Neonatal Cardiopulmonary Bypass Research Articles

Impact of pre-bypass ultrafiltration on prime values and clinical outcomes in neonatal and infant cardiopulmonary bypass

Background: A standard blood prime for cardiopulmonary bypass (CPB) in congenital cardiac surgery may possess non-physiologic values for electrolytes, glucose, and lactate. Pre-bypass Ultrafiltration (PBUF) can make these values more physiologic and standardized prior to bypass initiation. We aimed to determine if using PBUF on blood primes including packed red blood cells and thawed plasma would make prime values more predictable and physiologic. Additionally, we aimed to evaluate whether the addition of PBUF had an impact on outcome measures. Methods: Retrospective review of consecutive patients ≤ 1 year of age undergoing an index cardiac operation on CPB between 8/2017 and 9/2021. As PBUF was performed at the perfusionists’ discretion, a natural grouping of patients that received PBUF vs. those that did not occur. Differences in electrolytes, glucose, and lactate were compared at specific time points using Fisher’s exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Clinical outcomes were also assessed. Results: In both cohorts, the median age at surgery was 3 months and 47% of patients were female; 308/704 (44%) of the PBUF group and 163/414 (39%) of the standard prime group had at least one preoperative risk factor. The proportion of PBUF circuits which demonstrated more physiologic values for glucose (318 [45%]), sodium (434, [62%]), potassium (688 [98%]), lactate (612 [87%]) and osmolality (595 [92%]) was significantly higher when compared to standard prime circuit levels for glucose (8 [2%]), sodium (13 [3%], potassium (150 [36%]), lactate (56 [13%]) and osmolality (23 [6%]) prior to CPB initiation. There were no differences in clinical outcomes or rates of major adverse events between the two cohorts. Conclusions: PBUF creates standardized and more physiologic values for electrolytes, glucose, and lactate before the initiation of bypass without significant impacts on in-hospital outcomes.

Perioperative brain injury marker concentrations in neonatal open-heart surgery: a prospective observational study.

Neonates with critical congenital heart defects undergoing open-heart surgery on cardiopulmonary bypass circulation are at risk for white matter brain injury. This article reports on pre- and postoperative plasma concentrations of brain injury markers glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and Tau, and their respective associations with white matter lesions detected on postoperatively performed brain MRI. Forty term newborns with isolated critical congenital heart defects were included in a prospective observational study. Brain injury marker plasma concentrations were determined prior to surgery and at postoperative days 1, 2 and 3. Brain magnetic resonance imaging was performed pre- and postoperatively. Concentrations of brain injury markers were analysed using ultrasensitive single molecule array technology. Absolute pre- and postoperative plasma biomarker concentrations, and postoperative concentrations adjusted for preoperative concentrations were used for subsequent analysis. Plasma concentrations of GFAP, NfL and Tau displayed a well-defined temporal trajectory after neonatal cardiopulmonary bypass circulation. GFAP and Tau reached peak concentrations at postoperative day 2 (median concentrations 170.5 and 67.2 pg/ml, respectively), whereas NfL continued to increase throughout the study period (median concentration at postoperative day 3 191.5 pg/ml). Adjusted Tau at postoperative day 2 was significantly higher in infants presenting with white matter lesions on postoperative MRI compared to infants without white matter injury.

Cardiopulmonary bypass in neonates and infants: advantages of high flow high hematocrit bypass strategy-clinical practice review.

Cardiopulmonary bypass is an integral and indispensable part of surgical repair of congenital heart defects. While the complications and morbidity secondary to the use of cardiopulmonary bypass has decreased considerably, there remains a significant incidence of clinically relevant renal and neurological injury. To provide more physiological delivery of oxygenated blood to the end-organs, our center has been successfully using a high-flow, high hematocrit cardiopulmonary bypass strategy since 2006. The essential components of this strategy include maintaining high flows (typically 200 mL/kg/min in neonates, 150-175 mL/kg/min in older infants weighing <10 kg, and 2.6 L/min/m2 in older children) throughout the duration of cardiopulmonary bypass irrespective of patient temperature, as well as maintaining a hematocrit of at least 32% on cardiopulmonary bypass. The incidence of post-operative acute kidney injury (around 3%) and clinical acute neurological events (<1%) with this strategy is considerably less when compared to other contemporary publications using the conventional cardiopulmonary bypass strategy. In this review, we discuss the rationale behind our approach and present evidence to support the high-flow, high-hematocrit strategy. We also discuss the practical aspects of our strategy and describe the adjuncts we use to derive additional benefits. These adjuncts include the use of a hybrid pH/alpha stat strategy during cooling/rewarming, aggressive use of conventional ultrafiltration during cardiopulmonary bypass, a terminal hematocrit of 40-45%, and avoidance of milrinone and albumin in the early peri-operative period. This results in a very low incidence of post-operative bleeding, facilitates chest closure in the operating room even in most neonates, helps in reducing the need for post-operative blood product transfusion and helps in achieving a favorable post-operative fluid balance early after surgery.

Haemodynamic effects of prophylactic post-operative hydrocortisone following cardiopulmonary bypass in neonates undergoing cardiac surgery.

Multiple studies have endeavoured to define the role of steroids in paediatric congenital heart surgery; however, steroid utilisation remains haphazard. In September, 2017, our institution implemented a protocol requiring that all neonates undergoing cardiac surgery with the use of cardiopulmonary bypass receive a five-day post-operative hydrocortisone taper. This single-centre retrospective study was designed to test the hypothesis that routine post-operative hydrocortisone administration reduces the incidence of capillary leak syndrome, leads to favourable postoperative fluid balance, and less inotropic support in the early post-operative period. Data were gathered on all term neonates who underwent cardiac surgery with the use of bypass between September, 2015 and 2019. Subjects who were unable to separate from bypass, required long-term dialysis, or long-term mechanical ventilation were excluded. Seventy-five patients met eligibility criteria (non-hydrocortisone group = 52; hydrocortisone group = 23). For post-operative days 0-4, we did not observe a significant difference in net fluid balance or vasoactive inotropic score between study groups. Similarly, we saw no major difference in secondary clinical outcomes (post-operative duration of mechanical ventilation, ICU/hospital length of stay, and time from surgery to initiation of enteral feeds). In contrast to prior analyses, our study was unable to demonstrate a significant difference in net fluid balance or vasoactive inotropic score with the administration of a tapered post-operative hydrocortisone regimen. Similarly, we saw no effect on secondary clinical outcomes. Further long-term randomised control studies are necessary to validate the potential clinical benefit of utilising steroids in paediatric cardiac surgery, especially in the more fragile neonatal population.

Neurodevelopmental and functional outcome in hypoplastic left heart syndrome after Hybrid procedure as stage I.

Patients with hypoplastic left heart syndrome (HLHS) undergoing staged palliation until Fontan procedure are at risk for impaired neurodevelopmental (ND) outcome. The Hybrid procedure with bilateral pulmonary artery banding, ductal stenting, and balloon atrioseptostomy may offer a less invasive stage I procedure compared to the Norwood stage I procedure avoiding early neonatal cardiopulmonary bypass (CPB) surgery. Despite altered fetal cerebral hemodynamics, the type of stage I procedure may be a covariate influencing ND outcome and functional outcome may also be altered due to postponing neonatal CPB surgery. Within this review, we analyzed ND outcome as well as functional outcome after Hybrid procedure as stage I procedure. The review analyzed original publications (OPs) published before March 15, 2022, identified by Cochrane, EMBASE, OVID, Scopus, and Web of science. An OP was included if short-to-long-term neurodevelopment outcome, brain development, somatic, and cardiac outcome in patients for HLHS and variants treated by Hybrid procedure were analyzed. In addition to database searches, we reviewed all references of the analyzed OP to obtain a comprehensive list of available studies. The author, year of publication, demographic characteristics of study population, study design (prospective or retrospective), study assessment, and main findings were summarized. Twenty-one OPs were included with data of patients with ND outcome and functional cardiac outcome. Overall, there is an impaired mid-term ND outcome in patients with Hybrid procedure as stage I for HLHS. Only slight differences between stage I procedures (Hybrid vs. Norwood) in two comparing studies have been determined affecting right ventricular remodeling, short- and mid-term ND outcome, reduced brain growth until two years of age, sufficient quality of life, and altered hemodynamics influencing brain volumes and cerebral perfusion pattern. Despite some minor differences regarding the mid-term follow-up in patients with HLHS comparing Hybrid vs. Norwood procedure, its impact on ND outcome seems rather low. This may be explained by the large number of covariates as well as the small study populations and the different selection criteria for patients undergoing Hybrid or Norwood procedure as stage I.

Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates.

Infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) frequently receive intraoperative methylprednisolone (MP) to suppress CPB-related inflammation; however, the optimal dosing strategy and efficacy of MP remain unclear. We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014-2017 at our institution. We combined real-world dosing data from the electronic health record (EHR) and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration (Cmax) and area under the concentration-time curve for 24 h (AUC24) for MP and the inflammatory cytokines interleukin-6 (IL-6) and interleukin-10 (IL-10). We evaluated the relationships between post-operative, safety, and other clinical outcomes obtained from the EHR with each predicted exposure using non-parametric tests. A total of 142 infants with median post-natal age 8 (interquartile range [IQR]: 5, 37) days received a total dose of 30 (19, 49) mg/kg of MP. Twelve (8%) died, 37 (26%) met the composite post-operative outcome, 114 (80%) met the composite safety outcome, and 23 (16%) had a major complication. Predicted median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major complications. Predicted median Cmax and AUC24 MP exposure was significantly higher for infants requiring insulin. No exposure was associated with death or other safety outcomes. Pro-inflammatory IL-6, but not MP exposure, was associated with post-operative organ dysfunction, suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical outcomes. Prospective study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants.

Cardiovascular surgery in very low birth weight (≤ 1500g) neonates.

Low birth weight and prematurity are known risks of increased morbidity and mortality with undergoing cardiovascular surgery. Our aim was to review the outcomes of very low birth weight (≤ 1500 g) patients who have undergone cardiovascular surgery. A retrospective review was performed for 32 very low birth weight (≤ 1500 g) patients who underwent cardiovascular surgery from 2004 to 2021 in our institution. Fifteen patients weighting ≤ 1500 g at surgery (≤ 1500 g group) were compared to 17 patients born with a weigh ≤ 1500 g and weighting between 1500 g and 2500 g at surgery (>1500 g to ≤ 2500 g group) in this study. In-hospital mortality was 33% (5/15) in ≤ 1500 g group and 24% (4/17) in > 1500 g to ≤ 2500 g group (p = 0.55). All patients with simple biventricular lesion survived following full repair. The occurrence of postoperative intracerebral haemorrhage was significantly higher in those operated at weight ≤ 1500 g than those weighting >1500 g to ≤ 2500 g (40% vs 0%; p = 0.01). The 1- and 3-year survival rates were 66.0 ± 12.4% and 46.2 ± 14.8% in ≤ 1500 g group and 76.5 ± 10.3% and 70.6 ± 11.1% in > 1500 g to ≤ 2500 g group (Log-rank p = 0.12). Cardiac surgery for very low birth weight neonate resulted in a high early and late mortality. Early surgery is only acceptable for simple biventricular lesion if needed. Delayed surgery seems to provide better long-term outcomes in patients with complex lesions. Alternative strategies to neonatal cardiopulmonary bypass should be investigated in patients with complex biventricular and single ventricle lesions.

Defining the optimal historical control group for a phase 1 trial of mesenchymal stromal cell delivery through cardiopulmonary bypass in neonates and infants.

The Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery study is a prospective, open-label, single-centre, dose-escalation phase 1 trial assessing the safety/feasibility of delivering mesenchymal stromal cells to neonates/infants during cardiac surgery. Outcomes will be compared with historical data from a similar population. We aim to define an optimal control group for use in the Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial. Consecutive patients who underwent a two-ventricle repair without aortic arch reconstruction within the first 6 months of life between 2015 and 2020 were studied using the same inclusion/exclusion criteria as the Phase 1 Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial (n = 169). Patients were allocated into one of three diagnostic groups: ventricular septal defect type, Tetralogy of Fallot type, and transposition of the great arteries type. To determine era effect, patients were analysed in two groups: Group A (2015-2017) and B (2018-2020). In addition to biological markers, three post-operative scoring methods (inotropic and vasoactive-inotropic scores and the Pediatric Risk of Mortality-III) were assessed. All values for three scoring systems were consistent with complexity of cardiac anomalies. Max inotropic and vasoactive-inotropic scores demonstrated significant differences between all diagnosis groups, confirming high sensitivity. Despite no differences in surgical factors between era groups, we observed lower inotropic and vasoactive-inotropic scores in group B, consistent with improved post-operative course in recent years at our centre. Our studies confirm max inotropic and vasoactive-inotropic scores as important quantitative measures after neonatal/infant cardiac surgery. Clinical outcomes should be compared within diagnostic groupings. The optimal control group should include only patients from a recent era. This initial study will help to determine the sample size of future efficacy/effectiveness studies.

Cell-Free Hemoglobin Concentration in Blood Prime Solution Is a Major Determinant of Cell-Free Hemoglobin Exposure during Cardiopulmonary Bypass Circulation in the Newborn

Exposure to circulating cell-free hemoglobin is a ubiquitous feature of open-heart surgery on cardiopulmonary bypass circulation. This study aims to determine the origins and dynamics of circulating cell-free hemoglobin and its major scavenger proteins haptoglobin and hemopexin during neonatal cardiopulmonary bypass. Forty neonates with an isolated critical congenital heart defect were included in a single-center prospective observational study. Blood samples were obtained preoperatively, hourly during bypass circulation, after bypass separation, at admission to the pediatric intensive care unit, and at postoperative days 1–3. Concentrations of cell-free hemoglobin, haptoglobin and hemopexin were determined using ELISA. Neonates were exposed to significantly elevated plasma concentrations of cell-free hemoglobin and a concomitant depletion of scavenger protein supplies during open-heart surgery. The main predictor of cell-free hemoglobin exposure was the concentration of cell-free hemoglobin in blood prime solution. Concentrations of haptoglobin and hemopexin in prime solution were important determinants for intra- and postoperative circulating scavenger protein resources.

Cerebral Sinus Venous Thrombosis in Infants after Surgery for Congenital Heart Disease

To determine the prevalence of and risk factors for cerebral sinus venous thrombosis (CSVT) in neonates undergoing congenital heart disease (CHD) repair. Neonates who had CHD repair with cardiopulmonary bypass and postoperative brain magnetic resonance imaging (MRI) between 2013 and 2019 at a single tertiary care center were identified from institutional databases. Demographic, clinical, and surgical data were abstracted from these databases and from the medical record; 278 neonates with CHD had cardiopulmonary bypass, 184 of whom had a postoperative brain MRI. Eight patients (4.3%) had a CSVT. Transposition of the great arteries with an intact ventricular septum (P<.01) and interrupted aortic arch (P=.02) were associated with an increased risk for CSVT. Other risk factors for CSVT included cross-clamp time (98 [IQR, 77.5-120] minutes vs 67 [IQR, 44-102] minutes; P=.03), units of platelets (3.63 [IQR, 3-4] vs 2.17 [IQR, 1-4]; P<.01) and packed red blood cells (0.81 [IQR, 0.25-1] vs 1.21 [IQR, 1-1]; P=.03) transfused intraoperatively, and time between surgery and MRI (10 [IQR, 7-12.5] days vs 20 [IQR, 12-35] days; P<.01). Five patients (62.5%) were treated with anticoagulation. All patients had complete or partial resolution of their CSVT, regardless of treatment. Brain MRI after cardiopulmonary bypass in neonates revealed a low prevalence of CSVT (4.3%). Further studies are needed to establish best practices for surveillance, prevention, and treatment of CSVT in this population.

Impact of a Multidisciplinary Research Team Approach to Prevent Avoidable Mistakes for Neonatal CPB Population.

Significant progress has been made in neonatal cardiopulmonary bypass (CPB) over the years. At Penn State Health Children's Hospital, we have established a multidisciplinary research team that brings clinicians, engineers, scientists, research nurses, neuromonitoring technicians, perfusionists, and students from various departments to help reduce adverse outcomes following CPB in neonates. With the help of this team, we evaluate each CPB component in simulated conditions identical to those used in clinical practice. The objective of this review is to demonstrate the results of these translational projects and present critical mistakes to avoid for neonatal CPB patients.

Mechanical ventilation during cardiopulmonary bypass in neonates improves postoperative outcome.

Cardiopulmonary bypass generates a systemic inflammatory response. This inflammatory response is reduced if patients are ventilated during bypass, as evidenced by lower levels of postoperative circulating inflammatory mediators. However, this does not appear to make much clinical difference in adults, at least not consistently, but, to our knowledge, has never been assessed in paediatric cardiac surgery, which is the objective of this study. This is a prospective clinical study of 12 consecutive neonates operated for the correction of either transposition of the great arteries ± ventricular septal defect or aortic arch hypoplasia ± ventricular septal defect, who were ventilated during cardiopulmonary bypass. These were compared to 11 neonates with the same malformations, who had undergone the same operations but without being ventilated during bypass (historical control group). One patient from the control group died on the 15th postoperative day due to sepsis and multi-organ failure. Bypass times and cross-clamp times were similar in the 2 groups. Ventilation on bypass was associated with significantly lower postoperative serum concentrations of C-reactive protein, shorter mechanical ventilation and lower vasoactive-inotropic score. Duration of stay on intensive care unit (ICU) showed a tendency to be shorter in patients who were ventilated on bypass, but this did not reach statistical significance. There were no differences between the 2 groups with respect to postoperative mixed venous oxygen saturations and serum concentrations of lactate and troponin I. Mechanical ventilation during cardiopulmonary bypass in neonates improves postoperative outcome.

Oral Aversion in Infants With Congenital Heart Disease: A Single-Center Retrospective Cohort Study.

Neonates undergoing cardiac surgery are at risk for oral aversion (OA). OA is not well described outside of the index hospitalization and impacts patients and families. We evaluated the prevalence of OA at 1 year old after neonatal cardiopulmonary bypass (CPB) surgery. Retrospective cohort study. Single quaternary care hospital. Our cohort included 157 neonates who underwent CPB surgery from 2014 to 2017 and had follow-up data available at 1 year old. None. Three feeding experts reviewed the medical record to define children with OA; 30% of charts were evaluated in triplicate for validation. Neonates with and without OA were compared in univariate analysis, and risk factors for OA were explored in a limited multivariable analysis. OA was present at 1 year in 37 patients (23.6%) and other feeding difficulties were present in an additional 29 patients (18.5%). Thirty-eight patients (24.2%) had a feeding tube, including 12 (7.6%) with a gastrostomy tube. Factors associated with OA at 1 year included total ICU days, duration of mechanical ventilation, total number of nil per os days, and number of postoperative days (PODs) until oral feeding initiation (all p < 0.0001). Number of POD until oral feeding initiation remained independently associated with OA at 1 year in multivariable analysis (adjusted odds ratio, 1.08; 95% CI, 1.04-1.12; p < 0.0001). Infants with any oral intake at discharge had lower odds of OA at 1 year (0.21; 95% CI, 0.08-0.5; p = 0.0003). At hospital discharge, 132 patients (84.1%) were taking some oral feeds, and 128 patients (81.5%) received tube feeding. OA and other feeding difficulties are common at 1 year old in neonates undergoing CPB surgery. Delayed exposure to oral intake may be a modifiable risk factor for OA and efforts to improve early oral feeding could lead to better functional outcomes.

Abstract 13579: Serum Neural Biomarkers and Neuroimaging Markers in Neonates With Congenital Heart Disease Undergoing Cardiac Surgery

Introduction: Congenital heart disease (CHD) patients requiring neonatal cardiopulmonary bypass (CPB) surgery often experience abnormal neurodevelopment. Open heart surgery and anesthesia induce changes in the developing brain concomitant with an increase in the level of neuromarkers. The aim of this study is to assess the relationship between neuromarkers, brain dysplasia and neurodevelopmental outcomes for CHD patients undergoing neonatal CPB. Hypothesis: Neuromarkers and neuroimaging brain dysplasia can predict the neurodevelopmental outcomes for CHD patients undergoing neonatal CPB. Methods: 42 neonates with CHD requiring CPB were included in this prospective, observational study. Using the Neurology 4-Plex A Assay, serum levels of glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), neurofilament light (NF-L), and Tau protein were measured pre-operatively and at 0 hours, 24 hours, and 48 hours post-operatively. Brain MRIs were obtained in 24 neonates. Neurodevelopment testing was completed at 6 months to 36 months of age using the Bayley-III Scales of infant. Findings of brain MRI were scored using an internally developed scoring system which evaluates the brains structures individually on degrees of dysplasia, hypoplasia, and abnormalities, as well as providing a comprehensive assessment of overall brain development combining the individual structural abnormalities into a composite total brain dysplasia score (TBDS). Results: Bayley-III scales were negatively correlated with NF-L and Tau. For UCH-L1, a positive correlation was seen at immediate postop. Hemorrhage is associated with low language score (P=0.009) and elevated UCH-L1 levels at 24 hours and 48 hours. Infraction (P=0.0375) and lower maturation (P=0.03) are associated with low fine motor scores. Lower maturation is related to more domains below average (P=0.01). Infarction is associated with high postoperative Tau level (P=0.04).TBDS is associated with high levels of GFAP, NFL-1, and decreased language development. Conclusion: A negative correlation of Tau and NF-L to Bayley-III scales was consistent with their known roles as markers of neural injury. High NF-L and GFAP are associated with brain dysplasia.

MP07-20 INITIAL EXPERIENCE: EX-VIVO PERFUSED PIG KIDNEY TO STUDY URINARY OXALATE EXCRETION

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-20 INITIAL EXPERIENCE: EX-VIVO PERFUSED PIG KIDNEY TO STUDY URINARY OXALATE EXCRETION Jonathan Pavlinec, Mark Martin, William Donelan, Elizabeth Kwenda, Paul Dominguez-Gutierrez, Vincent Bird, and Benjamin Canales Jonathan PavlinecJonathan Pavlinec More articles by this author , Mark MartinMark Martin More articles by this author , William DonelanWilliam Donelan More articles by this author , Elizabeth KwendaElizabeth Kwenda More articles by this author , Paul Dominguez-GutierrezPaul Dominguez-Gutierrez More articles by this author , Vincent BirdVincent Bird More articles by this author , and Benjamin CanalesBenjamin Canales More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Existing animal models of renal oxalate excretion utilize either gut or peritoneal cavity for oxalate absorption. Ex vivo renal perfusion is an established tool for graft preservation. We sought to repurpose this concept in order to study the early pathogenesis of urinary lithiasis. METHODS: Juvenile female Yorkshire porcine kidneys were removed laparoscopically and placed on an ex vivo neonatal cardiopulmonary bypass circuit utilizing whole-blood based perfusate oxygenated with 95% carbogen. Pre-defined goals were identified for each attempt (n=5) with plans to increase physiologic model complexity. Tissue perfusion and oxygenation was monitored by serial perfusate iSTAT testing. Once steady urine production was achieved, aqueous oxalate was injected into the perfusate. Renal outcomes were assessed by histology and blood/urinary assays. RESULTS: After demonstrating proof-of-concept in early trials, normothermic (37C) ex vivo whole-blood perfusion with Steen SolutionTM was performed exceeding three hours at physiologic mean arterial pressures. Circuit parameters remained in the physiologic range for electrolytes, temperature, mean arterial pressure, lactate, and pH. Urine was produced in three experiments, with two additional attempts stopped early due to challenges related to hilar cannulation. Urinary filtrate demonstrated consistently higher urine creatinine compared to perfusate, and arterial perfusate oxalate boluses lead to urinary oxalate spikes followed by continuous oxalate clearance. Histopathologic analysis with H&E and Pizzolato’s method staining demonstrated formation of calcium oxalate crystals. CONCLUSIONS: In light of promising renal urinary oxalate and creatinine clearance, ex vivo porcine renal perfusion appears to be a feasible alternative to study oxalate excretion. Longer validation studies are necessary to establish this technique as a model for kidney stone pathogenesis. Source of Funding: No extra-instatutional funding was utilized for this project © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e147-e148 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan Pavlinec More articles by this author Mark Martin More articles by this author William Donelan More articles by this author Elizabeth Kwenda More articles by this author Paul Dominguez-Gutierrez More articles by this author Vincent Bird More articles by this author Benjamin Canales More articles by this author Expand All Advertisement Loading ...

Coagulation Profile of Neonates Undergoing Arterial Switch Surgery With Crystalloid Priming of the Cardiopulmonary Bypass Circuit

ObjectivesThe aim was to evaluate changes in the coagulation profile of cyanotic neonates, to analyze the effects of cardiopulmonary bypass (CPB) with crystalloid priming on their coagulation status, and to determine factors predicting a requirement for hemostasis-derived transfusion. DesignRetrospective cohort. SettingSingle-center, tertiary academic hospital. ParticipantsIn total, 100 consecutive neonates who underwent arterial switch surgery between December 2014 and June 2020. InterventionsRotational thromboelastometry (ROTEM) and coagulation parameters before surgery and before termination of CPB were evaluated. Transfusion of platelets, fresh frozen plasma, and fibrinogen, defined as hemostasis-derived transfusion (HD transfusion), were determined. Patients with and without HD transfusion were compared to identify predictors. Measurements and Main ResultsAfter CPB, fibrinogen was reduced by 24.5% (interquartile range [IQR] 8.9-32.1) to 201 mg/dL (IQR 172-249), resulting in a reduction of FIBTEM A10 by 20% (1.8-33.3) to 8 mm (6-11). The platelet count decreased by a median of 47.2% (25.6-61.3) to 162 × 103/µL (119-215). However, the median fibrinogen concentration and platelet count remained within normal range. Neonates with abnormal ROTEM results were more likely to receive HD transfusions. The HD transfusions were more likely with lower preoperative FIBTEM maximum clot firmness values (p = 0.031), lower hemoglobin concentrations at termination of CPB (p = 0.02), and longer CPB duration (p = 0.017). Perioperative hemostasis without any HD transfusion was achieved in 64 neonates. ConclusionsGuidance from ROTEM analyses facilitates hemostasis management after neonatal CPB. Circuit miniaturization with transfusion-free CPB is associated with acceptable changes in ROTEM in most patients, and allows sufficient hemostasis without any HD transfusions in most patients.

The lower threshold of hypothermic oxygen delivery to prevent neonatal acute kidney injury.

Oxygen delivery during cardiopulmonary bypass (CPB) is closely related to postoperative acute kidney injury (AKI). The value of critical indexed oxygen delivery (DO2i) is a key indicator to reflect oxygen supply in cardiovascular surgery. However, the target DO2i value for neonates undergoing hypothermic CPB remains unclear. One hundred and twenty-six consecutive newborns (≤28 days) undergoing arterial switch operations were retrospectively divided into two groups according to AKI occurrence. Baseline characteristics, intraoperative variables, and clinical outcomes were collected. Multivariate logistic regression analysis and receiver-operating characteristic curve were performed to investigate the association between DO2i and AKI. Neonates in the no-AKI group (n = 67) had significantly higher nadir bypass flow and DO2i during the hypothermic phase compared with the AKI group (n = 59). AKI group had remarkably higher incidences of hepatic dysfunction and peritoneal dialysis requirement compared with newborns without AKI. Mixed venous oxygen saturation (SvO2) was comparable between the two groups. Base excess (BE)(P = 0.011) value during the hypothermic phase of the AKI group was higher than the no-AKI group. Multivariate analysis showed that hypothermic DO2i was negatively associated with AKI. The cut-off value of hypothermic DO2i was 269 mL min-1 m-2. The importance of hypothermic DO2i should be highlighted, even when SvO2 was satisfactory. A lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of postoperative AKI. The key message of our article is that the lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of AKI after on-pump hypothermic cardiovascular surgery. The critical DO2i value for neonates undergoing hypothermic CPB remains unclear, and our study may add new evidence for this matter based on the 6-year experience of our center. In this study, the lowest critical value of DO2i in neonatal hypothermic CPB is determined for the first time, which provides a reference for intra-CPB management strategy to improve the postoperative outcomes of newborns.

Plasma Proteolytic Cascade Activation and Control during Neonatal Cardiopulmonary Bypass Surgery

Introduction: As blood passes through the cardiopulmonary bypass (CPB) circuit, foreign surface exposure activates cells producing tissue factor expression and microparticles that induce procoagulant and pro-inflammatory responses. In the neonate, higher pump flow rates, longer bypass times and decreased levels of endogenous plasma proteins, make plasma proteolytic cascades vulnerable to uncontrolled activation. Changes in the plasma concentrations and structures of five plasma protease inhibitors regulating coagulation, inflammation, fibrinolysis and complement were examined in neonates undergoing CPB to understand how deregulation of proteolytic cascades may contribute to excessive bleeding, which continues to be a common problem in these patients.Methods: Blood samples were obtained at baseline (Draw 1), on CPB (Draw 2), following protamine (Draw 3) and in the intensive care unit (Draw 4). Plasma total protein and the concentrations of the serpins, antitrypsin, antithrombin, antiplasmin and C1-inhibitior, and the Kunitz inhibitor, tissue factor pathway inhibitor (TFPI) were measured. Serpin structures were examined using transverse urea gradient (TUG) gels. TFPI degradation was examined by SDS-PAGE. Excessive bleeding was defined by meeting one or more of the following: ≥ 84 mL/kg total chest tube output (CTO) in the first 24 hours, ≥ 7 mL/kg/hr CTO for ≥2 consecutive hours in the first 12 hours, or re-exploration in the first 24 hours for bleeding or tamponade.Results: Of 44 neonates, 16 (36%) were classified as bleeders. The total plasma protein concentration was 60% that of adults at Draw 1. Adult plasma transfusion increased total protein by 43%, 59% and 32% at Draws 2, 3 and 4. The concentration of each inhibitor changed over the course of surgery (p<0.001 for all). Antitrypsin, an inhibitor of inflammation, and C1-inhibitor, an inhibitor of complement, are acute phase proteins. C1-Inhibitor increased in neonates by 56% and 81% at Draws 2 and 3, returning to baseline at Draw 4. However, antitrypsin decreased 30% between Draws 1 and 2, and remained low at Draws 3 and 4, suggesting it is consumed during surgery. Antithrombin and antiplasmin inhibit coagulation and fibrinolysis, respectively. Changes in antithrombin concentration mirrored those of total protein, while antiplasmin remained stable or decreased, again suggesting consumption. TFPI inhibits coagulation. It is a heparin-releasable protein that increased 5-fold at Draw 2, and remained 4-fold and 3-fold elevated following protamine at Draws 3 and 4. Comparisons of neonates who bled with those who did not revealed that antithrombin was higher in those bleeding at Draw 2 (p=0.031). There was no difference between groups in other inhibitors. TUG gels produce a unique unfolding signature for each serpin and differentiate virgin, proteolytically cleaved, protease complexed and polymerized forms. TUG signatures revealed only virgin antitrypsin, C1-inhibitor and antiplasmin at all 4 draws. Heparin administration at Draw 2 produced antithrombin-FXa and antithrombin-thrombin complexes, as well as proteolytically cleaved forms of antithrombin. These were also variably present at Draws 3 and 4. Western blots for TFPI revealed the appearance of degraded forms at Draws 3 and 4 in some patients.Conclusions: C1-inhibitor concentration increased during surgery, consistent with it being an acute phase reactant. Changes in antithrombin concentration mirrored the conversion to adult plasma, while antitrypsin and antiplasmin decreased in concentration suggesting consumption and clearance. Structural analysis of serpins, other than antithrombin, revealed only the virgin form, indicating the absence of widespread, unregulated proteolysis by plasma proteolytic cascades. Antithrombin displayed complexed and cleaved forms following heparin administration, consistent with its role as an anticoagulant during surgery. TFPI increased 5-fold following heparin administration and remained 3-fold elevated at Draw 4. A portion of this elevation could be attributed to proteolytic degradation, but it is unclear why levels remained so high following protamine reversal. TFPI levels were not different between neonates who bled or not. In contrast, elevated antithrombin levels at Draw 2 were more common in neonates who bled, suggesting that administration of recombinant antithrombin may worsen bleeding in these patients. DisclosuresMast:Novo Nordisk: Research Funding.

The Characterization of Postoperative Mechanical Respiratory Requirement in Neonates and Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass in a Single Tertiary Institution

Although neonates and infants undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at high risk of developing perioperative morbidity and mortality, including lung injury, the intraoperative profile of lung injury in this cohort is not well-described. Given that the postoperative course of patients in the pediatric cardiac surgical arena has become increasingly expedited, the objective of this study was to characterize the profiles of postoperative mechanical ventilatory support in neonates and infants undergoing cardiac surgery on CPB and to examine the characteristics of lung mechanics and lung injury in this patient population who are potentially amendable to early postoperative recovery in a single tertiary pediatric institution. A retrospective data analysis of neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. A single-center, university teaching hospital. The study included 328 neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. A subset of 128 patients were studied: 58 patients undergoing ventricular septal defect (VSD) repair, 36 patients undergoing complete atrioventricular canal (CAVC) repair, and 34 patients undergoing bidirectional Glenn (BDG) shunt surgery. Of the entire cohort, 3.7% experienced in-hospital mortality. Among all surgical procedures, VSD repair (17.7%) was the most common, followed by CAVC repair (11.0%) and BDG shunt surgery (10.4%). Of patients who underwent VSD repair, CAVC repair, and BDG shunt surgery, 65.5%, 41.7%, and 67.6% were off mechanical ventilatory support within 24 hours postoperatively, respectively. In all three of the surgical repairs, lung compliance decreased after CPB compared to pre-CPB phase. Sixty point three percent of patients with VSD repair and 77.8% of patients with CAVC repair showed a PaO2/FIO2 (P/F) ratio of <300 after CPB. Post- CPB P/F ratios of 120 for VSD patients and 100 for CAVC patients were considered as optimal cutoff values to highly predict prolonged (>24 hours) postoperative mechanical ventilatory support. A higher volume of transfused platelets also was associated with postoperative ventilatory support ≥24 hours in patients undergoing VSD repair, CAVC repair, and BDG shunt surgery. There was a high incidence of lung injury after CPB in neonates and infants, even in surgeries amendable for early recovery. Given that CPB-related factors (CPB duration, crossclamp time) and volume of transfused platelet were significantly associated with prolonged postoperative ventilatory support, the underlying cause of cardiac surgery-related lung injury can be multi-factorial.

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.