Sinus Arrest Related to Dexmedetomidine Infusion in an Infant; a Case Report and Review of Current Literature.

Background: Dexmedetomidine, an alpha 2 agonist, has emerged as a desirable sedative agent in the pediatric intensive care unit due to its minimal effect on respiratory status and reduction in delirium. Bradycardia and hypotension are common side effects, however there are emerging reports of more serious cardiovascular events, including sinus arrest and asystole. These case reports have been attributed to high vagal tone or underlying cardiac conduction dysfunction. Objectives: To describe the development of sinus arrest during sedation with dexmedetomidine in a patient without clinical features of high vagal tone, underlying cardiac conduction dysfunction, or intervening episodes of bradycardia. Case Presentation: An 11 month-old patient requiring sedation during mechanical ventilation for acute respiratory failure secondary to Adenovirus. To facilitate sedation, a dexmedetomidine infusion was initiated at .5 mcg/kg/hr and increased to maximum 1 mcg/kg/hr. Within 8 hours of initiating therapy, the patient had three episodes of sinus arrest. There was no intervening bradycardia between episodes and no further episodes occurred following discontinuation of dexmedetomidine. The patient did not have any clinical features associated with high vagal tone or underlying cardiac conduction dysfunction. Conclusions: As result of these findings, understanding risk factors for bradycardia, or more serious hemodynamic instability with dexmedetomidine infusions, is important to help identify high risk patients and weigh the associated risks and benefits of its administration.

Sotalol versus amiodarone for postoperative junctional tachycardia after congenital heart surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) is a common arrhythmia after congenital heart disease surgery. There is variability in the choice of antiarrhythmic therapy, with amiodarone used commonly. Intravenous (IV) sotalol is a newly available agent that may be useful for JET. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of IV sotalol for postoperative JET and compare outcomes with IV amiodarone. METHODS: This is a retrospective single-center study of all patients who received IV sotalol or IV amiodarone for postoperative JET at Texas Children's Hospital from December 15, 2015, to December 15, 2020. Data included antiarrhythmic efficacy, hemodynamics, and adverse effects. Successful JET control was defined as a decrease in JET rate to <170 beats/min (or decrease by >20%), or conversion to sinus rhythm, with persistent control over 24 hours without requiring alternative antiarrhythmics or mechanical support. RESULTS: A total of 32 patients (median age 71 days; interquartile range 17-221 days) received IV amiodarone (n = 20 [62%]) or IV sotalol (n = 12 [38%]) for postoperative JET. Amiodarone was successful in treating JET in 75% of cases; sotalol was successful in 83%. The JET rate decreased faster over the first 90 minutes after a sotalol bolus (25 beats/min per hour) than after an amiodarone bolus (8 beats/min per hour) (P < .01); no heart rate difference was seen after 24 hours. Amiodarone infusion was discontinued early because of hypotension/bradycardia in 2 patients; this was not required in any patients receiving sotalol. CONCLUSION: For children with postoperative JET, both IV sotalol and amiodarone are safe and efficacious. IV sotalol may lead to a faster improvement in heart rate.

ATP1A3-Encoded Sodium-Potassium ATPase Subunit Alpha 3 D801N Variant Is Associated With Shortened QT Interval and Predisposition to Ventricular Fibrillation Preceded by Bradycardia.

Background Pathogenic variation in the ATP1A3-encoded sodium-potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown. The objective was to determine the role of ATP1A3 genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements. Methods and Results We analyzed 12-lead ECG recordings from 62 patients (male subjects=31, female subjects=31) referred for AHC evaluation. Patients were grouped according to AHC presentation (typical versus atypical), ATP1A3 variant status (positive versus negative), and ATP1A3 variant (D801N versus other variants). Manual remeasurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. QTc measurements were significantly shorter in patients with positive ATP1A3 variant status (P<0.001) than in patients with genotype-negative status, and significantly shorter in patients with the ATP1A3-D801N variant than patients with other variants (P<0.001). The mean QTc for ATP1A3-D801N was 344.9 milliseconds, which varied little with age, and remained <370 milliseconds throughout adulthood. ATP1A3 genotype status was significantly associated with shortened QTc by multivariant regression analysis. Two patients with the ATP1A3-D801N variant experienced ventricular fibrillation, resulting in death in 1 patient. Rare variants in ATP1A3 were identified in a large cohort of genotype-negative patients referred for arrhythmia and sudden unexplained death. Conclusions Patients with AHC who carry the ATP1A3-D801N variant have significantly shorter QTc intervals and an increased likelihood of experiencing bradycardia associated with life-threatening arrhythmias. ATP1A3 variants may represent an independent cause of sudden unexplained death. Patients with AHC should be evaluated to identify risk of sudden death.

Application of simultaneous selective pressures slows adaptation.

Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. We evolved a strain of Saccharomyces cerevisiae that could not produce its own histidine or uracil for ~500 generations under one or three selective pressures: limitation of the concentration of glucose, histidine, and/or uracil in the media. The rate of adaptation was obtained by measuring evolved relative fitness using competition assays. Populations evolved under a single selective pressure showed a statistically significant increase in fitness on those pressures relative to the ancestral strain, but the populations evolved on all three pressures did not show a statistically significant increase in fitness over the ancestral strain on any single pressure. Simultaneously limiting three essential nutrients for a population of S. cerevisiae effectively slows the rate of evolution on any one of the three selective pressures applied, relative to the single selective pressure cases. We identify possible mechanisms for fitness changes seen between populations evolved on one or three limiting nutrient pressures by high-throughput sequencing. Adding multiple selective pressures to evolving disease like cancer and infectious diseases could reduce the rate of adaptation and thereby may slow disease progression, prolong drug efficacy and prevent deaths.

Association of Extracorporeal Membrane Oxygenation Support Adequacy and Residual Lesions With Outcomes in Neonates Supported After Cardiac Surgery.

OBJECTIVES: There is a paucity of data regarding the impact of extracorporeal membrane oxygenation support, adequacy of surgical repair, and timing of intervention for residual structural lesions in neonates cannulated to extracorporeal membrane oxygenation after cardiac surgery. Our goal was to determine how these factors were associated with survival. DESIGN: Retrospective study. SETTING: Cardiovascular ICU. SUBJECTS: Neonates (≤ 28 d old) with congenital heart disease cannulated to extracorporeal membrane oxygenation after cardiac surgery during 2006-2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-four neonates were cannulated to venoarterial extracorporeal membrane oxygenation after cardiac surgery. Survival to discharge was 50%. There was no difference in survival based on surgical complexity and those with single or biventricular congenital heart disease. Prematurity (≤ 36 wk gestation; odds ratio, 2.33; p = 0.01), preextracorporeal membrane oxygenation pH less than or equal to 7.17 (odds ratio, 2.01; p = 0.04), need for inotrope support during extracorporeal membrane oxygenation (odds ratio, 3.99; p = 0.03), and extracorporeal membrane oxygenation duration greater than 168 hours (odds ratio, 2.04; p = 0.04) were all associated with increased mortality. Although preextracorporeal membrane oxygenation lactate was not significantly different between survivors and nonsurvivors, unresolved lactic acidosis greater than or equal to 72 hours after cannulation (odds ratio, 2.77; p = 0.002) was associated with increased mortality. Finally, many patients (n = 70; 83%) were noted to have residual lesions after cardiac surgery, and time to diagnosis or correction of residual lesions was significantly shorter in survivors (1 vs 2 d; p = 0.02). CONCLUSIONS: Our data suggest that clearance of lactate is an important therapeutic target for patients cannulated to extracorporeal membrane oxygenation. In addition, timely identification of residual lesions and expedient interventions on those lesions may improve survival.

Updated guidelines for lipid screening in children and adolescents.

Elevated serum lipoproteins in childhood and adolescence are associated with health consequences and poor outcomes in adulthood. Universal screening, recommended in recent guidelines from the National Heart, Blood, and Lung Institute and supported by the American Academy of Pediatrics, may help identify a significant number of children who would be missed by targeted screening.

Burn-induced cardiac dysfunction increases length of stay in pediatric burn patients.

The aim of this study was to evaluate cardiac function and clinical outcomes in perioperative pediatric burn patients. Transesophageal echocardiography data were collected on 40 patients from 2004 to 2007. Of the 40 patients who received exams, a complete set of cardiac parameters and outcome variables was obtained in 26 patients. The mean age of the patients was 9.7 ± 0.9 years, and the mean TBSA burn size was 64 ± 3%. Patients were divided into two groups based on systolic function. One group represented patients with ejection fractions of >50% and the other ≤50%. Clinical variables were then compared among the groups. In our cohort, systolic dysfunction was observed in 62% of patients (EF ≤ 50%). Systolic dysfunction was associated with a statistically significant increase in number of surgeries, ventilator days, and length of stay in the intensive care unit. The length of stay in patients with preserved systolic function and those with systolic dysfunction was 34.3 ± 3.3 days and 67.2 ± 4.0 days, respectively. Diastolic function measurements were obtained in 65%, and 88% had evidence of diastolic dysfunction. Diastolic dysfunction was not associated with any statistically significant correlations. This study lends evidence to the well-supported basic science models showing cardiac dysfunction after burns. Additionally, it shows that cardiac dysfunction can have clinical consequences. To our knowledge, this is the first study that shows the clinical sequelae of systolic dysfunction in the perioperative pediatric burn population.