Bubble Counts Research Articles

Sequential Blood Filtration for Extracorporeal Circulation: Initial Results from a Proof-of-Concept Prototype

Micropore filters are used during extracorporeal circulation to prevent gaseous and solid particles from entering the patient’s systemic circulation. Although these devices improve patient safety, limitations in current designs have prompted the development of a new concept in micropore filtration. A prototype of the new design was made using 40-μm filter screens and compared against four commercially available filters for performance in pressure loss and gross air handling. Pre- and postfilter bubble counts for 5- and 10-mL bolus injections in an ex vivo test circuit were recorded using a Doppler ultrasound bubble counter. Statistical analysis of results for bubble volume reduction between test filters was performed with one-way repeated-measures analysis of variance using Bonferroni post hoc tests. Changes in filter performance with changes in microbubble load were also assessed with dependent t tests using the 5- and 10-mL bolus injections as the paired sample for each filter. Significance was set at p < .05. All filters in the test group were comparable in pressure loss performance, showing a range of 26–33 mmHg at a flow rate of 6 L/min. In gross air-handling studies, the prototype showed improved bubble volume reduction, reaching statistical significance with three of the four commercial filters. All test filters showed decreased performance in bubble volume reduction when the microbubble load was increased. Findings from this research support the underpinning theories of a sequential arterial-line filter design and suggest that improvements in microbubble filtration may be possible using this technique.

Sclerosant Foam Structure and Stability is Strongly Influenced by Liquid Air Fraction

To determine the effects of sclerosant foam preparation and composition on foam structure, the time course of liquid drainage, and foam coarsening. Sodium tetradecyl sulphate (STS) and polidocanol (POL) foams were investigated in a range of concentrations (0.5-3%) and liquid-plus-air fractions (LAF; 1 + 2 to 1 + 8). Foam was injected into a vein simulation model (polyvinyl chloride tubing, inner diameter 3 mm, constant pressure 5-7 mmHg) filled with saline or blood. Liquid drainage, bubble count, and diameter were measured and documented by serial photography. Liquid drainage was faster in the vertical position than the horizontal one. In all variations, very small bubbles (diameter <30 μm) were generated initially that coarsened to form micro-foams (<250 μm). By 3 minutes mini-foams (>250 μm) and by 7.5 minutes macro-foams (>500 μm) were formed. Following injection, the upper regions of foam coarsened faster as liquid drained to the bottom of the vessel. Wet preparations produced significantly smaller bubbles. Low concentration POL foam produced significantly higher bubble counts and coarsened slower than STS. Foam structure is strongly influenced by the LAF. Despite the initial formation of micro-bubbles in the syringe, mini- and macro-bubbles are formed in target vessels with time post-injection.

Excessive negative venous line pressures and increased arterial air bubble counts during miniaturized cardiopulmonary bypass: an experimental study comparing miniaturized with conventional perfusion systems

Miniaturized cardiopulmonary bypass (MCPB) is increasingly used in cardiac surgery, because it can lower clinically significant complications such as systemic inflammatory response, haemolysis and high transfusion requirements. A limitation of MCPB is the risk of excessive negative pressure in the venous line during volume depletion, probably leading to gaseous microembolism. In an experimental study with 24 pigs, we compared conventional open cardiopulmonary bypass (CCPB group, n = 11) with MCPB (n = 13). The same pump and identical tubing materials were used in both groups. Primary endpoints were pressure values in the venous line and the right atrium as well as the amount of air bubbles >500 µm. Secondary endpoints were biochemical parameters of systemic inflammatory response, ischaemia, haemodilution and haemolysis. Nearly 20% of venous pressure values were below -150 mmHg and approximately 10% of the right atrial pressure values were below -100 mmHg in the MCPB group, during the experiment. No such low values were observed in the CCPB group. In addition, the number of large arterial air bubbles was higher in the MCPB group compared with the CCPB group (mean ± standard deviation [SD]: 13 444 ± 5709 vs 0.9 ± 0.6, respectively; P < 0.001). Bubble volume was also significantly larger during MCPB compared with CCPB (mean ± SD: 1522 ± 654 vs 4.1 ± 2.5 µl, respectively; P < 0.001). Blood levels of interleukin-6, free haemoglobin and creatine kinase were significantly higher in the CCPB group compared with the MCPB group. Despite the benefits of MCPB regarding systemic inflammatory response and haemolysis, this technique is associated with excessive negative venous line pressures and a significant increase in the number and volume of arterial air bubbles compared with CCPB. Mini-perfusion systems and the management of MCPB require further refinements to avoid such adverse effects.

Patient Warming Excess Heat

Patient warming has become a standard of care for the prevention of unintentional hypothermia based on benefits established in general surgery. However, these benefits may not fully translate to contamination-sensitive surgery (i.e., implants), because patient warming devices release excess heat that may disrupt the intended ceiling-to-floor ventilation airflows and expose the surgical site to added contamination. Therefore, we studied the effects of 2 popular patient warming technologies, forced air and conductive fabric, versus control conditions on ventilation performance in an orthopedic operating room with a mannequin draped for total knee replacement. Ventilation performance was assessed by releasing neutrally buoyant detergent bubbles ("bubbles") into the nonsterile region under the head-side of the anesthesia drape. We then tracked whether the excess heat from upper body patient warming mobilized the "bubbles" into the surgical site. Formally, a randomized replicated design assessed the effect of device (forced air, conductive fabric, control) and anesthesia drape height (low-drape, high-drape) on the number of bubbles photographed over the surgical site. The direct mass-flow exhaust from forced air warming generated hot air convection currents that mobilized bubbles over the anesthesia drape and into the surgical site, resulting in a significant increase in bubble counts for the factor of patient warming device (P < 0.001). Forced air had an average count of 132.5 versus 0.48 for conductive fabric (P = 0.003) and 0.01 for control conditions (P = 0.008) across both drape heights. Differences in average bubble counts across both drape heights were insignificant between conductive fabric and control conditions (P = 0.87). The factor of drape height had no significant effect (P = 0.94) on bubble counts. Excess heat from forced air warming resulted in the disruption of ventilation airflows over the surgical site, whereas conductive patient warming devices had no noticeable effect on ventilation airflows. These findings warrant future research into the effects of forced air warming excess heat on clinical outcomes during contamination-sensitive surgery.

Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles

Micron sized, lipid stabilized bubbles of gas are of interest as contrast agents for ultra-sound (US) imaging and increasingly as delivery vehicles for targeted, triggered, therapeutic delivery. Microfluidics provides a reproducible means for microbubble production and surface functionalisation. In this study, microbubbles are generated on chip using flow-focussing microfluidic devices that combine streams of gas and liquid through a nozzle a few microns wide and then subjecting the two phases to a downstream pressure drop. While microfluidics has successfully demonstrated the generation of monodisperse bubble populations, these approaches inherently produce low bubble counts. We introduce a new micro-spray flow regime that generates consistently high bubble concentrations that are more clinically relevant compared to traditional monodisperse bubble populations. Final bubble concentrations produced by the micro-spray regime were up to 10(10) bubbles mL(-1). The technique is shown to be highly reproducible and by using multiplexed chip arrays, the time taken to produce one millilitre of sample containing 10(10) bubbles mL(-1) was ∼10 min. Further, we also demonstrate that it is possible to attach liposomes, loaded with quantum dots (QDs) or fluorescein, in a single step during MBs formation.

Forced-air warming and ultra-clean ventilation do not mix

We investigated the capacity of patient warming devices to disrupt the ultra-clean airflow system. We compared the effects of two patient warming technologies, forced-air and conductive fabric, on operating theatre ventilation during simulated hip replacement and lumbar spinal procedures using a mannequin as a patient. Infection data were reviewed to determine whether joint infection rates were associated with the type of patient warming device that was used. Neutral-buoyancy detergent bubbles were released adjacent to the mannequin's head and at floor level to assess the movement of non-sterile air into the clean airflow over the surgical site. During simulated hip replacement, bubble counts over the surgical site were greater for forced-air than for conductive fabric warming when the anaesthesia/surgery drape was laid down (p = 0.010) and at half-height (p < 0.001). For lumbar surgery, forced-air warming generated convection currents that mobilised floor air into the surgical site area. Conductive fabric warming had no such effect. A significant increase in deep joint infection, as demonstrated by an elevated infection odds ratio (3.8, p = 0.024), was identified during a period when forced-air warming was used compared to a period when conductive fabric warming was used. Air-free warming is, therefore, recommended over forced-air warming for orthopaedic procedures.

Distribution of surface shear forces and bubble characteristics in full-scale gas sparged submerged hollow fiber membrane modules

Gas sparging is commonly used in submerged membrane systems to induce shear forces at the membrane surface, which removes the accumulated foulants. However, limited knowledge exists regarding the magnitude and distribution of these forces, especially in submerged hollow fiber membrane systems. The present study focuses on addressing this current knowledge gap by mapping the shear forces induced by gas sparging in full-scale submerged hollow fiber membrane modules. The shear forces were observed to be highly variable over time and heterogeneously distributed within the system, ranging from 0.1 to over 10Pa. The shear force measurements and the bubble counts indicated that the narrow gap between the membrane modules likely provided sufficient resistance to direct a substantial amount of the sparged bubbles to the side of the modules rather than between the membrane modules, and that regardless of the sparging flow rate, the amount of sparged bubbles that rose between the modules was constant. Increasing the sparging flow rate simply directed more of the sparged bubbles to the side of the membrane modules. As a result, the shear forces were heterogeneously distributed within the system. No correlation was observed between the shear force and bubble count or rise velocity. The distribution of sparged bubbles, the bulk liquid flow and the surface shear forces in the system were highly affected by the system geometry (e.g. module spacing, tank configuration and diffuser nozzle size).

A rat model for cerebral air microembolisation

Subtle cerebral air microembolisation (CAM) is a typical complication of various medical interventions such as open heart surgery or angiography and can cause transient or permanent neurological and neuropsychological deficits. Evaluation of the underlying pathophysiology requires animal models that allow embolisation of air bubbles of defined diameter and number. Herein we present a method for the production of gas bubbles of defined diameter and their injection into the carotid artery of rats. The number of gas microemboli injected is quantified digitally using a high speed optical image capturing system and a custom-made software.In a first pilot study, 0, 50, 100, 400 and 800 gas bubbles of 160μm in diameter were injected into the carotid artery of rats. Offline evaluation revealed a high constancy of the bubble diameters (mean 159.95±9.25μm, range 144–188μm) and the number of bubbles injected. First preliminary data indicate that with increasing number of bubbles embolised, more animals revealed neurological deficits and (particularly with higher bubble counts) brain infarctions on TTC-staining. Interestingly, also animals without overt infarcts on TTC-staining displayed neurological deficits in an apparently dose dependent fashion, indicating subtle brain damage by air embolism.In conclusion, the method presented allows injecting air bubbles of defined number and diameter into cerebral arteries of rats. This technique facilitates animal research in the field of air embolisation.

Abstract 3433: The Effect of Normal Pulmonary Arterial Bed Bubble Contrast Conductance and Latency on Bubble Contrast Echocardiography: Does “Any Bubbles” in the left atrium always mean Patent Foramen Ovale (PFO)?

BACKGROUND: The presence of a PFO remains a controversial possible mechanism for a significant number of cryptogenic strokes. However, unvalidated and arbitrary criteria of left heart contrast-bubble appearance on echocardiography form the basis for PFO diagnosis, treatment, and research. We postulated that variable conductance of contrast bubbles through the pulmonary artery (PA) vascular bed, as well as bubble latency can result in the misdiagnosis of PFO. METHODS: Consecutive pts (N=50) undergoing PFO closure by intra-cardiac echocardiography (ICE) guided imaging and right heart catheterization were studied. PULMONARY CONDUCTANCE: Prior to septal closure, ICE imaging of the left atrium was performed during selective PA bubble contrast injections (BCI) at baseline and after injection of 200micrograms of nitroprusside (NP). The appearance of left atrial bubbles was quantified by a validated 1–5 grading system (5–100 bubbles) at rest and following NP. A definite NP response was determined to be present if 2 observers agreed there was at least one grade level increase in bubble conductance from rest. PULMONARY LATENCY: 120 seconds after right atrial BCI, trans-tricuspid ICE pulmonic valve imaging was performed for count of residual bubbles as a correlate of bubbles remaining in the PA at rest. RESULTS: Age was 42 ± 18 years; 70% were female. Pulmonary conductance was present in most pts (84% =grade 1–2, 8% =grade 3– 4). Residual bubbles at the pulmonic valve at 2 minutes were common (range 0 –30 bubbles, mean 6.2 ± 6.5; 42% &gt;5 bubbles). “Definite” increase in conductance after NP was present in 38% of pts. The difference between baseline and NP grade agreed with subjective “definitive” change and “no change” readings (1.26 vs −0.03; p=0.0001). Augmentation of pulmonary conductance by NP was significant (grade 1.32 ±.79 vs 1.74 ± 1.1; p=0.0001) and definitive change was more likely in women than in men (45.7% vs 20.0%; p=0.08). CONCLUSION: We conclude that: pulmonary conductance of bubbles is common, variable, modifiable, and more common in women. Bubble latency in the pulmonary system may erroneously augment Valsalva shunt evaluation. Caution should be exercised when equating lower bubble counts on echocardiography with the diagnosis of PFO.

Mass transfer and chemical reactions in bubble swarms with dynamic interfaces

AbstractDetailed, high‐resolution numerical simulations have been performed on the buoyancy‐driven motion of deformable, chemically reacting bubbles for different operating conditions, that is, Weber, Morton, and Schmidt numbers. In our simulations different bubble shapes and types of bubble wakes were observed. The wake types range from a closed wake without recirculation, to a closed wake with recirculation, to an unsteady wake, leading to vortex‐shedding wakes. Two different bubble‐rise trajectories were observed for different conditions: straight and zigzag shaped. The mass‐transfer rates and the yields and selectivities of liquid‐phase chemical reactions were determined for each case. A detailed analysis of the results was carried out, relating the differences in chemical reaction efficiencies to the dynamics of each flow. Furthermore, to obtain a better understanding of the dynamics of the flows inside bubble swarms and their impact on chemical reactions, numerical simulations were performed of multiple bubbles rising in a swarm. Different bubble counts, geometric configurations, and size distributions were considered. Mass‐transfer rates and chemical reaction selectivities were determined and a comparison is presented between the results for bubble swarms and single bubbles. It was shown that for mixing‐sensitive reaction networks, the hydrodynamics of the bubble swarm may significantly impact the reaction selectivity. Furthermore, it was demonstrated that bubble swarm dynamics differ from the dynamics of single bubbles. © 2005 American Institute of Chemical Engineers AIChE J, 2005

Cavitation in flowing media by lithotripter shock waves in vitro and in vivo

Cavitation produced by lithotripter shock waves was characterized in vitro in water and blood, and in vivo in aortic blood by means of a resonant bubble detector. The 1.6‐MHz detector can detect and count 4 ± 1‐μm‐diam bubbles flowing through it by receiving their second harmonic emissions at 3.2 MHz. Spark‐gap lithotripters were used to expose the flowing liquid upstream of the detector at the shock wave focus. This system was readily able to detect bubbles resulting from shock wave‐induced cavitation in both water and blood flowing through plastic tubes in vitro, and even in blood pumped by the heart through a plastic arteriovenous shunt. Multiple (up to several hundred) bubble counts were obtained for each shock wave. However, for 200–400 shock wave exposures of each of two dogs, this system was unable to detect evidence of shock wave‐induced cavitational activity occurring within the intact vascular system in vivo. [Work supported by Dornier Medizintechnik and by NIH Grant CA 42947.]

Surface wettability modification of poly(vinyl siloxanes) with nonionic surfactants

Poly(vinyl siloxanes) are widely used as dental impression materials because of their superior dimensional accuracy and stability in comparison with the other elastomeric impression materials. However, the materials have low surface free energies, making them difficult to wet with the gypsum slurries which are subsequently poured into the impressions. The resultant bubble entrapment discourages their use. In this study, polyy(vinyl siloxane) impression materials were modified by the incorporation of members of a homologous series of nonylphenoxypoly(ethyleneoxy)ethanols and selected surfactants of substantially different chemistries. Contact angles with saturated aqueous gypsum and bubble counts in critical impressions were determined. The resultant contact angles fit a bilinear regression curve when angle is plotted against surfactant HLB number. For members of the homologous series, contact angles for surfactant blends were as predicted by the results for the pure components. Blends of surfactants with markedly different chemistries produced neither a clear minimum contact angle nor a bilinear curve of contact angle versus HLB. For the optimal surfactant, the improved wetting was substantially unaffected by rinsing. The improved wettability for optimally surfactant modified elastomer was reflected by the marked decrease in bubble counts in gypsum pours. The surfactant addition did not significantly degrade either dimensional accuracy or stability.

A Technique for the Effective Removal of Air from a Hollow Fiber Membrane Oxygenator Circuit

This paper describes some of the ways unwanted air can be introduced into a cardiopulmonary bypass circuit and a technique which has been shown to significantly decrease the resultant bubble counts. In this study air was introduced into a circuit (Hct. 20%) containing a Hollow Fiber Membrane Oxygenator (HFMO). Conventional techniques of recirculation (3 L/min.) and vigorous agitation/percussion were compared to recirculation with vacuum (gas phase of HFMO) for efficiency in reducing bubble counts measured after three minutes by a microbubble counter. Conventional methods were ineffective after three minutes while vacuum for 3 minutes significantly (p = .001) reduced bubble counts (bubbles &gt; 100 microns). The microporous membrane allows efficient air removal with vacuum while recirculation/percussion did little to remove air which, in a blood perfusate, was not visible to the naked eye. The application of vacuum not only increases safety but convenience when used in the priming and de bubbling of a circuit in routine and emergency case.

Characterization of cavitation in a flow-through exposure chamber by means of a resonant bubble detector

Ultrasonic cavitation at frequencies of 0.514, 0.866, 1.03 and 1.61 MHz in water flowing through tubes was observed by counting bubbles downstream with a resonant bubble detector (RBD) operated at 0.89 or 1.7 MHz. In a 21 mm diameter, thin-walled tube, cavitation thresholds in tap water flowing at 5.3 cm s −1 ranged from 2.0 – 2.5 bar at 0.514 MHz to 3 – 4 bar at 1.61 MHz. When high speed injections were employed to trigger the ultrasonic cavitation with hydrodynamically-generated bubbles, the thresholds were reduced to about 2 bar and bubble production was enhanced for 1.03 and 1.61 MHz exposures. Ultrasonic radiation forces on the bubbles and bubble coalescence appeared to cause, under some conditions, a reduction in bubble counts during subthreshold exposures when bubbles were injected into the flow. The RBD method is a useful tool for detecting and semi-quantitatively observing cavitation in a flow-through exposure system.

Skins of varying permeability: A stabilization mechanism for gas cavitation nuclei

Numerous experiments suggest that bubble formation in water is initiated by preexisting gas nuclei. This is unexpected since gas phases larger than the order of 1 μm in radius ought to rise to the surface of a standing liquid, whereas smaller ones should dissolve rapidly via the outward diffusion of gas that results from surface tension. Several mechanisms for stabilizing gas nuclei have been proposed, but in each case there is experimental evidence to the contrary. In this article, a model is investigated in which stability is maintained by surface-active skins of varying gas permeability. Data on ultrasonic cavitation and on bubble formation by counter-diffusion indicate that such skins, if they exist, must be initially permeable. Quantitative comparisons with bubble counts obtained recently from supersaturated gelatin lead to the further conclusion that nuclear skins become effectively impermeable if the static pressure is raised rapidly by a sufficiently large amount. The surface area, length, and energy per skin molecule deduced from these comparisons are remarkably similar to those of known surfactants, such as lung extract, lecithin, and oleyl alcohol.