Background: Fontan-associated liver disease (FALD) is a universal complication of the Fontan palliation characterized by chronic congestion and progressive hepatic fibrosis. Current diagnostics rely on invasive biopsies or non-specific biomarkers that fail to capture early fibrogenesis, creating a need for non-invasive biomarkers to stratify disease severity. Methods: We utilized an ovine Fontan model (n = 19) to investigate circulating serum extracellular vesicles (sEVs) as reporters of hepatic pathology. Longitudinal samples paired with liver elastography were collected, and sEVs were subjected to multi-omic profiling including small RNA sequencing and proteomics. Regularized regression was used to identify transcriptomic predictors, which were integrated with time post-surgery into an ordinal logistic regression framework to construct the Fontan EV Score (FES). Model performance was evaluated on a held-out test cohort and benchmarked against established fibrosis indices. To validate the biological relevance of the FES , TGF-β-treated human liver organoids were generated and scored miRNA expression was assessed. Results: The sEV proteome exhibited robust separation by surgical physiology, while the small RNA cargo was primarily stratified by fibrotic status. Bioinformatics confirmed a high hepatic origin for these transcripts and identified enrichment of inflammatory pathways including Toll-like receptor and Interleukin-17 cascades in fibrotic subjects. The FES, incorporating time post-surgery and eleven small RNA biomarkers, demonstrated high predictive accuracy in the independent testing cohort with an AUC of 0.876 for moderate and 0.963 for severe fibrosis, substantially outperforming APRI (AUC = 0.618) and FIB-4 (AUC = 0.731). In human liver organoids, several scoring miRNAs, including miR-125a-5p and miR-193b-5p, were directionally responsive to profibrotic stimulation. Conclusions: Circulating sEVs carry a liver-associated cargo that can be leveraged for the non-invasive prediction of FALD severity. The FES provides a biologically validated scoring system that substantially outperforms existing serological indices and offers a new avenue for early detection and risk stratification of FALD.

Malignant hyperthermia (MH) is an inherited disorder of muscle physiology, triggered by various pharmacologic agents including succinylcholine or the volatile anesthetic agents. In susceptible patients, intraoperative care may be provided by total intravenous anesthesia (TIVA) with propofol or other sedative-hypnotic agents. Remimazolam is a novel benzodiazepine which possesses sedative, anxiolytic, and amnestic properties similar to those of midazolam. Metabolism by tissue esterases results in a half-life of 5 - 10 min, a limited context sensitive half-life, which may make it a suitable agent for continuous administration during TIVA. We present anecdotal experience with the use of remimazolam as an adjunct to general anesthesia during the intraoperative care of a 6-month-old patient undergoing surgery for congenital heart disease with cardiopulmonary bypass. Previous reports regarding the use of remimazolam in MH-susceptible patients are reviewed, and its role in this clinical scenario is discussed.

Pain following thoracotomy is one of the most severe forms of postoperative pain. Post-thoracotomy pain may increase the risk of post-surgical pulmonary complications, postoperative mortality, prolong hospitalization, and increase utilization of healthcare resources. To mitigate these effects, anesthesia providers commonly employ continuous epidural infusions, paravertebral blocks, and systemic opioids for pain management and improvement of pulmonary mechanics. We report the use of a continuous erector spinae plane block (ESPB) via a peripheral nerve catheter for postoperative pain management of an 18-year-old patient who underwent complex aortic coarctation repair via lateral thoracotomy, aided by cardiopulmonary bypass. Continuous ESPB proved to be an acceptable alternative for postoperative pain control, producing a substantial multi-dermatomal sensory block, resulting in adequate pain control, reduced opioid consumption, and a potentially shorter hospital stay.

Background:Remimazolam is a benzodiazepine which, like midazolam, has sedative, anxiolytic, and amnestic properties. Ester metabolism results in a half-life of 5 - 10 min, a limited context sensitive half-life, and rapid recovery when the infusion is discontinued. Methods:Following the Institutional Review Board (IRB) approval, we performed a retrospective chart review of patients who received remimazolam in the cardiac catheterization, cardiac magnetic resonance imaging (MRI), and electrophysiology suites. The primary objective was to assess efficacy and safety. The secondary objective was to describe bolus and infusion dosing of remimazolam and the need for adjunctive agents to optimize procedural sedation conditions. Results:The study cohort included 26 patients with a median age of 18 years and a total of 33 anesthetic encounters. The most common procedures were endomyocardial biopsy or isolated hemodynamic assessment (right or left heart catheterization). Remimazolam was the primary agent for sedation in 82% of the procedures. The majority of cases (25 encounters, 76%) included a bolus dose of remimazolam prior to the start of an infusion. For those patients who received a starting bolus dose, dosing typically ranged between 30 and 110 µg/kg. Continuous infusion rates of remimazolam varied from 5 to 20 µg/kg/min. No adverse hemodynamic or respiratory effects were noted. Midazolam, fentanyl, and dexmedetomidine were the most frequently used adjunctive agents. One patient required transition to general anesthesia due to the need for a surgical intervention based on the findings of the cardiac catheterization. All other patients were effectively sedated. Conclusions:Our preliminary experience demonstrates that remimazolam effectively provided sedation for diagnostic and therapeutic cardiovascular procedures. Future studies are needed to further define dosing parameters for both bolus dosing and continuous infusion as well as to compare remimazolam to other commonly used for procedural sedation in patients with congenital and acquired heart disease.

Introduction: Children born with single ventricle heart disease must undergo Fontan palliation. The lack of chronic preclinical animal models has limited the study of the significant end-organ complications that reduce the quality and duration of life. Here, we explore surgical strategies to improve animal survival in a chronic model of Fontan palliation. Methods: Sheep were divided based on the surgical approach: single stage Fontan (SS) versus staged Fontan. Controls were age/sex matched to the surgical cohort. The SS surgery consists of the Glenn, direct anastomosis of the SVC to the main pulmonary artery (MPA), and the Fontan, IVC connection to the MPA using a Gore-Tex conduit. Stage palliation consists of two stages. During stage 1 (S1), the IVC is connected to the MPA. A year later, stage 2 (S2) Glenn surgery is completed. Early post-op hemodynamics were monitored for 2 weeks through daily blood gases, an implanted telemetry device, and chest tube output. Results: SS had 5/6 sheep survive. S1 had 8/9 sheep survive (7/9 sheep continued to S2). S2 had 3/7 sheep survive. The trend in heart rate was not significantly different across the groups. However, we note a trend of an increase in heart rate in all groups on post-operation day (POD) 3 (144.90±20.72 BPM), which normalized POD10 (118.63±23.84 BPM) (p=0.006). Similarly, lactate peaked on POD0 (3.37±2.53mmol/L) and normalized POD2 (0.59±0.20 mmol/L) (p=0.0003) with no significant difference across groups. Creatine increased (SS) 1.7-fold (p=0.016) and (S2) 1.4-fold (p=0.032) from PO to POD1 and normalized by POD14. There was no significant elevation in creatine in S1. The chest tube output was not significantly (p=0.270) different across SS (4827.83±435.71 mL (11.6 days)), S1 (3305.33±1086.18 mL (10.5 days)), and S2 (4056±1890.26 mL (7 days)). Conclusions: We have demonstrated a similar clinical course for both surgical approaches of our ovine model with animals alive 1 to 3-year(s) post-operation. Future studies will follow the single stage approach given the improved animal survival and reduced surgical complexity. The ovine surgical model will allow the study of Fontan associated end-organ complications and be a testbed for potential curative solutions.

Objectives: Our goal was to conduct a hemodynamic analysis of a novel animal model of Fontan physiology. Poor late-term outcomes in Fontan patients are believed to arise from Fontan-induced hemodynamics, but the mechanisms remain poorly understood. Recent advances in surgical experimentation have resulted in the development of a chronic sheep model of Fontan physiology; however, detailed analysis of this model is lacking. Methods: We created a single-stage Fontan model in juvenile sheep with normal biventricular circulation. The superior vena cava was anastomosed to the main pulmonary artery, and the inferior vena cava was connected to the main pulmonary artery using an expanded polytetrafluoroethylene conduit. Longitudinal hemodynamics, including catheterization and magnetic resonance imaging were evaluated. Results: Four out of 12 animals survived, with the longest surviving animal living 3 years after single-stage Fontan. We showed a significant era effect regarding survival (1 out of 8 and subsequently 3 out of 4 animals surviving beyond 2 months) attributed in large part to the procedural learning curve. Key characteristics of Fontan hemodynamics, namely systemic venous hypertension and low normal cardiac output, were observed. However, recapitulation of passive human Fontan hemodynamics is affected by volume loading of the right ventricle given an anatomic difference in sheep azygous venous anatomy draining to the coronary sinus. Conclusions: A significant learning curve exists to ensure long-term survival and future surgical modifications, including banding of the main pulmonary artery and ligation of the azygous to coronary sinus connection are promising strategies to improve the fidelity of model hemodynamics. (JTCVS Open 2024;21:268-78)

Remimazolam is a novel benzodiazepine with sedative and amnestic properties similar to midazolam. Ester metabolism results in a half-life of 5 - 10 min and a limited context sensitive half-life. We present preliminary retrospective experience with its use as a primary agent for procedural sedation for brief invasive and noninvasive procedures. The study cohort included seven patients, ranging in age from 14 to 51 years. Remimazolam administration included bolus dosing in two patients and a combination of bolus dosing followed by an infusion in the other five patients. The initial bolus dose of remimazolam ranged from 2.5 to 5 mg. Starting doses for the infusion ranged from 10 to 30 µg/kg/min with titration of the continuous infusion during the procedure, ranging from 10 - 30 µg/kg/min. Median dose infusion requirements were 15 - 20 µg/kg/min. One procedure was completed with remimazolam as the sole anesthetic agent while the other six patients received adjunctive agents. Changes in blood pressure or oxygen saturation were noted which resolved with minimal interventions such as a decrease in remimazolam infusion rate or an increase in supplemental oxygen administration. Our anecdotal experience provides further support for the efficacy of remimazolam as an agent for procedural sedation.

General anesthesia or procedural sedation may be required to ensure immobility, facilitate completion of the procedure, and ensure patient comfort during diagnostic or therapeutic procedures in the cardiac cath-eterization suite. Although propofol and dexmedetomidine are two of the more commonly chosen agents, concerns regarding their impact on inotropic, chronotropic or dromotropic function may limit their appli-cability based on underlying patient comorbid conditions. We present three patients with comorbid conditions involving pacemaker (natu-ral or implanted) function or cardiac conduction which impacted the choice of agent for procedural sedation during procedures in the cardiac catheterization suite. Remimazolam, a novel ester-metabolized benzo-diazepine, was used as the primary agent for sedation in an effort to lim-it detrimental effects on chronotropic and dromotropic function which may be seen with propofol or dexmedetomidine. Remimazolam's po-tential utility in procedural sedation is discussed, previous reports of its use are reviewed, and dosing algorithms are presented.

Cardio-vocal or Ortner's syndrome is dysphonia or hoarseness resulting from left recurrent laryngeal nerve palsy caused by a mechanical effect on the nerve due to enlarged cardiovascular or mediastinal structures. It was first described in adults with left atrial enlargement due to mitral stenosis. To date, there are a paucity of reports regarding its occurrence in infants and children. We report hoarseness and left vocal cord paresis in an infant with a large left-to-right shunt associated with a patent ductus arteriosus. The history of Ortner's syndrome is presented, its pathogenesis described, and previous reports of its occurrence in infants and children reviewed.

Percutaneous-based patent ductus arteriosus closure is technically feasible among infants less than 1.5 kg. However, marked heterogeneity in the type and nature of adverse events obscures current safety profile assessments. Although data on the risks of postdevice closure syndrome remain promising, a lack of comparative trials of surgical ductal ligation and inconsistent surveillance across published studies obscure confidence in present estimates of safety and efficacy. To minimize risk and yield the greatest benefits, clinical studies of patent ductus arteriosus treatment should consider incorporating more robust assessments to ensure that infants at greatest risk for adverse ductal consequences are included.

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Various clinical scenarios may require the short or longterm administration of agents to provide anticoagulation. In the vast majority of scenarios and clinical situations, heparin remains the agent of choice. However, patient concerns or conditions such as heparin-induced thrombocytopenia (HIT) or religious concerns regarding the use of porcine-derived medications may require the use of alternative anticoagulants. We present the use of bivalirudin for anticoagulation during a cardiac catheterization procedure in a 9-year-old patient of the Islamic faith who requested no porcine-derived medications. Basic principles of bivalirudin are discussed, previous reports of its use during cardiac catheterization reviewed, and clinical guidelines for its use in this clinical scenario presented.

Foreign body ingestion is a common event among pediatric patients, especially in children less than 6 years of age. Although most cases are relatively benign, with the foreign body passing spontaneously or requiring a brief endoscopic procedure for removal, button battery ingestion is known to cause significant morbidity with the potential for mortality. Although aorto-esophageal fistula (AEF) is a rare complication following button battery ingestion, its clinical manifestations are significant and outcomes are poor. Early diagnosis and aggressive treatment are key in preventing fatal complications. We describe the successful management of an AEF which presented with hematemesis 8 days after removal of a button battery in a 17-month-old female. The literature regarding button battery ingestion and AEF is reviewed and treatment options including intraoperative anesthetic care discussed.

The opioid crisis in the United States has been pandemic. As such, anesthesia providers are frequently faced with patients who have a history of opioid abuse or are currently receiving chronic therapy for such disorders. The chronic administration of medications such as buprenorphine-naloxone can impact the choice of perioperative anesthesia and pain control. Furthermore, the postoperative administration of opioids may lead to relapse in patients with a history of opioid abuse. We present a 26-year-old male with a history of opioid abuse on maintenance therapy with buprenorphine-naloxone, who presented for median sternotomy, cardiopulmonary bypass, and pulmonary valve replacement. The perioperative implications of buprenorphine-naloxone and implementation of multimodal analgesia are discussed, along with options to decrease or eliminate the perioperative use of opioids.

Urgent or emergent surgical procedures may be required during pregnancy. During this time, the perioperative care extends to include not only the patient but also monitoring and preservation of the fetal well-being. Assurance of adequate placental blood flow, avoidance of teratogenic agents, and prevention of preterm labor add to the complexity of perioperative management. We present a 35-year-old woman who required anesthetic care at 12 weeks gestation for exchange of a battery in her automatic implantable cardiac defibrillator (AICD). The physiologic changes induced by pregnancy are presented, their anesthetic impact reviewed, and specific perioperative considerations of the pregnant patient discussed.

Background: Although preoperative anemia has been suggested to predict postsurgical morbidity and mortality among infants < 1 year of age, the data were drawn from heterogeneous patient cohorts including severely ill infants undergoing complex, high-risk procedures. We aimed to determine whether untreated preoperative anemia was associated with increased risk of postoperative complications in infants <1 year of age who underwent pyloromyotomy, a common and relatively simple surgery. Methods: Infants <1 year of age undergoing pyloromyotomy were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatric database. Preoperative anemia was defined as a hematocrit <= 40% for infants 0-30 days of age and <= 30% for infants more than 30 days of age. Patients who received pre- or postoperative blood transfusions were excluded. Results: We identified 2948 patients who met our inclusion criteria, of whom 843 were anemic (29%). The overall rate of complications in this cohort was 6%. The most common postoperative complications were readmission (97 cases), surgical site infection (43), reoperation (39), prolonged hospital stay (24), urinary tract infection (3), 30-day mortality (3) and cardiac arrest (2). We found no differences in the incidence of complications in anemic versus nonanemic patients on bivariate analysis or multivariable logistic regression (adjusted odds ratio = 12; 95% confidence interval: 0.8-1.7; P = 0.319). Conclusions: In relatively healthy infants undergoing pyloromyotomy, untreated preoperative anemia was not associated with postoperative compilations and should not be considered a significant risk factor. (C) 2019 Elsevier Inc. All rights reserved.

OBJECTIVE:Accurate assessment of risk factors such as congenital heart disease (CHD) can aid in risk stratification of children presenting for surgery. Risk stratification is especially important in tonsillectomy ± adenoidectomy (T/A), a common pediatric procedure that is usually performed electively, but that has a high rate of adverse events. In this study, we examined the association of CHD with revisits after T/A. METHODS:We identified children who underwent T/A at hospitals and hospital-owned facilities during 2010 to 2014 using the State Inpatient Databases and State Ambulatory Surgery and Services Databases of Florida, Georgia, Iowa, New York, and Utah. We evaluated the association between CHD severity and the occurrence of an unplanned hospital readmission or ED visit within 30 days following discharge using multivariable logistic regression. RESULTS:The analysis included 244,598 patients, of whom 858 had minor or major CHD. In multivariable analysis, CHD was not associated with an increased risk of 30-day revisits (minor OR = 1.1; 95% CI: 0.8, 1.5; P = .65; major OR = 1.2; 95% CI: 0.9, 1.6; P = .34). Other comorbidities, including chromosomal anomalies (OR = 1.4; 95% CI: 1.2, 1.6; P < .001), congenital airway anomalies (OR = 1.3; 95% CI: 1.03, 1.7; P = .03), and neuromuscular impairment (OR = 1.4; 95% CI: 1.2, 1.7; P < .001) predicted an increased likelihood of revisits. CONCLUSION:Neither minor nor major CHD was independently associated with an increased risk of 30-day revisits among children undergoing T/A. Other characteristics, particularly non-cardiac comorbidities, socioeconomic status, and geographic region may be of greater utility for predicting revisit risk following pediatric T/A. LEVEL OF EVIDENCE:2b.

Avoidance of red blood cell (RBC) transfusions in patients awaiting heart transplantation (HTx) has been suggested to minimize the risk of allosensitization. Although recent studies have suggested that an immature immune system in younger HTx recipients may reduce risks associated with RBC transfusion, the role of age in moderating the influence of transfusion on HTx outcomes remains unclear. We used available data from a national transplant registry to explore whether the association between pre-transplant transfusions and outcomes of pediatric HTx varies by patient age. De-identified data were obtained from the United Network for Organ Sharing registry, including first-time recipients of isolated HTx performed at age 0–17 years in 1995–2015. The primary exposure was receiving blood transfusions within 2 weeks prior to HTx. Patient survival after HTx was evaluated using multivariable Cox proportional hazards, where age at transplant was interacted with exposure to pre-transplant transfusion. Age-specific hazard ratios (HRs) of pre-transplant transfusion were plotted across ages at transplant. There were 4883 patients meeting inclusion criteria, of whom 1258 died during follow-up (mean follow-up duration 6 ± 5 years). Patients receiving pre-transplant transfusions were distinguished by younger age, higher prevalence of prior cardiac surgery, greater likelihood of being in the intensive care unit, and greater use of left ventricular assist device bridge to transplant. In multivariable analysis, pre-transplant transfusions were associated with increased mortality hazard among infants < 1 year of age (HR = 1.46; 95% CI 1.23, 1.74; p < 0.001). For each additional year of age, the excess hazard associated with pre-transplant transfusions decreased by 3% (interaction HR = 0.97; 95% CI 0.98, 0.99; p = 0.003). By age 8, the association between pre-transplant transfusions and post-transplant mortality was no longer statistically significant (HR = 1.15; 95% CI 0.99, 1.32; p = 0.060). Pre-transplant transfusions were associated with increased mortality hazard only among younger children (age < 8 years) undergoing HTx. These data support the current practices of transfusion avoidance prior to HTx, particularly in younger patients.

Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. NBS for the proximal UCDs involves the detection in NBS spots of low citrulline values, a finding which is often overlooked because it is considered to be inadequate. We retrospectively analyzed NBS blood spots from known UCD patients comparing the utility of the Region 4 Stork (R4S) interpretive tools to conventional cutoff based interpretation. This study shows the utility of R4S tools in detecting all UCDs, and provides evidence to support the nomination to add proximal UCDs to the recommended uniform screening panel.

Background: As management of congenital heart disease (CHD) improves, children with CHD increasingly present for noncardiac surgery. Prior studies report conflicting results on the association between CHD and adverse outcomes in noncardiac surgery. Studies reporting no such association predominantly analyze older children and adolescents. We evaluated whether the association between CHD and adverse surgical outcomes was attenuated by increased age. Methods: Patients aged 0-17 y, undergoing elective noncardiac surgery, were identified in the National Surgical Quality Improvement Program-Pediatric registry. CHD status was classified as none, minor, major, or severe. Multivariable logistic regression evaluated the association of CHD status with the occurrence of any postoperative complication for groups defined by quintiles of patient age (<1, 1-3, 4-8, 9-13, and 14-17 y). Specific complications included cardiac arrest, reintubation, infection, renal failure, neurological complication, thromboembolic complication, reoperation, 30-d unplanned revisit, 30-d prolonged hospital stay, and mortality. Results: The analysis included 131,164 children, of whom 6420 had minor CHD, 3825 had major CHD, and 963 had severe CHD. The overall rate of complications was 9%. In multivariable analysis, children <1 y old had greater risk of postoperative complications if they had minor (odds ratio [OR] = 1.97; 95% confidence interval [CI]: 1.70, 2.20; P < 0.001), major (OR = 2.58; 95% CI: 2.28, 2.91; P < 0.001), or severe CHD (OR = 4.37; 95% CI: 3.45, 5.54; P < 0.001). In older age groups, however, the presence of CHD was not independently associated with postoperative complications. Conclusions: In pediatric noncardiac surgery, an independent association of CHD with postoperative complications was only evident among children <1 y old. (C) 2018 Elsevier Inc. All rights reserved.