After the experimental and phase one studies of our so-called "artificial blood," Fluosol-DA (20%), an emulsified mixture of perfluorodecalin and perfluorotripropylamine, were successfully completed, phase two and three clinical studies were carried out on 186 patients in Japan. The initial dose was 20 ml/Kg body weight (BW), and additional 10 ml/Kg BW doses were applied as needed. Oxygen-supplying and plasma-extending effects were established. No untoward reaction was observed in any of the 186 cases except in a case that involved long-term repeated administration. Initial studies on FLuosol-DA suggest reasonable safety; however, additional clinical trials appear warranted.

Over 10 years of research has led to the development of a perfluorochemical (PFC) emulsion that can be utilized clinically as a blood gas carrier. The physiochemical properties of this PFC emulsion and their biophysiological effects on animals meet the minimum requirements of an oxygen transport medium. As PFC is chemically and biochemically inert, its toxicity is extremely low. Acute toxicity was related chiefly to the particle size of the emulsion. PFC particles injected intravenously are phagocytized in the reticuloendothelial system as foreign bodies and are excreted from the lungs. The excretion rate was roughly proportional to the vapor pressure of each PFC. An emulsion consisting of 7 parts perfluorodecalin and 3 parts perfluorotripropylamine, 20% (wt/vol) PFC final, Fluosol-DA 20%, was selected as the best formulation in view of efficacy, stability, and excretion rate. No untoward reactions were observed after administration of this emulsion. More than 400 patients have received intravenous Fluosol-DA 20% in Japan.

In summary, we have discussed PFC emulsions as oxygen carriers, and concluded as follows: PFC emulsions which are clinically usable at present, such as Fluosol-DA, have some negative points. For instance, there is the requirement of relatively high FiO2 level, short retention time in the blood stream, slow excretion rate from the organs, limited dosage for infusion, and so on. However, in the clinical cases of moderate acute anemia, the consumed oxygen in the PFC phase was nearly 30% of that in the hemoglobin phase in the administration of only 1,000 ml of Fluosol-DA. It strongly suggests that PFC emulsion can carry a considerable amount of oxygen to the tissues and play an important role in improving the tissue hypoxia. Moreover, we surgeons wish to say that there is a great difference for the surgeons' mental state during a surgical operation between the cases where no blood transfusion is allowed for a religious or other reason, and the cases where we may use Fluosol-DA depending on the patients' condition. In the former cases, surgeons will be under stress such that he or she might cause the patients to lose blood excessively. On the other hand, when the surgeon has something in reserve, that is, when he or she may use Fluosol-DA if needed, a good result will usually be obtained in the operation, even without actually using Fluosol-DA. One might be led to say that a key point for the success of operations is the surgeon's mental condition, freedom from anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)

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