BACKGROUND AND PURPOSE: The Microcirculatory Shock Occurrence in Acutely Ill Patients (micro-SOAP) study investigated associations of microcirculation and mortality. Risk stratification in critically ill patients is of utmost interest. Established score such as APACHE2 (Acute Physiology And Chronic Health Evaluation 2) are relatively complex and might therefore be of limited use. Blood urea nitrogen (BUN) was described to be associated with mortality in various diseases. We therefore aimed (i) to evaluate BUN for prediction of mortality in a cohort of critically ill patients and (ii) to investigate associations of BUN with microcirculation. METHODS: 412 patients were included in our post-hoc analysis of the prospective multicenter microSOAP study. Assesment of the sublingual microcirculation (Sidestream Dark Field (SDF) imaging) and collection of laboratory values were performed on the same day in this point prevalence study. Evaluation of associations with mortality was done by logistic regression analysis. An optimal BUN cut-off was calculated by means of the Youden Index. RESULTS: Median BUN was 9.0mmol/L. BUN was associated with in-hospital-mortality in a logistic regression analysis (HR 1.03; 95% CI 1.01-1.05; p90/min), lactate above 1.5mmol/L, age above 80 years; HR 2.43 95% CI 1.50-3.92; p<0.001). Parameters of microvascular perfusion were associated neither with BUN nor mortality. CONCLUSIONS: BUN is associated with hospital mortality and a combination of BUN and clinical signs might constitute a powerful but easy-to-use tool for risk stratification in critically ill patients and help improve their outcome. BUN was not associated with parameters of microcirculation which were not associated with mortality

Microcirculatory perfusion and vascular reactivity are altered in post cardiac arrest patients, irrespective of target temperature management to 33 °C vs 36 °C

In previous reports both microcirculatory alterations and impaired vascular reactivity have been described in post cardiac arrest patients treated with mild therapeutic hypothermia. As of now it is unknown whether these alterations are related to the temperature management or to the cardiac arrest itself. Aim of the present study was to investigate the potential difference in microcirculatory alterations and vascular reactivity in comatose patients after out of hospital cardiac arrest treated with target temperature management of 33 °C (TTM33) in comparison to patients treated with 36 °C (TTM36). Our study was designed as a predefined substudy of the open label randomized controlled TTM trial in 2 Dutch mixed ICU's. Sublingual microvascular flow index (MFI) was assessed by Side Stream Darkfield imaging and vascular reactivity at the thenar region of the hand by near infrared spectroscopy. Variables, including systemic hemodynamics were recorded at start study (T1), after 12h (T2) and after 24h (T3). 22 patients were included, 13 in TTM33 and 9 in TTM36. At T1 MFI between groups did not differ significantly (1.08 [0.4-1.9] versus 1.67 [0.7-2.4] respectively, p = 0.59). The difference between groups remained insignificant over time. At T1 tissue oxygenation (StO2) was significantly lower in TTM36 in comparison to TTM33: (44.6 ± 15.8 versus 58.9 ± 13.5, p = 0.03). Over time this difference between groups disappeared. However, vascular reactivity, expressed as the descending and ascending slope of StO2 after a standardized ischemic occlusion test was similar between groups. In this relatively small sample size study microcirculatory blood flow and vascular reactivity did not differ nor change between TTM33 and TTM3

Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp substrates. To clarify whether Pgp is involved in the sensitizing effect of celecoxib, we investigated in vivo whether celecoxib is a substrate of Pgp and whether it can affect the efflux activity of the pump. Methods: In control rats and in rats treated with the Pgp modulator cyclosporin A (CsA), cerebral accumulation of radiolabeled [C-11] celecoxib was investigated by ex vivo biodistribution and micro-positron emission tomography imaging. In addition, the effect of unlabeled celecoxib and CsA (positive control) on the cerebral uptake of the Pgp substrate [C-11]verapamil was studied. Results: [C-11]Celecoxib uptake in rat brain was relatively high and homogeneously distributed. Treatment of rats with CsA only marginally increased cerebral tracer uptake, which is most likely due to reduced tracer clearance from plasma. [C-11]Verapamil brain uptake was more than 10-fold higher after treatment with CsA. In contrast, a high dose of celecoxib increased cerebral [C-11]verapamil uptake only twofold, which was accompanied by a similar increase in tracer concentration in plasma. Conclusions: This study shows that celecoxib is not a substrate of Pgp and does not substantially affect the Pgp-mediated efflux of [C-11] verapamil. Therefore, celecoxib-induced augmentation of the efficacy of chemotherapeutic and neurotropic drugs must be due to another mechanism than modulation of Pgp-mediated drug efflux. (C) 2008 Elsevier Inc. All rights reserved

International study on microcirculatory shock occurrence in acutely Ill patients

Objectives: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. Design: Multicenter observational point prevalence study. Setting: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. Patients: A heterogeneous ICU population consisting of 501 patients. Interventions: None. Measurements and Main Results: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index ( 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. Conclusions: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death

International Study on Microcirculatory Shock Occurrence in Acutely Ill Patients

Objectives: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. the prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables.Design: Multicenter observational point prevalence study.Setting: the Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide.Patients: A heterogeneous ICU population consisting of 501 patients.Interventions: None.Measurements and Main Results: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index ( 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. in reference to microvascular flow index, a significant interaction was observed with tachycardia. in patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients.Conclusions: in a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.Erasmus MC Univ Med Ctr, Dept Intens Care Adults, Rotterdam, NetherlandsMed Ctr Leeuwarden, Dept Intens Care, Leeuwarden, NetherlandsUniv Politecn Marche, Dept Biomed Sci & Publ Hlth, Ancona, ItalyServ Terapia Intens Sanatorio Otamendi & Miroli, Buenos Aires, DF, ArgentinaBeth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USABarts & London Queen Marys Sch Med & Dent, London, EnglandUniversidade Federal de São Paulo, São Paulo, BrazilUniv Klinikum RWTH Aachen, Klin Anesthesiol, Aachen, GermanyKosuyolu Univ, K Kosuyolu High Specialty Educ & Res Hosp, Istanbul, TurkeyLithuanian Univ Hlth Sci, Dept Intens Care, Kaunas, LithuaniaCooper Univ Hosp, Sect Cardiol, Camden, NJ USAUniv Basel Hosp, Med Intens Care Unit, CH-4031 Basel, SwitzerlandSt Antonius Hosp, Dept Anesthesiol Intens Care & Pain Manag, Nieuwegein, NetherlandsOnze Lieve Vrouw Hosp, Dept Intens Care, Amsterdam, NetherlandsSt Louis Univ Hosp, Mercy Hosp St Louis, St Louis, MO USAUniv Plymouth, Peninsula Sch Med, Derriford Hosp, Plymouth PL4 8AA, Devon, EnglandHacettepe Univ, Intens Care Unit, Ankara, TurkeyUDELAR, Sch Med, Hosp Espanol ASSE, Intens Care Unit, Montevideo, UruguayNew Cross Hosp, Intens Care Unit, Wolverhampton, W Midlands, EnglandUniv Paris 07, Hop Lariboisiere, AP HP, Dept Anesthesiol Crit Care & SMUR, Paris, FranceCanberra Hosp, Intens Care Unit, Canberra, ACT, AustraliaRoyal Brisbane & Womens Hosp, Dept Intens Care Med, Brisbane, Qld, AustraliaIspat Hosp, Intens Care Unit, Rourkela, Orissa, IndiaUniv Pittsburgh, Pittsburgh, PA USAUniv Calif San Diego, Sch Med, San Diego, CA 92103 USAJoan XXIII Univ Hosp, Dept Crit Care, Tarragona, SpainPontificia Univ Catolica Chile, Fac Med, Escuela Med, Dept Med Intens, Santiago, ChileHosp San Martin, Intens Care Unit, La Plata, Buenos Aires, ArgentinaUniv Paris 11, Hop Bicetre, AP HP, Hop Univ Paris Sud,Dept Anesthesie Reanimat, Paris, FranceGelre Ziekenhuizen, Intens Care Unit, Apeldoorn, NetherlandsRoyal Marsden Hosp, Intens Care Unit, London SW3 6JJ, EnglandRoyal Devon & Exeter Hosp, Intens Care Unit, Exeter EX2 5DW, Devon, EnglandSanta Maria Angeli Hosp, Intens Care Unit, Pordenone, ItalyUniv Jena, Univ Klinikum Jena, Dept Internal Med 1, Jena, GermanyRoyal Free Hosp, Intens Care Unit, London NW3 2QG, EnglandDipartimento Anestesia Rianimaz & Terapia Intens, Treviso, ItalyUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Private Equity funds and their performance in the post-crisis period

The work covers the topic of private equity funds performance and attempt to identify the impact of macroeconomic conditions on the entire industry. The recent central banks' actions put a question about the impact of changes in interest rates on the private equity funds performance. With the sample of 100 observations provided by Cambridge Associates, we identified the significant negative effect of prevailing low interest rates on the growth of private equity funds performance. We further attempt to answer the question, whether private equity funds operating in post-crisis years has on average higher growth rate, however, we could not provide the answer as we failed to reject the null, neutral effect hypothesis. Additionally, with a sample of 3092 observations provided by Bloomberg, we found that the effect of cheap debt has increased on average in the postcrisis period, predicting that the private equity performance can suffer once the interest rates rises enough