Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl.

BACKGROUND: A low dose solution of adrenaline 2 microg x ml(-1), fentanyl 2 microg x ml(-1) and bupivacaine 1 mg x ml(-1) has been reported to give superior pain control when used for epidural analgesia after major surgery. The present paper describes the compounding and chemical stability of this triple-component solution during storage and use. METHODS: Sterile triple-component concentrates (11X) were diluted by the use of gas isolator technology to give ready-to-use infusion solutions. Eight solutions were analysed by reverse phase high-performance liquid chromatography (HPLC) methods, and assays were performed on 1, 45, 90 and 180 days after storage at 2-8 degrees C. After 180 days the solutions were subsequently stored at 22 degrees C for four days before they were reanalysed. HPLC quantification of adrenaline was also performed on samples from solutions given to 28 different patients. RESULTS: The concentration of adrenaline and fentanyl decreased approximately 3.5% from 1 to 180 days at 4 degrees C and four days at 22 degrees C. The corresponding figure for bupivacaine was an apparent increase by 2.4% in concentration. No absorption to the polypropylene plastic bags of fentanyl and bupivacaine was detected. None of the 28 samples derived from used infusion bags contained less than 95% of the declared content of adrenaline. CONCLUSIONS: The triple-component epidural analgesic solution remained stable during six months of cold storage, followed by four days of storage at room temperature. No significant degradation of adrenaline was observed in infusion solutions returned from the wards.

Photodestabilization of epinephrine by sodium metabisulfite.

The effect of light and bisulfite on infusion solutions containing epinephrine (2 micrograms/mL), bupivacaine hydrochloride (1 mg/mL), fentanyl (2 micrograms/mL) and sodium edetate (0.18 microgram/mL) was investigated. Solutions were made isotonic using sodium chloride, and they contained either 1.82 micrograms/mL sodium metabisulfite or no metabisulfite at all. The infusions were stored in polypropylene infusion bags (550 mL) and were subjected to light from a xenon burner with a specter similar to sunlight behind a glass window. The contents of epinephrine, bupivacaine and fentanyl were determined with stability indicating methods using a HPLC system. In two identical experiments epinephrine was demonstrated to be more stable under irradiation in the absence of sodium metabisulfite (89.3% and 91.3% remaining of initial concentration) than in its presence (64.5% and 60.1% remaining). Bupivacaine and fentanyl showed no degradation as a function of light exposure, and the stability was not affected by the presence or absence of bisulfite. After two weeks exposure to natural light (Oslo, 60 degrees N, March) the content of epinephrine was 45.0% of the initial concentration in the solutions containing bisulfite and 95.6% in the solutions without bisulfite (n = 3). The relationship between various concentrations of bisulfite and the photo-stability of three epinephrine solutions (2 micrograms/mL, 20 micrograms/mL and 110 micrograms/mL) were tested. The results indicated that approximately equimolar concentration of epinephrine compared to bisulfite, or bisulfite in some excess, was least favorable to the stability of epinephrine. A possible explanation for the photo-destabilizing effect of bisulfite can be the conversion of superoxide radicals (O2-) to highly reactive hydroxyl radicals (.OH) by bisulfite. From these results it can be concluded that solutions containing epinephrine and bisulfite should be protected from light not only during storage but also during use in cases where the infusion time amounts to several days. An alternative, wherever possible, would be to omit bisulfite in the solutions.

A new injectable carbamazepine solution--antiepileptic effects and pharmaceutical properties.

Carbamazepine (CBZ) could be dissolved in Glycofurol (polyethylene glycol monotetra-hydrofurfuryl ether) with concentrations up to 100 mg/ml, and the solutions were stable for at least 14 days. Ethanol or benzyl alcohol was added without loss in solubility, while water, human serum albumin or Intralipid always led to immediate precipitation. The effect of a CBZ/Glycofurol solution on focal seizure threshold in the visual cortex in cats was investigated using a cerveau isolé preparation. Fourteen experiments were performed using i.v. injections of CBZ with concentrations ranging from 0.2 to 20 mg/kg. In all experiments with doses greater than 1 mg/kg the CBZ/Glycofurol injections exerted a pronounced and immediate effect on the seizure threshold, while Glycofurol alone was ineffective. On average, seizure threshold increased more than 5-fold with doses in the range of 5-20 mg/kg. Investigating the effect of CBZ/Glycofurol on picrotoxin-induced seizure activity in cats, 2 injections of 5 mg/ml of CBZ immediately stopped the seizure activity as evaluated by electrocorticography, while interictal activity remained.

Effects of different rinsing regimen on totally implantable vascular access after 70 days infusion of total parenteral nutrition in vitro.

Totally implantable vascular access catheters with injection ports (IP) have been used for total parenteral nutrition (TPN). It is well known that thrombosis may cause occlusion of catheters. Recently we have experienced occlusion of the vascular access chambers in TPN-patients because of precipitation from the solutions. Three different IPs were tested in vitro: Port-A-Cath (PAC), Vascular-Access-Port (VAP), and Implantofix (IMP). Each received a daily infusion of a 2.5-liter solution consisting of fat emulsion, amino acids, glucose, and additives from a "3-liter bag." After infusions, the IPs were washed with three different rinsing methods, one including 45% v/v alcohol. After 70 days the ports were opened and examined for precipitation. Ports washed with alcohol showed no signs of precipitation, while four of six ports which were washed with conventional rinsing methods had precipitates.