February 1999, VOLUME103 /ISSUE 2

Indications for Surfactant Therapy—The aAPo2 Coming of Age

  1. Robert T. Hall, MD
  1. 1Department of Pediatrics
  2. 2Kansas City School of Medicine
  3. 3University of Missouri
  4. 4Children's Mercy Hospital
  5. 5Kansas City, MO 64108-4698


Indications for administration of surfactant to infants with established respiratory distress syndrome (RDS; rescue therapy) remains an area of continued investigation. Current recommendations vary from use in infants who are intubated and have an aAPo2 <0.22 to use in infants receiving ≥40% oxygen administered in a hood when the Pao2 is <80 TORR (aAPo2 approximately <0.36).

This commentary is written in response to the article by Verder et al, in this issue of Pediatrics, who evaluated early versus late treatment of RDS in 60 preterm infants <30 weeks' gestation receiving nasal continuous positive airway pressure (CPAP). Early-treated infants (aAPo2, 0.22 to 0.35; mean, 0.26) had a lower incidence of mechanical ventilation or death (21%) than did late-treated infants (63%), who did not receive surfactant treatment until the aAPo2 was <0.22 (0.15 to 0.21; mean, 0.16). The authors conclude that although approximately half of infants <30 weeks' gestation with RDS can be treated with nasal CPAP alone, early treatment with surfactant when the aAPo2 is 0.22 to 0.36 reduced significantly the need for mechanical ventilation.

Limitations of applicability of the study to widespread use include determination of Po2 values from transcutaneous measurements, which may vary from those obtained from arterial samples and affect significantly aAPo2 ratios. Likewise, use of nasal CPAP significantly affects oxygenation, and interpretation of results cannot be extrapolated to intubated infants or those receiving oxygen delivered under a hood. Nonetheless, the use of the aAPo2 ratio and early administration of surfactant are supported by this study.

  • arterial to alveolar oxygen tension ratio
  • nasal continuous positive airway pressure
  • respiratory distress syndrome
  • surfactant
  • transcutaneouso2 determinations
  • very low birth weight

The laboratory and clinical investigation of exogenous pulmonary surfactant therapy for respiratory distress syndrome (RDS) in preterm infants is one of the most comprehensive therapeutic adventures in neonatal medicine of this decade. Mortality in the very low birth weight infant with RDS clearly has improved along with a reduction in the incidence of pulmonary interstitial emphysema, pneumothorax, and bronchopulmonary dysplasia.

One issue that remains unresolved is the use of surfactant as prophylaxis versus rescue therapy in infants with established disease. Installation before or at the initiation of respiration is no longer believed to be essential for successful intrapulmonary distribution or clinical response; however, early treatment of infants with RDS may be beneficial.

Clearly, gestational age and birth weight are directly related to endogenous surfactant production. However, multiple variables including maternal steroid administration, duration of ruptured membranes, amniotic fluid volume, intrauterine growth, infection, and other forms of intrauterine stress make the decision to treat a clinical one rather than a decision based on gestational age and birth weight alone. Unfortunately, no rapid test for identification of surfactant deficiency has emerged, and clinical features of grunting, nasal flaring, and retracting, plus radiographic features and oxygen needs remain the mainstay for evaluation of disease severity.

In this issue of Pediatrics electronic pages, Verder and colleagues1 extend their observations on the early use of surfactant for the treatment of established RDS. This group demonstrated previously that surfactant therapy given to infants with moderate to severe RDS receiving nasal continuous positive airway pressure (CPAP) reduced the need for mechanical ventilation.2 The current study extends and confirms those observations in infants <30 weeks' gestation.

The measure of disease severity in both studies was the arterial to alveolar O2 oxygen tension ratio (aAPo2). The earlier study group2had an aAPo2 of 0.17 at randomization, with a rise to 0.37 ± 0.15 in the surfactant-treated group 6 hours after therapy, compared with 0.25 ± 0.10 in untreated control subjects. Subsequent mechanical ventilation was required in 43% (15/35) and 85% (28/33), respectively (P = .003). In the current study, the aAPo2 was 0.26 ± 0.06 at the time of surfactant therapy in the early-treated group and 0.16 ± 0.04 in the late-treated group (P = .0001). The 6-hour aAPo2 response was greater in the early-treated group, 0.48 ± 0.18 versus 0.36 ± 0.18 in the late-treated group (P = .02). Fewer early-treated infants required mechanical ventilation or died within 7 days of age, 21% (7/33) versus 63% (17/27) (P = .0013). The authors conclude from the current study that although approximately half of infants <30 weeks' gestational age with RDS can be treated with nasal CPAP alone, early treatment with surfactant when the aAPo2 is 0.22 to 0.36 reduced significantly the need for mechanical ventilation.

Almost all modern blood gas machines now use co-oximetry with measurement (rather than estimation) of hemoglobin and oxygen saturation in addition to pH, Pco2, and Po2. Providing Fio2, therefore, allows calculation of the aA ratio, AaDo2, and oxygen content, which are available as reported values.

The magnitude of the effect of measurement of Po2 on aA ratios at inspired O2concentrations from 0.3 to 0.5 is shown in Table 1. The Verder et al data suggest that all infants <30 weeks' gestation with RDS requiring an Fio2 ≥0.5 would benefit from surfactant. However, there may be considerable variation among infants qualifying to receive surfactant whose Fio2 is 0.3 to 0.5. Therefore, the precision of the measurement may affect the number of infants receiving early surfactant treatment.

Table 1.

aAo2 Ratios at Varying Fio2 and Pao2 Values

The variations in transcutaneous o2determinations likely affected infants similarly in early- and late-treated patients in the current study and do not detract from the value of the results. Early treatment is better than late treatment. Unfortunately, both studies fell short of the projected number of subjects planned. Additional data involving patients with and without nasal CPAP, ie, those receiving hood o2 and correlation of transcutaneous with arterial Po2, would be helpful. In the meantime, data are mounting that spontaneously breathing, very low birth weight infants with RDS will benefit from surfactant therapy when the aAPo2 is <0.36 corresponding to Fio2 <0.5. The observation supplements existing recommendations that infants with RDS requiring mechanical ventilation receive surfactant when the aAPo2is <0.22.

nasal continuous positive airway pressure
aAPo2 =
arterial to alveolar oxygen tension ratio
respiratory distress syndrome
Fio2 =
fraction of inspired oxygen