Methylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial.

BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes. RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001). CONCLUSIONS: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).

Nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass in infants: A pilot randomized controlled trial.

Our objective was to assess the effect of nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) in infants on platelet count, platelet function, clinical outcomes, and safety. A randomized, double-blinded, placebo-controlled clinical trial in infants less than a year of age undergoing cardiac surgery requiring CPB was undertaken. Nitric oxide at a dose of 20 ppm was added to the sweep gas in the treatment group. Blood was collected at baseline and prior to separation from CPB to measure platelet count and function as determined by responsiveness to specific agonists. Clinical outcomes were observed through hospital discharge. Methemoglobin levels were measured preoperatively, at the conclusion of CPB, and upon admission to the ICU. Forty patients consented and were randomized in the trial. Eighteen patients were randomized to the treatment group and 22 were included in the placebo group. The groups were similar in terms of age, weight, gender, and surgical complexity. No significant differences were found in measures of platelet count, platelet response to agonist, or clinical outcomes. Patients in the treatment group had higher methemoglobin levels after receiving nitric oxide, but no levels approached toxicity (maximum 2.4%). Nitric oxide added to the sweep gas of the oxygenator during CPB in infants did not have an appreciable effect on the preservation of platelet count, platelet responsiveness to agonist, or clinical outcomes. Methemoglobin levels were increased after receiving nitric oxide but were far below a toxic level of 15%.

COVID-19 pre-procedural testing strategy and early outcomes at a large tertiary care children's hospital.

PURPOSE: With the emergence of the coronavirus disease-2019 (COVID-19) pandemic, institutions were tasked with developing individualized pre-procedural testing strategies that allowed for re-initiation of elective procedures within national and state guidelines. This report describes the experience of a single US children's hospital (Children's Wisconsin, CW) in developing a universal pre-procedural COVID-19 testing protocol and reports early outcomes. METHODS: The CW pre-procedural COVID-19 response began with the creation of a multi-disciplinary taskforce that sought to develop a strategy for universal pre-procedural COVID-19 testing which (1) maximized patient safety, (2) prevented in-hospital viral transmission, (3) conserved resources, and (4) allowed for resumption of procedural care within institutional capacity. RESULTS: Of 11,209 general anesthetics performed at CW from March 16, 2020 to October 31, 2020, 11,150 patients (99.5%) underwent pre-procedural COVID-19 testing. Overall, 1.4% of pre-procedural patients tested positive for COVID-19. By June 2020, CW was operating at near-normal procedural volume and there were no documented cases of in-hospital viral transmission. Only 0.5% of procedures were performed under augmented COVID-19 precautions (negative pressure environment and highest-level personal protective equipment). CONCLUSION: CW successfully developed a multi-disciplinary pre-procedural COVID-19 testing protocol that enabled resumption of near-normal procedural volume within three months while limiting in-hospital viral transmission and resource use.

A novel escalation from veno-venous bypass to veno-venous ECMO during orthotopic liver transplantation. A case report.

We describe the challenging perioperative course of a 55-year-old patient with hepatic failure requiring liver transplantation (LT). Different modalities of the extracorporeal device were successfully used, ranging from veno-veno bypass to partial and full veno-veno extracorporeal membrane oxygenation (ECMO) in order to optimize preload, reduce bleeding from the collateral circulation, optimize acid base balance and/or improve oxygenation. The case highlights the potential use of the device as a rescue method in challenging cases. Furthermore this is the first documented case that extracorporeal CO2 removal (ECCO2R) is used to optimize the biochemistry profile intraoperatively during a LT. The patient was weaned off the device at the end of the case and has been discharged home.

Why do lung transplant patients discontinue triazole prophylaxis?

BACKGROUND: Lung transplant recipients are prone to invasive fungal infections prompting many transplant centers to use prolonged triazole antifungal prophylaxis. From a practical standpoint, it is unclear if lung transplant recipients are able to continue prolonged or lifelong prophylaxis without premature discontinuation from side effects, drug interactions, development of fungal disease, or medication cost. We examined the number of patients that are able to reach a prophylactic endpoint and understand the reasons for early termination. METHODS: We conducted a retrospective chart review of all lung and heart-lung transplant patients at Mayo Clinic Rochester from May 1, 2002 to December 31, 2017. Type, duration, and reason for discontinuation of triazole prophylaxis were examined. RESULTS: During the study period, 193 patients underwent lung or heart-lung transplantation. Itraconazole, voriconazole, and posaconazole were given to 180, 73, and 60 post-transplant patients, respectively. Providers switched itraconazole to another prophylactic antifungal medication for reasons other than prophylactic completion in 61.8% (126 out of 204) of exposure episodes; this was similar with voriconazole (68.8%, 53 out of 77, P = 0.41). Posaconazole was actively discontinued significantly less often (18.3%, 11 out of 60, P < 0.05). The most common reasons for discontinuing itraconazole were malabsorption (15.5% of exposure episodes) and concern for breakthrough fungal infection (10.2%). In comparison, the most common reason for voriconazole discontinuation was side effect or intolerance (54.5% of VR exposure episodes vs 9.8% of IT exposure episodes, P < 0.05). CONCLUSIONS: Itraconazole and posaconazole appeared to have fewer side effects prompting discontinuation than voriconazole, but itraconazole was discontinued more often because of malabsorption and clinical suspicion of fungal infections.

Perioperative anticoagulation practices for pediatric liver transplantation.

Despite continued advancements in perioperative care for pediatric liver transplant (LT), graft-threatening vascular occlusion events including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) remain a source of significant morbidity and mortality. Perioperative anticoagulation is commonly used for the prevention of HAT and PVT, but evidence-based guidelines are lacking. The goals of this survey were to determine the frequency of use of an anticoagulation protocol and to describe variation in anticoagulation practices among pediatric LT centers. The study consisted of an online survey distributed to members of SPLIT. The survey focused on institutional anticoagulation practices employed to reduce the incidence of graft and life-threatening vascular occlusion events. Responses were received from 31 of 39 SPLIT centers. All respondents report using anticoagulation after pediatric LT, and approximately 90% have institutional anticoagulation protocols. Subgroup analysis of high volume pediatric LT centers revealed similar variability in anticoagulation patterns. All participating SPLIT centers reported the use of post-transplant anticoagulation and nearly all use a protocol. However, there is marked variability in the type and dose of anticoagulation as well as the timing of initiation and duration of therapy across centers.

Central ECMO for circulatory failure following pediatric liver transplantation.

We describe the case of a 4-year-old male with a past medical history significant for nephrotic syndrome, short-bowel syndrome and fulminant hepatic failure status post (s/p) liver transplant (LT) who developed early post-transplant allograft dysfunction (hyperbilirubinemia, coagulopathy) and septic shock requiring central extracorporeal membrane oxygenation (ECMO). He remained on ECMO for 85 hours before he was decannulated without event and later underwent repeat LT. This case highlights the potential of central ECMO to provide the circulatory output necessary to reverse distributive shock physiology in patients with sepsis and hepatic dysfunction following LT. Furthermore, this is the first documented example of central ECMO as a bridge to recovery for repeat LT.

Droperidol transiently prolongs the QT interval in children undergoing single ventricle palliation.

Historically, droperidol was commonly used for postoperative sedation of critically ill children. A FDA black box warning regarding its arrhythmogenic potential greatly reduced its use. We hypothesized that administration of neuroleptic dose droperidol during volatile anesthesia would transiently prolong the corrected QT interval (QTc) in patients undergoing single ventricle palliation. As part of a prospective study in children undergoing stage 2 or 3 single ventricle palliation, we recorded electrocardiograms preoperatively, after induction of volatile anesthesia, immediately after completion of 30 min intravenous infusion of 75 mcg/kg droperidol, and shortly after arrival in the cardiac intensive care unit. Mean absolute QT intervals and heart rate data were analyzed in a blinded fashion and the longest QT interval was determined. QT intervals were corrected for heart rate (QTc) with the Bazett and Friderici formulae. Any perioperative arrhythmias were recorded. Complete data were available for 62 patients. Volatile anesthesia was associated with significant prolongation of the QTc interval. Administration of droperidol after cardiopulmonary bypass was associated with further significant QTc prolongation. All QTc changes were transient and the postoperative QTc, while still prolonged relative to baseline, was significantly shorter than the QTc immediately postdroperidol. No episodes of Torsades de Pointes (TdP) or ventricular arrhythmias were observed. The administration of a neuroleptic dose of droperidol during volatile anesthesia in patients undergoing single ventricle palliation was associated with a significant prolongation of QTc, which was transient and did not result in TdP or other ventricular arrhythmias in our study population.

Stereoselective formation of trisubstituted vinyl boronate esters by the acid-mediated elimination of α-hydroxyboronate esters.

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki-Miyaura coupling reaction to obtain alkenes of known geometry.

Near-infrared spectroscopy: exposing the dark (venous) side of the circulation.

The safety of anesthesia has improved greatly in the past three decades. Standard perioperative monitoring, including pulse oximetry, has practically eliminated unrecognized arterial hypoxia as a cause for perioperative injury. However, most anesthesia-related cardiac arrests in children are now cardiovascular in origin, and standard monitoring is unable to detect many circulatory abnormalities. Near-infrared spectroscopy provides noninvasive continuous access to the venous side of regional circulations that can approximate organ-specific and global measures to facilitate the detection of circulatory abnormalities and drive goal-directed interventions to reduce end-organ ischemic injury.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Comparison of Prothrombin Complex Concentrate with Activated Factor VII Use for Bleeding Following Cardiopulmonary Bypass in Children.

OBJECTIVE: This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children. DESIGN/METHODS: This is a retrospective chart review of a single institution comprising patients aged 0 to 18 years old with congenital heart disease. Patients must have received either PCC or rFVIIa after coming off CPB. Our primary efficacy endpoint is time in the operating room from off-CPB to pediatric intensive care unit admission. Our primary safety endpoint is thrombosis through 30 days. RESULTS: Our primary efficacy outcome was significantly shorter in the PCC group compared with the rFVIIa group (P < .0001). Similarly, secondary efficacy outcomes of packed red blood cell administration, chest tube output, and transfusion exposures all significantly favored PCC administration. However, CPB time was significantly longer, and body temperatures were significantly lower, in the rFVIIa group. Safety outcomes, including our primary safety outcome of thrombosis through 30 days, were similar between the two groups. CONCLUSION: This study questions whether PCC could be favored over rFVIIa for hemostasis in children with congenital heart disease following CPB surgery. In addition, this study has found no difference when comparing PCC and rFVIIa in terms of safety outcomes, particularly thrombosis events. There are several limitations to this study due to the retrospective nature of the design and the differences between the two study groups. Despite the limitations, this study suggests that relatively early administration of PCC could be favored over delayed administration of rFVIIa to control recalcitrant post-CPB bleeding in the operating room.

Fatal Infections Differentially Involve Allograft and Native Lungs in Single Lung Transplant Recipients.

CONTEXT.­: Respiratory infections complicate lung transplantation and increase the risk of allograft dysfunction. Allograft lungs may have different susceptibilities to infection than native lungs, potentially leading to different disease severity in lungs of single lung transplant recipients (SLTRs). OBJECTIVE.­: To study whether infections affect allograft and native lungs differently in SLTRs but similarly in double LTRs (DLTRs). DESIGN.­: Using an institutional database of LTRs, medical records were searched, chest computed tomography studies were systematically reviewed, and histopathologic features were recorded per lung lobe and graded semiquantitatively. A multilobar-histopathology score (MLHS) including histopathologic data from each lung and a bilateral ratio (MLHSratio) comparing histopathologies between both lungs were calculated in SLTRs and compared to DLTRs. RESULTS.­: Six SLTRs died of infection involving the lungs. All allografts showed multifocal histopathologic evidence of infection, but at least 1 lobe of the native lung was uninvolved. In all 5 DLTRs except 1, histopathologic evidence of infection was seen in all lung lobes. On computed tomography, multifocal ground-glass and/or nodular opacities were found in a bilateral distribution in all DLTRs but in only 2 of 6 SLTRs. In SLTRs, the MLHSAllograft was higher than MLHSNative (P = .02). The MLHSratio values of SLTR and DLTR were significantly different (P < .001). CONCLUSIONS.­: Allograft and native lungs appear to harbor different susceptibilities to infections. The results are important for the management of LTRs.

Nuclear Cell-Free DNA Predicts Adverse Events After Pediatric Cardiothoracic Surgery.

BACKGROUND: Preoperative risk stratification in cardiac surgery includes patient and procedure factors that are used in clinical decision-making. Despite these tools, unidentified factors contribute to variation in outcomes. Identification of latent physiologic risk factors may strengthen predictive models. Nuclear cell-free DNA (ncfDNA) increases with tissue injury and drops to baseline levels rapidly. The goal of this investigation is to measure and to observe ncfDNA kinetics in children undergoing heart operations with cardiopulmonary bypass (CPB), linking biomarkers, organ dysfunction, and outcomes. METHODS: This is a prospective observational study of 116 children <18 years and >3 kg undergoing operations with CPB. Plasma ncfDNA samples were collected and processed in a stepwise manner at predefined perioperative time points. The primary outcome measure was occurrence of postoperative cardiac arrest or extracorporeal membrane oxygenation. RESULTS: Data were available in 116 patients (median age, 0.9 years [range, 0-17.4 years]; median weight, 7.8 kg [range, 3.2-98 kg]). The primary outcome was met in 6 of 116 (5.2%). Risk of primary outcome was 2% with ncfDNA <20 ng/mL and 33% with ncfDNA >20 ng/mL (odds ratio, 25; CI, 3.96-158; P = .001). Elevated ncfDNA was associated with fewer hospital-free days (P < .01). CONCLUSIONS: This study analyzes ncfDNA kinetics in children undergoing operations with CPB for congenital heart disease. Elevated preoperative ncfDNA is strongly associated with postoperative arrest and extracorporeal membrane oxygenation. Further studies are needed to validate this technology as a tool to predict morbidity in children after cardiac surgical procedures.

Case report: giant cardiac malignancy in a nine-year-old female.

PURPOSE: To describe the management of a giant cardiac malignancy initially diagnosed as an anterior mediastinal mass. CLINICAL FEATURES: A nine-year-old female with right facial swelling and chronic cough was diagnosed with a large right mediastinal mass. Intermittent ventricular and supraventricular arrhythmias were noted on admission electrocardiograms. Empiric corticosteroid and radiation therapy did not reduce the size of the tumour, and initial tissue biopsies were non-diagnostic. Due to worsening tamponade physiology and persistent arrhythmias, the patient was scheduled for tumour debulking with potential resection. Prior to surgery, a multidisciplinary team was assembled to delineate team member responsibilities and treatment algorithms. The procedure was performed under general anesthesia with spontaneous ventilation preserved during endotracheal intubation and invasive line placement. The team was prepared to provide extracorporeal mechanical support if needed. The child required inotropic and vasoactive medications after transitioning to positive pressure ventilation, but her hemodynamics improved with sternotomy. The lesion was identified as a malignant cardiac clear-cell tumour that was unresectable. Her sternum was left open, as attempted closure led to the re-creation of tamponade physiology. She underwent delayed sternal closure days later. After months of chemotherapy that resulted in significant tumour involution, she underwent successful surgical resection. CONCLUSION: Giant primary cardiac tumours may present similarly to large anterior mediastinal masses. The care of patients with these lesions requires an understanding of the risks associated with mediastinal masses as well as those unique to cardiac tumours. A multidisciplinary approach is critical to providing safe and effective care throughout this process.

Common Presentations of Rare Drug Reactions and Atypical Presentations of Common Drug Reactions in the Intensive Care Unit.

Adverse drug events (ADRs) are a significant source of iatrogenic injury that may be challenging to diagnose and treat. Patient outcomes range from mild symptoms to death. Critically ill children are at unique risk for ADR development because of age-dependent pharmacokinetic differences and off-label prescribing.

Effects of Arterial Carbon Dioxide Tension on Cerebral and Somatic Regional Tissue Oxygenation and Blood Flow in Neonates After the Norwood Procedure With Deep Hypothermic Cardiopulmonary Bypass.

Neonates undergoing the Norwood procedure for hypoplastic left heart syndrome are at higher risk of impaired systemic oxygen delivery with resultant brain, kidney, and intestinal ischemic injury, shock, and death. Complex developmental, anatomic, and treatment-related influences on cerebral and renal-somatic circulations make individualized treatment strategies physiologically attractive. Monitoring cerebral and renal circulations with near infrared spectroscopy can help drive rational therapeutic interventions. The primary aim of this study was to describe the differential effects of carbon dioxide tension on cerebral and renal circulations in neonates after the Norwood procedure. Using a prospectively-maintained database of postoperative physiologic and hemodynamic parameters, we analyzed the relationship between postoperative arterial carbon dioxide tension and tissue oxygen saturation and arteriovenous saturation difference in cerebral and renal regions, applying univariate and multivariate multilevel mixed regression techniques. Results were available from 7,644 h of data in 178 patients. Increases in arterial carbon dioxide tension were associated with increased cerebral and decreased renal oxygen saturation. Differential changes in arteriovenous saturation difference explained these effects. The cerebral circulation showed more carbon dioxide sensitivity in the early postoperative period, while sensitivity in the renal circulation increased over time. Multivariate models supported the univariate findings and defined complex time-dependent interactions presented graphically. The cerebral and renal circulations may compete for blood flow with critical limitations of cardiac output. The cerebral and renal-somatic beds have different circulatory control mechanisms that can be manipulated to change the distribution of cardiac output by altering the arterial carbon dioxide tension. Monitoring cerebral and renal circulations with near infrared spectroscopy can provide rational physiologic targets for individualized treatment.