Risk factors for hemolysis with centrifugal pumps in pediatric extracorporeal membrane oxygenation: Is pump replacement an answer?

INTRODUCTION: Hemolysis during pediatric extracorporeal membrane oxygenation (ECMO) is associated with increased risk for renal failure and mortality. OBJECTIVES: We aim to describe risk factors for hemolysis in pediatric ECMO supported by centrifugal pumps. METHODS: We conducted an analysis of retrospective data collected at an academic children's hospital from January 2017 to December 2019. MEASUREMENTS AND RESULTS: Plasma-free hemoglobin (PFH) levels were measured daily, and hemolysis was defined as PFH>50 mg/dL. Of 46 ECMO runs over 528 ECMO days, hemolysis occurred in 23 (58%) patients over a total of 40 (8%) ECMO days. In multivariable logistic regression models, VA-ECMO (aOR=4.69, 95% CI: 1.01-21.83) and higher hemoglobin (aOR = 1.38, 95% CI: 1.06-1.81) were independently associated with hemolysis. There were also non-significant trends toward increased risk for hemolysis with higher rotational pump speed (aOR=2.39, 95% CI: 0.75-7.65), higher packed red blood cell transfusions (aOR=1.15, 95% CI: 0.99-1.34), and higher cryoprecipitate transfusions (aOR=2.01, 95% CI: 0.83-4.86). Isolated pump exchanges that were performed in 12 patients with hemolysis led to significant decreases in PFH levels within 24 h (89 vs 11 mg/dL, p<0.01). CONCLUSIONS: Hemolysis is common in pediatric ECMO using centrifugal pumps. Avoidance of high pump speeds and conservative administration of blood products may help to mitigate the risk for hemolysis. Furthermore, pump exchange may be an effective first-line treatment for hemolysis.

Investigation of the observed rupture lines in abdominal aortic aneurysms using crack propagation simulations.

OBJECTIVE: To use crack propagation simulation to study the rupture site characteristics in ruptured abdominal aortic aneurysms (AAA). METHODS: Rupture lines were precisely documented in four ruptured AAA harvested whole from cadavers. Wall thickness and material parameters were experimentally determined. Using subject-specific 3D geometry and subject-specific finite elastic model parameters, crack propagation simulations were conducted based on basic fracture mechanics principles to investigate if and how localized weak spots may have led to the observed rupture lines. RESULTS AND CONCLUSION: When an initial crack was imposed at the site of peak wall stress, the propagated path did not match the observed rupture line. This indicates that in this study population, the peak wall stress was unlikely to have caused the observed rupture. When cracks were initiated at random locations in the AAA along random orientations for random initial lengths, the orientation of the resulting propagated rupture line was consistently longitudinal. This suggests that the AAA morphology predisposes the AAA to rupture longitudinally, which is consistent with observations. It was found that, in this study population, rupture may have initiated at short segments of less than about 1 cm that then propagated to form the observed rupture lines. This suggests that ex vivo experimental and in vivo elastography studies should seek a spatial resolution (approx. 1 cm) to reliably identify weak spots in AAA. The small study population and lack of a reliable failure model for AAA tissue make these findings preliminary.

Volumetry and biomechanical parameters detected by 3D and 2D ultrasound in patients with and without an abdominal aortic aneurysm.

The objective was to demonstrate the ability of ultrasound (US) with 3D properties to evaluate volumetry and biomechanical parameters of the aorta in patients with and without abdominal aortic aneurysm (AAA). Thirty-one patients with normal aortas (group 1), 46 patients with AAA measuring 3.0-5.5 cm (group 2) and 31 patients with AAA ⩾ 5.5 cm (group 3) underwent a 2D/3D-US examination of the infra-renal aorta, and the images were post-processed prior to being analyzed. In the maximum diameter, the global circumferential strain and the global maximum rotation assessed by 2D speckle-tracking algorithms were compared among the three groups. The volumetry data obtained using 3D-US from 40 AAA patients were compared with the volumetry data obtained by a contemporary computed tomography (CT) scan. The median global circumferential strain was 2.0% (interquartile range (IR): 1.0-3.0), 1.0% (IR: 1.0-2.0) and 1.0% (IR: 1.0-1.75) in groups 1, 2 and 3, respectively (p < 0.001). The median global maximum rotation decreased progressively from group 1 to group 3 (1.38º (IR: 0.77-2.13), 0.80º (IR: 0.57-1.0) and 0.50º (IR: 0.31-0.75), p < 0.001). AAA volume estimations by 3D-US correlated well with CT (R(2) = 0.76). In conclusion, US with 3D properties is non-invasive and has the potential to evaluate volumetry and biomechanical characteristics of AAA.

Histologic, histochemical, and biomechanical properties of fragments isolated from the anterior wall of abdominal aortic aneurysms.

OBJECTIVE: To analyze biomechanical, histologic, and histochemical properties of anterior fragments of abdominal aortic aneurysms (AAA) and to correlate them with the maximum transverse diameter (MTD) and symptoms associated to the aneurysms. METHODS: Fragments of the anterior aneurysm wall were obtained from 90 patients submitted to open repair of AAA of degenerative etiology from 2004 to 2009 in the Clinics Hospital of São Paulo University Medical School. Two specimens were produced from the fragments: one for histologic analysis for quantification of collagen fibers, elastic fibers, smooth muscle cells, and degree of inflammatory activity and the other for uniaxial tensile test to assess biomechanical failure properties of the material, such as strength, tension, and stress. Cases were classified according to symptoms and to the AAA MTD. RESULTS: Fragments from AAA with MTD < 5.5 cm showed higher values for biomechanical failure properties than those of AAA with MTD < 5.5 cm (strength, 5.32 ± 2.07 × 4.1 ± 2.41 N; tension, 13.83 ± 5.58 × 10.82 ± 6.48 N/cm; stress, 103.02 × 77.03 N/cm(2); P < .05). No differences were observed between the groups in relation to failure strain (0.41 ± 0.12 × 0.37 ± 0.14; P = .260) and thickness of the fragments (1.58 ± 0.41 × 1.53 ± 0.42 mm; P = .662). The average values of fiber compositions of all the fragments were as follows: collagen fibers, 44.34 ± 0.48% and 61.85 ± 10.14% (Masson trichrome staining and Picrosirius red staining, respectively); smooth muscle cells, 3.46 ± 2.23% (immunohistochemistry/alpha-actin); and elastic fibers, less than 1% (traces) (Verhoeff-van Gieson staining). No differences in fiber percentages (collagen, elastic, and smooth muscle) were observed in fragments from AAA with MTD <5.5 cm and <5.5 cm, but more intense inflammatory activity was seen in larger AAA (grade 3; 70% × 28.6%; P = .011). Compared with asymptomatic aneurysms, symptomatic aneurysms showed no differences in the biomechanical failure properties (strength, 5.32 ± 2.36 × 4.65 ± 2.05 N; P = .155; tension, 14.08 ± 6.11 × 12.81 ± 5.77 N/cm; P = .154; stress, 103.02 × 84.76 N/cm(2); P = .144), strain (0.38 ± 0.12 × 0.41 ± 0.13; P = .287), thickness of the fragments (1.56 ± 0.41 × 1.57 ± 0.41 mm; P = .848), and histologic composition (collagen fibers, 44.67 ± 11.17 × 44.02 ± 13.79%; P = .808; smooth muscle fibers, 2.52 × 2.35%; P = .751; elastic fibers, <1%) CONCLUSIONS: Fragments of the anterior wall from larger aneurysms were more resistant than those from smaller AAA, with no tissue properties that could explain this phenomenon in the histologic or histochemical analyses utilized. CLINICAL RELEVANCE: The fragments of the anterior midsection from larger aneurysms were more resistant than those from smaller abdominal aortic aneurysms, with no tissue properties that could explain this phenomenon in the histologic or histochemical analyses. Larger aneurysms, at least in this place may be stronger than smaller aneurysms. It could point toward regional differences (heterogeneity, localized pathologies) as an important player in aneurysm rupture. Uniaxial strain tests are an important tool for the comprehension of a complex behavior such as that from an aneurysmal aortic wall. However, these tests still have limitations in providing information that would allow the calculation of the risk of rupture for abdominal aortic aneurysms.

Role of lung lobar sliding on parenchymal distortion during breathing.

Sliding between lung lobes along lobar fissures is a poorly understood aspect of lung mechanics. The objective of this study was to test the hypothesis that lobar sliding helps reduce distortion in the lung parenchyma during breathing. Finite element models of left lungs with geometries and boundary conditions derived from medical images of human subjects were developed. Effect of lobar sliding was studied by comparing nonlinear finite elastic contact mechanics simulations that allowed and disallowed lobar sliding. Lung parenchymal distortion during simulated breath-holds and tidal breathing was quantified with the model's spatial mean anisotropic deformation index (ADI), a measure of directional preference in volume change that varies spatially in the lung. Models that allowed lobar sliding had significantly lower mean ADI (i.e., lesser parenchymal distortion) than models that disallowed lobar sliding under simulations of both tidal breathing (5.3% median difference, P = 0.008, n = 8) and lung deformation between breath-holds at total lung capacity and functional residual capacity (3.2% median difference, P = 0.03, n = 6). This effect was most pronounced in the lower lobe where lobar sliding reduced parenchymal distortion with statistical significance, but not in the upper lobe. In addition, more lobar sliding was correlated with greater reduction in distortion between sliding and nonsliding models in our study cohorts (Pearson's correlation coefficient of 0.95 for tidal breathing, 0.87 for breath-holds, and 0.91 for the combined dataset). These findings are consistent with the hypothesis that lung lobar sliding reduces parenchymal distortion during breathing.NEW & NOTEWORTHY The role of lobar sliding in lung mechanics is poorly understood. Delineating this role could help explain how breathing is affected by anatomical differences between subjects such as incomplete and missing lobar fissures. We used computational contact mechanics models of lungs from human subjects to delineate the effect of lobar sliding by comparing simulations that allowed and disallowed sliding. We found evidence consistent with the hypothesis that lung lobar sliding reduces parenchymal distortion during breathing.

Cerebral aneurysm sac growth as the etiology of recurrence after successful coil embolization.

BACKGROUND AND PURPOSE: Coil compaction is thought to be the main mechanism for recurrence in cerebral aneurysms with previously successful coil embolization. We hypothesize that sac growth may be equally or more important. The objective was to study the relative roles of coil compaction and sac growth as explanations for aneurysm recurrence requiring retreatment in a study population using quantitative 3D image processing methods. METHODS: From July 2009 to December 2010, 175 aneurysms were coiled at the University of Iowa hospitals and clinics. Eight aneurysms had major recurrence requiring retreatment (4.4-12.1 months between procedures; mean: 7.2 months). The 3D structures of the vessel and coil mass were reconstructed using rotational angiography data scanned before and after both initial coil embolization and retreatment. Changes in the sac and coil mass over time were visualized using model registration techniques and quantified using volume calculations. RESULTS: All 8 of the coiled aneurysms with major recurrence had significant aneurysm sac growth (15% to 102% increase in volume), independent of change in coil volume. Five aneurysms with major recurrence had sufficient data for assessment of coil compaction. The coil mass volume decreased in 1 aneurysm (12% compaction by volume), did not change significantly in 1 aneurysm (increased by 1%), and significantly increased in 3 aneurysms (8%, 21%, and 25%) between the first treatment and before the second treatment. CONCLUSIONS: In this study population, aneurysm sac growth, not coil compaction, was the primary mechanism associated with recurrence after initial coil embolization.

Role of aortic stent graft oversizing and barb characteristics on folding.

OBJECTIVE: To evaluate folding in infrarenal stent grafts in relation to oversizing, barb angle, and barb length using computed tomography images of stent grafts deployed in explanted bovine aortas. METHODS: Computed tomography data from an in vitro investigation on the effect of oversizing of 4% to 45% (n = 19), barb length of 2 to 7 mm (n = 11), and barb angle of 10° to 90° (n = 7) on device fixation were examined for instances of folding. Folding was classified as circumferential or longitudinal and quantified on an ordinal scale based on codified criteria. Cumulative fold ranking from 0 (no fold) to 6 (two severe folds) for each deployment was used as the measure of folding observed. RESULTS: Of the 37 cases, cumulative mean ± standard deviation fold ranking for stent grafts oversized >30% (n = 5) was significantly greater than the rest (3.4 ± 1.7 vs 0.5 ± 1.2, respectively; Mann-Whitney U test; P < .005). When barb length was varied from 2 to 7 mm (oversizing held at 10%-20%), folding was noted in one of 11 cases. Similarly, when barb angle was varied from 0° (vertical) to 90° (horizontal), folding was not noted in any of the seven cases. The pullout force was not significantly different between stent grafts with and without folding (5.4 ± 1.95 vs 5.12 ± 1.89 N, respectively; P > .5). At least one instance of folding was noted in the seven of seven (100%) stent grafts with oversizing >23.5% and in only five of 30 (14%) stent grafts with oversizing <23.5%. CONCLUSIONS: Stent graft folding was prevalent when oversized >30%. Large variations in barb length and angle did not aggravate folding risk when oversized within the recommended range of 10% to 20%.

Characterizing heterogeneous properties of cerebral aneurysms with unknown stress-free geometry: a precursor to in vivo identification.

Knowledge of elastic properties of cerebral aneurysms is crucial for understanding the biomechanical behavior of the lesion. However, characterizing tissue properties using in vivo motion data presents a tremendous challenge. Aside from the limitation of data accuracy, a pressing issue is that the in vivo motion does not expose the stress-free geometry. This is compounded by the nonlinearity, anisotropy, and heterogeneity of the tissue behavior. This article introduces a method for identifying the heterogeneous properties of aneurysm wall tissue under unknown stress-free configuration. In the proposed approach, an accessible configuration is taken as the reference; the unknown stress-free configuration is represented locally by a metric tensor describing the prestrain from the stress-free configuration to the reference configuration. Material parameters are identified together with the metric tensor pointwisely. The paradigm is tested numerically using a forward-inverse analysis loop. An image-derived sac is considered. The aneurysm tissue is modeled as an eightply laminate whose constitutive behavior is described by an anisotropic hyperelastic strain-energy function containing four material parameters. The parameters are assumed to vary continuously in two assigned patterns to represent two types of material heterogeneity. Nine configurations between the diastolic and systolic pressures are generated by forward quasi-static finite element analyses. These configurations are fed to the inverse analysis to delineate the material parameters and the metric tensor. The recovered and the assigned distributions are in good agreement. A forward verification is conducted by comparing the displacement solutions obtained from the recovered and the assigned material parameters at a different pressure. The nodal displacements are found in excellent agreement.

Methodology for Estimation of Annual Risk of Rupture for Abdominal Aortic Aneurysm.

BACKGROUND AND OBJECTIVE: Estimating patient specific annual risk of rupture of abdominal aortic aneurysm (AAA) is currently based only on population. More accurate knowledge based on patient specific data would allow surgical treatment of only those AAAs with significant risk of rupture. This would be beneficial for both patients and health care system. METHODS: A methodology for estimating annual risk of rupture (EARR) of abdominal aortic aneurysms (AAA) that utilizes Bayesian statistics, mechanics and patient-specific blood pressure monitoring data is proposed. EARR estimation takes into consideration, peak wall stress in AAA computed by patient-specific finite element modeling, the probability distributions of wall thickness, wall strength, systolic blood pressure and the period of time that the patient is known to have already survived with the intact AAA. Initial testing of proposed approach was performed on fifteen patients with intact AAA (mean maximal diameter 51mm±8mm). They were equipped with a pressure holter and their blood pressure was recorded over 24 hours. Then, we calculated EARR values for four possible scenarios - without considering any days of survival prior identification of AAA at computed tomography scans (EARR_0), considering past survival of 30 (EARR_30), 90 (EARR_90) and 180 days (EARR_180). Finally, effect of patient-specific blood pressure variability was analyzed. RESULTS: Consideration of past survival does indeed significantly improve predictions of future risk: EARR_30 (1.04%± 0.87%), EARR_90 (0.67%± 0.56%) and EARR_180 (0.47%± 0.39%) which are unrealistically high otherwise (EARR_0 5.02%± 5.24%). Finally, EARR values were observed to vary by an order as a consequence of blood pressure variability and by factor of two as a consequence of neglected growth. CONCLUSIONS: Methodology for computing annual risk of rupture of AAA was developed for the first time. Sensitivity analyses showed respecting patient specific blood pressure is important factor and should be included in the AAA rupture risk assessment. Obtained EARR values were generally low and in good agreement with confirmed survival time of investigated patients so proposed method should be further clinically validated.

Semiautomated 3D mapping of aneurysmal wall enhancement with 7T-MRI.

Aneurysm wall enhancement (AWE) after the administration of contrast gadolinium is a potential biomarker of unstable intracranial aneurysms. While most studies determine AWE subjectively, this study comprehensively quantified AWE in 3D imaging using a semi-automated method. Thirty patients with 33 unruptured intracranial aneurysms prospectively underwent high-resolution imaging with 7T-MRI. The signal intensity (SI) of the aneurysm wall was mapped and normalized to the pituitary stalk (PS) and corpus callosum (CC). The CC proved to be a more reliable normalizing structure in detecting contrast enhancement (p < 0.0001). 3D-heatmaps and histogram analysis of AWE were used to generate the following metrics: specific aneurysm wall enhancement (SAWE), general aneurysm wall enhancement (GAWE) and focal aneurysm wall enhancement (FAWE). GAWE was more accurate in detecting known morphological determinants of aneurysm instability such as size ≥ 7 mm (p = 0.049), size ratio (p = 0.01) and aspect ratio (p = 0.002). SAWE and FAWE were aneurysm specific metrics used to characterize enhancement patterns within the aneurysm wall and the distribution of enhancement along the aneurysm. Blebs were easily identified on 3D-heatmaps and were more enhancing than aneurysm sacs (p = 0.0017). 3D-AWE mapping may be a powerful objective tool in characterizing different biological processes of the aneurysm wall.