Anthropometric Landmarking for Diagnosis of Cranial Deformities: Validation of an Automatic Approach and Comparison with Intra- and Interobserver Variability.

Shape analysis of infant's heads is crucial to diagnose cranial deformities and evaluate head growth. Currently available 3D imaging systems can be used to create 3D head models, promoting the clinical practice for head evaluation. However, manual analysis of 3D shapes is difficult and operator-dependent, causing inaccuracies in the analysis. This study aims to validate an automatic landmark detection method for head shape analysis. The detection results were compared with manual analysis in three levels: (1) distance error of landmarks; (2) accuracy of standard cranial measurements, namely cephalic ratio (CR), cranial vault asymmetry index (CVAI), and overall symmetry ratio (OSR); and (3) accuracy of the final diagnosis of cranial deformities. For each level, the intra- and interobserver variability was also studied by comparing manual landmark settings. High landmark detection accuracy was achieved by the method in 166 head models. A very strong agreement with manual analysis for the cranial measurements was also obtained, with intraclass correlation coefficients of 0.997, 0.961, and 0.771 for the CR, CVAI, and OSR. 91% agreement with manual analysis was achieved in the diagnosis of cranial deformities. Considering its high accuracy and reliability in different evaluation levels, the method showed to be feasible for use in clinical practice for head shape analysis.

Reference Charts for Neonatal Cranial Volume Based on 3D Laser Scanning to Monitor Head Growth.

Background: Postnatal brain growth is an important predictor of neurodevelopmental outcome in preterm infants. A new reliable proxy for brain volume is cranial volume, which can be measured routinely by 3-D laser scanning. The aim of this study was to develop reference charts for normal cranial volume in newborn infants at different gestational ages starting from late preterm for both sexes. Methods: Cross-sectional cohort study in a German university hospital, including singleton, clinically stable, neonates born after 34 weeks of gestation. Cranial volume was measured in the first week of life by a validated 3-D laser scanner. Cranial volume data was modeled to calculate percentile values by gestational age and birth weight and to develop cranial volume reference charts for girls and boys separately. Results: Of the 1,703 included infants, 846 (50%) were female. Birth weights ranged from 1,370 to 4,830 grams (median 3,370). Median cranial volume ranged from 320 [interquartile range (IQR) 294-347] ml at 34 weeks to 469 [IQR 442-496] ml at 42 weeks and was higher in boys than in girls. Conclusions: This study presents the first reference charts of cranial volume which can be used in clinical practice to monitor brain growth between 34 and 42 weeks gestation in infants.

Non-invasive estimation of brain-volume in infants.

BACKGROUND: Neurological development is determined by brain growth. Methods to measure total brain volume (TBV) in clinical settings are limited. MR-imaging represents the gold-standard. AIMS: The present study tests the hypotheses that in infants without any brain pathology, TBV - as determined by MRI - can be accurately estimated by cranial volume (CrV), measured by 3D-laser scanning. In case of good correlation of CrV with TBV it was further tested, whether CrV can be also estimated by (I) head circumference (HC) or (II) by other technology than laser scanning. STUDY DESIGN & SUBJECTS: To test the hypothesis, that TBV can be reliably estimated by CrV-measurement, data from routine MRI and 3D-laser-scanner measurements were analyzed in infants if no major structural brain anomaly was found in MR-imaging. To test whether CrV can be predicted by HC-measurements during infancy, data from routine follow-up visits were used from preterms born in a two year period. Preterms are invited for a routine follow-up visit (which includes laser scanning of the head) at an age of 3 months and, for further follow-ups at 6, 9 or 12 months. To compare accuracy of CrV measurement by other techniques, a puppet head was measured, using different 3D-measurement principles: (i) Structured light projection system, (ii) The non-invasive laser-shape-digitizer, and (iii) Structure-from-motion (SFM) technique. OUTCOME MEASURES: TBV was compared with CrV using a Passing-Bablok-Regression. To determine how well HC predicts CrV, the coefficient of determinant (R2) was calculated for each age group. RESULTS: CrV and TBV of 25 infants (median age 19 month, body weight of 11 kg) showed a median bias of -86.7 mm3 with a slightly smaller TBV (median of 1034.1 mm3, IQR 875.9 … 1179.8 mm3) than CrV (median 1092.2, IQR 950.5 … 1258.4 mm3). CrV was poorly estimated by HC, with R2 between 0.79 and 0.87 at 3 and 9 month of age respectively. For the non-invasive laser-shape-digitizer and the SFM-technique the accuracy was good (radial coordinate differences ±0.3 vs. ±0.5 mm). CONCLUSION: The present study provides convincing evidence that CrV can be used to estimate TBV in routine care, whereas HC is a poor predictor of individual CrV.

Analyzing support of postnatal transition in term infants after c-section.

BACKGROUND: Whereas good data are available on the resuscitation of infants, little is known regarding support of postnatal transition in low-risk term infants after c-section. The present study was performed to describe current delivery room (DR) management of term infants born by c-section in our institution by analyzing videos that were recorded within a quality assurance program. METHODS: DR- management is routinely recorded within a quality assurance program. Cross-sectional study of videos of term infants born by c-section. Videos were analyzed with respect to time point, duration and number of all medical interventions. Study period was between January and December 2012. RESULTS: 186 videos were analyzed. The majority of infants (73%) were without support of postnatal transition. In infants with support of transition, majority of infants received respiratory support, starting in median after 3.4 minutes (range 0.4-14.2) and lasting for 8.8 (1.5-28.5) minutes. Only 33% of infants with support had to be admitted to the NICU, the remaining infants were returned to the mother after a median of 13.5 (8-42) minutes. A great inter- and intra-individual variation with respect to the sequence of interventions was found. CONCLUSIONS: The study provides data for an internal quality improvement program and supports the benefit of using routine video recording of DR-management. Furthermore, data can be used for benchmarking with current practice in other centers.

Individual course of cranial symmetry and proportion in preterm infants up to 6 months of corrected age.

INTRODUCTION: A significant proportion of preterm infants have dolichocephaly and/or deformational plagiocephaly (DP) at term equivalent age. However, quantitative data on the clinical course after discharge is limited in these infants. AIMS: To quantify the individual course of cranial symmetry and proportion in infants born <32 gestational weeks up to six months of corrected age (CA) and to investigate, whether measurements at discharge predict subsequent cranial deformations. METHODS: A total of 56 infants were examined at discharge, three and six months of CA. Cranial proportion and symmetry were quantified using a 3D laser scan method. Classification and prevalence data were obtained using age related reference values. Predictive value of DP at discharge regarding subsequent deformation was evaluated. RESULTS: Cranial Vault Asymmetry Index was 3.9% at discharge, 4.5% at three months and 3.7% at six months of CA. Prevalence of DP was 34% at discharge, 46% at three months and 27% at six months. Cranial Index was 71.4% at discharge and constantly increased over the examination period. Prevalence of dolichocephaly was high at discharge (77%) and subsequently decreased. While severe DP at discharge was predictive for a persistent deformation (PPV 0.78), 46% of infants without DP at discharge developed DP by six months of CA. DISCUSSION: Despite a high prevalence at discharge, the decreased prevalence of DP and dolichocephaly at six months of CA suggests an optimistic course. However, changes in head shape are hardly predictable for the individual infant. Thus, an accurate quantification should be part of neonatal follow-up programs.

Prevalence of head deformities in preterm infants at term equivalent age.

INTRODUCTION: Due to a rising number of head deformities in healthy newborns, there has been an increasing interest in nonsynostotic head deformities in children over recent years. Although preterm infants are more likely to have anomalous head shapes than term newborns, there is limited data available on early prevalence of head deformities in preterm infants. AIMS: The purposes of the present study were to acquire quantitative data on head shape of preterm infants at Term Equivalent Age (TEA), to determine the prevalence of symmetrical and asymmetrical head deformities and to identify possible risk factors. METHODS: In a cross-sectional study design, Cranial Vault Asymmetry Index (CVAI) and Cranial Index (CI) calculated from routine head-scans with a non-invasive laser shape digitizer were recorded and categorized in type and severity of deformation for three different groups of gestational age. Perinatal and postnatal patient data was tested for possible associations. RESULTS: Scans of 195 infants were included in the study. CVAI at TEA was higher in very preterm (4.1%) compared to term and late preterm infants. Prevalence of deformational plagiocephaly was 38% in very preterm infants. CI was lower in very (71.4%) and late (77.2%) preterm infants compared to term infants (80.0%). Compared to term babies (11%), a large number of very (73%) and late (28%) preterm infants exhibited dolichocephaly at TEA. DISCUSSION: Prevalence of symmetrical and asymmetrical head deformities in preterm infants is high at TEA. Interventions are required to prevent head deformities in preterm infants during the initial hospital stay.

Three-dimensional digital capture of head size in neonates - a method evaluation.

INTRODUCTION: The quality of neonatal care is mainly determined by long-term neurodevelopmental outcome. The neurodevelopment of preterm infants is related to postnatal head growth and depends on medical interventions such as nutritional support. Head circumference (HC) is currently used as a two-dimensional measure of head growth. Since head deformities are frequently found in preterm infants, HC may not always adequately reflect head growth. Laser aided head shape digitizers offer semiautomatic acquisition of HC and cranial volume (CrV) and could thus be useful in describing head size more precisely. AIMS: 1) To evaluate reproducibility of a 3D digital capture system in newborns. 2) To compare manual and digital HC measurements in a neonatal cohort. 3) To determine correlation of HC and CrV and predictive value of HC. METHODS: Within a twelve-month period data of head scans with a laser shape digitizer were analysed. Repeated measures were used for method evaluation. Manually and digitally acquired HC was compared. Regression analysis of HC and CrV was performed. RESULTS: Interobserver reliability was excellent for HC (bias-0.005%, 95% Limits of Agreement (LoA) -0.39-0.39%) and CrV (bias1.5%, 95%LoA-0.8-3.6%). Method comparison data was acquired from 282 infants. It revealed interchangeability of the methods (bias-0.45%; 95%LoA-4.55-3.65%) and no significant systematic or proportional differences. HC and CrV correlated (r(2) = 0.859, p<0.001), performance of HC predicting CrV was poor (RSD ±24 ml). Correlation was worse in infants with lower postmenstrual age (r(2) = 0.745) compared to older infants (r(2) = 0.843). DISCUSSION: The current practice of measuring HC for describing head growth in preterm infants could be misleading since it does not represent a 3D approach. CrV can vary substantially in infants of equal HC. The 3D laser scanner represents a new and promising method to provide reproducible data of CrV and HC. Since it does not provide data on cerebral structures, additional imaging is required.

Continuous noninvasive monitoring of lung recruitment during high-frequency oscillatory ventilation by electrical impedance measurement: an animal study.

BACKGROUND: Ventilatory pressures should target the range between the upper and lower inflection point of the pressure volume curve in order to avoid atelecto- and volutrauma. During high-frequency oscillatory ventilation (HFOV), this range is difficult to determine. Quadrant impedance measurement (QIM) has recently been shown to allow accurate and precise measurement of lung volume changes during conventional mechanical ventilation. OBJECTIVES: To investigate if QIM can be used to determine a static pressure-residual impedance curve during a recruitment-derecruitment manoeuvre on HFOV and to monitor the time course of alveolar recruitment after changing mean airway pressure (MAP). METHODS: An incremental and decremental MAP trial (6 cm H2O to 27 cm H2O) was conducted in five surfactant-depleted newborn piglets during HFOV. Ventilatory, gas exchange and haemodynamic parameters were recorded. Continuous measurement of thoracic impedance change was performed. RESULTS: Mean residual impedance (RI) increased with each stepwise increase of MAP resulting in a total mean increase of +26.5% (±4.0) at the highest MAP (27 cm H2O) compared to baseline ventilation at 6 cm H2O. Upon decreasing MAP levels, RI fell more slowly compared to its ascent; 83.4% (±19.1) and 84.8% (±16.4) of impedance changes occurred in the first 5 min after an increase or decrease in airway pressure, respectively. CONCLUSIONS: QIM could be used for continuous monitoring of thoracic impedance and determination of the pressure-RI curve during HFOV. The method could prove to be a promising bedside method for the monitoring of lung recruitment during HFOV in the future.

Persurf, a new method to improve surfactant delivery: a study in surfactant depleted rats.

PURPOSE: Exogenous surfactant is not very effective in adults with ARDS, since surfactant does not reach atelectatic alveoli. Perfluorocarbons (PFC) can recruit atelectatic areas but do not replace impaired endogenous surfactant. A surfactant-PFC-mixture could combine benefits of both therapies. The aim of the proof-of-principal-study was to produce a PFC-in-surfactant emulsion (Persurf) and to test in surfactant depleted Wistar rats whether Persurf achieves I.) a more homogenous pulmonary distribution and II.) a more homogenous recruitment of alveoli when compared with surfactant or PFC alone. METHODS: Three different PFC were mixed with surfactant and phospholipid concentration in the emulsion was measured. After surfactant depletion, animals either received 30 ml/kg of PF5080, 100 mg/kg of stained (green dye) Curosurf™ or 30 ml/kg of Persurf. Lungs were fixated after 1 hour of ventilation and alveolar aeration and surfactant distribution was estimated by a stereological approach. RESULTS: Persurf contained 3 mg/ml phospholipids and was stable for more than 48 hours. Persurf-administration improved oxygenation. Histological evaluation revealed a more homogenous surfactant distribution and alveolar inflation when compared with surfactant treated animals. CONCLUSIONS: In surfactant depleted rats administration of PFC-in-surfactant emulsion leads to a more homogenous distribution and aeration of the lung than surfactant alone.

Continuous non-invasive monitoring of tidal volumes by measurement of tidal impedance in neonatal piglets.

BACKGROUND: Electrical Impedance measurements can be used to estimate the content of intra-thoracic air and thereby give information on pulmonary ventilation. Conventional Impedance measurements mainly indicate relative changes, but no information concerning air-volume is given. The study was performed to test whether a 3-point-calibration with known tidal volumes (VT) during conventional mechanical ventilation (CMV) allows subsequent calculation of VT from total Tidal-Impedance (tTI) measurements using Quadrant Impedance Measurement (QIM). In addition the distribution of TI in different regions of the thorax was examined. METHODOLOGY AND PRINCIPAL FINDINGS: QIM was performed in five neonatal piglets during volume-controlled CMV. tTI values at three different VT (4, 6, 8 ml/kg) were used to establish individual calibration curves. Subsequently, each animal was ventilated with different patterns of varying VT (2-10 ml/kg) at different PEEP levels (0, 3, 6, 9, 12 cmH(2)O). VT variation was repeated after surfactant depletion by bronchoalveolar lavage. VT was calculated from tTI values (VT(calc)) and compared to the VT delivered by the ventilator (VT(PNT)). Bland-Altman analysis revealed good agreement between VT(calc) and VT(PNT) before (bias -0.08 ml; limits of agreement -1.18 to 1.02 ml at PEEP = 3 cmH(2)O) and after surfactant depletion (bias -0.17 ml; limits of agreement -1.57 to 1.22 ml at PEEP = 3 cmH(2)O). At higher PEEP levels VT(calc) was lower than VT(PNT), when only one fixed calibration curve (at PEEP 3 cmH(2)O) was used. With a new calibration curve at each PEEP level the method showed similar accuracy at each PEEP level. TI showed a homogeneous distribution over the four assessed quadrants with a shift toward caudal regions of the thorax with increasing VT. CONCLUSION: Tidal Impedance values could be used for precise and accurate calculation of VT during CMV in this animal study, when calibrated at each PEEP level.

Intratracheal perfluorocarbons diminish LPS-induced increase in systemic TNF-alpha.

Perfluorocarbons (PFC) reduce the production of various inflammatory cytokines, including TNF-alpha. The anti-inflammatory effect is not entirely understood. If anti-inflammatory properties are caused by a mechanical barrier, PFC in the alveoli should have no effect on the inflammatory response to intravenous LPS administration. To test that hypothesis, rats (n=31) were administered LPS intravenously and were either spontaneously breathing (Spont), conventionally ventilated (CMV), or receiving partial liquid ventilation (PLV). Serum concentration of TNF-alpha was measured. The pulmonary expressions of TNF-alpha and TNF-alpha receptor 1 protein and of TNF-alpha and ICAM-1 mRNA were determined. LPS caused a significant (P<0.001) increase in serum TNF-alpha. Serum TNF-alpha concentration was similar in LPS/Spont (525+/-180 pg/ml) and LPS/CMV (504+/-154 pg/ml) but was significantly (P<0.001) lower in animals of the LPS/PLV group (274+/-101 pg/ml). Immunohistochemical data on TNF-alpha protein expression showed a LPS-induced increase in TNF-alpha and TNF-alpha receptor 1 expression that was diminished by partial liquid ventilation. PCR measurements revealed a lower expression of TNF-alpha and ICAM-1 mRNA in LPS/PLV than in LPS/CMV or LPS/Spont animals. Semiquantitative histological evaluation revealed only minor alveolar inflammation with no significant differences between the groups. Low serum TNF-alpha concentration in PFC-treated animals is most likely explained by a decreased production of TNF-alpha in the lung.

Alterations of alveolar type II cells and intraalveolar surfactant after bronchoalveolar lavage and perfluorocarbon ventilation. An electron microscopical and stereological study in the rat lung.

BACKGROUND: Repeated bronchoalveolar lavage (BAL) has been used in animals to induce surfactant depletion and to study therapeutical interventions of subsequent respiratory insufficiency. Intratracheal administration of surface active agents such as perfluorocarbons (PFC) can prevent the alveolar collapse in surfactant depleted lungs. However, it is not known how BAL or subsequent PFC administration affect the intracellular and intraalveolar surfactant pool. METHODS: Male wistar rats were surfactant depleted by BAL and treated for 1 hour by conventional mechanical ventilation (Lavaged-Gas, n = 5) or partial liquid ventilation with PF 5080 (Lavaged-PF5080, n = 5). For control, 10 healthy animals with gas (Healthy-Gas, n = 5) or PF5080 filled lungs (Healthy-PF5080, n = 5) were studied. A design-based stereological approach was used for quantification of lung parenchyma and the intracellular and intraalveolar surfactant pool at the light and electron microscopic level. RESULTS: Compared to Healthy-lungs, Lavaged-animals had more type II cells with lamellar bodies in the process of secretion and freshly secreted lamellar body-like surfactant forms in the alveoli. The fraction of alveolar epithelial surface area covered with surfactant and total intraalveolar surfactant content were significantly smaller in Lavaged-animals. Compared with Gas-filled lungs, both PF5080-groups had a significantly higher total lung volume, but no other differences. CONCLUSION: After BAL-induced alveolar surfactant depletion the amount of intracellularly stored surfactant is about half as high as in healthy animals. In lavaged animals short time liquid ventilation with PF5080 did not alter intra- or extracellular surfactant content or subtype composition.

Perfluorocarbons decrease Chlamydophila pneumoniae-mediated inflammatory responses of rat type II pneumocytes in vitro.

Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-kappaB) is activated and tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-alpha. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-alpha and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-alpha (43 +/- 10 versus 661 +/- 41 pg/mL) and MIP-2 (573 +/- 41 versus 4786 +/- 502 pg/mL). The C. pneumoniae-induced 2.2-fold increase of TNF-alpha Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IkappaBalpha (3.7 +/- 0.3 versus 14 +/- 1) and increased NF-kappaB p65 (31 +/- 7.5 versus 3.6 +/- 1.1) compared with control. PF5080 prevented NF-kappaB activation. TLR4 expression was 1.5-fold higher after C. pneumoniae incubation, but remained at control levels after PF5080 pretreatment. After 24 h of C. pneumoniae incubation, in 88 +/- 6% of cells bacteria were found in the perinuclear region and in 50% of these cells bacteria adhered to cellular surface. After PF5080 preincubation, C. pneumoniae were in 32 +/- 4% attached to and in 5 +/- 1% internalized in ATII-cells. Since PF5080 was found in ATII-cell membranes, PF5080 effect could be explained by an alteration of the cellular membrane, preventing activation of the inflammatory cascade.

Perfluorocarbon species and nebulizer type influence aerosolization rate and particle size of perfluorocarbon aerosol.

PURPOSE: Aerosolization of perfluorocarbons (PFC) has been proven beneficial in vivo. The present in vitro study was performed to investigate, how PFC-aerosolization is affected by type of nebulizer and PFC properties. MATERIALS AND METHODS: Aerosolization rate was studied of 4 different PFC that were nebulized using 3 different jet nebulizers (operating at different flows: 4.1; 7.1; 13 l/min) and one ultrasonic nebulizer. Distribution of aerosol particle size was determined with a laser diffraction device. RESULTS: Between the studied nebulizers, considerable differences in the aerosolization rate were found. Aerosolization rate was significantly lower for PFOB (0.48-1.24 mL/min), when compared with PF 5080, RM 101 and FC 77 (1.33-4.75 mL/min). The ultrasonic nebulizer did not generate an aerosol but rather PFC vapor. Lowest mass median diameter (MMD) was found for PFOB and varied between the jet nebulizers from 2.2 and 3.7 microm, with a small range in particle size (maximum of 7.3 microm). FC 77 had highest MMD (3.5 to 9.2 microm) and greatest range of particle size of up to 13 microm. CONCLUSIONS: Our in vitro data show that aerosolization rate depends mainly on density of PFC and the flow of nebulizer. Particle size distribution is affected by PFC properties. Our result may explain controversial results of published in vivo studies.

Changes in FiO2 affect PaO2 with minor alterations in cerebral concentration of oxygenated hemoglobin during liquid ventilation in healthy piglets.

OBJECTIVE: To measure the impact of changes in the fraction of inspired oxygen (FiO2) on systemic and cerebral oxygen supply in gas and liquid ventilated healthy animals. DESIGN: Interventional prospective animal study. SETTING: University research laboratory. PARTICIPANTS: Ten healthy, new-born piglets. INTERVENTIONS: Variations in FiO2 during conventional mechanical ventilation (CMV) followed by partial liquid ventilation (PLV) with two different filling volumes of PF 5080 (10 vs. 30 ml/kg). MEASUREMENTS AND RESULTS: Arterial blood gases were obtained 15 min after changing FiO2 and concentrations of cerebral oxygenated and total hemoglobin were determined with near infrared spectroscopy. During CMV an increase in FiO2 1.0 was associated with a constant rise in PaO2 but only a small increase in the cerebral concentration of oxygenated Hb. Initiation of PLV (at FiO2 of 1.0) caused a rapid drop in PaO2 towards values that were similar to CMV at FiO2 of 0.5. At FiO2 of 0.5 a reduction in oxygenated Hb was found in the 30 ml/kg filling group. Complete filling of the lungs with PFC caused a significant drop in total cerebral Hb concentration. CONCLUSIONS. According to our data, PLV in healthy lungs should be performed with a FiO2 of 1.0 and a small filling volume to avoid deterioration in cerebral oxygen supply.

Perfluorocarbons are taken up by isolated type II pneumocytes and influence its lipid synthesis and secretion.

OBJECTIVE: Because alveoli fill with perfluorocarbons during liquid ventilation, an uptake of perfluorocarbons by type II pneumocytes can be postulated that might affect synthesis and secretion of pulmonary surfactant. The study was performed to answer the following questions: Do isolated type II pneumocytes take up perfluorocarbons? Do perfluorocarbons affect lipid synthesis of type II cells? Do perfluorocarbons change surfactant secretion of type II pneumocytes? DESIGN: Controlled experiments that used isolated type II pneumocytes. SETTING: Experimental laboratory of a university hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: To study perfluorocarbon uptake, isolated type II cells were incubated with fluorescence-labeled perfluorocarbons and examined with a laser scanning microscope. The effect of perfluorocarbons on biosynthesis of phospholipids and triglycerides was measured by incubating cells that were pulse-labeled with [H]-palmitic acid for 30 secs, with two different perfluorocarbons (PF 5080 or RM 101) for 10 mins. The effect of perfluorocarbon incubation on lipid secretion was studied by transmission electron microscopy. To quantify secretion, adherent type II pneumocytes (containing radioactively labeled phospholipids) were incubated with perfluorocarbons, and extra- and intracellular radioactivity was measured. MEASUREMENTS AND MAIN RESULTS: We found a significant uptake of labeled perfluorocarbons into lamellar bodies within 10 mins. Both perfluorocarbon species significantly (p <.05) reduced the biosynthesis of phospholipids when compared with control. Perfluorocarbon incubation did not affect mitochondrial activity, tested by MitoTracker staining. Transmission electron microscopy revealed changes that suggest an increased secretion of surfactant by type II cells. Studies with radioactively labeled surfactant revealed a significantly (p <.01) higher amount of extracellular lipids after RM 101 and PF 5080 treatment (RM 101, 17 +/- 7.9%; PF 5080, 9 +/- 1.9%) compared with control (5.3 +/- 1.9%). CONCLUSIONS: Our results suggest that perfluorocarbons are taken up by type II pneumocytes and cause an increased secretion of surfactant, despite a relative reduction in the synthesis of phospholipids.

Aerosolization of perfluorocarbons during mechanical ventilation: an in vitro study.

OBJECTIVE: Inhalation of perfluorocarbons (PFC) has been suggested as a new and promising technique of PFC delivery in animal models of severe lung injury. However, no in vitro data were available on the efficacy of PFC aerosolization during mechanical ventilation. Therefore, the aim of the in vitro study was to investigate the influence of physical properties of PFC and the ventilatory settings on the amount of PFC delivered into the lung. DESIGN: In vitro lung model study. SETTING: University research laboratory. MEASUREMENTS AND RESULTS: Two different PFC (PF 5080 and PFOB) were aerosolized with a PariBoy jet nebulizer. Using a PFC selective adsorber, the effect of endotracheal tube size (2 mm and 3 mm diameter) on delivery of PFC was investigated. PFC delivery was estimated by continuous measurement of weight gain of the adsorber (adsorption rate). Finally, the influence of respiratory rate and tidal volume on adsorption rate (AR) was studied. AR was significantly reduced by a decreasing tube diameter and ranged from 1.45+/-0.03 ml/min (no tube) to 0.93+/-0.03 ml/min (2.0 mm) for PF 5080 (vapor pressure 51 mmHg) and from 0.49+/-0.06 ml/min to 0.32+/-0.04 ml/min for PFOB (11 mmHg). PFC-aerosolization into a ventilatory circuit with simulation of spontaneous tidal breathing (minute volume 600 ml) reduced AR to 0.16+/-0.02 ml/min. During mechanical ventilation, changes in respiratory rate and tidal volume, which reduce minute ventilation, caused a decrease in AR. CONCLUSION: The amount of PFC that can be delivered into the lung by aerosolization is very small and is influenced by PFC properties, tube size, and ventilatory settings.

Cerebral oxygenation is affected by filling mode and perfluorochemical volume in partial liquid ventilation of healthy piglets.

Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO(2)) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO(2), PaO(2) and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO(2), HbO(2) and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO(2)). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.