A dual stable isotope tracer method for the measurement of surfactant disaturated-phosphatidylcholine net synthesis in infants with congenital diaphragmatic hernia

he aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hemia [CDH; birth weight, 3.4 \ub1 0.2; gestational age, 39.8 \ub1 0.4 wk] and 6 4ge-matched control subjects with no lung disease (birth weight, 3.2 0.3 kg; gestational age, 39.1 \ub1 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 dipalmitoyl- phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean \ub1 SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 \ub1 2.2 and 8.1 \ub1 1.5 mg\ub7kg-1\ub7d -1; P = 0.7). DSPC apparent pool size was 36.7 \ub1 7.5 and 58.5 \ub1 9.1 mg/kg (P = 0.07) and half-life was 26.7 \ub1 4.5 and 50.3 \ub1 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was 3c8 mg\ub7kg-1\ub7d-1. No significant differences were found between control subjects and infants with CDH. DSPC tumover was faster in infants with CDH presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained

Modes and strategies for providing conventional mechanical ventilation in neonates

Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice

Pulmonary Surfactant Disaturated-Phosphatidylcholine (DSPC) Turnover and Pool Size in Newborn Infants with Congenital Diaphragmatic Hernia (CDH)

In animal CDH models, surfactant deficiency contributes to the pathophysiology of the condition but information on human disease is very limited. The aim of our study was to investigate surfactant kinetics in CDH newborns. We studied surfactant disaturated-phosphatidylcholine (DSPC) half-life, turnover and apparent pool size by stable isotope methodology in CDH new-borns with no ExtraCorporeal Membrane Oxygenation (ECMO) support (n = 13, birth weight (BW) 3.2 \ub1 2.2 kg, gestational age (GA) 39 \ub1 0.4 wks, postnatal age 43 \ub1 11 h) and in 8 term infants with no lung disease (CONTROLS, BW 2.7 \ub1 0 kg, GA 38 \ub1 0.8 wks, postnatal age 96 +\ub1 26 h). We administered a trace dose of 13C-palmitic acid dipalmitoyl-phosphatidylcholine (DPPC) through the endotracheal (ET) tube and we measured DSPC kinetics by gas chromatography-mass spectrometry from DSPC 13C-enrichment decay curves obtained from sequential tracheal aspirates. DSPC amount from tracheal aspirates (TA-DSPC) was measured by gas chromatography. In CDH infants DSPC half-life was shorter (24 \ub1 4 and 53 \ub1 11 h, p = 0.01), turnover faster (0.6 \ub1 0.1 and 1.5 \ub1 0. 3 d-1 p = 0.01), apparent pool size smaller (34 \ub1 6 and 57 \ub1 7 mg/kg body weight, p = 0.02) and tracheal aspirates DSPC amount lower (2.4 \ub1 0.4 and 4.6 \ub1 0.5 mg/mL Epithehal Lining Fluid (ELF), p = 0.007) than in CONTROLS. In conclusion surfactant kinetics is grossly abnormal in mechanically ventilated CDH. Whether alterations of DSPC kinetics in CDH infants are caused by a primary surfactant deficiency or are secondary to oxygen therapy and ventilator support has still to be determined

Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia

BACKGROUND Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONS In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768. opens in new tab.