The Experimental Study Using Beagle Dogs for the Clinical Application of Poloxamer-solutol Propofol / 대한마취과학회지

BACKGROUND: To reduce side effects such as hyperlipidemia, pain on injection, and bacterial growth of the present formation of propofol, many attempts to change its formulation have been tried. We have developed a newly formulated poloxamer-solutol propofol, which is includes soy bean oil and egg phosphatide as sufactants. The aim of this study was to evaluate the poloxamer-solutol propofol regarding its pharmacokinetic and pharmacodynamic characteristics and bacterial growth compared to original propofol. METHODS: Thirty Beagle dogs weighing around 10-15 kg were randomly assigned to one of two groups. Group 1 received Diprivan propofol 1% (AstraZeneca Co. UK), Group 2 received poloxamer-solutol formulated propofol by continuous intravenous infusion at 35 mg/kg/h for 3 hours. Three, 6, 9 and 12 hours after the discontinuation of the propofol infusion, venous samples from the anterior tibial vein were analysed for liver and renal function test. Also, blood lipid levels were checked after 3 hours of infusion and blood propofol concentrations were checked every hour during infusion. Eye opening time and orientation time, represented by walking on four legs, were evaluated. Also, broth cultures (100microliter) of four standard preservative efficacy test organisms (Staphylococcus Aureus, Pseudomonas Aeruginosa, Escherichia Coli, Candida Albicans) were added to 9.9 ml of four test formulations at approximately 200 colony forming units/ml. The subjected formulations were; original propofol (AstraZeneca Co, 1% solution, UK), EDTA added propofol (0.0055% EDTA added propofol), Poloxamer-Solutol formulated propofol (poloxamer 188/407 and solutol mixture), and normal saline. The test formulations were incubated at 25degrees C and 32.5degrees C (Tryptic soy agar medium for bacteria and Sabrouraud dextrose agar medium for fungus) and tested for viable counts after 24 and 48 hours. RESULTS: Poloxamer-solutol propofol showed no increase of triglyceride and the propofol concentrations showed no difference between the two groups. Also the original propofol supported the growth of all microorganisms at both temperatures and times. EDTA added propofol inhibited the growth of microorganisms more than the original propofol, but not as much as the poloxamer-solutol formulated propofol. Saline showed a similar pattern as the propofol with added EDTA. CONCLUSIONS: The poloxamer-solutol formulated propofol has advantages by pharmacokinetic-pharmacodynamic studies in terms of the initial TG level during propofol infusion, and shows more bacteriostatic activity against all four microorganisms than the original propofol and the propofol with added EDTA.

The Comparison for the Growth of Microorganisms in Original Propofol, Ethylenediaminetetraacetic Acid (EDTA) Added Propofol, and Poloxamer-Solutol Formulated Propofol / 대한마취과학회지

BACKGROUND: Because there is difficulty in the addition of known preservatives to oil in water emulsion such as propofol, ethylenediaminetetraacetic acid (EDTA) added to this may formulate for the antimicrobial activity; however, this formulation has side effects such as hyperlipidemia and pain on injection. We have developed a newly formulated poloxamer-solutol propofol which is considered to be free from hyperlipidemia. The aim of this study was to evaluate the possibility of bacterial growth in poloxamer-solutol formulated propofol compared to original propofol and EDTA added propofol. METHODS: Broth cultures (100nl) of four standard preservative efficacy test organisms (Staphylococcus Aureus, Pseudomonas Aeruginosa, Escherichia Coli, Candida Albicans) were added to 9.9 ml of four test formulations. Subjected formulations were original propofol (AstraZeneca Co, 1% solution, UK), EDTA added propofol (0.0055% EDTA added propofol), Poloxamer-Solutol formulated propofol (poloxamer 188/407 and solutol mixture), and normal saline at approximately 200 colony forming units/ml. The test formulations were incubated at 25degreesC and 32.5degreesC (Tryptic soy agar medium for bacteria and Sabrouraud dextrose agar medium for fungus) and tested for viable counts after 24 and 48 hours. RESULTS: Original propofol supported the growth of all microorganisms at both temperature and time. EDTA added propofol inhibited the growth of microorganisms more than the original propofol, but not so much as the poloxamer-solutol formulated propofol. Saline showed a similar pattern as EDTA added propofol. CONCLUSIONS: Poloxamer-solutol formulated propofol possesses more bacteriostatic activity against all four microorganisms than the original and EDTA added propofol.

Equianalgesic Concentration of Fentanyl Comparable to 67% N2O during Propofol Based General Anesthesia / 대한마취과학회지

BACKGROUND: When using a target controlled infusion (TCI) of propofol, combination with N2O or fentanyl as an analgesic adjuvant is common in clinical practice. In a previous study, a minimal steady state plasma concentration necessary to prevent a response in 50% of the patients following a skin incision (Cp50i) for propofol was reduced from 6ng/ml to 4.5ng/ml with 67% nitrous oxide/oxygen compared to air/oxygen. The goal of this study was to quantify the effect site concentration of fentanyl required to replace 67% N2O at a propofol effect site target concentration of 4.5ng/ml. METHODS: Forty six ASA class I or II adult patients scheduled for lower extremity surgery were randomly allocated to one of three groups according to assigned effect site concentration of fentanyl. Group 1, n = 15; 0.5 ng/ml, Group 2, n = 15; 1.0 ng/ml, Group 3, n = 15; 1.5 ng/ml. Patients received propofol with target concentration 4.5ng/ml and predetermined target concentration of fentanyl in three groups. A laryngeal mask airway was placed after anesthesia induction and all patients were controlled ventilation with 67% air/33% oxygen. The response to the skin incision was observed and the patients categorized as movers or non-movers according to Eger's criteria. Cp50i for fentanyl was evaluated using nonlinear regression analysis. RESULTS: Non-movers to skin incision was 20%, 43.7%, 73.7% in groups 1 3 respectively. Cp50i for fentanyl combined with propofol 4.5ng/ml was 1.08 ng/ml. CONCLUSIONS: We concluded that the MAC for 67% N2O is equivalent to an effect site target fentanyl concentration of 1.08 ng/ml in terms of no movement to skin incision.