Empirical Probability of Positive Response to PEEP Changes and Mechanical Ventilation Factors Associated With Improved Oxygenation During Pediatric Ventilation.

BACKGROUND: PEEP is titrated to improve oxygenation during mechanical ventilation. It is clinically desirable to identify factors that are associated with a clinical improvement or deterioration following a PEEP change. However, these factors have not been adequately described in the literature. Therefore, we aimed to quantify the empirical probability of PEEP changes having a positive effect upon oxygenation, compliance of the respiratory system (CRS), and the ratio of dead space to tidal volume (VD/VT). Further, clinical factors associated with positive response during pediatric mechanical ventilation are described. METHODS: Mechanically ventilated pediatric subjects in the ICU were eligible for inclusion in the study. During PEEP increases (PEEPincrease), a responder was defined as having an improved SpO2 /FIO2 ratio; non-responders demonstrated a worsening SpO2 /FIO2 ratio in the following hour. When PEEP was decreased (PEEPdecrease), a responder was anyone who maintained or increased the SpO2 /FIO2 ratio; non-responders demonstrated a worsening SpO2 /FIO2 ratio. Features from continuous mechanical ventilation variables were extracted, and differences between responders and non-responders were identified. RESULTS: 286 PEEP change cases were eligible for analysis in 76 subjects. For PEEPincrease cases, the empirical probability of positive response was 56%, 67%, and 54% for oxygenation, CRS, and VD/VT, respectively. The median SpO2 /FIO2 increase was 13. For PEEPdecrease, the empirical probability of response was 46%, 53%, and 46% for oxygenation, CRS, and VD/VT, respectively. PEEPincrease responders had higher FIO2 requirements (70.8 vs 52.5%, P < .001), mean airway pressure (14.0 vs 12.9 cm H2O, P = .03), and oxygen saturation index (9.9 vs 7.5, P = .002) versus non-responders. For PEEPdecrease, VD/VT was lower in responders (0.46 vs 0.50, P = .031). CONCLUSIONS: In children requiring mechanical ventilation, the responder rate was modest for both PEEPincrease and PEEPdecrease cases. These data suggest that PEEP titration often does not have the desired clinical effect, and predicting which patients will manifest a positive response is complex, requiring more sophisticated means of assessing individual subjects.

Equilibration Time Required for Respiratory System Compliance and Oxygenation Response Following Changes in Positive End-Expiratory Pressure in Mechanically Ventilated Children.

OBJECTIVES: Increases in positive end-expiratory pressure are implemented to improve oxygenation through the recruitment and stabilization of collapsed alveoli. However, the time it takes for a positive end-expiratory pressure change to have maximum effect upon oxygenation and pulmonary compliance has not been adequately described in children. Therefore, we sought to quantify the time required for oxygenation and pulmonary system compliance changes in children requiring mechanical ventilation. DESIGN: Retrospective analysis of continuous data. SETTINGS: Multidisciplinary ICU of a pediatric university hospital. PATIENTS: Mechanically ventilated pediatric subjects. INTERVENTIONS: A case was eligible for analysis if during a 90-minute window following an increase in positive end-expiratory pressure, no other changes to the ventilator were made, ventilator and physiologic data were continuously available and a positive oxygenation response was observed. Time to 90% (T90) of the maximum change in oxygenation and compliance was computed. Differences between oxygenation and compliance T90 were compared using a paired t test. The effect of severity of illness (by oxygen saturation index) upon oxygenation and compliance was analyzed. MEASUREMENTS AND MAIN RESULTS: A total of 200 subjects were enrolled and 1,150 positive end-expiratory pressure change cases were analyzed. Of these, 54 subjects with 171 positive end-expiratory pressure change case were included in the analysis (67% were responders).Changes in dynamic compliance (T90 = 38 min) preceded changes in oxygenation (T90 = 71 min; p < 0.001). Oxygenation response differed depending on severity of illness quantified by oxygen saturation index; lung dysfunction was associated with a longer response time (p = 0.001). CONCLUSIONS: T90 requires 38 and 71 minutes for dynamic pulmonary compliance and oxygenation, respectively; the latter was directly observed to be dependent upon severity of illness. To our knowledge, this is the first report of oxygenation and compliance equilibration data following positive end-expiratory pressure increases in pediatric mechanically ventilated subjects.

Not All Pacifiers Are Created Equal: A Mechanical Examination of Pacifiers and Their Influence on Suck Patterning.

PURPOSE: Many pacifier companies advertise that their product is the "best choice" to support proper sucking, feeding, and dental development; however, very little evidence exists to support these claims. As the primary differences across pacifiers are structural and mechanical, the goals of this study were to measure such properties of commercially available pacifiers and to examine how these properties alter suck patterning in healthy, full-term infants. METHOD: Seven commonly utilized pacifiers were mechanically tested for pull and compression stiffness levels and categorized into nipple shape types based on their aspect ratio. Next, 3 pacifiers (Soothie, GumDrop, and Freeflow) with the most salient differences in pull stiffness levels with 2 different pacifier nipple types were tested clinically on 16 full-term infants (≤ 6 months old) while measuring non-nutritive suck (NNS). RESULTS: A repeated measures analysis of variance revealed significant differences between NNS burst duration (p = .002), NNS cycles per burst (p = .002), and NNS cycles per minute (p = .006) and pacifier type. With each significant dependent measure, pairwise comparisons showed that the GumDrop and Freeflow pacifiers differed significantly on these measures. CONCLUSIONS: Pacifier compression, pull stiffness, and nipple shape type yield different NNS dynamics. These findings motivate further investigation into pacifier properties and suck patterning in young infants.

Rebound mechanics of micrometre-scale, spherical particles in high-velocity impacts.

The impact mechanics of micrometre-scale metal particles with flat metal surfaces is investigated for high-velocity impacts ranging from 50 m s-1 to more than 1 km s-1, where impact causes predominantly plastic deformation. A material model that includes high strain rate and temperature effects on the yield stress, heat generation due to plasticity, material damage due to excessive plastic strain and heat transfer is used in the numerical analysis. The coefficient of restitution e is predicted by the classical work using elastic-plastic deformation analysis with quasi-static impact mechanics to be proportional to [Formula: see text] and [Formula: see text] for the low and moderate impact velocities that span the ranges of 0-10 and 10-100 m s-1, respectively. In the elastic-plastic and fully plastic deformation regimes the particle rebound is attributed to the elastic spring-back that initiates at the particle-substrate interface. At higher impact velocities (0.1-1 km s-1) e is shown to be proportional to approximately [Formula: see text]. In this deeply plastic deformation regime various deformation modes that depend on plastic flow of the material including the time lag between the rebound instances of the top and bottom points of particle and the lateral spreading of the particle are identified. In this deformation regime, the elastic spring-back initiates subsurface, in the substrate.

High Oxygen Concentrations Adversely Affect the Performance of Pulmonary Surfactant.

BACKGROUND: Although effective in the neonatal population, exogenous pulmonary surfactant has not demonstrated a benefit in pediatric and adult subjects with hypoxic lung injury despite a sound physiologic rationale. Importantly, neonatal surfactant replacement therapy is administered in conjunction with low fractional FIO2 while pediatric/adult therapy is administered with high FIO2 . We suspected a connection between FIO2 and surfactant performance. Therefore, we sought to assess a possible mechanism by which the activity of pulmonary surfactant is adversely affected by direct oxygen exposure in in vitro experiments. METHODS: The mechanical performance of pulmonary surfactant was evaluated using 2 methods. First, Langmuir-Wilhelmy balance was utilized to study the reduction in surface area (δA) of surfactant to achieve a low bound value of surface tension after repeated compression and expansion cycles. Second, dynamic light scattering was utilized to measure the size of pulmonary surfactant particles in aqueous suspension. For both experiments, comparisons were made between surfactant exposed to 21% and 100% oxygen. RESULTS: The δA of surfactant was 21.1 ± 2.0% and 35.8 ± 2.0% during exposure to 21% and 100% oxygen, respectively (P = .02). Furthermore, dynamic light-scattering experiments revealed a micelle diameter of 336.0 ± 12.5 µm and 280.2 ± 11.0 µm in 21% and 100% oxygen, respectively (P < .001), corresponding to a ∼16% decrease in micelle diameter following exposure to 100% oxygen. CONCLUSIONS: The characteristics of pulmonary surfactant were adversely affected by short-term exposure to oxygen. Specifically, surface tension studies revealed that short-term exposure of surfactant film to high concentrations of oxygen expedited the frangibility of pulmonary surfactant, as shown with the δA. This suggests that reductions in pulmonary compliance and associated adverse effects could begin to take effect in a very short period of time. If these findings can be demonstrated in vivo, a role for reduced FIO2 during exogenous surfactant delivery may have a clinical benefit.

Toward Monitoring Parkinson's Through Analysis of Static Handwriting Samples: A Quantitative Analytical Framework.

Detection of changes in micrographia as a manifestation of symptomatic progression or therapeutic response in Parkinson's disease (PD) is challenging as such changes can be subtle. A computerized toolkit based on quantitative analysis of handwriting samples would be valuable as it could supplement and support clinical assessments, help monitor micrographia, and link it to PD. Such a toolkit would be especially useful if it could detect subtle yet relevant changes in handwriting morphology, thus enhancing resolution of the detection procedure. This would be made possible by developing a set of metrics sensitive enough to detect and discern micrographia with specificity. Several metrics that are sensitive to the characteristics of micrographia were developed, with minimal sensitivity to confounding handwriting artifacts. These metrics capture character size-reduction, ink utilization, and pixel density within a writing sample from left to right. They are used here to "score" handwritten signatures of 12 different individuals corresponding to healthy and symptomatic PD conditions, and sample control signatures that had been artificially reduced in size for comparison purposes. Moreover, metric analyses of samples from ten of the 12 individuals for which clinical diagnosis time is known show considerable informative variations when applied to static signature samples obtained before and after diagnosis. In particular, a measure called pixel density variation showed statistically significant differences ( ) between two comparison groups of remote signature recordings: earlier versus recent, based on independent and paired t-test analyses on a total of 40 signature samples. The quantitative framework developed here has the potential to be used in future controlled experiments to study micrographia and links to PD from various aspects, including monitoring and assessment of applied interventions and treatments. The inherent value in this methodology is further enhanced by its reliance solely on static signatures, not requiring dynamic sampling with specialized equipment.

Pressure attenuation during high-frequency airway clearance therapy across different size endotracheal tubes: An in vitro study.

PURPOSE: High-frequency airway clearance therapy is a positive pressure secretion clearance modality used in pediatric and adult applications. However, pressure attenuation across different size endotracheal tubes (ETT) has not been adequately described. This study quantifies attenuation in an in vitro model. MATERIALS AND METHODS: The MetaNeb® System was used to deliver high-frequency pressure pulses to 3.0, 4.0, 6.0 and 8.0mm ID ETTs connected to a test lung during mechanical ventilation. The experimental setup included a 3D-printed trachea model and imbedded pressure sensors. The pressure attenuation (Patt%) was calculated: Patt%=[(Pproximal-Pdistal)/Pproximal]x100. The effect of pulse frequency on Pdistal and Pproximal was quantified. RESULTS: Patt% was inversely and linearly related to ETT ID and (y=-7.924x+74.36; R(2)=0.9917, P=.0042 for 4.0Hz pulse frequency and y=-7.382+9.445, R(2)=0.9964, P=.0018 for 3.0Hz pulse frequency). Patt% across the 3.0, 4.0, 6.0 and 8.0mm I.D. ETTs was 48.88±10.25%, 40.87±5.22%, 27.97±5.29%, and 9.90±1.9% respectively. Selecting the 4.0Hz frequency mode demonstrated higher Pproximal and Pdistal compared to the 3.0Hz frequency mode (P=.0049 and P=.0065). Observed Pdistal was <30cmH2O for all experiments. CONCLUSIONS: In an in vitro model, pressure attenuation was linearly related to the inner diameter of the endotracheal tube; with decreasing attenuation as the ETT size increased.

Bioinspired hybrid materials from spray-formed ceramic templates.

Thermally sprayed ceramics, when infiltrated with polymer, exhibit synergistic increases in strength and toughness. The structure of such composites-a dense, brick-mortar arrangement-is strikingly similar to that of nacre, as are the mechanisms underlying the robust mechanical behavior. This industrial-scale process thus presents an exciting tool for bio-mimetic exploration.

Mechanical and optical dynamic model of lung.

A multiscale, multiphysics model generates synthetic images of alveolar compression under spherical indentation at the visceral pleura of an inflated lung. A mechanical model connects the millimeter scale of an indenter tip to the behavior of alveoli, walls, and membrane at the micrometer scale. A finite-difference model of optical coherence tomography (OCT) generates the resulting images. Results show good agreement with the experiments performed using a unique indenter-OCT system. The images depict the physical result with the addition of refractive artifacts and speckle. Compression of the alveoli alters the refractive effects, which introduce systematic errors in the computation of alveolar volume. The complete computational model is useful to evaluate new proposed imaging instrumentation and to develop algorithms for obtaining quantitative data on deformation. Among the potential applications, a better understanding of recruitment of alveoli during inflation of a lung, obtained through a combination of models and imaging could lead to improvements in noninvasive treatment of atelectasis.

Refractive effects on optical measurement of alveolar volume: a 2-D ray-tracing approach.

Lung imaging and assessment of alveoli geometry in the lung tissue is of great importance. Optical coherence tomography (OCT) is a real-time imaging technique used for this purpose, based on near-infrared interferometry, that can image several layers of distal alveoli in the lung tissue. The OCT measurements use low coherence interferometry, where light reflections from surfaces in the tissue are used to construct 2D images of the tissue. OCT images provide better depth compared to other optical microscopy techniques such as confocal reflectance and two-photon microscopy. Therefore, it is important to detect and verify optical distortions that happens with OCT, including refractive effect at the tissue-air alveoli wall interface which is not taken into account in the OCT imaging model. In this paper, the refractive effect at the tissue-air interface of the alveoli wall is modeled using exact ray tracing and direct implementation of Snell's law, and differences between alveoli area computed from OCT imaging and those measured by exact ray tracing of the OCT signal are analyzed.

Uniform-intensity, visible light source for in situ imaging.

A flexible, low-cost, high-brightness light source for biological and biomedical imaging is presented. The illuminating device consists of a custom-size square plastic pouch 10 to 20 mm on a side and 1 to 3 mm thick that can be inserted fully or partially into both in situ or in vitro specimens to be imaged. The pouch contains a silicone-based gel medium embedded with silica particles that scatters light and provides a reasonably uniform, planar light source. Light is delivered to the pouch using a multimode optical fiber and a high-intensity tungsten lamp. Pouch size and geometry can be readily altered as needed for a particular application. Benefits of the device include reasonably uniform light intensity, low temperature rise (<2 degrees C), a nearly white light spectrum, and a thin (<2 mm thick) flexible form factor. The design, fabrication, and preliminary results from the device are presented using hamster cheek pouch tissue, with comparisons to standard intravital microscopy, along with suggestions for further improvement and potential uses.

Mechanically strong double network photocrosslinked hydrogels from N,N-dimethylacrylamide and glycidyl methacrylated hyaluronan.

Hyaluronan (HA) is a natural polysaccharide abundant in biological tissues and it can be modified to prepare biomaterials. In this work, HA modified with glycidyl methacrylate was photocrosslinked to form the first network (PHA), and then a series of highly porous PHA/N,N-dimethylacrylamide (DAAm) hydrogels (PHA/DAAm) with high mechanical strength were obtained by incorporating a second network of photocrosslinked DAAm into PHA network. Due to the synergistic effect produced by double network (DN) structure, despite containing 90% of water, the resulting PHA/DAAm hydrogel showed a compressive modulus and a fracture stress over 0.5 MPa and 5.2 MPa, respectively. Compared to the photocrosslinked hyaluronan single network hydrogel, which is generally very brittle and fractures easily, the PHA/DAAm hydrogels are ductile. Mouse dermal fibroblast was used as a model cell line to validate in vitro non-cytotoxicity of the PHA/DAAm hydrogels. Cells deposited extracellular matrix on the surface of these hydrogels and this was confirmed by positive staining of Type I collagen by Sirius Red. The PHA/DAAm hydrogels were also resistant to biodegradation and largely retained their excellent mechanical properties even after 2 months of co-culturing with fibroblasts.

Lubrication regimes in mesothelial sliding.

To function normally, the lungs, heart, and other organs must undergo changes in shape and size, sliding against surrounding body walls. It is not known whether the delicate mesothelial surfaces covering these organs and body wall are in contact during sliding, or if hydrodynamic pressure in the lubricating liquid increases separation between their surfaces. To address this question, we measured the coefficient of friction (mu) of the mesothelial surface of nine rat-abdominal walls sliding in saline on a smooth glass surface. Sliding at physiological velocities of 0.0123-6.14 cm/s with normal stresses of 50-200 Pa, mu varied with velocity (P<0.001). On average, mu was relatively high at low speeds (0.078 at 0.041 cm/s), decreased to a minimum at intermediate speeds (0.034 at 1.23 cm/s), and increased slightly again at higher speeds (0.045 at 6.14 cm/s), consistent with a mixed lubrication regime in which there is at least partial hydrodynamic separation of surfaces. We conclude that mesothelial surfaces, sliding under physiological conditions, are protected from excessive shear by hydrodynamic pressures that increase separation of surfaces.

Stiffness of the pleural surface of the chest wall is similar to that of the lung.

To address the role of the parietal pleura in reduction of mesothelial shear stresses during breathing, we measured the stiffness of the parietal pleural surface of mammalian chest walls using microindentation. The pleural surface was indented over ribs and intercostal spaces with rigid flat punches (tip radii of 0.01, 0.02, and 0.1 cm) to probe stiffness at length scales comparable with those of surface asperities. We found a tissue shear modulus of 6700 dyn/cm2 and pleural membrane tension of 4900 dyn/cm, with a geometric standard deviation of 0.42. These values are similar to those measured for the lung by Hajji et al., using indentation (Hajji MA, Wilson TA, and Lai-Fook SJ. J Appl Physiol Respirat Environ Exerc Physiol 47: 175-181, 1979). Surprisingly, the pleural surface over ribs and intercostal spaces exhibited similar stiffness. In addition, caudal regions exhibited lower stiffness than cranial regions. In the context of elastohydrodynamic lubrication, these results suggest that shear-induced pressures during breathing deform the chest wall and lung surfaces to a similar extent, promoting spatial uniformity of pleural fluid thickness and reducing shear stresses.

Elastohydrodynamic separation of pleural surfaces during breathing.

To examine effects of lung motion on the separation of pleural surfaces during breathing, we modeled the pleural space in two dimensions as a thin layer of fluid separating a stationary elastic solid and a sliding flat solid surface. The undeformed elastic solid contained a series of bumps, to represent tissue surface features, introducing unevenness in fluid layer thickness. We computed the extent of deformation of the solid as a function of sliding velocity, solid elastic modulus, and bump geometry (wavelength and amplitude). For physiological values of the parameters, significant deformation occurs (i.e. bumps are 'flattened') promoting less variation in fluid thickness and decreased fluid shear stress. In addition, deformation is persistent; bumps of sufficient wavelength, once deformed, require a recovery time longer than a typical breath-to-breath interval to return near their undeformed configuration. These results suggest that in the pleural space during normal breathing, separation of pleural surfaces is promoted by the reciprocating sliding of lung and chest wall.

Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells.

We describe a novel synchronous detection approach to map the transmission of mechanical stresses within the cytoplasm of an adherent cell. Using fluorescent protein-labeled mitochondria or cytoskeletal components as fiducial markers, we measured displacements and computed stresses in the cytoskeleton of a living cell plated on extracellular matrix molecules that arise in response to a small, external localized oscillatory load applied to transmembrane receptors on the apical cell surface. Induced synchronous displacements, stresses, and phase lags were found to be concentrated at sites quite remote from the localized load and were modulated by the preexisting tensile stress (prestress) in the cytoskeleton. Stresses applied at the apical surface also resulted in displacements of focal adhesion sites at the cell base. Cytoskeletal anisotropy was revealed by differential phase lags in X vs. Y directions. Displacements and stresses in the cytoskeleton of a cell plated on poly-L-lysine decayed quickly and were not concentrated at remote sites. These data indicate that mechanical forces are transferred across discrete cytoskeletal elements over long distances through the cytoplasm in the living adherent cell.

Relative motion of lung and chest wall promotes uniform pleural space thickness.

The pleural space is modeled in two dimensions as a thin layer of fluid separating a deformable membrane and a rigid surface containing a bump. We computed the steady-state membrane configuration and fluid pressure distribution during relative sliding of the two surfaces. For physiologically relevant values of membrane tension, shear flow-induced pressures near the bump and far-field pressure gradients are similar to those measured in vivo within the pleural space (e.g. Lai-Fook et al.) [J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 56 (1984) 1633-1639]. Deformation of the membrane over the bump suggests that the pressure field generated by the sliding motion promotes an even layer of fluid in the pleural space, preventing asperities from touching. Results also suggest a possible mechanism for pleural fluid redistribution during breathing, whereby irreversible fluid motion is associated with the deformability of the membrane.