[No increase of incidence of retinopathy of prematurity and improvement of its outcome in a university perinatal centre level III - a prospective observational study from 1978 to 2007]. / Kein Anstieg von Inzidenz, Therapie- und Erblindungsrate der Retinopathia praematurorum in einem universitären Perinatalzentrum Level 1 - eine prospektive Beobachtungsstudie von 1978 - 2007.

BACKGROUND: There is a controversy over whether the improved survival rate of extremely low birth weight (ELBW; birth weight < 1000 g) and of extremely low gestational age (ELGA; gestational age < 28 weeks) infants has resulted in a higher incidence of severe retinopathy of prematurity (ROP) and induced blindness. We studied the incidence, treatment and the structural outcome of ROP in a Perinatal Centre Level III over a 30-year period in infants < 1500 g birth weight (VLBW = very low birth weight). PATIENTS AND METHODS: 1473 VLBW infants, who survived the first 28 days, had ocular examinations from 1978 to 2007. Neonatal and ROP data were collected prospectively. Proliferative ROP, threshold disease and high-risk prethreshold ROP indicated treatment for peripheral retinal ablation in respect to the CRYO-ROP and ETROP studies. Incidence, treatment and structural outcome of ROP were analysed for the periods 1978 - 1992 (P1) and 1993 - 2007 (P2) and for children with BW < 1000 g and > 1000 g. RESULTS: In P 1 43.1 % (n = 87) ELBW infants survived and 82.3 % (n = 372) in P 2, whereas the survival rates of the infants with a BW of 1000 - 1499 g were 74.6 % (n = 453) and 95.1 % (561), respectively. The ROP incidence was decreased from 27.6 % (n = 149) in P 1 to 15.1 % (n = 141) in P 2 significantly (p < 0.003) as well the mean BW 1136.6 ± 211.3 g to a mean BW 822.3 ± 215.3 g and the mean gestational age (GA) 29.3 ± 2.2 weeks and to a mean GA 26.4 ± 2 weeks, respectively (both differences p < 0.001). Also the coagulation rate was significantly decreased from 13 % (n = 70) in P 1 to 6.8 % (n = 63) in P 2 (p = 0.043). The blindness rates (structurally unfavourable outcome of both eyes) of 1.5 % in P 1 and 1.0 % in P 2 were not significantly reduced (p = 0.543). Among the ELBW the number of ROP infants was increased from 39 in P 1 to 117 in P 2 while the ROP incidence decreased from 44.8 % to 31.5 % (p = 0.053) and the ROP-OP rate from 19.5 % to 14.8 % (p = 0.029). Also among the ELGA the number ROP infants was increased from 66 in P 1 to 121 in P 2 but the ROP incidence was reduced from 70.2 % to 27.6 % and the ROP-OP rate from 30.9 % to 13.2 % (both p < 0.001). CONCLUSIONS: Inspite of an increase of the number of ELBW/ELGA infants and their survival rate in 1978 - 2007 there is no increase in the incidence of ROP, operations and blindness among the VLBW and VLGA infants.

Positive effects of early continuous positive airway pressure on pulmonary function in extremely premature infants: results of a subgroup analysis of the COIN trial.

OBJECTIVE: Early continuous positive airway pressure (CPAP) may reduce lung injury in preterm infants. PATIENTS AND METHODS: Spontaneously breathing preterm infants were randomised immediately after birth to nasal CPAP or intubation, surfactant treatment and mechanical ventilation. Pulmonary function tests approximately 8 weeks post-term determined tidal breathing parameters, respiratory mechanics and functional residual capacity (FRC). RESULTS: Seventeen infants received CPAP and 22 mechanical ventilation. Infants with early CPAP had less mechanical ventilation (4 vs 7.5 days; p=0.004) and less total respiratory support (30 vs 47 days; p=0.017). Post-term the CPAP group had lower respiratory rate (41 vs 48/min; p=0.007), lower minute ventilation (223 vs 265 ml/min/kg; p=0.009), better respiratory compliance (0.99 vs 0.82 ml/cm H(2)O/kg; p=0.008) and improved elastic work of breathing (p=0.004). No differences in FRC were found. CONCLUSIONS: Early CPAP is feasible, shortens the duration of respiratory support and results in improved lung mechanics and decreased work of breathing.

The effect of surgery on lung volume and conventional monitoring parameters in ventilated newborn infants.

In newborn infants, thoraco-abdominal surgery is a serious intervention with respect to gas exchange and lung mechanics. This prospective clinical study compared surgery-induced changes in functional residual capacity (FRC) and ventilation inhomogeneity (VI) indices with changes in conventional monitoring parameters. Of 29 ventilated newborns (mean weight 2,770+/-864 g at surgery), 13, nine and seven underwent thoracic, abdominal or congenital diaphragmatic hernia (CDH) surgery, respectively. The multiple breath washout (MBWO) technique using heptafluoropropane as tracer gas (Babylog 8000; Dräger, Lübeck, Germany) was performed <6 h before surgery, 22-24 h after surgery and <6 h before extubation. Gas exchange, respiratory mechanics, FRC and VI index data were recorded. Thoraco-abdominal surgery resulted in changes to FRC and VI indices in a procedure-specific manner; however, these changes were not reflected in conventional mechanical or ventilatory monitoring parameters. FRC decreased in non-CDH infants, while FRC increased and VI indices decreased in CDH infants. Despite improvements, the differences in FRC and VI between CDH and non-CDH infants indicated persistent impaired lung function in CHD infants. MBWO can be advantageously used to measure the effect of surgery on the lung. While FRC and VI indices changed following surgery, conventional monitoring parameters did not.

Influence of bathing or washing on skin barrier function in newborns during the first four weeks of life.

BACKGROUND AND OBJECTIVES: After birth, skin barrier function is in state of flux and at risk of dysfunction. In a prospective clinical study, we compared the effects of 2 standard cleansing procedures on skin barrier function in newborns. METHODS: Fifty-seven healthy full-term neonates aged < or = 48 h were randomly assigned to either a bathing group (group B; n = 29), who were bathed with clear water twice weekly, or to a washing group (group W; n = 28), who were washed with a washcloth moistened with clear water twice weekly. Transepidermal water loss (TEWL), skin pH, stratum corneum hydration (SCH) and sebum production were measured at days 2, 7 and 28 of life on the forehead, abdomen, upper leg and buttock. RESULTS: Group B showed significantly lower TEWL on the buttock and higher SCH on the abdomen and forehead compared to group W at day 28. CONCLUSIONS: Both skin care regimens do not harm the adaptation of the skin barrier in healthy neonates within the first 4 weeks of life. Skin barrier function differentiates after birth in a regionally specific fashion.

Assessment of volume and leak measurements during CPAP using a neonatal lung model.

Although several commercial devices are available which allow tidal volume and air leak monitoring during continuous positive airway pressure (CPAP) in neonates, little is known about their measurement accuracy and about the influence of air leaks on volume measurement. The aim of this in vitro study was the validation of volume and leak measurement under CPAP using a commercial ventilatory device, taking into consideration the clinical conditions in neonatology. The measurement accuracy of the Leoni ventilator (Heinen & Löwenstein, Germany) was investigated both in a leak-free system and with leaks simulated using calibration syringes (2-10 ml, 20-100 ml) and a mechanical lung model. Open tubes of variable lengths were connected for leak simulation. Leak flow was measured with the flow-through technique. In a leak-free system the mean relative volume error +/-SD was 3.5 +/- 2.6% (2-10 ml) and 5.9 +/- 0.7% (20-60 ml), respectively. The influence of CPAP level, driving flow, respiratory rate and humidification of the breathing gas on the volume error was negligible. However, an increasing F(i)O(2) caused the measured tidal volume to increase by up to 25% (F(i)O(2) = 1.0). The relative error +/- SD of the leak measurements was -0.2 +/- 11.9%. For leaks > 19%, measured tidal volume was underestimated by more than 10%. In conclusion, the present in vitro study showed that the Leoni allowed accurate volume monitoring under CPAP conditions similar to neonates. Air leaks of up to 90% of patient flow were reliably detected. For an F(i)O(2) > 0.4 and for leaks > 19%, a numerical correction of the displayed volume should be performed.

Use of continuous positive airway pressure (CPAP) in neonatal units--a survey of current preferences and practice in Germany.

UNLABELLED: There is only limited evidence regarding the equipment or the settings (pressure and flow) at which CPAP should be applied in neonatal care. Aims of this nationwide survey of German neonatal units were to investigate (1) for which clinical indications CPAP was employed, (2) which CPAP equipment was used, (3) which CPAP settings were applied. A questionnaire on the use of CPAP was sent to all children's hospitals in Germany. Data were stratified and compared by level of medical care provided (non-academic children's hospital, academic teaching hospital and university children's hospital). 274 institutions were contacted by mailed questionnaire. The response rate was 86%, 90 non-academic children's hospitals, 119 academic teaching hospitals and 26 university children's hospitals replied. (1) There were no statistically significant difference in CPAP use between the institutions: 231 (98%) used CPAP for treating respiratory distress syndrome, 225 (96%) for treating apnoea-bradycardia-syndrome and 230 (98%) following extubation. (2) Commercial CPAP systems were employed by 71% of units, the others used a combination of different devices. Respirator generated CPAP was most commonly used. Exclusively mononasal CPAP was used by only 9%, and binasal CPAP by 55% of institutions. (3) Median CPAP was 4.5 cm H2O (range 3-7), median maximum CPAP was 7 cm H2O (range 4-10), with no statistically significant differences between the hospitals. CONCLUSION: Between units, CPAP was given via a broad range of CPAP systems and at varying pressure settings. The reported differences reflects personal experiences and preferences, rather than sound evidence from clinical trials.

The effect of changing ventilator settings on indices of ventilation inhomogeneity in small ventilated lungs.

BACKGROUND: In ventilated newborns the use of multiple breath washout (MBW) techniques for measuring both lung volume and ventilation inhomogeneity (VI) is hampered by the comparatively high dead space fraction. We studied how changes in ventilator settings affected VI indices in this particular population. METHODS: Using a computer simulation of a uniformly ventilated volume the interaction between VI indices (lung clearance index (LCI), moment ratios (M1/M0, M2/M0, AMDN1, AMDN2) of the washout curve) and tidal volume (VT), dead space (VD) and functional residual capacity (FRC) were calculated. The theoretical results were compared with measurements in 15 ventilated piglets (age <12 h, median weight 1135 g) by increasing the peak inspiratory pressure (PIP). FRC and VI indices were measured by MBW using 0.8% heptafluoropropane as tracer gas. RESULTS: The computer simulation showed that the sensitivity of most VI indices to changes in VD/VT and VT/FRC increase, in particular for VD/VT > 0.5. In piglets, the raised PIP caused a significant increase of VT from 15.4 +/- 9.5 to 21.9 +/- 14.7 (p = 0.003) and of the FRC from 31.6 +/- 14.7 mL to 35.0 +/- 15.9 mL (p = 0.006), whereas LCI (9.15 +/- 0.75 to 8.55 +/- 0.74, p = 0.019) and the moment ratios M1/M0, M2/M0 (p < 0.02) decreased significantly. No significant changes were seen in AMDN1 and AMDN2. The within-subject variability of the VI indices (coefficient of variation in brackets) was distinctly higher (LCI (9.8%), M1/M0 (6.6%), M2/M0 (14.6%), AMDN1 (9.1%), AMDN2 (16.3%)) compared to FRC measurements (5.6%). Computer simulations showed that significant changes in VI indices were exclusively caused by changes in VT and FRC and not by an improvement of the homogeneity of alveolar ventilation. CONCLUSION: In small ventilated lungs with a high dead space fraction, indices of VI may be misinterpreted if the changes in ventilator settings are not considered. Computer simulations can help to prevent this misinterpretation.

Differences in tidal breathing between infants with chronic lung diseases and healthy controls.

BACKGROUND: The diagnostic value of tidal breathing (TB) measurements in infants is controversially discussed. The aim of this study was to investigate to what extent the breathing pattern of sleeping infants with chronic lung diseases (CLD) differ from healthy controls with the same postconceptional age and to assess the predictive value of TB parameters. METHODS: In the age of 36-42 postconceptional weeks TB measurements were performed in 48 healthy newborns (median age and weight 7d, 3100 g) and 48 infants with CLD (80d, 2465 g)) using the deadspace-free flow-through technique. Once the infants had adapted to the mask and were sleeping quietly and breathing regularly, 20-60 breathing cycles were evaluated. Beside the shape of the tidal breathing flow-volume loop (TBFVL) 18 TB parameters were analyzed using ANOVA with Bonferroni correction. Receiver-operator characteristic (ROC) curves were calculated to investigate the discriminative ability of TB parameters. RESULTS: The incidence of concave expiratory limbs in CLD infants was 31% and significantly higher compared to controls (2%) (p < 0.001). Significant differences between CLD infants and controls were found in 11/18 TB parameters. The largest differences were seen in the mean (SD) inspiratory time 0.45(0.11)s vs. 0.65(0.14)s (p < 0.0001) and respiratory rate (RR) 55.4(14.2)/min vs. 39.2(8.6)/min (p < 0.0001) without statistically significant difference in the discriminative power between both time parameters. Most flow parameters were strongly correlated with RR so that there is no additional diagnostic value. No significant differences were found in the tidal volume and commonly used TB parameters describing the expiratory flow profile. CONCLUSION: The breathing pattern of CLD infants differs significantly from that of healthy controls. Concave TBFVL and an increased RR measured during quiet sleep and under standardized conditions may indicate diminished respiratory functions in CLD infants whereas most of the commonly used TB parameters are poorly predictive.

Perinatal management of right aortic arch with aberrant left subclavian artery associated with critical stenosis of the subclavian artery in a newborn.

A right-sided aortic arch with an aberrant left subclavian artery is a congenital vascular anomaly that is easily detectable in utero at the level of the three vessels and trachea view, but which is rarely symptomatic in the neonate. We present a newborn with prenatally diagnosed right-sided aortic arch and aberrant subclavian artery who showed a clinically relevant stenosis of the subclavian artery during the first week of life. An intravascular stent was implanted into the stenosis of the aberrant left subclavian artery by catheterization. This case report demonstrates that a right-sided aortic arch with an aberrant subclavian artery can be diagnosed prenatally, that in these patients a stenosis of the subclavian artery can occur in early infancy and requires awareness of the neonatologist or pediatrician, and that stent implantation represents a minimally invasive therapeutic approach.

Reliability of the lung-to-head ratio in predicting outcome and neonatal ventilation parameters in fetuses with congenital diaphragmatic hernia.

OBJECTIVES: The ratio of the lung area (on the contralateral side of the hernia) to the head circumference, the lung-to-head ratio (LHR), has been proposed as a reliable tool in the assessment of the prognosis of congenital diaphragmatic hernia (CDH). An LHR < 0.6 has been associated with poor outcome whereas one > 1.4 has been associated with survival. We aimed to analyze the role of LHR in predicting fetal outcome and ventilation parameters in cases of isolated CDH in our center. METHODS: During the 40-month study period, 22 fetuses with an isolated CDH were delivered alive under optimized conditions at our perinatal center. LHR was measured at the time of diagnosis (median, 27 weeks' gestation). In addition to survival, postnatal ventilation parameters including pCO2, pO2, inspiratory O2 partial pressure, inspiratory pressure and oxygenation index were determined, as was the occurrence of pulmonary hypertension. RESULTS: The overall survival rate was 59%. The LHR was not able to predict fetal outcome reliably. There was no correlation between the liver herniation, LHR and fetal outcome. The prenatally determined lung size reflected in the LHR did not show any significant association with individual ventilation parameters. Eleven of 17 infants examined had signs of pulmonary hypertension and the LHR did not predict this condition. CONCLUSION: Our study cannot support the optimistic results reported by other groups on the use of LHR as a reliable predictor of outcome in fetuses with CDH. The LHR, as a reflection of lung size, correlates neither with survival patterns nor with various postnatal ventilation parameters.

Breathing gas perfluorocarbon measurements using an absorber filled with zeolites.

BACKGROUND: Perfluorocarbon (PFC) has been widely used in the treatment of respiratory diseases; however, PFC content of the breathing gases remains unknown. Therefore, we developed an absorber using PFC selective zeolites for PFC measurement in gases and investigated its accuracy. METHODS: To generate a breathing gas with different PFC contents a heated flask was rinsed with a constant air flow of 4 litre x min(-1) and 1, 5, 10, and 20 ml of PFC were infused over 20 min using an infusor. The absorber was placed on an electronic scale and the total PFC volume was calculated from the weight gain. RESULTS: Steady-state increase in weight was achieved 3.5 min after stopping the infusion. The calculated PFC volume was slightly underestimated but the measuring error did not exceed -1% for PFC less than 1 ml. The measurement error decreased with increasing PFC volume. CONCLUSIONS: This zeolite absorber is an accurate method to quantitatively determine PFC in breathing gases and can be used as a reference method to validate other PFC sensors.

Effects of perfluorocarbons and perfluorocarbons/surfactant emulsions on growth and viability of group B streptococci and Escherichia coli.

OBJECTIVE: Partial liquid ventilation with perfluorocarbons (PFC) might be used as a new ventilatory strategy to treat respiratory insufficiency in congenital pneumonia. The present study investigates for the first time effects of PFC on growth and viability of group B streptococci (GBS) and Escherichia coli, bacteria frequently causing congenital pneumonia. DESIGN: Prospective, in vitro study. SETTING: Research laboratory in a university. MATERIAL: Group B streptococci 090 Ia HD Colindale and E. coli K12, JM 101. INTERVENTIONS: E. coli (10(7)/mL) were grown in the absence or presence of different PFC (RM 101, PF 5080, FO 6167) for up to 6 hrs. To study bacterial viability, GBS (5 x 10(7)/mL) were incubated in saline with or without different PFC, PFC/surfactant emulsions, or surfactant (Curosurf) for up to 5 hrs. Every 2 hrs, the colony forming units were determined by plating different dilutions of bacteria on agar. MEASUREMENTS AND MAIN RESULTS: RM 101 or PF 5080 alone and in emulsions with surfactant had no effect on viability of GBS or growth of E. coli. For FO 6167, a previously described toxicity was found, even if 1 mL of GBS suspension was incubated with only 100 microL of FO 6167, verifying the experimental design that guarantees a PFC bacteria contact. The toxic effects were almost prevented by forming a PFC-in-surfactant emulsion but not by preincubation of GBS with surfactant and subsequent FO 6167 exposure. CONCLUSION: RM 101 and PF 5080 did not influence bacterial growth in vitro; direct effects on bacterial proliferation during partial liquid ventilation in congenital pneumonia seem, therefore, unlikely. Interestingly, we found that the known toxic effects of FO 6167 can be prevented by covering PFC with a surfactant film. Surfactant reduced the cytotoxic effects of FO 6167, probably by preventing a direct contact between FO 6167 and the bacterial cell wall.

2nd European symposium on liquid ventilation.

After the successful meeting in Berlin, advances and research results in the understanding of liquid ventilation has been performed. About 80 applied and basic scientists met in the 1st European Symposium, from clinicians (pediatricians, neonatologists, intensivists, etc.) to other basic scientists (physiologists, biologists, bioengineerings, etc.). Furthermore, we also invited representatives of pharmaceutic industry interested in this hot topic. Our main goal is to provide an opportunity for all liquid researchers in this field to meet together and with the top scientists of Liquid Ventilation Research. We planned to provide both a scientific and a friendly atmosphere to enhance the exchange of experiences and to facilitate future plans. We hope this 2nd European Symposium will be a continuation point for collaboration of groups in Europe, to study all research aspects of the technique to carry on future trials. There are still a lot of unanswered questions to be solved. Among the unsolved issues and practical questions we would like to point out the following items: 1. Perfluorocarbon: which product to use and how to deliver it. 2. Perfluorocarbon interactions in the lung. 3. Perfluorocarbon. Toxicity and cytoprotection. 4. Partial Liquid Ventilation: ventilatory strategies from delivering to weaning. 5. Impact of Partial Liquid Ventilation Experimental and clinical aspects. 6. General discussion and plan for the future. We know that none of these questions can be completely answered now, but hope collaboration and communication will bring us closer to achieve these goals. Moreover, concerted actions should be started to search for research grant founding. For all those reasons we would like to thank all active and passive participants, who came to Bilbao to present, discuss and foster future work in Liquid Ventilation.

In vitro assessment of equipment and software to assess tidal breathing parameters in infants.

The aim of this in vitro study was to compare the measurement accuracy of two currently available devices for measuring tidal breathing in infants. A mechanical model pump was used to generate flow profiles which simulated those observed in infants. A range of flows was applied simultaneously to two different devices, namely the commercially available SensorMedics 2600 (SM 2600) and more recently developed, custom-made equipment based on the flow-through technique (FTT). Automatically derived values from both devices were compared with one another and with manual calculations of printouts of the same breaths. There were no differences in the raw flow signal obtained from the two devices, nor between values calculated automatically or manually from the FTT. Similarly, the deviations between the FTT and SM 2600 were <3% for tidal volume, respiratory frequency and minute ventilation. However, when comparing either with manually calculated values or those derived automatically from the FTT, there was a systematic and highly significant underestimation of shape-dependent parameters, such as the time to peak tidal expiratory flow as a proportion of tidal expiratory time (tPTEF/tE), derived by the SM 2600. The lower the applied flow, the higher the observed deviations, the underestimation being up to 60% when flows simulating those observed in preterm neonates were applied. These errors appear to result from differences in signal processing such as the algorithms used for breath detection and can only be detected if appropriate nonsinusoidal flow profiles representing those seen in infants are used to evaluate equipment.

Effect of apparatus dead space on breathing parameters in newborns: "flow-through" versus conventional techniques.

Commercial devices for tidal breathing measurements in newborns allow only short-term measurements, due to the high apparatus dead space of the face mask and pneumotachometer. The flow-through technique (FTT) minimizes the dead space by a background flow, thereby allowing long-term measurements. The aim of this study was to investigate the comparability of tidal breathing parameters using both techniques. Paired measurements of tidal breathing were performed in 86 sleeping infants (median (range) body weight 2.8 kg (1.9-5.3 kg), age 65 days (3-150 days)), using the FTT and SensorMedics 2600 (SM 2600). There was a significant bias (p <0.001) in all tidal breathing parameters. Compared with the FTT, increases (95% confidence interval (CI)) in tidal volume (VT), respiratory frequency (fR), and minute ventilation (V'E) were 0.74 (0.5-1.0) mL.kg(-1), 9.0 (6.9-11.2).min(-1) and 92 (74-109) mL.min(-1).kg(-1) when measured with the SM 2600, representing average increases of 13, 17 and 30%, respectively, in response to the added dead space. By contrast, time to peak tidal expiratory flow as a proportion of expiratory time (tPTEF/tE) was changed by -0.09 (-0.11-0.08). The mean (95% CI) change in tPTEF/tE of -54 (-62-45)%, when measured in infants by the SM 2600, was remarkably similar to that observed during in vitro validation studies (-59 (-73-44)%), suggesting that the discrepancies in timing parameters may be largely attributable to differences in signal processing. In conclusion, differences in measurement technique and precision of the devices used can result in significant differences in tidal breathing parameters. This may impede the comparison of results within and between infants and the clinical interpretation of tidal breathing measurements in newborns.

Longitudinal observation of deterioration of Doppler parameters, computerized cardiotocogram and clinical course in a fetus with growth restriction.

We report on a fetus with intrauterine growth restriction detected at 27 weeks' gestation, who was longitudinally followed up until delivery by cesarean section 33 days later (31 + 5 weeks) due to severe decelerations in CTG. Longitudinal Doppler assessment of the umbilical artery (UA), the middle cerebral artery (MCA) and the main branch of the right pulmonary artery (RPA), the ductus venosus (DV) and the left coronary artery was compared to clinical course and computerized CTG. At first presentation (day--33) increased resistance in both the UA and uterine arteries with bilateral notches was found. Absent enddiastolic flow (AED) in the UA was found at day--19 and reverse flow (RED) at day--11. The MCA showed a decreased pulsatility first at day--19 and again at day--11 together with RED in the UA. The RPA initially (day--33) showed increased PI which returned to normal values at day--19 but increased again at day--1, when the DV showed RED and the coronary arteries became visible. The DV was normal until day--11, then its PI began to increase together with occurence of RED in the UA, but reverse flow in the DV occurred only on the eve (day--1) of severe decelerations in CTG. Short-term variability in computerized CTG was stable at 6 to 7 ms, except for an intermediate drop to 4 ms at day--10. Maternal hypertension was found at day--19 and mild preeclampsia developed at day--12. A reduction of fetal movements was noticed at day--5. This report shows that at 29 weeks gestation despite detection of AED resp. RED in the UA a prolongation of pregnancy for 19 resp. 11 days is possible. In addition to abnormal CTG, late signs of fetal deterioration are reverse flow in the DV and visibility of the coronary arteries. The role of increased resistance in the main branches of the pulmonary arteries should be examined in the future.

Surfactant protein SP-B counteracts inhibition of pulmonary surfactant by serum proteins.

In addition to the primary surfactant deficiency in newborns with respiratory distress syndrome (RDS), in the later course of RDS substantial protein leakage into the alveolar spaces can occur by damage to the alveolocapillary membrane. Acute lung injury results in surfactant dysfunction due in part to inhibition by serum proteins. The aim of this study was to investigate the influence of SP-B on the inhibitory effects of albumin (alb) and fibrinogen (fib) on the surface activity of pulmonary surfactant, using a) surface tension measurement with the pulsating bubble surfactometer in suspensions and b) in surfactant films applying the hypophase exchanger. After hypophase exchange a preformed film of Survanta is very resistant to the inhibitory activity of alb or fib. The surface tensions of suspensions are significantly higher (p <0.001) than the surface tensions of preformed surfactant films if alb or fib were added, e.g., 42 (41 to 43) mN/m vs. 21 (19 to 22) mN/m for Survanta with 20 mg alb/ml. After additional supplementation of Survanta with SP-B the surface activity of Survanta/1% SP-B films did not show inhibition by fib (2 mg/ml), (surface tension 8 (4 to 13) mN/m). These results indicate that SP-B can play an important role to protect the pulmonary surfactant film from inactivation by serum proteins.

Preterm infants with high polyunsaturated fatty acid and plasmalogen content in tracheal aspirates develop bronchopulmonary dysplasia less often.

OBJECTIVE: Oxygen toxicity causes chronic bronchopulmonary dysplasia (BPD) in extremely preterm infants. Polyunsaturated fatty acids (PUFA) and plasmalogens are the two main substrates for lipid peroxidation in the pulmonary surfactant. In the present study, we tested whether low concentrations of both were associated with development of BPD and whether both were further reduced during mechanical ventilation with oxygen. DESIGN: Prospective, noninterventional, descriptive study. SETTING: Level III neonatal intensive care unit in a university hospital. PATIENTS: In 25 extremely low birth weight infants with respiratory distress syndrome, tracheal aspirates were collected immediately after birth and in the following 4 days. As control, tracheal and pharyngeal aspirates were collected from healthy infants immediately after birth. The amount of PUFA and dimethylacetals (DMA, representing plasmalogens) was determined gas-chromatographically. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The relative percentages of PUFA and DMA on all fatty acids in non-BPD infants (PUFA% 26+/-8.9, DMA% 3.5+/-1.2) were higher compared with infants who developed BPD (PUFA% 14.5+/-3.8, DMA% 1.8+/-0.9). In term healthy infants, DMA% and PUFA% were in the same range as in the BPD group. The higher levels found for non-BPD infants decreased after day 1 to values equal to the BPD group and remained low. CONCLUSIONS: The results suggest that initially higher levels of PUFA and plasmalogens in the tracheal effluent are associated with a reduced risk of developing BPD and are reduced during the first day of ventilation.

Effect of early ambroxol treatment on lung functions in mechanically ventilated preterm newborns who subsequently developed a bronchopulmonary dysplasia (BPD).

In a randomized trial in 102 preterm newborns with respiratory distress syndrome (RDS) it has been shown that early Ambroxol treatment (30 mg kg(-1) over the first 5 days) significantly reduces the incidence of RDS-associated complications [bronchopulmonary dysplasia (BPD), intraventricular haemorrhage, post-natal acquired pneumonia]. The aim of the present analysis was to investigate the effect of Ambroxol treatment on lung function in newborns who developed BPD. Respiratory function testing (RFT) was performed immediately after extubation and at day 28. Tidal volume (VT) and respiratory frequency (f) were measured during tidal breathing using the deadspace free flow-through technique. The lung mechanic parameter VT/maxPes was determined by measuring the maximal oesophageal pressure changes, maxPes, with a catheter tip pressure transducer. In the placebo group 36/50 infants were extubated within the first 28 days of life and 13/36 (36%) developed BPD. In the Ambroxol group 44/52 were extubated and 9/44 (20%) developed BPD. After extubation, RFT showed (i) no statistically significant difference in the ventilatory parameters of either treatment group, (ii) improved (P<0.05) lung mechanics (VT/maxPes) in Ambroxol group compared to controls (94+/-27 ml kPa(-1) vs. 8.1+/-2.6 ml kPa(-1)) and (iii) no statistically significant difference in lung function between infants with and without BPD. At day 28 we found (i) no effect of early Ambroxol treatment on lung functions, (ii) significantly (P < 0.05) higher f (58.5+/-11.7 min(-1) vs. 49.7+/-10.1 min(-1)) and significantly (P<0.01) lower V(T) (9.6+/-1.9 ml vs. 12.3+/-2.7 ml) and V(T)/maxPes (8.9+/-2.6 ml kPa(-1)] vs. 12.0+/-2.9 ml kPa(-1)) in infants with BPD compared to infants without and (iii) these differences are not influenced by early Ambroxol treatment. If the process of BPD development is induced, early Ambroxol treatment has no influence on impaired lung function at day 28.

Low-frequency respiratory rhythms in infants during the first six months of life.

The aim of the study was to investigate characteristics of low-frequency components in respiration. Sixteen healthy term infants were examined from the first day up to the 6th month of life. The respirogram, instantaneous respiratory frequency and respiratory amplitude of undisturbed segments of quiet sleep phases and periodic breathing (PB) were analysed via fast Fourier transformation. The peak frequency (PF) in the low-frequency range (0.04-0.2 Hz) was determined. PF for PB ranged from 0.056 to 0.1 Hz. Further, low-frequency rhythms (LFR) of the respirogram, which were stable during the recordings as well as during development, were found ranging from 0.045 to 0.067 Hz. The LFR of the respirogram is correlated with rhythmic changes in the relationship between inspiratory and expiratory amplitudes. The frequency of the LFR was significantly lower than that of the PB. The data indicate that LFR and PB are low-frequency respiratory rhythms which are separately controlled and perform independently.