In vivo effect of pneumonia on surfactant disaturated-phosphatidylcholine kinetics in newborn infants.

BACKGROUND: Bacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs. METHODS: We studied thirty-one term or near-term newborns (gestational age 39.7±1.7 weeks, birth weight 3185±529 g) requiring mechanical ventilation. Fifteen newborns had pneumonia, while 16 newborns were on mechanical ventilation but had no lung disease. Infants received an intratracheal dose of 13C labeled dipalmitoyl-phosphatidylcholine at the study start. We measured the amount and the isotopic enrichment of DSPC-palmitate from serial tracheal aspirates by gas chromatography and gas chromatography-mass spectrometry, respectively, and we calculated the DSPC half-life (HL) and pool size (PS) from the isotopic enrichment curves of surfactant DSPC-palmitate. RESULTS: The mean DSPC amount obtained from all tracheal aspirates did not differ between the two groups. DSPC HL was 12.7 (6.5-20.2) h and 25.6 (17.9-60.6) h in infants with pneumonia compared with control infants (p = 0.003). DSPC PS was 14.1 (6.6-30.9) mg/kg in infants with pneumonia and 34.1 (25.6-65.0) mg/kg in controls, p = 0.042. Myeloperoxidase (MPO) activity, as a marker of lung inflammation, was 1322 (531-2821) mU/ml of Epithelial Lining Fluid (ELF) and 371(174-1080) mU/ml ELF in infants with pneumonia and in controls, p = 0.047. In infants with pneumonia, DSPC PS and HL significantly and inversely correlated with mean Oxygenation Index (OI) during the study (DSPC PS vs. OI R = -0.710, p = 0.004 and HL vs. OI R = -0.525, p = 0.044, respectively). CONCLUSIONS: We demonstrated for the first time in vivo in humans that DSPC HL and PS were markedly impaired in neonatal pneumonia and that they inversely correlated with the degree of respiratory failure.

Pharmacokinetics and clinical predictors of surfactant redosing in respiratory distress syndrome.

RATIONALE: Limited data are available on predictors for surfactant retreatment in preterm infants with respiratory distress syndrome (RDS). OBJECTIVE: To study the pharmacokinetics of exogenous surfactant and the clinical parameters associated with surfactant redosing. METHODS: Exogenous surfactant pharmacokinetics was studied in 125 preterm infants (birth weight 997 ± 432 g; gestational age 28.0 ± 2.6 weeks) with moderate to severe RDS requiring mechanical ventilation. Clinical and respiratory parameters were recorded hourly, and surfactant disaturated-phosphatidylcholine (DSPC) half-life, pool size, and endogenous synthesis were calculated by stable isotope tracing of surfactant DSPC isolated from serial tracheal aspirates. Univariate and multiple logistic regression were used to study the effects of clinical and surfactant kinetic variables on the need for redosing. RESULTS: Fifty-three infants (42.4%) received one dose, 51 (40.8%) two doses, and 21 (16.8%) three doses. Median (interquartile range, IQR) DSPC half-life was 21 (13-39), 11 (7-17), and 10 (7-16) h after the first, second, and third dose, respectively (p = 0.07). Univariate analysis showed a significantly shorter DSPC half-life in infants requiring more surfactant doses. On logistic analysis, risk of redosing was higher with lower birth weight, worse radiological score, shorter DSPC half-life, and surfactant dose of 100 mg/kg, whilst it was lower with elective high-frequency ventilation at time of intubation, instead of conventional ventilation. CONCLUSIONS: When optimizing surfactant replacement therapy and its cost-benefit ratio, pharmacokinetics and clinical variables associated with need of redosing should be taken into account.

Dosing of porcine surfactant: effect on kinetics and gas exchange in respiratory distress syndrome.

OBJECTIVE: The goal was to study exogenous surfactant disaturated phosphatidylcholine (DSPC) kinetics in preterm infants with respiratory distress syndrome (RDS) who were treated with 100 or 200 mg/kg porcine surfactant. METHODS: Sixty-one preterm infants with RDS undergoing mechanical ventilation received, within 24 hours after birth, 100 mg/kg (N = 40) or 200 mg/kg (N = 21) porcine surfactant mixed with [U-(13)C]dipalmitoylphosphatidylcholine. Clinical and respiratory parameters were recorded, and DSPC half-life and pool size and endogenous DSPC synthesis rate were calculated. RESULTS: Clinical characteristics and short-term outcomes did not differ between groups. In the 100 mg/kg group, 28 infants (70%) received a second dose after 25 +/- 11 hours and 9 (22.5%) a third dose after 41 +/- 11 hours; in the 200 mg/kg group, 6 infants (28.6%) received a second dose after 33 +/- 8 hours and 1 a third dose. The DSPC half-life was longer in the 200 mg/kg group (first dose: 32 +/- 19 vs 15 +/- 15 hours [P = .002]; second dose: 43 +/- 32 vs 21 +/- 13 hours [P = .025]). DSPC synthesis rates and pool sizes before the first and second doses did not differ between the groups. The 200 mg/kg group exhibited a greater reduction in the oxygenation index than did the 100 mg/kg group after the first (P = .009) and second (P = .018) doses. CONCLUSIONS: Porcine surfactant given to preterm infants with RDS at a dose of 200 mg/kg resulted in a longer DSPC half-life, fewer retreatments, and better oxygenation index values.