Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship

Extraction of purine alkaloids from mate (Ilex paraguariensis) using supercritical CO2

Experimental data for the supercritical CO2 extraction of purine alkaloids (caffeine, theobromine, and theophylline) from ground herbal mate tea (Ilex paraguaryensis) using a high-pressure apparatus are presented. Caffeine, theophylline, and theobromine were identified in the extracted fractions using HPLC. Results indicated a much higher CO2 selectivity for caffeine in comparison with those for theophylline and theobromine. Solubilities of pure compounds in carbon dioxide were also determined at 313.2, 323.2, 338.2, and 343.2 K, and pressures ranging from 14 to 24 MPa. Caffeine solubility exhibited a retrograde behavior with temperature while theophylline and theobromine manifested a normal behavior at conditions explored in this study. Solubilities in binary CO2/purine alkaloid model systems were much higher than those obtained during extraction of mate tea, demonstrating the difficulty of using binary data in predicting complex multicomponent behavior.4793804380

Decaffeination of guarana seeds in a microextraction column using water-saturated CO2

Experimental data on the reduction of the caffeine content of guarana seeds with water-saturated supercritical carbon dioxide were obtained in order to provide information on the ability of supercritical fluids for the decaffeination of widely consumed caffeine-rich natural products. The extraction was performed using a semi-continuous flow high-pressure micro-extraction apparatus at 40 and 70 degreesC and pressures of 100, 200 and 400 bar. Carbon dioxide flow rates of 5.7 and 9.4 g min(-1) were used. The extraction curves obtained showed the existence of thermodynamic solubility dependent, intermediate and diffusion controlled regions. Extraction at 400 bar and 70 degreesC using water-saturated supercritical carbon dioxide at a flow rate of 5.7 g min(-1) allowed the removal of almost 98% of the initial caffeine content in wet ground guarana seeds, in a period of 240 min. When extractions were performed at lower pressures or temperatures, additional time and larger amounts of carbon dioxide were necessary to achieve the same yield. Increasing carbon dioxide flow rate did not present any economic advantage unless the extraction was limited to the thermodynamic solubility region. For total extraction of caffeine, the use of low flow rates resulted in a similar final product yield but at a much lower solvent consumption. A retrograde behavior for the extraction of caffeine from guarana seeds was also observed at 100 bar for the 40 and 70 degreesC isotherms. (C) 2002 Elsevier Science B.V. All rights reserved.22211912

Extraction of methylxanthines from guarana seeds, mate leaves, and cocoa beans using supercritical carbon dioxide and ethanol

New experimental data on the extraction of caffeine from guarana seeds and mate tea leaves, and theobromine from cocoa beans, with supercritical CO(2) were obtained using a high-pressure extraction apparatus. The effect of the addition of ethanol to carbon dioxide on the extraction efficiency was also investigated. Caffeine extraction yields of 98% of the initial caffeine content in both wet ground guarana seeds and mate tea leaves were obtained. Extractions of caffeine from guarana seeds and mate tea leaves also exhibited a retrograde behavior for the two temperatures considered in this work. In the removal of theobromine from cocoa beans, a much smaller extraction yield was obtained with longer extraction periods and consequently larger solvent requirements. The results of this study confirm the higher selectivity of CO(2) for caffeine in comparison with that for theobromine, and also the influence of other components in each particular natural product on the extraction of methylxanthines. The effect of the addition of ethanol to carbon dioxide on the extraction of methylxanthines was significant, particularly in the extraction of theobromine from cocoa beans. In general, the use of ethanol results in lower solvent and energy requirements and thereby improved extraction efficiency.50174820482

Extraction of caffeine, theobromine, and cocoa butter from Brazilian cocoa beans using supercritical CO2 and ethane

Supercritical extraction using ethane and CO2, acceptable solvents for food products, was explored for the recovery of the methylxanthines caffeine and theobromine and cocoa butter from cocoa beans using a high-pressure apparatus. Continuous extraction of cocoa beans was performed at 343.2 K using CO2 at pressures of 20 and 40 MPa and ethane at pressures of 15.2, 24.8, and 28.3 MPa. The extraction yields of cocoa butter obtained with ethane were much higher than those obtained with CO2 because of the higher solubility of this fat in ethane. A pronounced effect of pressure on the extraction of methylxanthines and cocoa butter was observed for both solvents. Extraction curves revealed the greater facility of these solvents to extract cocoa butter followed by caffeine and theobromine. This behavior suggests a range of possible conditions under which the extraction and isolation of cocoa butter, caffeine, and theobromine from cocoa beans can be achieved. The methylxanthines in cocoa beans were slightly more soluble in ethane than in CO2 probably because of co-solvency effects of cocoa butter, which was extracted more easily using supercritical ethane. Despite the higher cost of ethane, its critical pressure is lower than that of CO2, and the higher butter solubility could render ethane a viable solvent through lower energy costs.41266751675

Induction of pilocarpine formation in jaborandi leaves by salicylic acid and methyljasmonate

Jaborandi seedlings were subjected to different treatments in order to study the induction of pilocarpine in the leaves. In addition four extraction methods were assessed to extract the alkaloid from dried leaves. The highest yielding extraction and recovery was observed when dried leaves were first treated with base and then extracted with chloroform. Salt stress (NaCl), wounding, hypoxia, and N and K omission of the nutrient soln caused reductions in pilocarpine contents. Whereas complete nutrient soln and P omission maintained normal levels of the alkaloid. Salicylic acid and methyljasmonate induced a 4-fold increase of pilocarpine, but this increase was dependent on the concentration and time after exposure. (C) 2003 Elsevier Science Ltd. All rights reserved.63217117