Effects of propofol in lipid emulsion and micro-emulsion in the incidence of endothelial injury: an experimental study in rabbits

• Grant number: 11/19940-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2011
• End date: November 30, 2012
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Luiz Antonio Vane
• Grantee: Rafael Bicarato de Andrade
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Propofol is one of the most popular drugs used in clinical practice by anesthesiologists. The active principle of propofol is insoluble in water, so to allow its diffusion in biological compartments without the involvement of the anesthetic properties. Some commercial formulations of PLA add components known as an antimicrobial activity such as ethylenediaminetetraacetic acid (EDTA) which also has antioxidant properties. Complications resulting from prolonged infusion syndrome (PIS) are severe metabolic acidosis, rhabdomyolysis, hypertriglyceridemia, acute renal failure, and heart. It may affect adults and children, although it seems to be more reported in children receiving infusion rates above 4 mg.kg-1.h-1 in periods longer than 24 hours. In the new formulation, the PLA has been modified in order to provide greater comfort to the patient in seeking to overcome or minimize the undesirable effect of pain on injection, a negative factor that stimulated efforts to improve the formulation of this problem in order composto. Tendo designed a new diluent for propofol, mainly based on microemulsions. Instead of the lipid emulsion, dispersion of oil and water, containing particles of 500 nm shows the microemulsion particles smaller than 100 nm. This new dosage form is stabilized by an emulsifier coemulsificante and a transparent and thermodynamically stable. The microemulsions also have low viscosity, high capacity for transporting drugs, demonstrate proven proprietary absorption promoters for running drugs and are more easily obtained, without the need for sophisticated equipment for their production. The new formulation, not lipid microemulsion propofol (MP) was synthesized based on the replacement of components of the formula and method for obtaining the emulsion. Because it is a product under development, was not given the composition of the formulation used in this project, as well as details of his produção. Objetivo home - compare the incidence of endothelial injury after the infusion of propofol as a single dose and infusion continuing with the traditional solvent (lipid emulsion) or diluent in microemulsion (proposed). Methodology - The animals are divided into 5 groups of 6 animals: Group I-Control (n = 6) who will receive 2 ml IV saline, Group II traditional propofol (n = 6), which traditionally receive propofol (2 mg / kg) IV bolus, Group III modified propofol (n = 6) modified to receive propofol (2 mg / kg) IV bolus, Group IV Propofol traditional (n = 6), which traditionally receive propofol (2 mg / kg) by IV infusion 60 min and propofol modified Group V (n = 6) modified to receive propofol (2 mg / kg) continuous infusion IV for 60 min. Hemodynamic parameters will be studied, blood and tissue. The statistical analysis is performed using the computer program in BASIC language, using the Profile Analysis (Morrison, 1967), with testing of hypotheses. For variables with normal distribution and homogeneity of variances will be used to profile analysis, otherwise, there will be the Friedman test for comparison of the moments in each group and the Kruskal-Wallis test to compare groups at each time. The variable volume of urine is also adjusted in the logistic model for each of the groups. (AU)