Plasma Free Hemoglobin Levels Research Articles

The true incidence and risk factors of hemolysis in patients with Impella CP placement

Abstract Background The Impella, a micro axial-flow pump, is effective in treating cardiogenic shock. However, compared to other mechanical circulatory support devices, its high pump speeds can result in complications like hemolysis and subsequent renal failure. Previous reports have defined hemolysis based on the elevation of LDH levels or the presence of hemoglobinuria, but this approach may underestimate its occurrence. Hemolysis is commonly assessed using the hemolysis index, which is calculated through biochemical auto-analysis based on the absorbance measure of the red color change. However, since the hemolysis index is not highly sensitive, it is recommended to measure plasma free hemoglobin (PFHb) for accurate diagnosis of hemolysis. Purpose The aim of this single-center retrospective cohort study is to investigate the frequency of hemolysis in Impella CP using PFHb measurements and its association with the Impella support level. Methods Between December 2019 and June 2023, we included 116 patients who had the Impella CP device implanted at our hospital. For these patients, PFHb was measured twice daily during the Impella placement period (up to 13 days). A PFHb value of 0.06 or higher was considered indicative of hemolysis, at which point a haptoglobin preparation of 4000 units was administered. Separately, the hemolysis index was defined as hemolysis at a level of 41 mg/dL. We investigated the relationship between daily Impella settings, PFHb, and hemolysis index for each patient. Results The average age was 70 ± 13 years. 59% underwent ECPELLA, and 15% were introduced to renal replacement therapy (RTT) due to severe renal failure. During Impella placement, hemolysis was diagnosed in 33% of patients based on PFHb, while only 18% were diagnosed with hemolysis according to the hemolysis index. Upon separate analysis for Impella and ECPELLA during the initial three days, the support levels of Impella were significantly higher in the Impella group on Days 1 and 2, with no significant difference noted on Day 3. Moreover, PFHb levels were significantly higher in the Impella group on Day 1, while on Day 3, the levels were higher in the ECPELLA group. Patients on RRT had significantly higher max PFHb levels than those not on RRT (0.19 vs. 0.06 g/dL; p < 0.001). Next, we investigated the relationship between PFHb levels and Impella support levels in patients with either Impella or ECPELLA over 711 data points. Dividing Impella support into low (P1-3), middle (P4-6), and high (P7-9) categories, PFHb values were significantly higher at high P levels compared to low and middle P levels. Similar results were observed for both Impella and ECPELLA. Conclusion There is a possibility of underestimating hemolysis associated with Impella if PFHb measurement is not performed. Hemolysis showed a significant correlation with higher P levels (P7 and above) for both Impella and ECPELLA.

Hemolysis Index Correlations with Plasma-Free Hemoglobin and Plasma Lactate Dehydrogenase in Critically Ill Patients under Extracorporeal Membrane Oxygenation or Mechanical Circulatory Support-A Single-Center Study.

Monitoring for thrombosis and hemolysis is crucial for patients under extracorporeal or mechanical circulatory support, but it can be costly. We investigated correlations between hemolysis index (HI) and plasma-free hemoglobin (PFH) levels on one hand, and between the HI and plasma lactate dehydrogenase (LDH) levels on the other, in critically ill patients with and without extracorporeal or mechanical circulatory support. Additionally, we calculated the cost reductions if monitoring through HI were to replace monitoring through PFH or plasma LDH. In a single-center study, HI was compared with PFH and plasma LDH levels in blood samples taken for routine purposes in critically ill patients with and without extracorporeal or mechanical circulatory support. A cost analysis, restricted to direct costs associated with each measurement, was made for an average 10-bed ICU. This study included 147 patients: 56 patients with extracorporeal or mechanical circulatory support (450 measurements) and 91 patients without extracorporeal or mechanical circulatory support (562 measurements). The HI correlated well with PFH levels (r = 0.96; p < 0.01) and poorly with plasma LDH levels (r = 0.07; p < 0.01) in patients with extracorporeal or mechanical circulatory support. Similarly, HI correlated well with PFH levels (r = 0.97; p < 0.01) and poorly with plasma LDH levels (r = -0.04; p = 0.39) in patients without extracorporeal or mechanical circulatory support. ROC analyses demonstrated a strong performance of HI, with the curve indicating excellent discrimination in the whole cohort (area under the ROC of 0.969) as well as in patients under ECMO or mechanical circulatory support (area under the ROC of 0.988). Although the negative predictive value of HI for predicting PFH levels > 10 mg/dL was high, its positive predictive value was found to be poor at various cutoffs. A simple cost analysis showed substantial cost reduction if HI were to replace PFH or plasma LDH for hemolysis monitoring. In conclusion, in this cohort of critically ill patients with and without extracorporeal or mechanical circulatory support, HI correlated well with PFH levels, but poorly with plasma LDH levels. Given the high correlation and substantial cost reductions, a strategy utilizing HI may be preferable for monitoring for hemolysis compared to monitoring strategies based on PFH or plasma LDH. The PPV of HI, however, is unacceptably low to be used as a diagnostic test.

Hemolysis Precedes Urine Color Change in Patients Undergoing Open-Heart Surgery on Cardiopulmonary Bypass.

Red-colored urine often occurs in patients in the perioperative period who undergo cardiac surgery using cardiopulmonary bypass (CPB). This urine color change has been utilized for approximating hemolysis during CPB without a proven relationship for ongoing hemolysis. This case series study aimed to examine the relationship between plasma free hemoglobin (Hb) levels and quantified measures of urine color. Ten patients were enrolled in this study. Blood and urine were collected for analyses for the following time points: before surgery, two hours after the initiation of CPB, every 30 min during CPB thereafter, and 0, 2, 4, 12, and 24 hours after the completion of CPB. We measured free Hb in plasma and urine using the azide-methemoglobin method. Photographs of urine were obtained, and the luminance of the three basic colors (red/green/blue) was analyzed by quantitative luminance contrast analysis to find a correlation for hemolysis. Median levels of plasma free Hb were 0.015 (0.010-0.080, n = 10) g/dL at baseline. During the CPB, increases in plasma free Hb levels were measured: median plasma free Hb levels were increased to0.100 g/dL(0.020-0.240, p = 0.039, vs. baseline, n = 9) at two hours into CPB, median and range, respectively.In contrast, increases in urinary free Hb levels and/or urine color changes were measured only after cessation of CPB in nine patients. Urine color change or elevation of urinary free Hb levels followed the elevation of plasma free Hb levels with considerable delay.

Carboxyhemoglobin and Methemoglobin Levels and Hemolysis in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Hemolysis is a complication of cardiopulmonary bypass (CPB). Carboxyhemoglobin (COHb) and methemoglobin (MetHb) were suggested as potential hemolysis biomarkers. This retrospective study was based on a prospective registry aimed to determine the association of COHb and MetHb levels with hemolysis in pediatric patients <4 years old who underwent cardiac surgery with CPB. Plasma-free hemoglobin (PFH), COHb, and MetHb levels were measured before CPB; every 30 minutes during CPB; and on postoperative days 1, 2, and 3. Patients were classified into hemolysis and nonhemolysis groups based on the maximum PFH levels during CPB. A total of 193 patients were included. No significant difference was observed in the maximum COHb levels during CPB (COHb CPB ) between the hemolysis and nonhemolysis groups (1.2% [interquartile range {IQR} 0.9-1.4%] vs. 1.1% [IQR: 0.9-1.4%]; p = 0.17). The maximum MetHb levels during CPB (MetHb CPB ) were significantly higher in the hemolysis group than in the nonhemolysis group (1.3% [IQR: 1.1-1.5%] vs. 1.2% [IQR: 1.0-1.4%]; p = 0.007). Areas under the receiver operating curves of COHb CPB and MetHb CPB were 0.557 (95% confidence interval: 0.475-0.640) and 0.615 (95% confidence interval: 0.535-0.695), respectively. Therefore, the predictive ability of both hemolysis biomarkers during CPB is limited.

Blood Transfusion-Related Change in Circulating Plasma-Free Hemoglobin Levels and its Impact on Microvascular Oxygenation: A Prospective, Observational Study

Background and Objectives: Transfusion of stored, packed red blood cells (PRBCs) is a common therapeutic intervention; however, development of hemolysis during storage might contributes to some negative consequences due to the release of free hemoglobin (fHb), a potent nitric oxide scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. We undertook this study to find out the change in fHb levels in recipients, whether this affects microvascular oxygenation posttransfusion. Methods: Eighty stable transfusion recipients were selected for this prospective observational study and were divided into three groups as per the age of blood transfused (&lt;7 days, 7–14 days, and &gt;14 days). Blood samples were collected to analyze the plasma levels of fHb in the bag. The patient's circulating plasma Hb (FHb) and pO2 by venous blood gas analysis were studied before and after 1 h of transfusion. Data were analyzed through paired t-test, ANOVA, and Pearson's correlation coefficient using the SPSS version 23. Results: Overall, there was a significant difference between the three groups in terms of change in plasma fHb (g/dL) from pretransfusion to the 1 h posttransfusion time points (P &lt; 0.05). Significant increase in pO2 Levels was noticed from the pretransfusion to 1 h posttransfusion time points in bags &lt;7 days old (t = −4.6, P &lt; 0.001). Furthermore, a strong negative correlation was obtained between FHb and pO2 using Pearson's correlation coefficient (r = −0.738; P &lt; 0.001). Conclusion: This study concludes that red blood cell transfusion can significantly increase posttransfusion plasma Hb levels depending upon the age of PRBC units and has an implication on microvascular oxygenation. However, the effect on the clinical outcome of the patient was not studied, and it would be worthwhile to investigate whether the age of the blood transfused affects the patient morbidity or mortality.

P36: Filling the Gap: Developing the Penn State University Child Pump

Study: Despite the need for suitable Mechanical Circulatory Support (MCS) for pediatric patients between 10 and 30 kg, there are currently no long-term implantable devices for this patient cohort. In order to address this need, we are developing the Penn State Child Pump, a continuous flow ventricular assist device (cf-VAD) that will remove the risks of device size mismatch and running at suboptimal operating conditions. Methods: A prototype PSU Child Pump was manufactured based on our experiences with adult cf-LVADs and cf-RVADs. The pump size was tailored to the average chest size of the target pediatric patient population (Figure 1A). In-vitro hemolysis was evaluated under three conditions on our small volume mock circulatory loop with bovine blood (Figure 1B): 1) 8300 RPM, ΔP = 60 mmHg, 3.5 LPM; 2) 8200 RPM, ΔP = 20 mmHg, 5.1 LPM; 3) 8400 RPM, ΔP = 70 mmHg, 3.2 LPM. Results: The initial design of the device has an approximate 38% reduction in size compared to our adult cf-VAD. A mock fit study was conducted using a 3D printed model of a 19 kg patient’s thoracic cavity to compare the size of the PSU Child Pump to the HVAD (Medtronic, Minneapolis, MN) (Figure 1A). In-vitro testing revealed the hemolysis levels at conditions 1, 2, and 3 were 0.037 mg/dL, 0.022 mg/dL, and 0.021 mg/dL, respectively (Figure 1C). Conclusions: The PSU Child Pump prototype was constructed and evaluated, yielding initial results indicating promising hemocompatibility under the given testing conditions. Using a computational fluid dynamics-based optimization platform, the PSU Child Pump will be optimized to meet maximum physiological requirements while minimizing the potential for thrombus formation, plasma-free hemoglobin levels, and degradation of von Willebrand factor. The in-silico optimization results will be validated through a series of 30-day in-vivo studies in sheep.

A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Results of the Interlaboratory Computational Fluid Dynamics Study of the FDA Benchmark Blood Pump.

Computational fluid dynamics (CFD) is widely used to simulate blood-contacting medical devices. To be relied upon to inform high-risk decision making, however, model credibility should be demonstrated through validation. To provide robust data sets for validation, researchers at the FDA and collaborators developed two benchmark medical device flow models: a nozzle and a centrifugal blood pump. Experimental measurements of the flow fields and hemolysis were acquired using each model. Concurrently, separate open interlaboratory CFD studies were performed in which participants from around the world, who were blinded to the measurements, submitted CFD predictions of each benchmark model. In this study, we report the results of the interlaboratory CFD study of the FDA benchmark blood pump. We analyze the results of 24 CFD submissions using a wide range of different flow solvers, methods, and modeling parameters. To assess the accuracy of the CFD predictions, we compare the results with experimental measurements of three quantities of interest (pressure head, velocity field, and hemolysis) at different pump operating conditions. We also investigate the influence of different CFD methods and modeling choices used by the participants. Our analyses reveal that, while a number of CFD submissions accurately predicted the pump performance for individual cases, no single participant was able to accurately predict all quantities of interest across all conditions. Several participants accurately predicted the pressure head at all conditions and the velocity field in all but one or two cases. Only one of the eight participants who submitted hemolysis results accurately predicted absolute plasma free hemoglobin levels at a majority of the conditions, though most participants were successful at predicting relative hemolysis levels between conditions. Overall, this study highlights the need to validate CFD modeling of rotary blood pumps across the entire range of operating conditions and for all quantities of interest, as some operating conditions and regions (e.g., the pump diffuser) are more challenging to accurately predict than others. All quantities of interest should be validated because, as shown here, it is possible to accurately predict hemolysis despite having relatively inaccurate predictions of the flow field.

P-028: CIRCULATING CD34+CD235A+ CELL COUNT CORRELATES WITH LEVELS OF HBF IN SICKLE CELL ANEMIA PATIENTS UNDER HYDROXYUREA TREATMENT

Purpose: Studying stress erythropoiesis (SE) in sickle cell anemia (SCA) is difficult because of the rigor in accessing bone marrow samples. However, the characterization of circulating cell populations reflecting SE is feasible and critical, especially in the perspectives of gene therapy. Materials and methods: Clinical and laboratory data were collected from 49 subjects with SCA (SS-genotype) under chronic transfusion (CT, n = 15), hydroxyurea therapy (HC, n = 20), or under both treatments (CT/HC, n = 14) at the Blood Center of Ribeirão Preto - Brazil. The mean age was 35.22 y/o (20-64), and 53.06% were males. Six patients from each group, under steady-state, and five healthy donors (HD group) were selected for downstream analysis of PBMCs. Briefly, 5 mL of blood were collected in EDTA-evacuated tubes and processed immediately with Ficoll-Paque PLUS (Cytiva). 106 live cells were stained with anti-CD235a, -CD123, -CD36, and -CD34 (stemness and erythroid maturation markers) BD Biosciences antibodies and analyzed by FACS in a BD FACSCanto II. FACS analysis was conducted in the FlowJo software v.11, using conventional gating strategies and dimensionality reduction machine learning algorithms. Complete blood and reticulocyte count, liver function, hemoglobin profiling, and FACS data were plotted for statistical comparison of mean ranks using Kruskal-Wallis, Dunn’s multiple comparisons, or Spearman’s rank-order correlation tests. Data analysis was performed in statistical software GraphPad Prism v.6.0 and open-source statistical programming language R v.4.0.2, using packages ‘Hmisc’ and ‘corrplot’ for correlation analysis and visualization of results. Significance levels were considered when p<0.05 in which ‘*’, ‘**’, ‘***’ and ‘****’ indicate p<0.05; p<0.01, p<0.001, and p<0.0001, respectively. Results: Subjects under HC had overall higher median Hb, HCt, MCV, MCH, HBS, and HBF while CT groups presented higher RDW. The number of nucleated RBCs (nRBC) was similar among groups and the ratio of RBCHb/RetHb increased under HC treatment. Also, levels of plasma-free hemoglobin (calculated based on total and cellular Hb) were lower in HC. Reticulocytosis was higher in CT and hemolysis parameters appeared discretely lower in HC (Table 1). FACS analysis revealed that patients had higher circulating CD34+ cell counts. Levels of CD235+ cells inside the PBMC compartment were higher in HC patients. Also, CD34+CD235a+ population counts were significantly higher in HC than in CT and CT/HC, representing more than 15% of the circulating CD34+ compartment in some patients. Up to 60% of the CD34+CD235a+ were also CD36+ (Figure 1 A). In contrast, CD34+CD123+ were increased among CT and CT/HC groups. CD235a+ and CD34+CD235a+ populations positively correlated with HbF levels in the HC group, whilst its dose did not associate with any blood count or hemoglobin parameters (Figure 1 B). Interestingly, the same population counts positively correlated with age among non-HC takers. Conclusion: These results reaffirm the capacity of HC treatment to improve hematological parameters in SCA. Notwithstanding, HC presented increased levels of SE cell populations than the CT groups, reflecting different mechanisms of SE onset between CT and HC treated patients. Financial Support: CAPES, CTC/FAPESP-(2013/08135-2); INCTC-(465539/2014-9).Complete blood count and hemolysis biomarkers of HC and CT / HC groups compared with CT, calculated using Kruskal-Wallis test. ‘*’, ‘**’, ‘***’ and ‘****’ indicate p?0.05; p?0.01, p?0.001, and p?0.0001, respectively.A) Levels of CD34+ and CD34+CD235a+ cell populations. B) Correlogram of stress erythropoiesis cell FACS data versus hematological parameters of hydroxyurea treatment groups. Levels of stress cells are positively correlated with levels of HbF. The authors do not declare any conflict of interest

Seven-day in vivo testing of a novel, low-resistance, pumpless pediatric artificial lung for long-term support

IntroductionFor children with end-stage lung disease that cannot wean from extracorporeal life support (ECLS), a wearable artificial lung would permit extubation and provide a bridge to recovery or transplantation. We evaluate the function of the novel Pediatric MLung—a low-resistance, pumpless artificial lung developed specifically for children—in healthy animal subjects. MethodsAdolescent “mini sheep” weighing 12–20 kg underwent left thoracotomy, cannulation of the main pulmonary artery (PA; inflow) and left atrium (outflow), and connection to the MLung. ResultsThirteen sheep were studied; 6 were supported for 7 days. Mean PA pressure was 23.9 ± 6.9 mmHg. MLung blood flow was 633±258 mL/min or 30.0 ± 16.0% of CO. MLung pressure drop was 4.4 ± 3.4 mmHg. Resistance was 7.2 ± 5.2 mmHg/L/min. Device outlet oxygen saturation was 99.0 ± 3.3% with inlet saturation 53.8 ± 7.3%. Oxygen delivery was 41.1 ± 18.4 mL O2/min (maximum 84.9 mL/min) or 2.8 ± 1.5 mL O2/min/kg. Platelet count significantly decreased; no platelet transfusions were required. Plasma free hemoglobin significantly increased only on day 7, at which point 2 of the animals had plasma free hemoglobin levels above 50 mg/dL. ConclusionThe MLung provides adequate gas exchange at appropriate blood flows for the pediatric population in a PA-to-LA configuration. Further work remains to improve the biocompatibility of the device. Level of evidenceN/A

LVAD Outflow Graft Compression Presenting as Pump Thrombosis

<h3>Introduction</h3> Pump thrombosis is a serious adverse event in patients with left ventricular assist devices (LVAD). Pump thrombosis is a complication of LVAD implantation, affecting approximately five percent of patients. It often presents with clinically significant hemolysis, device alarms and can progress to heart failure and cardiogenic shock. We present a case of a patient with a Heartmate II LVAD who presented with a rising LDH that led to investigation to diagnose a potential pump thrombosis. <h3>Case Report</h3> The patient is a 73 year old male who was implanted with a HeartMate II LVAD as destination therapy (DT) for ischemic cardiomyopathy (ICM). Approximately 3 years after implant, the patient was noted to have a markedly elevated LDH on routine lab work. After 8 months of event-free observation, the patients LDH trended up again and the plasma free hemoglobin level was also elevated. An ECHO with limited ramp study was performed. The power and flow responded appropriately however LVEDD showed no applicable change. To further investigate a potential thrombosis, a CT angiogram was obtained. The CT demonstrated a significant obstruction to the outflow graft within the bend relief. The initial intervention was a balloon angioplasty of the outflow graft. The angioplasty was technically successful, and the balloon fully expanded. A repeat CT 2 weeks later showed the obstruction was still present. Interestingly, the patient remained asymptomatic and his LDH normalized. The decision was made to continue observation. Six months later, his LDH was noted to be increasing. A repeat CT showed that the outflow obstruction was worsening. The outflow graft appeared to be at least 90% obstructed. Again, the patient was taken to the OR for an intervention. Balloon angioplasty was repeated to predilate the lesion. Three endovascular stents were placed in the outflow graft within the bend relief. Completion angiogram confirmed the stents to be fully expanded with no residual obstruction. There were no complications from the procedure. The patient remains event-free 8 months later. <h3>Summary</h3> In conclusion, the patient demonstrated signs of pump thrombosis mediated by an extrinsic compression of the outflow graft. In this case, the problem was treated with angioplasty with excellent result. The patient remains under surveillance but has been event-free for one year.

Outcomes With Impella 5.0 And 5.5 In Cardiogenic Shock

<h3>Background</h3> : Cardiogenic shock is associated with a mortality rate between 40-60%, and as high as 70% in the setting of ST-elevation myocardial infarction.^1-5 In patients with cardiogenic shock, mechanical support is often needed for temporary support as a bridge to decision. The Impella 5.0 and 5.5 (Abiomed, Danvers, Massachusetts) micro-axial pumps are left ventricular assist devices (LVAD) that pull blood from the left ventricle into the ascending aorta.⁶ We sought to describe outcomes and potential complications associated with extended Impella 5.5 and 5.0 in cardiogenic shock. <h3>Methods</h3> We retrospectively evaluated patients who underwent implantation of Impella 5.0 and 5.5 in the operating room due to cardiogenic shock between August 1^st, 2018 and December 31^st, 2020 at our institution. Hemolysis was defined as plasma free hemoglobin level above 50 mg/dL, a lactate dehydrogenase (LDH) level above 500 units/L, and bilirubin increase above 1 mg/dL. <h3>Results</h3> 19 patients underwent insertion of Impella 5.0 or 5.5 in the operating room with 14 patients receiving Impella 5.5 and 5 receiving Impella 5.0. Devices were placed in the axillary artery (14), ascending aorta (3), and carotid artery (2). Mean age was 52.6 ± 13.3 years, and most patients (84%) were male. The mean left ventricular ejection fraction (LVEF) was 13.7 ± 6.8%, with 58% of patients with EF 10% or less. The etiology was acute decompensated heart failure in 14 patients and acute myocardial infarction in 5 patients. The average duration of Impella 5.5/5.0 support was 12.5 days (1, 40). Six patients (32%) had the device for more than 14 days. Four patients had Impella CP placed prior to 5.5 for 4.75 days (1,8), and two patients required support with extracorporeal membrane oxygenation (ECMO), both after CP but prior to 5.0. Seven patients (37%) were successfully bridged to either left ventricular assist device (LVAD) or heart transplantation on average of 13 ± 10.8 days after Impella insertion with 43% (6/14) of the 5.5 cohort, and 20% (1/5) of the 5.0 cohort. Overall survival rate was 32% (6/19) with rate of 36% (5/14) for Impella 5.5 and 20% (1/5) for Impella 5.0<b>.</b> Overall hemolysis rate was 47%, with 60% (3/5) in the 5.0 cohort and 43% (6/14) in the 5.5 cohort. Other complications included significant upper extremity neuropathy (1), improper positioning (6), hematoma (3), thrombus (1), and stroke (3). <h3>Conclusion</h3> : There is high mortality associated with cardiogenic shock. The Impella 5.0 and 5.5 can provide additional cardiac support and help with bridging to LVAD or heart transplantation. About a third of the patients were successfully bridged, but serious complications do occur with extended support, including hemolysis, hematoma, thrombus, and stroke. Six patients survived to discharge.

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

Hemolysis during pediatric extracorporeal membrane oxygenation (ECMO) is associated with increased risk for renal failure and mortality. We aim to describe risk factors for hemolysis in pediatric ECMO supported by centrifugal pumps. We conducted an analysis of retrospective data collected at an academic children's hospital from January 2017 to December 2019. Plasma-free hemoglobin (PFH) levels were measured daily, and hemolysis was defined as PFH>50mg/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 24h (89 vs 11mg/dL, p<0.01). 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.

A Randomized Clinical Trial of Perfusion Modalities in Pediatric Congenital Heart Surgery Patients

BackgroundThe objective of this randomized clinical trial was to investigate the effects of perfusion modalities on cerebral hemodynamics, vital organ injury, quantified by the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score, and clinical outcomes in risk-stratified congenital cardiac surgery patients. MethodsThis randomized clinical trial included 159 consecutive congenital cardiac surgery patients in whom pulsatile (n = 83) or nonpulsatile (n = 76) perfusion was used. Cerebral hemodynamics were assessed using transcranial Doppler ultrasound. Multiple organ injury was quantified using the PELOD-2 score at 24, 48, and 72 hours. Clinical outcomes, including intubation time, intensive care unit length of stay (LOS), hospital LOS, and mortality, were also evaluated. ResultsThe Pulsatility Index at the middle cerebral artery and in the arterial line during aortic cross-clamping was consistently better maintained in the pulsatile group. Demographics and cardiopulmonary bypass characteristics were similar between the 2 groups. While risk stratification with The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Mortality Categories was similar between the groups, Mortality Categories 1 to 3 demonstrated more patients than Mortality Categories 4 and 5. There were no differences in clinical outcomes between the groups. The PELOD-2 scores showed a progressive improvement from 24 hours to 72 hours, but the results were not statistically different between the groups. ConclusionsThe Pulsatillity Index for the pulsatile group demonstrated a more physiologic pattern compared with the nonpulsatile group. While pulsatile perfusion did not increase plasma-free hemoglobin levels or microemboli delivery, it also did not demonstrate any improvements in clinical outcomes or PELOD-2 scores, suggesting that while pulsatile perfusion is a safe method, it not a “magic bullet” for congenital cardiac operations.

A retrospective analysis of the hemolysis occurrence during extracorporeal membrane oxygenation in a single center.

Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients. This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020. Daily plasma-free hemoglobin (pfHb) and haptoglobin (Hpt) levels were chosen as hemolysis markers and they were analyzed along with patients' characteristics, daily laboratory findings, and corresponding ECMO system variables, as well as continuous renal replacement therapy (CRRT) when administered, looking for factors influencing their trends over time. Among the many settings related to the ECMO support, the presence of CRRT connected to the ECMO circuit has been found associated with both higher daily pfHb levels and lower Hpt levels. After correction for potential confounders, hemolysis was ascribable to circuit-related variables, in particular the membrane oxygenation dead space was associated with an Hpt reduction (B = -215.307, p = 0.004). Moreover, a reduction of ECMO blood flow by 1L/min has been associated with a daily Hpt consumption of 93.371mg/dL (p = 0.001). Technical-induced hemolysis during ECMO should be monitored not only when suspected but also during quotidian management and check-ups. While considering the clinical complexity of patients on ECMO support, clinicians should not only be aware of and anticipate possible circuitry malfunctions or inadequate flow settings, but they should also take into account the effects of an ECMO circuit-connected CRRT, as an equally important key factor triggering hemolysis.

Retrograde autologous priming method reduces plasma free hemoglobin level in aortic surgery.

Background:Although conventional cardiopulmonary bypass (cCPB) is still the most widely used method in open heart surgery, methods such as retrograde autologous priming (RAP) are increasingly popular in terms of limiting hemodilution. Our hypothesis is that the use of the RAP method in aortic surgery may result in a limitation of hemodilution and a decrease in fHb levels. For this purpose, plasma free hemoglobin (fHb) levels were investigated in adult open aortic arch repair with axillary artery cannulation patients using cCPB and rRAP methods.Materials and Methods:In this study, a total of 36 patients undergoing aortic surgery using rRAP and standard cCPB were investigated. Measurements were performed at five time points: After induction of anesthesia, 5th minute of CPB, 10th minute of antegrade cerebral perfusion, 30th minute after declamping of aorta, and at sternum closure. Besides hemodynamic variables, arterial blood gas analysis and postoperative variables, patients were assessed for fHb levels.Results:The rRAP group had a significantly lower increase in fHb levels in T3, T4, and T5 time points, when compared to the cCPB group (p = 0.002, 0.047, 0.009, respectively). There was no significant difference between the rRAP and cCPB groups in other intraoperative, and postoperative variables. Also, it was observed that rRAP did not make a difference in terms of blood and blood product transfusion.Conclusion:In this study, in patients undergoing aortic surgery, a reduction in the increase of fHb was observed with the rRAP method which is a simple procedure that does not require high cost or advanced technology.

Magnetic levitation pump versus constrained vortex pump: a pilot study on the hemolysis effect during minimal invasive extracorporeal circulation

BackgroundElevated plasma free hemoglobin is associated with multi-organ injury. In this context, minimally invasive extracorporeal technologies represent a way to reduce this complication following cardiac surgery.MethodsWe present a pilot study focused on plasma free hemoglobin levels in 40 patients undergoing isolated coronary artery bypass grafting (CABG). The same circuits for minimally invasive extracorporeal circulation (MiECC) were used in all patients. The ECMOLIFE magnetic levitation pump was used in the study group (n = 20), and the AP40 Affinity CP centrifugal blood pump was used in the control group (n = 20).ResultsIn the immediate postoperative period, plasma free hemoglobin (PFH) and lactate dehydrogenase (LDH) were significantly lower in the study group than in the control group (10.6 ± 0.7 vs 19.9 ± 0.3 mg/dL, p = 0.034; and 99.16 ± 1.7 vs 139.17 ± 1.5 IU/L, p = 0.027, respectively). Moreover, patients treated with the magnetic levitation pump showed lower creatinine and indirect bilirubin (0.92 vs 1.29 mg/dL, p = 0.030 and 0.6 ± 0.4 vs 1.5 ± 0.9 mg/dL, p = 0.022, respectively) at 24 h after the procedure, and received fewer transfusions during the whole postoperative period (3 vs 9 red blood cell units (RBC), p = 0.017).ConclusionOur pilot study suggests that the use of magnetically levitated centrifugal pumps for extracorporeal circulation support is associated with a lower risk of hemolysis, though larger studies are warranted to confirm our results.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p= .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p&lt; .01, Rho = .439), AST (p&lt; .01, Rho = .439), RDW (p&lt; .01, Rho = .190), LDH (p&lt; .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p&lt; .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation.

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p = .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p < .01, Rho = .439), AST (p < .01, Rho = .439), RDW (p < .01, Rho = .190), LDH (p < .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p < .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Hemolysis and von Willebrand factor degradation in mechanical shuttle shear flow tester

Chronic blood trauma caused by the shear stresses generated by mechanical circulatory support (MCS) systems is one of the major concerns to be considered during the development of ventricular assist devices. Large multimers with high-molecular-weight von Willebrand factor (VWF) are extended by the fluid forces in a shear flow and are cleaved by ADAMTS13. Since the mechanical revolving motions in artificial MCSs induce cleavage in large VWF multimers, nonsurgical bleeding associated with the MCS is likely to occur after mechanical hemodynamic support. In this study, the shear stress (~ 600 Pa) and exposure time related to hemolysis and VWF degradation were investigated using a newly designed mechanical shuttle shear flow tester. The device consisted of a pair of cylinders facing the test section of a small-sized pipe; both the cylinders were connected to composite mechanical heads with a sliding-sleeve structure for axial separation during the withdrawing motion. The influence of exposure time, in terms of the number of stress cycles, on hemolysis and VWF degradation was confirmed using fresh goat blood, and the differences in the rates of dissipation of the multimers were established. The plasma-free hemoglobin levels showed a logarithmic increase corresponding to the number of cycles, and the dissipation of large VWF multimers occurred within a few seconds under high shear stress flow conditions.