Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome.
Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pediatrics, Kapiolani Medical Center for Women and Children, John A. Burns School of Medicine, Honolulu, Hawaii 96826.
Pelke
S
S
Nakamura
K T
KT
Barrett
J
J
Balaraman
V
V
Loo
S W
SW
Ibarra-Pratt
E
E
Smith
M B
MB
D004334:Drug Administration Schedule; D004338:Drug Combinations; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000627:therapeutic use; D005233:Fatty Alcohols / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000627:therapeutic use; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D012189:Retrospective Studies
D004338:Drug Combinations; D015507:Drugs, Investigational; D005233:Fatty Alcohols; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination