Present Status of Clinical Studies of Fluosol-DA (20%) in Japan

Abstract

Fluosol-DA (20%) is a fine-particle stable emulsion with low toxicity and rapid elimination from the body. Based on comprehensive animal experiments and phase one human studies, Fluosol-DA (20%) has been given clinically to 401 patients in Japan. In 270 of these patients, it was given to treat severe hemorrhage, and in 131, it was given to improve impaired cerebral circulation or for other nonhemorrhagic indications. In these studies, Fluosol-DA (20%) was effective as a blood gas carrier as well as a plasma expander. After infusion of 20 ml of Fluosol-DA (20%) per kilogram of body weight, while maintaining the FIO2 at or near 0.5 or 0.6, PFCs transport an amount of oxygen equivalent to approximately 6.3 +/- 1.4% of the oxygen transported by the hemoglobin phase and approximately 100% of the oxygen transported by plasma. The arteriovenous oxygen difference in the PFC phase was approximately 25 to 30% of that in the hemoglobin phase. Of the oxygen consumed by the tissues, approximately 17% was provided by the PFC phase after treatment with Fluosol-DA (20%). Hemodynamic parameters of patients with hemorrhage were either maintained or recovered to normal levels after Fluosol-DA (20%) infusion. No acute or chronic untoward reactions were observed either early or late after infusion of Fluosol-DA (20%), except for a transient decrease in neutrophils and platelets after the initial administration of a test dose of 1 ml, and these parameters recovered spontaneously in 30 minutes. No abnormal findings that could be attributed to Fluosol-DA (20%) were found in the heart, lungs, liver, spleen, kidneys, bone marrow, endocrine system, or other organs. Organ retention of PFC particles was evaluated in 6 autopsy cases in Japan. Although PFCs were detected in many organs several months after a single Fluosol-DA (20%) injection of 20 ml per kilogram of body weight, PFCs were not found in body tissues of those who were autopsied more than 7 months after its infusion. RES function was slightly depressed for a few days in patients receiving 20 ml of Fluosol-DA (20%) per kilogram of body weight. It was also depressed for several days in rats given 40 ml per kilogram of body weight. Compared with that of control patients, recovery to preoperative levels was slightly delayed in patients receiving Fluosol-DA (20%). Despite this, administration of up to 20 ml of Fluosol-DA (20%) per kilogram of body weight should be safe with respect to the RES function.(ABSTRACT TRUNCATED AT 400 WORDS)