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Abstract Convenient and widespread serology testing may alter the trajectory of the COVID-19 pandemic. This study seeks to leverage high-throughput, multiplexed serologic assays, which have been adopted as benchmarks for vaccine efficacy, to support large-scale surveys of SARS-CoV-2 immunity using finger-stick blood and/or saliva. Specifically, we optimized MSD’s serology assays, which were analytically validated for serum, to test self-collected finger-stick blood and saliva samples to identify prior infection. We show that these assays can be used with FDA-registered specimen collection devices to obtain quantitative measurements for self-collected samples. First, we show that salivary antibodies are stable without refrigeration or preservatives for at least 5 days. We selected classification thresholds for antibodies against SARS-CoV-2 N, RBD and Spike in finger-stick blood and saliva that provided 98% specificity in a set of individuals without known COVID-19 exposure. Using matched samples, we show that testing of saliva and finger-stick blood equivalently identified individuals with humoral responses to CoV-2 antigens. Moreover, we piloted a simple saliva collection kit that can be used to safely send samples through the mail using written instructions only. This work establishes key parameters to robustly assay self-collected finger-stick blood and saliva using quantitative immunoassays that could support large-scale serology testing.

The presence of 25 polycyclic aromatic hydrocarbons (PAHs) in tea and coffee were investigated with focus on four PAHs (PAH4), classified by the European Food Safety Authority (EFSA) as suitable indicators; benz[a]anthracene (BaA), chrysene (CHR), benzo[b]fluoranthene (BbF) and benzo[a]pyrene (BaP). PAH4 from samples of 18 brands of tea leaves and 13 brands of coffee were extracted by pressurized liquid extraction (PLE) followed by highly automated clean up steps for gel permeation chromatography (SX-3) and solid phase extraction (500mg silica). GC-MS were applied for detection of PAH4. The limit of detection (LOD) ranged from 0.1–0.3 μg/kg with recoveries from 94–106% for PAH4. Concentrations of PAH4 followed the pattern of the total sum of 25 PAHs with higher concentrations with a maximum of 115 μg/kg in tea leaves compared to 5.1 μg/kg in coffee. The highest PAH4 levels were found in black tea leaves. An additional 18 samples were used for estimation of transfer from solids to ready-to-drink preparations. Only up to 2% PAH4 were detected in the ready-to-drink tea, while for coffee the PAH4 transfer was up to 14%. The estimated exposure to PAH4 from tea infusions and coffee brew for the average Danish consumption is 29% of the total exposure to PAH4 for Danish consumers. [ABSTRACT FROM AUTHOR]

Indications for heart-only (HT) versus combined heart-liver transplantation (cHLT) in Fontan patients are still evolving. Current methods to assess liver disease have limitations. At time of transplant, an intra-operative liver inspection done early in the case can allow for a decision to proceed with HT rather than cHLT. We describe the outcomes of Fontan patients listed for cHLT who underwent HT based on direct inspection of the liver at time of transplant. Data are presented as medians (range). Five Fontan patients, ages 15 (11-24) years, were listed for cHLT, including 3 who had worsening liver disease after 11-52 months waiting for HT only. After 112 (2-296) days waiting for cHLT, gross liver inspection via a limited laparotomy at time of transplant did not demonstrate cirrhosis. All patients proceeded with HT only. All donor livers were procured and delivered to back-up recipients. Table 1 shows details of the 5 patients compared to previously published descriptions of HT and cHLT Fontan patients from our center. Post-transplant length of stay was 48 (19-117) days, compared to 26 days for HT and 29 days for cHLT Fontan patients. Prior to discharge, 3 patients were treated for Grade 2R/3A cellular rejection and 1 patient was treated for clinical rejection due to graft dysfunction and arrhythmia without biopsy data. All 5 patients are alive with 19 (9-39) months of post-HT follow-up. Post-transplant liver imaging (by CT in 2 and ultrasound in 3) showed persistent liver disease in 3 patients (heterogeneity ± nodules ± splenomegaly) and worsened findings in 2 patients (increased heterogeneity and splenomegaly, development of new nodules); none have yet demonstrated imaging improvement. Intra-operative gross liver inspection at the time of transplant can result in successful HT in Fontan patients with liver disease. However, continued post-transplant liver evaluation is still needed to determine long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: An increasing number of centers are undertaking combined heart and liver transplantation in adult and pediatric patients with congenital heart disease., Aim: The primary aim of this study was to describe the perioperative management of a single center cohort, identifying challenges and potential solutions., Methods: We conducted a retrospective review of all patients undergoing combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022. Preoperative information included cardiac diagnosis, hemodynamics, and severity of liver disease. Intraoperative data included length of surgery, cardiopulmonary bypass time, and blood products transfused. Postoperative data included blood products transfused in the intensive care unit, time to extubation, length of intensive care unit stay, survival outcomes and 30-day adverse events., Results: Eighteen patients underwent en bloc combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022, and the majority 15 (83%) were transplanted for failing Fontan circulation with Fontan Associated Liver Disease. Median surgical procedure time was 13.4 [11.5, 14.5] h with a cardiopulmonary bypass time of 4.3 [3.9, 5.8] h. Median total blood products transfused in the operating room post cardiopulmonary bypass was 89.4 [63.9, 127.0] mLs/kg. Nine patients (50%) had vasoplegia during cardiopulmonary bypass. Activated prothrombin complex concentrates were used post cardiopulmonary bypass in 15 (83%) patients with a 30-day thromboembolism rate of 22%. Median time to extubation was 4.0 [2.8, 6.5] days, median intensive care unit length of stay 20.0 [7.8, 48.3] days and median hospital length of stay 54.0 [30.5, 68.3] days. Incidence of renal replacement therapy was 11%; however, none required renal replacement therapy by the time of hospital discharge. Neurological events within 30 days were 17% and the 30 day and 1 year survival was 89%., Conclusions: Perioperative challenges include major perioperative bleeding, unstable hemodynamics, and end organ injury including acute kidney injury and neurological events. Successful outcomes for en bloc combined heart and liver transplantation are possible with careful multidisciplinary planning, communication, patient selection, and integrated peri-operative management., (© 2024 John Wiley & Sons Ltd.)

Patients with congenital heart disease are living longer due to improved medical and surgical care. Congenital heart disease encompasses a wide spectrum of defects with varying pathophysiology and unique anesthetic challenges. These patients often present for noncardiac surgery before or after surgical repair and are at increased risk for perioperative morbidity and mortality. Although there is no singular safe anesthetic technique, identifying potential error traps and tailoring perioperative management may help reduce morbidity and mortality. In this article, we discuss five error traps based on the collective experience of the authors. These error traps can occur when providing perioperative care to patients with congenital heart disease for noncardiac surgery and we present potential solutions to help avoid adverse outcomes., (© 2024 John Wiley & Sons Ltd.)

Objective: To describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index., Design: Prospective, open-label, nonrandomized study (NCT04463394)., Setting: Cardiac catheterization laboratory at Lucile Packard Children's Hospital, Stanford., Patients: Patients 3-50 years old with a Fontan circulation who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention., Interventions: A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/kg/min (maximum dose 0.03 U/min)., Measurements and Main Results: Comprehensive cardiac catheterization measurements before and after vasopressin administration. Measurements included pulmonary artery, atrial, and systemic arterial pressures, oxygen saturations, and systemic and pulmonary flows and resistances. There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg ( Z value -4.6, p < 0.001) and 3.8 (1.8, 7.5) Wood Units ( Z value -4.6, p < 0.001), respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU ( t statistic 6.2, p < 0.001), and the left atrial pressure increased by 1.0 (0.0, 2.0) mm Hg ( Z value -3.5, p < 0.001). The PVR:SVR decreased by 0.04 ± 0.03 ( t statistic 8.1, p < 0.001). Neither the pulmonary artery pressure (median difference 0.0 [-1.0, 1.0], Z value -0.4, p = 0.69) nor cardiac index (0.1 ± 0.3, t statistic -1.4, p = 0.18) changed significantly. There were no adverse events., Conclusions: In Fontan patients undergoing cardiac catheterization, vasopressin administration resulted in a significant increase in systolic blood pressure, SVR, and left atrial pressure, decrease in PVR, and no change in cardiac index or pulmonary artery pressure. These findings suggest that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Intraoperative imaging determines the integrity of surgical repairs. Transoesophageal echocardiography represents standard care for intraoperative imaging in CHD. However, some conditions preclude its use, and epicardial echocardiography is used alternatively. Minimal literature exists on the impact of epicardial echocardiography versus transoesophageal echocardiography. We aimed to evaluate accuracy between the two modalities and hypothesised higher imaging error rates for epicardial echocardiography., Methods: We retrospectively reviewed all epicardial echocardiograms performed over 16 years and compared them to an age- and procedure-matched, randomly selected transoesophageal echocardiography cohort. We detected un- or misidentified cardiac lesions during the intraoperative imaging and evaluated patient outcomes. Data are presented as a median with a range, or a number with percentages, with comparisons by Wilcoxon two-sample test and Fisher's exact test., Results: Totally, 413 patients comprised the epicardial echocardiography group with 295 transoesophageal echocardiography matches. Rates of imaging discrepancies, re-operation, and incision infection were similar. About 13% of epicardial echocardiography patients had imaging discrepancies versus 16% for transoesophageal (p = 0.2352), the former also had smaller body sizes (p < 0.0001) and more genetic abnormalities (33% versus 19%, p < 0.0001). Death/mechanical support occurred more frequently in epicardial echocardiography patients (16% versus 6%, p < 0.0001), while hospitalisations were longer (25 versus 19 days, p = 0.0003)., Conclusions: Diagnostic accuracy was similar between patients undergoing epicardial echocardiography and transoesophageal echocardiography, while rates of death and mechanical support were increased in this inherently higher risk patient population. Epicardial echocardiography provides a reasonable alternative when transoesophageal echocardiography is not feasible.

Mechanical circulatory support (MCS), including ventricular assist device (VAD) support, is a leading cause of stroke in children; however, existing pediatric stroke recommendations do not apply to many pediatric VAD patients. We sought to develop a multidisciplinary pathway to improve timely and effective acute stroke care and examine the early performance of the pathway in expediting stroke care. Stakeholders from pediatric heart failure, cardiac intensive care, neurology, interventional radiology, neuroradiology, neurosurgery, pharmacy, and adult VAD care convened at Stanford University in August 2017 to discuss the challenges of providing high-quality acute stroke care to children on VAD support, and to develop multidisciplinary acute stroke pathways. Stakeholders identified multiple barriers to providing timely acute stroke care to pediatric VAD patients. These include delayed recognition of stroke, and lack of clarity related to the optimal imaging technique, when to emergently reverse antithrombotic therapy (AT), pediatric indications for thrombectomy and cranial decompression, and strategies to avoid unnecessary serial CTS. Four stroke pathways were created including evaluation and management of the pediatric patient with (1) an acute neurologic change before an imaging diagnosis; (2) an arterial ischemic stroke (AIS); (3) an intracerebral hemorrhage (ICH); and (4) a subdural hematoma (SDH). With the implementation of the stroke pathway, the median time-to-first-CT image decreased by 43 minutes from 66 to 23 minutes ( P < 0.001) while the proportion with a CT within 30 minutes increased from 0% to 67% ( P < 0.001). Despite a variety of challenges, multidisciplinary consensus can be achieved on a rapid stroke management pathway for children on VAD support that addresses important barriers to timely stroke care. Although too few stoke events occurred to differentiate clinical outcomes, the time-to-first-CT image was significantly shorter after pathway implementation., Competing Interests: Disclosure: The authors have no conflicts of interest., (Copyright © ASAIO 2023.)

Objective: To evaluate the long-term effects of a multilevel community intervention to improve the quality of prescription practice of potentially addictive medications (PAMs)., Design: We conducted a retrospective study, using anonymized data from the Norwegian prescription registry., Setting: Based on an initiative from the GPs in Molde Municipality in Norway, a multilevel community intervention was initiated by the municipal chief physician in 2018. The intervention targeted GPs, patients, and the public., Subjects: We retrieved prescription data from 26 of 36 GPs., Main Outcome Measures: By using the standardized defined daily dose (DDD), we compared prescription of three groups of PAMs from before the intervention (2017) throughout the intervention in 2018, and through 2020 to determine long-term effects., Results: Three years after the intervention, the GPs in our study sample prescribed 26% less opioids, 38% less benzodiazepines, and 16% less z-hypnotics. Overall prescription of PAMs decreased by 27%. The number of individuals receiving at least 90 DDD of benzodiazepines and z-hypnotics were reduced from 9 to 7 and 34 to 24 per 1000, respectively. Also, the number of individuals receiving two and three PAMs concomitantly were reduced., Conclusion: Addressing prescription practice among GPs in a community as a joint intervention, combined with addressing patients and the public may be a feasible method to obtain long-term reduction of PAM prescriptions.Key pointsNon-therapeutic prescriptions of potentially addictive medications (PAMs) are both a public health concern and a frequent challenge in general practice.A multilevel community intervention, targeting general practitioners, patients, and the public, led to 27% reduction in prescription of PAMs.Both the number of daily users and concomitant use of several PAMs were reduced.The reduction in prescription persisted for three years.

Background: Prothrombin complex concentrates are an emerging "off-label" therapy to augment hemostasis after cardiopulmonary bypass (CPB), but data supporting their use for neonatal cardiac surgery are limited., Methods: We retrospectively reviewed neonates undergoing open heart surgery with first-time sternotomy between May 2014 and December 2018 from a hospital electronic health record database. Neonates who received activated 4-factor prothrombin complex concentrate (a4FPCC) after CPB were propensity score matched (PSM) to neonates who did not receive a4FPCC (control group). The primary efficacy outcome was total volume (mL/kg) of blood products transfused after CPB, including the first 24 hours on the cardiovascular intensive care unit (CVICU). The primary safety outcome was the incidence of 7- and 30-day postoperative thromboembolism. Secondary outcomes included 24 hours postoperative chest tube output, time to extubation, duration of CVICU stay, duration of hospital stay, 30-day mortality, and incidence of acute kidney injury on postoperative day 3. We used linear regression modeling on PSM data for the primary efficacy outcome. For the primary safety outcome, we tested for differences using McNemar test on PSM data. For secondary outcomes, we used linear regression, Fisher exact test, or survival analyses as appropriate, with false discovery rate-adjusted P values., Results: A total of 165 neonates were included in the final data analysis: 86 in the control group and 79 in the a4FPCC group. After PSM, there were 43 patients in the control group and 43 in the a4FPCC group. We found a statistically significant difference in mean total blood products transfused for the a4FPCC group (47.5 mL/kg) compared with the control group (63.7 mL/kg) for PSM patients (adjusted difference, 15.3; 95% CI, 29.4-1.3; P = .032). We did not find a statistically significant difference in 7- or 30-day thromboembolic rate, postoperative chest tube output, time to extubation, incidence of postoperative acute kidney injury (AKI), or 30-day mortality between the groups. The a4FPCC group had a significantly longer length of intensive care unit stay (32.9 vs 13.3 days; adjusted P = .049) and hospital stay (44.6 vs 24.1 days; adjusted P = .049) compared with the control group., Conclusions: We found that the use of a4FPCC as a hemostatic adjunct for post-CPB bleeding in neonatal cardiac surgery was associated with a decrease in mean total blood products transfused after CPB without an increased rate of 7- or 30-day postoperative thromboembolism. Our findings suggest that a4FPCCs can be considered as part of a hemostasis pathway for refractory bleeding in neonatal cardiac surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Children on ventricular assist device (VAD) support can present several unique challenges, including small patient size, univentricular or biventricular congenital heart disease (1V- or 2V-CHD) and need for biventricular VAD (BiVAD) support. While cardiac catheterization can provide valuable information, it is an invasive procedure with inherent risks. We sought to evaluate the safety of catheterization in pediatric patients on VAD support. We performed a retrospective review of patients on VAD support who underwent catheterization at Lucile Packard Children's Hospital between January 1, 2014 and September 1, 2019. Using definitions adapted from Pedimacs, adverse events (AEs) after catheterization were identified, including arrhythmia; major bleeding or acute kidney injury within 24 hours; respiratory failure persisting at 24 hours; and stroke, pericardial effusion, device malfunction, bacteremia or death within 7 days. AEs were categorized as related or unrelated to catheterization. Sixty procedures were performed on 39 patients. Underlying diagnoses were dilated cardiomyopathy (48%), 1V-CHD (35%), 2V-CHD (8%), and other (8%). Devices were implantable continuous flow (72%), paracorporeal pulsatile (18%) and paracorporeal continuous flow (10%). Catheterizations were performed on patients in the ICU (60%), on inotropic support (42%), with deteriorating clinical status (37%) and on BiVAD support (12%). There were 9 AEs possibly related to catheterization including 6 episodes of respiratory failure, 2 major bleeding events, and 1 procedural arrhythmia. AE occurrence was associated with ICU status ( P = 0.01), BiVAD support ( P = 0.04) and procedural indication to evaluate worsening clinical status ( P = 0.04). Despite high medical acuity, catheterization can be performed with an acceptable AE profile in children on VAD support., Competing Interests: Disclosure: There are no conflicts of interest to report, (Copyright © ASAIO 2021.)

Background: To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant., Methods: This was a 2.5-year retrospective evaluation using 3 years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI., Results: There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p = .05) and a 17% reduction in Stage 2/3 acute kidney injury (p = .09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p = .03), achieving a central venous pressure of or less than 12 mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p = .03) and mean arterial pressure above 60 mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p = .05) in the first 48 h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p = .002)., Conclusions: This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion., (© 2021 Wiley Periodicals LLC.)

Objective: This study compared the percent change in systolic blood pressure and the incidence of adverse cardiac events (ACEs; defined as cardiac arrest, cardiopulmonary resuscitation, arrhythmias, or ST-segment changes) during anesthesia induction in patients with Williams syndrome (WS) before and after implementation of a perioperative management strategy., Design: Retrospective observational cohort study., Setting: Single quaternary academic referral center., Participants: The authors reviewed the records of all children with WS at the authors' institution who underwent general anesthesia for cardiac catheterization, diagnostic imaging, or any type of surgery between November 2008 and August 2019. The authors identified 142 patients with WS, 48 of whom underwent 118 general anesthesia administrations. A historic group (HG) was compared with the intervention group (IG)., Interventions: Change in perioperative management (three-stage risk stratification: preoperative intravenous hydration, intravenous anesthesia induction, and early use of vasoactives)., Measurements and Main Results: The authors determined event rates within 60 minutes of anesthesia induction. Standardized mean difference (SMD) was calculated (SMD >0.2 suggests clinically meaningful difference). Sixty-seven general anesthesia encounters were recorded in the HG (mean age, 4.8 years; mean weight, 16.3 kg) and 51 in the IG (mean age, 6.0 years; mean weight, 18.2 kg). The change in systolic blood pressure was -17.5% (-30.0, -5.0) in the HG versus -9% (-18.0, 5.0) in the IG (p = 0.015; SMD = 0.419), and the incidence of ACEs was 6% in the HG and 2% in the IG (p = 0.542; SMD = 0.207)., Conclusions: Preoperative risk stratification, preoperative intravenous hydration, intravenous induction, and early use of continuous vasoactives resulted in greater hemodynamic stability, with a 2% incidence of ACEs., Competing Interests: Conflict of Interest The authors report no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The incidence of neurological complications related to ventricular assist devices (VAD) remains high and includes life-threatening conditions such as intracranial hemorrhage or ischemic stroke. Although no definitive management guidelines exist, operative interventions may be required for major neurological injuries., Aims: This case series describes the perioperative management of children at a single center who underwent neurosurgical procedures for major intracranial bleeds or ischemic strokes while on VAD support., Methods: A database review identified all pediatric VAD patients who underwent a neurosurgical procedure for an intracranial hemorrhage or ischemic stroke from April 2014 to January 2020. Data regarding patient characteristics, preoperative medical management, intraoperative anesthetic management, and postoperative outcomes were collected using retrospective chart review., Results: Ninety VADs were implanted in 78 patients. Five neurosurgical interventions were performed: four for intracranial hemorrhages and one for an ischemic stroke. All four patients with hemorrhages were receiving anticoagulation at the time of their event and the three patients on warfarin received emergent reversal with prothrombin concentrate complex and vitamin K. Three patients also received pre-procedural platelet transfusions. Two of the five procedures were emergent bedside external ventricular drain placements, and three were surgical operations. All three patients who underwent operative procedures received invasive hemodynamic monitoring and were supported with a combination of inotropes and afterload reduction. One patient required a massive blood product transfusion. The two patients who underwent external ventricular drain placement had no further surgical interventions and died from the severity of their neurological injuries. All three patients who underwent operative procedures survived to transplantation and discharge home., Conclusions: Perioperative concerns for the anesthesiologist include VAD hemodynamic management, bleeding, VAD thrombosis, and prevention of secondary brain injury. A systematic, multidisciplinary approach to management is paramount to attain favorable outcomes., (© 2021 John Wiley & Sons Ltd.)

Acute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index ( p  = 0.001), higher hematocrit ( p  < 0.001), lower body temperature ( p  < 0.001), lower renal near-infrared spectroscopy ( p  = 0.001), lower postoperative mean arterial blood pressure (MAP: p  = 0.001), and higher central venous pressure (CVP; p  < 0.001). In multivariable analysis, postoperative CVP >12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48-12.3, p  = 0.007) and MAP <65 mm Hg (OR = 4.9; 95% CI: 1.07-22.5, p  = 0.04) were associated with early severe AKI. Children with severe AKI experienced longer ventilator, intensive care, and posttransplant hospital days and inferior survival ( p  = 0.01). Lower MAP and higher CVP are associated with severe AKI in pediatric HT recipients. Patients, who experienced AKI, experienced increased intensive care unit (ICU) morbidity and inferior survival. These data may guide the development of perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Indications for a heart‒liver transplantation (HLT) for Fontan recipients are not well defined. We compared listing characteristics, post-operative complications, and post-transplant outcomes of Fontan recipients who underwent HLT with those of patients who underwent heart-only transplantation (HT). We hypothesized that patients who underwent HLT have increased post-operative complications but superior survival outcomes compared with patients who underwent HT., Methods: We performed a retrospective review of Fontan recipients who underwent HLT or HT at a single institution. Characteristics at the time of listing, including the extent of liver disease determined by laboratory, imaging, and biopsy data, were compared. Post-operative complications were assessed, and the Kaplan‒Meier survival method was used to compare post-transplant survival. Univariate regression analyses were performed to identify the risk factors for increased mortality and morbidity among patients who underwent HT., Results: A total of 47 patients (9 for HLT, 38 for HT) were included. Patients who underwent HLT were older, were more likely to be on dual inotrope therapy, and had evidence of worse liver disease. Whereas ischemic time was longer for the group who underwent HLT, post-operative complications were similar. Over a median post-transplant follow-up of 17 (interquartile range: 5-52) months, overall mortality for the cohort was 17%; only 1 patient who underwent HLT died (11%) vs 7 patients who underwent HT (18%) (p = 0.64). Among patients who underwent HT, cirrhosis on pre-transplant imaging was associated with worse outcomes., Conclusions: Despite greater inotrope need and more severe liver disease at the time of listing, Fontan recipients undergoing HLT have post-transplant outcomes comparable with those of patients undergoing HT. HLT may offer a survival benefit for Fontan recipients with liver disease., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We present the successful perioperative management of an 11-year-old patient presenting for heart transplant with a left ventricular assist device, symptomatic acquired von Willebrand syndrome, and recent preoperative intracranial hemorrhage. A brief review of the pathophysiology of acquired von Willebrand syndrome is included. As the number of pediatric patients supported with ventricular assist devices continues to increase, the management of symptomatic acquired von Willebrand syndrome during the perioperative period is an important consideration for anesthesiologists.

Background: Given poor outcomes, strategies to improve ventricular assist devices (VADs) for single-ventricle patients with bidirectional Glenn (BDG) palliation are needed., Methods: This retrospective review describes an institutional experience with VAD support for patients with BDG from April 2011 to January 2019. Surgical strategies, complications, and causes of death are described. Survival to heart transplantation for various strategies are compared., Results: A total of 7 patients with BDG (weights, 5.6 to 28.8 kg; ages, 7 months to 11 years) underwent VAD implantation. Three patients underwent implantation of Berlin Heart EXCOR devices (Berlin Heart, Inc, Spring, TX), 2 had HeartWare HVADs (Medtronic, Minneapolis, MN) implanted, and 2 patients underwent implantation of paracorporeal continuous flow devices. Four patients underwent ventricular inflow cannulation, and 3 underwent atrial inflow cannulation. At the time of VAD implantation, the BDG was left intact in 3 patients, taken down in 3 patients, and created de novo in 1 patient. Over a total of 420 VAD support days, 2 patients survived to heart transplantation, 1 patient with HeartWare ventricular cannulation and intact BDG (after 174 days) and another with Berlin Heart atrial cannulation and BDG take-down (after 72 days). There were 3 deaths within 2 weeks of VAD implantation (2 from respiratory failure, 1 from infection) and 2 deaths after 30 days as a result of strokes., Conclusions: The surgical strategy and postoperative management of VAD with BDG are still evolving. Successful support can be achieved with (1) both pulsatile and continuous flow pumps, (2) atrial or ventricular cannulation, and (3) with or without BDG take-down. Surgical strategy should be determined by individual patient anatomy, physiology, and condition., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Pectoral nerve blocks (PECs) can reduce intraprocedural anesthetic requirements and postoperative pain. Little is known about the utility of PECs in reducing pain and narcotic use after pacemaker (PM) or implantable cardioverter-defibrillator (ICD) placement in children., Objective: The purpose of this study was to determine whether PECs can decrease postoperative pain and opioid use after PM or ICD placement in children., Methods: A single-center retrospective review of pediatric patients undergoing transvenous PM or ICD placement between 2015 and 2020 was performed. Patients with recent cardiothoracic surgery or neurologic/developmental deficits were excluded. Demographics, procedural variables, postoperative pain, and postoperative opioid usage were compared between patients who had undergone PECs and those who had undergone conventional local anesthetic (Control)., Results: A total of 74 patients underwent PM or ICD placement; 20 patients (27%) underwent PECs. There were no differences between PECs and Control with regard to age, weight, gender, type of device placed, presence of congenital heart disease, type of anesthesia, procedural time, or complication rates. Patients who underwent PECs had lower pain scores at 1, 2, 6, 18, and 24 hours compared to Control. PECs patients had a lower mean cumulative pain score [PECs 1.5 (95% confidence interval [CI] 0.8-2.2) vs Control 3.1 (95% CI 2.7-3.5); P <.001] and lower total opioid use [PECs 6.0 morphine milligram equivalent (MME)/m 2 (95% CI 3.4-8.6) vs Control 15.0 MME/m 2 (95% CI 11.8-18.2); P = .001] over the 24 hours postimplant., Conclusion: PECs reduce postoperative pain scores and lower total opioid usage after ICD or PM placement. PECs should be considered at the time of transvenous device placement in children., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients supported with a ventricular assist device are predisposed to severe bleeding at the time of orthotopic heart transplant due to several risk factors including anticoagulation with vitamin K antagonists. Kcentra, a four-factor prothrombin complex concentrate, has been approved by the FDA for warfarin reversal in adults prior to urgent surgery. There is a lack of published data on the preoperative use of four-factor prothrombin complex concentrates in pediatric patients undergoing cardiacsurgery., Methods: This is a single-center retrospective analysis of pediatric patients with a continuous-flow ventricular assist device who underwent heart transplant, comparing patients who received Kcentra for anticoagulation reversal with a historical patient cohort who did not. Consecutive patients from January 2013 to December 2017 were analyzed. The primary outcome was volume of blood product transfusion prior to cardiopulmonary bypass initiation. Secondary outcomes include blood product transfusion after cardiopulmonary bypass intraoperatively and up to 24 hours postoperatively, chest tube output within 24 hours of surgery, time to extubation, incidence of thromboembolism, and post-transplant length ofstay., Results: From 2013 to 2017, 31 patients with continuous-flow ventricular assist devices underwent heart transplant, with 27 patients included in the analysis. Fifteen patients received Kcentra compared with 12 patients who received fresh-frozen plasma for anticoagulation reversal. Compared with the control group, patients who received Kcentra had less packed red blood cells, fresh-frozen plasma, and platelets transfused prior to cardiopulmonary bypass initiation. The Kcentra group also received less packed red blood cells on bypass and less packed red blood cells after cardiopulmonary bypass termination. There were no differences in chest tube output, time to extubation, intensive care unit length of stay, or overall hospital length of stay. Neither group had thromboembolic complications detected during the first seven postoperative days., Conclusion: This small retrospective study indicates that preoperative warfarin reversal with Kcentra reduces blood product exposure in pediatric patients with ventricular assist devices undergoing heart transplant., (© 2020 John Wiley & Sons Ltd.)

Ventricular assist device (VAD) support for children with single ventricle (SV) heart disease remains challenging. We performed a single-center retrospective review of SV patients on VAD support and examined survival to transplant using the Kaplan-Meier method. Patients transplanted were compared with those who died on support. Between 2009 and 2017, there were 14 SV patients with 1,112 patient-days of VAD support. Stages of palliation included pre-Glenn (n = 5), Glenn (n = 5), and Fontan (n = 4). Eight patients (57%) were successfully bridged to transplant at a median 107 days. Deaths occurred early (n = 6, median 16 days) and in smaller patients (10.1 vs. 28.3 kg, P = 0.04). All Fontan patients survived to transplant, whereas only 20% of Glenn patients survived to transplant. Adverse events occurred in 79% (n = 11). Five patients met hospital discharge criteria, with two patients (one pre-Glenn, one Glenn) discharged and transplanted after 219 and 174 days of VAD support. All transplanted patients were discharged at a median 21 days posttransplant. SV patients in various stages of palliation can be successfully bridged to transplant with VAD support. With use of intracorporeal continuous-flow devices, longer-term support and hospital discharge are possible.

Pediatric ventricular assist devices (VADs) are evolving as a standard therapy for end stage heart failure in children. Major recent developments include the increased use of continuous flow (CF) devices in children and increased experience with congenital heart disease (CHD) and outpatient management. In the current and future era anesthesiologists will encounter more children presenting for VAD implantation, subsequent procedures and heart transplantation. Successful perioperative management requires an understanding of the interaction between the patient's physiology and the device and a framework to troubleshoot problems. This review focuses on CF devices, VAD support for CHD and perioperative management of pulsatile and CF devices in the pediatric population., (© 2019 John Wiley & Sons Ltd.)

Concerns remain regarding the use of direct thrombin inhibitors for cardiopulmonary bypass anticoagulation in pediatric patients with heparin-induced thrombocytopenia undergoing complex cardiac surgery. We describe the safe and effective use of epoprostenol sodium as an alternative therapy before heparin exposure for a pediatric patient with subacute heparin-induced thrombocytopenia and a ventricular assist device undergoing heart transplant.

Left ventricular outflow tract velocity time integral (LVOT-VTI), a Doppler-derived measure of stroke distance, is used as a surrogate marker of cardiac function in adults. LVOT-VTI is easily obtained, independent of ventricular geometry and wall motion abnormalities. We investigated the relationship between LVOT-VTI and conventional measures of function in young patients by comparing controls to children with dilated cardiomyopathy (DCM). Sixty-two healthy and 52 DCM patients over 1 year were studied retrospectively. The average pulsed (PW) and continuous wave (CW) LVOT-VTIs from apical views were measured from three cycles. Body surface area (BSA) and Ejection fraction (EF) were obtained. We compared LVOT-VTIs between study and control groups and assessed BSA's impact on LVOT-VTI. The entire cohort was classified into three levels of LV function which were compared. We determined LVOT-VTI cutoff values that indicated an EF <50%. The mean PW-LVOT-VTI in the DCM group was significantly lower than that of the normal group (0.15 vs. 0.18 m; p < 0.0012). The mean CW-LVOT-VTI was significantly lower in DCM (0.20 vs. 0.24 m; p < 0.0001). There was no impact of BSA on LVOT-VTI except when comparing BSA and CW-LVOT-VTI in the normal group. There was a positive relationship between LVOT-VTI and EF for PW (Rs = 0.29, p = 0.0022) and CW (Rs = 0.22, p = 0.0364) and a difference in mean LVOT-VTI between EF groups (p < 0.0001). ROC analysis demonstrated that PW-LVOT-VTI <0.17 m (AUC = 0.73; p < 0.0001) and CW-LVOT-VTI <0.22 m (AUC = 0.76; p < 0.0001) was associated with EF <50%. This study indicates that LVOT-VTI can be a useful alternative measure of LV performance in children over 1 year.

Background: Combined heart and liver transplantation (CHLT) in the pediatric population involves a complex group of patients, many of whom have palliated congenital heart disease (CHD) involving single ventricle physiology., Objective: The purpose of this study was to describe the perioperative management of pediatric patients undergoing CHLT at a single institution and to identify management strategies that may be used to optimize perioperative care., Methods: We did a retrospective database review of all patients receiving CHLT at a children's hospital between 2006 and 2014. Information collected included preoperative characteristics, intraoperative management, blood transfusions, and postoperative morbidity and mortality., Results: Five pediatric CHLTs were performed over an 8-year period. All patients had a history of complex CHD with multiple sternotomies, three of whom had failing Fontan physiology. Patient age ranged from 7 to 23 years and weight from 29.5 to 68.5 kg. All CHLTs were performed using an en-bloc technique where both the donor heart and liver were implanted together on cardiopulmonary bypass (CPB). The median operating room time was 14.25 h, median CPB time was 3.58 h, and median donor ischemia time was 4.13 h. Patients separated from CPB on dopamine, epinephrine, and milrinone infusions and two required inhaled nitric oxide. All patients received a massive intraoperative blood transfusion post CPB with amounts ranging from one to three times the patient's estimated blood volume. The patient who required the most transfusions was in decompensated heart and liver failure preoperatively. Four of the five patients received an antifibrinolytic agent as well as a procoagulant (prothrombin complex concentrate or recombinant activated Factor VII) to assist with hemostasis. There were no 30-day thromboembolic events detected. Postoperatively the median length of mechanical ventilation, ICU stay and stay to hospital discharge was 4, 8, and 37 days, respectively. All patients are alive and free from allograft rejection at this time., Conclusion: Combined heart and liver transplantation in the pediatric population involves a complex group of patients with unique perioperative challenges. Successful management starts with thorough preoperative planning and communication and involves strategies to deal with massive intraoperative hemorrhage and coagulopathy in addition to protecting and supporting the transplanted heart and liver and meticulous surgical technique. An integrated multidisciplinary team approach is the cornerstone for successful outcomes., (© 2016 John Wiley & Sons Ltd.)

Background: Surgical reconstruction is the primary method of treating airway obstruction in children. Tracheal stenosis is frequently associated with congenital heart defects, which may further complicate the overall management strategy. The purpose of this study was to review our experience with surgical reconstruction of airway obstruction in conjunction with congenital heart defects., Methods: This was a retrospective review of our surgical experience with tracheal stenosis from February 2003 to August 2011. Twenty-seven patients were identified in our database. Six patients had isolated, congenital tracheal stenosis, and 21 had tracheal stenosis in association with congenital heart defects. There were two identifiable subgroups. Thirteen patients had airway stenoses identified concurrently with congenital heart defects and underwent combined repair. The second group comprised 8 patients who had previous correction of their congenital heart defects and experienced delayed presentation of tracheal (n = 6) or bronchial (n = 2) obstruction., Results: The median age at surgery was 9 months. There were 2 postoperative deaths, both in children with single ventricle. The median duration of follow-up for the entire cohort of 25 surviving patients was 4 years. None of the patients have required reoperations on the trachea; 5 have had minor reinterventions., Conclusions: The data demonstrate that tracheal obstruction is frequently found in conjunction with congenital heart defects. Nearly one third of our patients had delayed presentation of airway obstruction that was identified subsequent to previous congenital heart defect repair. Tracheal reconstructive techniques were effective regardless of the cause of the airway obstruction., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

An increasing number of pediatric patients with permanent pacemakers and implantable cardioverter defibrillators (ICDs) require cardiac and noncardiac surgery. It is critical that the anesthesiologist caring for these patients understands the management of the device and the underlying heart disease. Children with these devices are more vulnerable to lead failure and inappropriate shocks compared with the adult population. Preoperative assessment and appropriate reprogramming of the device, in addition to minimizing sources of electromagnetic interference, are keystones in the perioperative care of these patients. Prior consultation with qualified programmers is recommended to enable timely optimization of the device. Magnets may be used in emergency situations but it is important to appreciate the limitations of magnet use on different models of pacemakers and ICDs. Safe and successful perioperative care is dependent upon a well-organized and coordinated multidisciplinary team approach., (© 2011 Blackwell Publishing Ltd.)

Objectives: Low cardiac output state is the principal cause of morbidity after surgical intervention for congenital heart disease. Myocardial ischemia-reperfusion injury, apoptosis, capillary leak syndrome, and myocardial edema are associated factors. We established a clinically relevant model to examine relationships between myocardial ischemia, edema, and cardiac dysfunction and to assess the role of the water transport proteins aquaporins., Methods: Sixteen lambs were studied. Seven were control animals not undergoing cardiopulmonary bypass, and 9 underwent bypass. Six had 90 minutes of aortic crossclamping with blood cardioplegia and moderate hypothermia. The remaining 3 underwent cardiopulmonary bypass without aortic crossclamping. Hemodynamic and biochemical data were recorded, and myocardial edema, apoptotic markers, and aquaporin expression were determined after death., Results: The group undergoing cardiopulmonary bypass with aortic crossclamping had a low cardiac output state, with early postoperative tachycardia, hypotension, increased serum lactate levels, and impaired tissue oxygen delivery (P < .05) compared with the group undergoing cardiopulmonary bypass without aortic crossclamping. The lambs undergoing cardiopulmonary bypass with aortic crossclamping had increased myocardial water (P < .05) compared with those not undergoing cardiopulmonary bypass and a 2-fold increase in aquaporin 1 mRNA expression (P < .05) compared with those not undergoing cardiopulmonary bypass and those undergoing cardiopulmonary bypass without aortic crossclamping., Conclusions: A temporal association between hemodynamic dysfunction, myocardial edema, and increased aquaporin 1 expression was demonstrated. Cardiopulmonary bypass without ischemia was associated with minimal edema, negligible myocardial dysfunction, and static aquaporin expression. Ischemic reperfusion injury is the main cause of myocardial edema and myocardial dysfunction, but a causal relationship between edema and dysfunction remains to be proved.

Cytotoxic T-lymphocytes (CTLs) are critical for the defense against herpesvirus infections, in which cell-to-cell spread occurs earlier than the hematogenous spread. The ability of bovine herpesvirus-1 (BHV-1) to undergo latency, to induce apoptosis of CD4(+) T-lymphocytes, and to down-regulate the expression of major histocompatibility complex (MHC) class I molecules, necessitates the development of immunization strategies that do not involve the live virus. The objective of this study was to evaluate the feasibility of DNA immunization as a means of induction of CTLs against BHV-1. Mice were injected either by intramuscular (IM) or intradermal (ID) route with a Sindbis virus-based plasmid carrying the gene encoding the glycoprotein D (gD) of BHV-1. Splenocytes from the immunized mice were re-stimulated in vitro with gD-transduced syngeneic fibroblasts. The CTLs generated specifically lysed syngeneic targets, either transduced with gD or infected with BHV-1. IM route of inoculation induced a better CTL response when compared to ID route with respect to onset, magnitude and duration of immunity. These results indicate the feasibility of using a plasmid carrying the gene encoding BHV-1 gD as an immunogen to induce CTLs against BHV-1.

Epitope-based vaccines offer a promising alternative to modified live vaccines against viruses such as herpesviruses which give rise to latent infections, and induce immunosuppression. The success of this approach depends on the ability to direct the CTL epitopes to the MHC class I antigen presentation pathway. The objective of this study was to evaluate the potential of the heat shock protein gp96 in this regard. A group of BALB/c mice was injected with three murine CTL epitope peptides of bovine herpesvirus 1 (BHV-1) complexed in vitro with bovine gp96 (gp96-peptides). Three other groups were injected with either the peptides alone, gp96 alone, or the peptides complexed with BSA. CTLs from mice immunized with gp96-peptides specifically lysed the peptide-pulsed syngeneic targets, as well as BHV-1-infected targets. CTLs from the other three groups did not lyse these targets. To further evaluate the utility of this approach, groups of BALB/c mice were immunized with gp96 isolated from a syngeneic cell-line transduced with BHV-1 glycoprotein D (BC-gD). Mice immunized with gp96 from BC-gD developed CTLs, as well as Abs specific for BHV-1 gD. Furthermore, in vitro stimulation of naive bovine PBMCs with gp96 from BC-gD resulted in CTLs specific for BHV-1. These results demonstrate the feasibility of using gp96-peptide complexes isolated from cells expressing BHV-1 proteins to induce CTL and Ab responses against BHV-1, without the prior knowledge of the CTL and Ab epitope sequences.