Fibrinolytic enzyme therapy of respiratory distress syndrome was explored in a controlled, randomized, double-blind clinical study. Of 100 infants entered in the study, 60 corresponded to all of the predetermined criteria and were included in the final evaluation. Infants with respiratory distress syndrome were admitted to the study if they were (1) premature, (2) from diabetic mothers, or (3) from mothers with hemorrhagic complications of pregnancy. In regard to sex, delivery route, maternal status, pretreatment respiratory rate, Silverman score, venous pressure, electrolytes, protein levels, and circulating levels of members of the fibrinolysin system, the placebo-treated control group and the experimental group were found to be comparable. The groups were comparable in regard to pretreatment blood pH and pCO2 as well, except that the subgroup that was treated with the enzyme preparation and expired showed a greater degree of acidosis than the other groups.

Patients in the experimental group received 5 RPMI units/kg of human plasmin activated with human urokinase (UK-plasmin) intravenously in 4 hours, plus 60 RPMI units/kg/day of enzyme by aerosol. In the placebo-treated control group, 11 of 28 infants recovered (39%) and in the UK-plasmin treated group, 23 of 32 recovered (72%). The difference is statistically significant at less than 5% level. Of the infants with a birth weight of 2 kg or less, 3 of 16 recovered in the placebo-treated control group (19%), and 10 of 16 recovered in the UK-plasmin treated group (63%); the difference is statistically significant at less than 5% level. No clinical side effects were seen in any of the patients.

Autopsy findings indicated a high degree accuracy of diagnosis. The incidence of hemorrhage diagnosed at autopsy was the same in the control and experimental groups. In all but one of the patients that expired in the UK-plasmin treated group, sufficient pathologic findings were obtained to account for death regardless of the presence of hyaline membrane disease. Similar findings were obtained in 9 of 17 patients who expired in the control group.

UK-plasmin therapy of respiratory distress syndrome of infants due to hyaline membrane disease appears to be worthy of further exploration. A diagram correlates certain features of the pathophysiology of this disease and the mechanism of action of therapy.

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