Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-(13)C]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Palmitic acid in surfactant PC became enriched 27 +/- 2 h after the start of the isotope infusion and was maximally enriched at 100 +/- 4 h. The fractional synthesis rate of PC palmitate in the beta group (1.5 +/- 0.2%/d) was increased by 129% above control (0.7 +/- 0.1%/d) (p < 0.02, Mann- Whitney U test). The absolute synthesis rate of PC in the beta group [1.6 +/- 0.3 micromol/kg/d] was increased by 128% above controls [0.7 +/- 0.2 micromol/kg/d] (p < 0.02). These data show that the synthesis of endogenous surfactant from plasma glucose as precursor is a slow process. It is shown, for the first time in vivo, that prenatal glucocorticosteroids stimulate the synthesis of surfactant PC in the very premature baboon

Rejection of erroneous saturation data in optical pulseoximetry and SaO2 variability in newborn patients

Pulse oximetry (PO) is extensively used in intensive care unit (ICU); this is mainly due to the fact that it is a non-invasive and real-time monitoring method. PO allows to measure arterial oxygen saturation (SaO(2)) and in particular hemoglobin oxygenation. Optical PO is typically realized by the use of a clip (to be applied on the ear or on the finger top) containing a couple of monochromatic LED sources and a photodiode. The main drawback with the use of PO is the presence of movement artifacts or disturbance due to optical sources and skin, causing erroneous saturation data. The aim of this work is to present the measurement procedure based on a specially developed algorithm able to reject erroneous oxygen saturation data during long lasting monitoring of patients in ICU and to compare measurement data with reference data provided by EGA. We have collected SaO(2) data from a standard PO and used an intensive care unit monitor to collect data. This device was connected to our acquisition system and heart rate (HR) and SaO(2) data were acquired and processed by our specially developed algorithm and directly reproduced on the PC screen for use by the clinicians. The algorithm here used for the individuation and rejection of erroneous saturation data is based on the assessment of the difference between the Heart Rate (HR) measured by respectively by the ECG and PO. We have used an emogasanalyzer (EGA) for comparison of the measured data. The study was carried out in a neonatal intensive care unit (NICU), using 817 data coming from 24 patients and the observation time was of about 10000 hours. Results show a reduction in the maximum difference between the SaO(2) data measured, simultaneously, on the same patient by the EGA and by the proposed method of 14.20% and of the 4.76% in average over the 817 samples. The measurement method proposed is therefore able to individuate and eliminate the erroneous saturation data due to motion artifacts and reported by the pulse oxymeter. Specifically in neonatal ICU, it allows to come to more efficient individuation of apnea, hypoxia and hyperoxia events and consequently to operate more adequate and efficient therapeutic actions

Pulmonary surfactant in ARDS

In the last decade there has been growing insight into surfactant function and metabolism and on how exogenous surfactant exerts its therapeutic effects on lungs mechanics, gas exchange and host defence. Furthermore the worldwide use of therapeutic surfactants for premature newborns, used in conjunction with prenatal steroids, has markedly reduced the morbidity and mortality from respiratory distress syndrome, disease that occurs in premature newborns as a result of lung immaturity and surfactant deficient state. Indications for surfactant replacement have widened in recent years and promising results have been obtained for adult conditions such as the acute respiratory distress syndrome (ARDS). This review will summarise the basic biophysics, physiology and biochemistry of surfactant components and will describe pathophysiological mechanisms interfering with surfactant function during the course of ARDS. It will also highlight how circumvention of these mechanisms may lead to improved surfactant treatment for ARDS in newborns, children and adults

Clinical use and efficacy of porcine surfactant for the treatment of RDS in infants with birth weight ≤1000 g: Experience of three years

Objective: Evaluate the clinical response to the first and subsequent doses of natural surfactant for the treatment of respiratory distress syndrome (RDS) in extremely low birth weight infants (ELBWI). Methods: Retrospective chart review of all ELBWI admitted to Neonatal Intensive Care Unit of Padova from July 1995 to December 1998 who received porcine surfactant for the treatment of RDS. Data collection included: (a) standard clinical variables (birth weight, gestational age, material steroid treatment, etc) (b) surfactant dosing), and (c) response to surfactant treatment as assessed by changes in the fraction of inspiratory oxygen (F102) and by the Oxygenation Index (OI). Outcome data (d) which included: death, duration of mechanical ventilation, duration of oxygen therapy, days in hospital stay, OI at 3,7 and 21 days of age, oxygen dependency at 28 days and at 36 week post conception were also collected. Data were analyzed by group comparison tests when comparing the groups that received one (S1), two (S2) or Three (S3) surfactant doses and by multiple regression for the "predictors" of the response to surfactant treatment and for the "predictors" of outcome. Results: Ninety-four ELBWI were evaluated. F1O2 at 12 hours after surfactant was reduced by more than one/third in 62% of the infants after the first dose, in 54% of the second doses and 61% of the third doses (non significant). S1, S2 and S3 groups had similar demographics and birth characteristics but the OI differed at 3 and 7 days (1.73±1.39, 3.34±2.15 and 6.45±5.23 at day 3 and 1.42±1.27, 1.98±1.83 and 4.03±3.91 at day 6 for S1, S2 and S3 respectively, p=0.003). The response of exogenous was not found to be a significant predictor in our multiple regression model for major outcome variables such as oxygen dependency at 28 d or 36 wk. Conclusions: In ELBWI in spite of the high percentages of good clinical response to the first, to the second and even to the third surfactant dose, response to surfactant treatment did not predict major general and respiratory outcomes

Pulmonary surfactant kinetics of the newborn infant: Novel insights from studies with stable isotopes

Deficiency or dysfunction of the pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases of the newborn. After a short review of the pulmonary surfactant, including its role in selected neonatal respiratory conditions, we describe a series of studies conducted by applying two recently developed methods to measure surfactant kinetics. In the first set of studies, namely \u2018endogenous studies\u2019, which used stable isotope-labeled intravenous surfactant precursors, we have shown the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors, including plasma glucose, plasma fatty acids and body water. In the second set of studies, namely \u2018exogenous studies\u2019, which used a stable isotope-labeled phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant disaturated phosphatidylcholine (DSPC) pool size and half-life. The major findings of our studies are presented here and can be summarized as follows: (a) the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm infants with respiratory distress syndrome (RDS) are very low with either precursor; (b) in preterm infants with RDS, pool size is very small and half-life much longer than what has been reported in animal studies; (c) patients recovering from RDS who required higher continuous positive airway pressure pressure after extubation or reintubation have a lower level of intrapulmonary surfactant than those who did well after extubation; (d) term newborn infants with pneumonia have greatly accelerated surfactant catabolism; and (e) infants with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, but those requiring extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases