Intensive Care Medicine

, Volume 37, Issue 3, pp 510–517 | Cite as

Pharmacokinetics and clinical predictors of surfactant redosing in respiratory distress syndrome

  • Paola E. Cogo
  • Maddalena Facco
  • Manuela Simonato
  • Daniele De Luca
  • Francesca De Terlizi
  • Umberto Rizzotti
  • Giovanna Verlato
  • Maria Paola Bellagamba
  • Virgilio P. Carnielli
Pediatric Original
First Online:
Received:
Accepted:

Abstract

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.

Keywords

Pulmonary surfactant Isotopes Low-birth-weight infants Respiratory distress syndrome 
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Notes

Acknowledgments

We thank all the nurses of the two neonatal intensive care units for their valuable contribution to the collection of the tracheal samples. The study was supported by a grant of the University of Padova, Italy on the “surfactant kinetics in humans with severe respiratory failure measured by stable isotopes.” Virgilio P. Carnielli has received a fee for speaking for an educational event sponsored by Dey Laboratories, Napa, CA, USA, and has received research grants from Chiesi Pharmaceuticals, Parma, Italy. All other authors declare no potential conflicts of interest with this work.

Supplementary material

134_2010_2091_MOESM1_ESM.doc (114 kb)
Supplementary material 1 (DOC 114 kb)

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Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Paola E. Cogo
    • 1
  • Maddalena Facco
    • 1
  • Manuela Simonato
    • 1
  • Daniele De Luca
    • 2
  • Francesca De Terlizi
    • 3
  • Umberto Rizzotti
    • 4
  • Giovanna Verlato
    • 1
  • Maria Paola Bellagamba
    • 2
  • Virgilio P. Carnielli
    • 2
  1. 1.Department of PaediatricsUniversity of PadovaPadovaItaly
  2. 2.Division of Neonatology, Institute of Clinical SciencesPolytechnic University of Marche and Azienda Ospedaliera Universitaria Ospedali Riuniti AnconaAnconaItaly
  3. 3.Igea Scientific DepartmentModenaItaly
  4. 4.Preformulation and DevelopmentVelferd srlPeschiera del GardaItaly

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