Published online July 1, 2008
PEDIATRICS Vol. 122 No. 1 July 2008, pp. 102-108 (doi:10.1542/peds.2007-1021)
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ARTICLE

Surfactant Status in Preterm Neonates Recovering From Respiratory Distress Syndrome

Giovanna Verlato, MD, PhDa, Paola Elisa Cogo, MD, PhDa, Marco Balzani, MDa, Antonina Gucciardi, PhDa, Ilaria Burattini, MDb, Fernando De Benedictis, MDc, Giovanna Martiri, MDb and Virgilio Paolo Carnielli, MD, PhDb,c

a Department of Pediatrics, University of Padova, Padova, Italy
b Division of Neonatology, Institute of Maternal-Infantile Sciences, Polytechnic University of Marche, Ancona, Italy
c Division of Pediatrics, Salesi Children Hospital, University of Ancona, Ancona, Italy


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. The goal was to establish whether reduced amounts of pulmonary surfactant contribute to postextubation respiratory failure in preterm infants recovering from respiratory distress syndrome.

METHODS. We prospectively recruited preterm infants who needed mechanical ventilation and exogenous surfactant for treatment of moderate/severe respiratory distress syndrome and could not be extubated before day 3 of life. 13C-labeled dipalmitoyl-phosphatidylcholine was administered endotracheally as tracer before extubation, for estimation of surfactant disaturated phosphatidylcholine pool size and half-life. Patients were retrospectively divided into 3 groups, that is, extubation failure if, after extubation, they needed reintubation or continuous positive airway pressure treatment of ≥6 cmH2O and fraction of inspired oxygen of >0.4, extubation success if they did not meet the failure criteria, and not extubated if they needed ongoing ventilation. Clinical and respiratory parameters were recorded hourly.

RESULTS. Reliable kinetic data could be obtained for 63 of the 88 enrolled neonates. Sixteen, 23, and 24 neonates were categorized in the extubation failure, extubation success, and not extubated groups, respectively. Clinical and demographic characteristics did not differ between the extubation failure and extubation success groups. Disaturated phosphatidylcholine pool size was smaller in the extubation failure group than in the extubation success group (25 ± 12 vs 43 ± 24 mg/kg) and was 37 ± 32 mg/kg in the not extubated group. Disaturated phosphatidylcholine half-life was 19 ± 7, 24 ± 12, and 28 ± 18 hours in the extubation failure, extubation success, and not extubated groups, respectively.

CONCLUSIONS. In a selected population of preterm infants with moderate/severe respiratory distress syndrome who could not be extubated in the first 3 days of life, infants who were reintubated or needed high continuous positive airway pressure settings after extubation had a smaller disaturated phosphatidylcholine pool size than did those who were successfully extubated or needed low continuous positive airway pressure settings.

Key Words: pulmonary surfactant • isotopes • low birth weight infants • respiratory distress syndrome

Abbreviations: CPAP—continuous positive airway pressure • DPPC—dipalmitoyl-phosphatidylcholine • EF—extubation failure • ES—extubation success • NE—not extubated • GA—gestational age • FIO2—fraction of inspired oxygen • PS—pool size • RDS—respiratory distress syndrome • DSPC—disaturated phosphatidylcholine • TA—tracheal aspirate • MAP—mean airway pressure

The pulmonary management of small preterm neonates is directed at minimizing the need for prolonged mechanical ventilation, with the aim of reducing its associated complications, such as ventilator-induced lung injury, pulmonary infections, and chronic lung disease.1,2 Early discontinuation of mechanical ventilation presents difficulties, and up to 25% to 52% of preterm neonates experience extubation failure (EF).3–5 Most articles dealing with EF in preterm neonates have focused on clinical variables and lung function measurements as predictors of EF/extubation success (ES).6,7 Several interventions to decrease the risk of EF have been studied.8,9 Among these, continuous positive airway pressure (CPAP) treatment, nasal intermittent positive pressure ventilation, and methylxanthine treatment have been proven to be effective, whereas other interventions (intravenous dexamethasone therapy, doxapram treatment, nebulized racemic epinephrine treatment, and chest physiotherapy) either are ineffective or are associated with unacceptable adverse effects.9

To our knowledge, the relationship between pulmonary surfactant status and EF has not yet been studied. The rationale for performing this study is based on 2 main observations, that is, (1) the synthesis of endogenous surfactant in preterm infants with respiratory distress syndrome (RDS) is a slow process and is especially slow in selected individuals10–12 and (2) the half-life of exogenous surfactant, although variable, is much shorter than that of endogenous surfactant.13,14 We hypothesized that, in selected individuals, when the effect of exogenous surfactant wears off and endogenous synthesis is still insufficient, a state of transient deficiency develops. This transient deficiency may not be clinically apparent, being masked by the widespread use of positive airway distending pressure applied during mechanical ventilation. After extubation, it may become apparent because of the loss of functional residual capacity. This may lead, in selected individuals, to increased respiratory distress, a need for higher distending pressures, and eventually increased risk for reintubation. In addition, multiple factors can be associated with reduced endogenous surfactant synthesis, such as prolonged mechanical ventilation,2 clinical lung infections,15 genetic predisposition,16–18 and nutritional status.19

We recently developed a technique, based on the use of stable isotopes, that allows estimation of the intrapulmonary surfactant disaturated phosphatidylcholine (DSPC) pool size (PS) and half-life. This is achieved through the endotracheal administration of a stable isotope-labeled tracer, dipalmitoyl-phosphatidylcholine (DPPC), and mathematical modeling of the isotopic enrichment curve over time for the surfactant DSPC in sequential tracheal aspirates (TAs).13,20,21 Stable isotopes are nonradioactive, and they can be used safely in vivo in humans. Their main advantage, compared with radioactive tracers, is that the stable isotope enrichments are not affected by the sample dilution, because the ratio between the stable isotope (tracer) and the respective nonlabeled molecules (tracee) remains constant when the sample is diluted, provided there is homogeneous mixing between the tracer and the tracee. By applying this technique, we found that preterm infants with RDS had a DSPC PS of 5.8 mg/kg.13 We also found that the DSPC PS was 57 ± 7 mg/kg in term neonates with normal lungs21 and 66 ± 16 mg/kg in small preterm neonates who had minimal lung disease and who underwent ventilation for ≥3 days.22 These in vivo estimates compared quite nicely with animal data, where DSPC pools were measured in alveolar lavage fluid and in lung tissue directly at autopsy or were derived from the instillation of radioactive tracers into the animals' airways.12,23,24

Preterm lambs with gestational age (GA) corresponding to 34 weeks of human pregnancy had DSPC PS of ~37 mg/kg at birth, ~66 mg/kg after 6 hours of CPAP therapy at 8 cmH2O, and 55 mg/kg after 6 hours of mechanical ventilation.23 In preterm baboons with GA corresponding to 27 to 35 weeks, DSPC PS ranged from 29 to 37 mg/kg at birth and increased to 125 mg/kg after 6 days of mechanical ventilation. Newborn baboons born at term had DSPC PS of 100 mg/kg, whereas the value for adult baboons was 10 to 15 mg/kg.24 For human adults, estimates of 10 mg/kg were also determined through direct measurements at autopsy.25

In this study, we measured preextubation DSPC PS in preterm infants recovering from moderate/severe RDS who could not be extubated during the first 3 days of life. We investigated whether a marginal surfactant deficiency (ie, a reduction in surfactant PS) could contribute to postextubation respiratory distress and EF.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Design
The study was conducted between January 2001 and December 2005 in the NICUs of the University Hospital of Padova (Padova, Italy) and the Polytechnic University of Marche (Ancona, Italy). The study was divided into 3 phases. The first phase was the recruitment period. Patients who were eligible for the study were a selected group of small preterm neonates with moderate/severe RDS who were treated with mechanical ventilation and exogenous surfactant and who could not be weaned from the ventilator before 72 hours of life. Patients were treated at the 2 institutions according to common guidelines. Predefined criteria were used for surfactant treatment, extubation and reintubation, ventilation, and CPAP use. All infants received conventional, synchronized, intermittent, mandatory ventilation (Draeger Babylog 8000 Plus [Draeger Medical Italia SpA, Milan, Italy] or Bird VIP Gold ventilator [Burke & Burke, Milan, Italy]). Exogenous surfactant (Curosurf; Chiesi, Parma, Italy) was given as early rescue when the infants needed endotracheal intubation at delivery or at admission to the NICUs. Infants who did not need immediate intubation began CPAP treatment and received surfactant if they were <28 weeks with CPAP levels of >6 cmH2O and fraction of inspired oxygen (FIO2) of >0.3 or if they were ≥28 weeks with CPAP levels of >6 cmH2O and FIO2 of >0.4.

Preterm newborns were enrolled prospectively in this study if they met the following inclusion criteria: (1) birth weight of ≤1500 g; (2) postnatal age between 3 and 20 days; (3) improving respiratory insufficiency, with FIO2 of ≤0.4, peak inspiratory pressure/end expiratory pressure of ≤18/4 cmH2O, respiratory rate of ≤40 breaths per minute, mean airway pressure (MAP) of ≤7.5 cmH2O, and inspiratory time of ≤0.5 seconds, with an arterial/capillary pH of >7.20 and PaCO2 of <60 mmHg; (4) likely to need mechanical ventilation for an additional 36 hours (to allow sufficient time for surfactant kinetic measurement); (5) at least 36 hours from the last exogenous surfactant dose; and (6) no postnatal corticosteroid treatment at any time. Infants were excluded from the study if they had (1) cardiovascular instability, (2) congenital infections, (3) major congenital anomalies, (4) severe asphyxia,26 (5) intracranial bleeding of grade 3 or higher, or (6) lack of parental consent.

The second phase was the study period. The start of the study was at any time between 3 and 20 days of age, if inclusion criteria were met, and coincided with the intratracheal administration of 13C-labeled DPPC (2.5 mg/kg 13C-labeled DPPC, mixed with ~5 mg/kg exogenous surfactant [Curosurf, Chiesi] as carrier). In this study, we used [13C]DPPC as tracer and we used the [13C]DPPC/DSPC ratio to derive the kinetic parameters. After routine endotracheal suctioning, a 6-French catheter was placed beyond the tip of the endotracheal tube and the prewarmed tracer was administered via the catheter. The neonate was then reconnected to the ventilator.

TAs were collected before tracer administration (time 0), every 6 hours until time 72 hours, and then every 12 hours until extubation. TAs were obtained as described previously.13 In brief, 0.5 mL/kg 0.45% saline solution was injected through the endotracheal tube. The neonate was treated with gentle hand-bagging for 30 seconds, and then tracheal secretions were collected through a Lukens trap. Each TA was kept at 4°C for ≤3 hours after collection, brought to a final volume of 2 mL with saline solution, and centrifuged at 150 x g for 10 minutes, and the supernatant was stored at –20°C until analysis.

The timing of extubation was decided by the attending physician in charge of the NICU, who was not involved in the study. Extubation was performed when FIO2 was <0.4, peak inspiratory pressure was <16 cmH2O, and respiratory rate was <20 breaths per minute. All study infants received caffeine before extubation (10 mg/kg caffeine as a bolus, followed by 5 mg/kg per day). Clinical and physiologic parameters (respiratory rate and heart rate) were measured hourly during the study.

The third phase was the follow-up period. After extubation, all study infants received oxygen therapy and nasal CPAP treatment starting at 4 cmH2O, which was increased to obtain arterial oxygen saturation values of 88% to 92%. Infants who required reintubation within 48 hours after extubation or who required CPAP levels of ≥6 cmH2O with FIO2 of >0.4 to obtain arterial oxygen saturation values of >88% were grouped in the EF group. The decision to reintubate was made by the attending physician in charge of the NICU, and reintubation was considered when patients experienced 1 of the following conditions: (1) >12 episodes of apnea or desaturation requiring stimulation in 24 hours; (2) mask-bagging >6 times in 24 hours; (3) respiratory insufficiency, defined as PaCO2 of >65 mmHg (8.5 kPa) and pH of <7.20 in arterial or arterialized capillary blood gas samples; or (4) FIO2 of >0.6 to maintain oxygen saturation values of 82% to 92%.

Study patients who were extubated within 5 days after the study start and did not meet the EF criteria were assigned to the ES group. Study infants who could not be weaned from the ventilator within 5 days after the study start were assigned to the not extubated (NE) group.

Analytical Methods
The analytical methods were described previously.13 In brief, lipids were extracted from TAs according to the method described by Bligh and Dyer,27 DSPC was separated by thin layer chromatography after treatment with osmium tetroxide, the amount was calculated by measuring the individual fatty acid components of DSPC with capillary gas chromatography, and values were normalized per milliliter of TA.13 The 13C enrichment of DSPC from the TAs was measured with gas chromatography-mass spectrometry, and results were expressed as mole percent excess.28 Personnel involved in the analytical determinations were unaware of the clinical conditions of the patients.

Ethical Approval
The local ethics committee approved the protocol. Written informed consent was obtained from at least 1 parent.

Calculations
DSPC PS and half-life were calculated from the monoexponential part of the DSPC decay enrichment curve over time.13 The software used for calculation of DSPC kinetics was PRISM 3.0 (GraphPad, San Diego, CA). Extrapolation back to the time of administration of the tracer (t = 0) yielded the 13C enrichment at t = 0, from which we calculated the dilution of the tracer. Data were expressed as individual values or mean ± SD and were compared with analysis of variance with the Bonferroni posthoc test. Significance was set at a level of .05. All statistical analyses were performed by using SPSS 12.0 (SPSS, Chicago, IL) and Microsoft Excel 2000 (Microsoft, Redmond, CA).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
We studied 88 ventilator-dependent, preterm neonates (birth weight: 825 ± 226 g; GA: 26.5 ± 2.3 weeks) who were recovering from moderate/severe RDS, at a mean postnatal age of 12 ± 8 days. Nine patients were excluded from the analysis because the study was performed after 20 days of age, in violation of the study protocol. Fourteen patients were lost to analysis because they were extubated too soon after the study start. Two more patients were lost to analysis because of analytical problems encountered during sample processing. Of the remaining 63 patients (birth weight: 843 ± 243 g; GA: 26.5 ± 2.4 weeks; age at study: 10 ± 7 days), 16 were in the EF group and 23 in the ES group. Twenty-four neonates could not be extubated within 5 days after the study start because of insufficient respiratory drive, slow clinical improvement, or worsening clinical conditions. Clinical characteristics at the study start and before extubation for the 3 study groups are presented in Table 1. Patients in the NE group had significantly lower birth weight and GA, compared with patients in the EF and ES groups (Table 1). In the EF group, 3 (19%) of 16 patients needed to be reintubated because of increasing respiratory distress. Extubation in the NE group was delayed because of metabolic acidosis (pH < 7.20) related to patent ductus arteriosus (n = 9), sepsis (n = 6), insufficient respiratory drive (n = 5), or other causes (n = 4). Cumulative doses of exogenous surfactant were similar among the 3 study groups (Table 1).


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  		TABLE 1 Clinical Characteristics of the Study Infants

 
The DSPC PS data are depicted in Fig 1. The EF group had significantly lower DSPC PS than did the ES group (P = .034). The differences were of the same degree in the subgroup of infants with birth weights of <1000 g, but the number of those infants was too small to yield a significant difference (data not shown). The DSPC half-life was 19 ± 7, 24 ± 12, and 28 ± 18 hours in the EF, ES, and NE groups, respectively; the differences were not significant (Fig 2). The DSPC amounts obtained from TAs were 29 ± 18, 33 ± 19, and 30 ± 19 mg/mL in the EF, ES, and NE groups, respectively (not significant).


Figure 1
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  		FIGURE 1 Surfactant DSPC PS in the EF, ES, and NE groups. Values are significantly different between the ES and EF groups.

 

Figure 2
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  		FIGURE 2 Surfactant DSPC half-life in the EF, ES, and NE groups. Values are not significantly different between the ES, EF, and NE groups.

 
No significant correlations were found between DSPC PS, half-life, and clinical data. Ventilator and oxygenation parameters for the EF, ES, and NE groups at the study start and during the study are presented in Table 1. There were no differences in ventilator support or degree of oxygen requirement, expressed as mean FIO2, peak inspiratory pressure, and MAP, at the start of the study. MAP x FIO2 values during the 12 hours before extubation were 1.6 ± 0.8 and 1.1 ± 0.4 cmH2O in the EF and ES groups, respectively (P < .05). DSPC PS did not correlate with postextubation FIO2 ({rho} = 0.016; P = .99) and CPAP or MAP values ({rho} = –0.04; P = .8, data not shown). No correlation was found also when DSPC half-life was assessed.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
The patients enrolled in this study represented a selected population of preterm infants who were suffering from moderate/severe RDS and for whom extubation during the first 3 days of life was not possible, despite optimal treatment. We estimated that this selected population of preterm infants with slow improvement of respiratory status represented no more than 10% of the preterm infants with RDS admitted to the 2 NICUs involved in the study. To understand more completely the surfactant status of this group of patients, we applied a technique13,22 based on the use of safe stable isotopes, which allows the assessment of surfactant status in vivo. We found that the infants who, after extubation, required the highest distending pressures and greatest FIO2 or required reintubation had a significantly smaller DSPC PS, compared with the infants who needed lower CPAP levels and lower FIO2. This finding adds novel information to the complexity of the multifactorial nature of postextubation respiratory failure/distress of preterm neonates recovering from RDS. We chose a "permissive" definition of EF because we could not study a large number of patients and because of the exploratory nature of this study. We simply wanted to study whether patients with more-severe postextubation respiratory distress had smaller amounts of pulmonary surfactant than did patients who fared better after extubation. The EF group had a mean DSPC PS of 25 mg/kg, whereas the value for the ES group was 43 mg/kg. This represents a mean reduction of 48% in the EF group, compared with the ES group. EF is undoubtedly multifactorial,4,6,7,29 with the most common causes being (1) residual lung disease, (2) neuromuscular failure, and (3) airway patency problems. In this pilot study, we did not record any respiratory function test results; therefore, we cannot elaborate on how our findings relate to lung function.

We think that the novelty of this study is that we found smaller surfactant PS in the EF group despite similar cumulative doses of exogenous surfactant. This finding raises 2 questions. (1) Why was exogenous surfactant not fully retained (or quickly catabolized) by the preterm lung in the EF group? (2) Was endogenous surfactant synthesis reduced in the EF group? We briefly address these 2 issues.

Scanty data exist on the pharmacokinetics of exogenous surfactant in humans13,14,30–32 and on the amount of pulmonary surfactant that is critical for maintaining adequate lung function and preventing alveolar collapse during expiration. Estimation of surfactant PS in preterm neonates with RDS was attempted with indirect methods.30,31 More recently, we developed a method to assess in vivo DSPC PS and half-life.13 In preterm neonates with RDS, the mean DSPC PS was 5.8 mg/kg at the time of administration of the first surfactant dose and increased to 17.3 ± 13.6 before the second surfactant dose.13 In term neonates with normal lungs, we found a much larger DSPC PS of 57 ± 7 mg/kg.21 With the use of the same technique in the present study, the DSPC PS was 25 ± 12 mg/kg in the EF group. This mean value was only 8 mg/kg higher than the 17 mg/kg found for preterm neonates at the time of the second surfactant administration.13 Of note, there was a large difference between the cumulative dose of exogenous surfactant administered (230 mg/kg total phospholipids, corresponding to ~92 mg/kg DSPC) and the DSPC PS before extubation. This finding can be explained by incomplete retention of exogenous surfactant, accelerated catabolism (or decreased recycling), and/or reduced endogenous synthesis. Alternatively, the reduced DSPC PS in infants with early failure might simply have been a reflection of more-severe underlying lung disease.

Genetic predisposition,16,17 variable degrees of lung inflammation,22,33 mechanical ventilation-induced injury,33 and possibly other factors all may contribute to our findings. More information is needed on the pharmacokinetics of exogenous surfactant and on the variables affecting endogenous synthesis. There is no doubt that ultimately the patient must rely on endogenous surfactant synthesis for optimal lung function. More information is now available on the capacity for endogenous surfactant synthesis in preterm and term infants.11,34–39 Recent in vivo studies showed that DSPC or phosphatidylcholine synthesis is a very slow process and also that very small amounts of surfactant proteins were detectable in the TAs of preterm infants who were mechanically ventilated and treated with artificial surfactant.34 In preterm infants with RDS, the mean DSPC fractional synthesis rates were calculated to be ~2.7% per day from plasma glucose and ~10% per day from plasma fatty acids.10,11 According to those studies, patients with fractional synthesis rates 1 SD below the mean would need ~6 to 8 days to synthesize 40 to 50 mg/kg DSPC endogenously. On the basis of this information, we suggest that a subgroup of preterm neonates could experience a temporary shortage of pulmonary surfactant when exogenous surfactant wears off and endogenous synthesis is reduced. In this scenario, preterm infants with resolving RDS could maintain alveolar distension and adequate functional residual capacity when mechanically ventilated (with adequate distending pressure), but they might experience progressive alveolar collapse, respiratory fatigue, and finally EF when weaned from the ventilator with insufficient distending pressure during CPAP treatment. Perhaps more importantly, our finding is the rationale for studying the use of additional doses of exogenous surfactant in this selected group of preterm infants. A randomized, clinical trial of exogenous surfactant supplementation before late extubation for the prevention of EF is in progress.

In the past, surfactant treatment has been given to preterm neonates with persistent respiratory failure and an ongoing need for respiratory support, with improvements in terms of oxygen dependency.40 However, those studies were not powered to detect significant clinical outcomes. Also, aggressive extubation was not attempted at the time of the maximal clinical effect. A more-recent study, reported in abstract form, showed that the administration of exogenous surfactant (Infasurf [Calfactant, Forest Pharmaceuticals, St Louis, MO], 3 mL/kg) to infants at <28 weeks of gestation and >7 days of age resulted in improvements in respiratory severity scores.41 Those studies support the hypothesis that surfactant shortage and dysfunction could play a role in respiratory failure, not only during the acute phase of RDS but also in cases of persistent respiratory failure. At variance with the aforementioned studies, our study patients were rather young, in terms of postnatal age, and were at low risk of developing bronchopulmonary dysplasia, they had only moderate respiratory failure at the time of the study, and they were candidates for extubation.

Half-life did not show significant differences between the EF and ES groups (P = .2). Half-life reflects the disappearance of label from sequential TAs and is an overall measure of turnover of surfactant, being influenced by reuptake in lung cells and degradation. The results of our study suggest a reduced endogenous DSPC PS in the absence of significant differences in DSPC turnover in preterm infants with mild respiratory disease.

During the study, MAP and FIO2 were recorded hourly. As shown in Table 1, mean FIO2 x MAP values 12 hours before extubation did differ between the EF and ES groups, whereas FIO2 was significantly higher in the NE group before the study start. We also recorded mean FIO2, CPAP, and FIO2 x MAP (or CPAP) values in the first 2 days after extubation. FIO2 x CPAP values were significantly higher in the EF group than in the ES group, as expected, but we could not find any significant correlations between these parameters and the DSPC PS in the ES and EF groups. A study with a larger number of patients might clarify whether significant correlations do exist between surfactant status and the indices of respiratory failure/support. Other ventilator parameters, such as tidal volumes and minute ventilation or derived indexes of respiratory mechanics and oxygenation, were not recorded consistently, given the exploratory nature of this study, but should be included in future studies.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Our results show that a marginal surfactant deficiency is associated with EF and with significant worsening of respiratory status after extubation. This suggests that there may be differences in surfactant metabolism in preterm neonates after surfactant replacement therapy. Understanding these differences may help in devising new therapeutic strategies. The role of nonconventional exogenous surfactant use for patients at high risk of EF should be further explored, especially in view of the willingness of most neonatologists to perform early extubation.


   ACKNOWLEDGMENTS
 
We are extremely grateful to the nurses of the NICUs of Padova and Ancona, who helped us by collecting TA samples. We also thank Dr Aparna Hoskote (Great Ormond Street Hospital, London, England) for helping us to revise the manuscript.


   FOOTNOTES
 
Accepted Oct 23, 2007.

Address correspondence to Paola Elisa Cogo, MD, PhD, Department of Pediatrics, University of Padova, Via Giustiniani 3, Padova 35128, Italy. E-mail: cogo{at}pediatria.unipd.it

The authors have indicated they have no financial relationships relevant to this article to disclose.


What's Known on This Subject

Predictors of extubation failure have been mainly identified among clinical variables and lung function measurements.

 

What This Study Adds

Preterm infants with severe respiratory distress syndrome who experienced extubation failure after ≥3 days of mechanical ventilation had a smaller surfactant disaturated phosphatidylcholine pool size, compared with preterm infants who were successfully extubated after 3 days of mechanical ventilation.

 


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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Pediatrics, February 1, 2009; 123(2): e367 - e367.
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