THE EFFICACY AND SAFETY OF KL(4)-SURFACTANT IN INFANTS WITH RESPIRATORY-DISTRESS SYNDROME

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL(4)), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL(4) peptide was synthe sized to resemble the amino acid pattern of surfactant protein B (SP-B ). Forty-seven infants with RDS were treated within 4 h of birth with the KL(4)-peptide/phospholipid mixture, called KL(4)-Surfactant. The a verage arterial-to-alveolar oxygen tension ratios (a/A O-2) of 39 pati ents included in efficacy analyses rose from pretreatment values of 0. 14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value greater than or equal to 0.40) by 12 h of age. Mean airway pressures and oxygenati on index values fell concomitantly, and expansion of the lungs was obs erved on radiographs. The median duration of mechanical ventilation wa s 5.0 d. Of the 39 included infants, 29 required only a single dose. R adiographic data indicate that those patients requiring a second insti llation of KL(4)-Surfactant but not showing a sustained rise in a/A O- 2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no hig her than found in other comparable published studies. The data demonst rate that the synthetic peptide, KL(4), which mimics the hydrophobic a nd hydrophilic pattern of SP-B, when formulated in an aqueous dispersi on with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and im provement of gas exchange in infants with RDS.