Congenital Cardiac Anesthesia Society
A Section of the the Society for Pediatric Anesthesia

{“questions”:{“sz7qf”:{“id”:”sz7qf”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Arturo Marrero MD, Georgetown Public Hospital Corporation, Georgetown, Guyana and\r\nDestiny F. Chau MD, Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR, USA \r\n\r\nUn beb\u00e9 de 4 meses se presenta para una reparaci\u00f3n quir\u00fargica completa de tetralog\u00eda de Fallot. El ecocardiograma transtor\u00e1cico preoperatorio demuestra una arteria coronaria descendente anterior izquierda que surge de la arteria coronaria derecha. Despu\u00e9s de la esternotom\u00eda media, el cirujano nota que una arteria coronaria cruza el tracto de salida del ventr\u00edculo derecho y planifica hacer un conducto del ventr\u00edculo derecho a la arteria pulmonar. \u00bfQu\u00e9 porcentaje de pacientes con tetralog\u00eda de Fallot tienen arterias coronarias que cruzan el tracto de salida del ventr\u00edculo derecho? \r\nA 4-month-old infant presents for complete surgical repair of Tetralogy of Fallot (TOF). The preoperative transthoracic echocardiogram demonstrated a left anterior descending coronary artery arising from the right coronary artery. After median sternotomy, the surgeon notes a coronary crossing the right ventricular outflow tract (RVOT) and plans for a right ventricle to pulmonary artery conduit. What percentage of patients with TOF have coronary arteries crossing the RVOT? “,”desc”:”Explicaci\u00f3n\/Explanation \r\n\r\nLa tetralog\u00eda de Fallot es el tipo m\u00e1s com\u00fan de cardiopat\u00eda cong\u00e9nita cian\u00f3tica y representa aproximadamente el 5 a 10% de todos los defectos card\u00edacos cong\u00e9nitos. Se describe como un grupo de cuatro anomal\u00edas caracter\u00edsticas: defecto del tabique ventricular o comunicaci\u00f3n interventricular (CIV), aorta superpuesta, obstrucci\u00f3n del tracto de salida del ventr\u00edculo derecho e hipertrofia del ventr\u00edculo derecho. \r\n\r\nLos objetivos quir\u00fargicos para la reparaci\u00f3n completa de la tetralog\u00eda de Fallot son el cierre de la CIV y la restauraci\u00f3n del flujo sangu\u00edneo pulmonar normal a trav\u00e9s del alivio de la obstrucci\u00f3n del tracto de salida del ventr\u00edculo derecho. La presencia de anomal\u00edas coronarias espec\u00edficas puede requerir modificaciones en la t\u00e9cnica quir\u00fargica. Para evitar el da\u00f1o iatrog\u00e9nico a las arterias coronarias, la delineaci\u00f3n preoperatoria precisa de la distribuci\u00f3n de las arterias coronarias es esencial, especialmente si se planea una ventriculotom\u00eda como parte de la operaci\u00f3n. \r\n\r\nLos pacientes con tetralog\u00eda de Fallot tienen una mayor incidencia de anomal\u00edas arteriales coronarias en comparaci\u00f3n con la poblaci\u00f3n general. Sin embargo, no todas las formas de anomal\u00eda de la arteria coronaria son quir\u00fargicamente importantes. Las de particular inter\u00e9s son aquellos vasos coronarios que cruzan el tracto de salida del ventr\u00edculo derecho, ya que puede ser necesaria una incisi\u00f3n a trav\u00e9s de esta \u00e1rea durante la reparaci\u00f3n quir\u00fargica. Esto tambi\u00e9n incluye variantes normales que cruzan el tracto de salida del ventr\u00edculo derecho, como una gran rama de la arteria conal. La presencia de arterias coronarias que cruzan el tracto de salida del ventr\u00edculo derecho proh\u00edbe el aumento con parche transanular. \r\n\r\nUn metan\u00e1lisis reciente de anomal\u00edas de las arterias coronarias en tetralog\u00eda de Fallot realizado por Koppel et al encontr\u00f3 que entre 6956 pacientes con tetralog\u00eda de Fallot en 28 estudios, el 6 % de los pacientes tienen arterias coronarias an\u00f3malas. De aquellos con arterias coronarias an\u00f3malas, el 72 % cruzaron el tracto de salida del ventr\u00edculo derecho ( 4 % de todos los pacientes con tetralog\u00eda de Fallot) y el resto sigui\u00f3 con mayor frecuencia un curso retroa\u00f3rtico. La arteria m\u00e1s com\u00fan que cruzaba el tracto de salida del ventr\u00edculo derecho es la arteria coronaria descendente anterior izquierda que surge de la arteria coronaria derecha o seno de Valsalva derecho. Adem\u00e1s, se encontr\u00f3 que el 6 % de los pacientes ten\u00eda una arteria conal grande que tambi\u00e9n cruza esta \u00e1rea. Por lo tanto, con una frecuencia combinada del 10%, es probable que uno de cada diez pacientes con tetralog\u00eda de Fallot tenga una arteria coronaria que cruce el tracto de salida del ventr\u00edculo derecho. \r\n\r\nDurante la separaci\u00f3n del bypass cardiopulmonar, la manifestaci\u00f3n de baja funci\u00f3n card\u00edaca y signos continuos de isquemia mioc\u00e1rdica son fuerte indicativos de la transecci\u00f3n de una arteria coronaria durante la reparaci\u00f3n de tetralog\u00eda de Fallot en la que se realiz\u00f3 una ventriculotom\u00eda derecha. En esta situaci\u00f3n, se necesita un bypass de arteria coronaria emergente para restaurar la circulaci\u00f3n coronaria. \r\n\r\n————————————————–\r\n\r\nTetralogy of Fallot is the most common type of cyanotic congenital heart disease, representing approximately 5-10% of all congenital heart defects. It consists of four characteristic abnormalities: ventricular septal defect (VSD), overriding aorta, right ventricular outflow tract obstruction (RVOTO) and right ventricular hypertrophy. \r\n\r\nThe surgical goals of complete repair of TOF are VSD closure, relief of RVOTO, and restoration of normal pulmonary blood flow. The presence of specific coronary abnormalities may require modifications to the surgical technique. To avoid coronary artery injury, accurate delineation of coronary artery distribution is essential, especially if a ventriculotomy is planned as a part of the repair. \r\n\r\nPatients with TOF have a higher incidence of coronary artery anomalies compared to the general population. Those of particular surgical importance are coronary arteries crossing the RVOT, as an incision across the RVOT may be required during the surgical repair. This includes normal variants crossing the RVOT such as a large conal branch. A coronary vessel crossing the RVOT precludes transannular patch augmentation. \r\n\r\nA recent meta-analysis of coronary artery anomalies in TOF by Koppel et al demonstrated that amongst 6956 patients with TOF across 28 studies, 6% of patients have anomalous coronary arteries. Of those with anomalous coronary arteries, 72% crossed the RVOT (4% overall in TOF) and the remaining most commonly followed a retro-aortic course. The most common artery crossing the RVOT was the left anterior descending artery (LAD) originating from the right coronary artery (RCA) or right sinus of Valsalva. Additionally, 6% of patients were found to have a large conal branch crossing the RVOT. Therefore, with a combined frequency of 10%, one in ten patients with TOF is likely to have a coronary artery crossing the RVOT. \r\n\r\nDuring separation from cardiopulmonary bypass, evidence of poor cardiac function and ongoing signs of myocardial ischemia are strongly indicative of coronary artery injury during repair in which a right ventriculotomy was performed. In this situation, an emergent coronary artery bypass is needed to restore the coronary circulation. \r\n\r\n\r\nReferencias\/References \r\nMiller JR, Stephens EH, Goldstone AB et al. The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: Management of infants and neonates with tetralogy of Fallot. J Thorac Cardiovasc Surg <\/em>. 2023; 165:221-50. doi.org\/10.1016\/j.jtcvs.2022.07.025 \r\n\r\n\r\nWise-Faberowski L, Asija R, McElhinney DB. Tetralogy of Fallot: Everything you wanted to know but were afraid to ask. Paediatr Anaesth<\/em>. 2019;29(5):475-482. doi:10.1111\/pan.13569 \r\n\r\nKoppel CJ, Jongbloed MRM, Ki\u00e8s P, et al. Coronary anomalies in tetralogy of Fallot – A meta-analysis. Int J Cardiol<\/em>. 2020;306:78-85. doi:10.1016\/j.ijcard.2020.02.037\r\n\r\nTalwar S, Sengupta S, Marathe S, Vaideeswar P, Airan B, Choudhary SK. Tetralogy of Fallot with coronary crossing the right ventricular outflow tract: A tale of a bridge and the artery [published correction appears in Ann Pediatr Cardiol. 2021 Oct-Dec;14(4):571]. Ann Pediatr Cardiol<\/em>. 2021;14(1):53-62. doi:10.4103\/apc.APC_165_19 \r\n\r\nJonas A. Tetralogy of Fallot with pulmonary stenosis. In: Jonas A, ed. Comprehensive Surgical Management of Congenital Heart Disease<\/em>. 2nd Edition. Boca Raton, Florida: Taylor & Francis Group, LLC; 2014: 351-361.\r\n\r\n\r\n”,”hint”:””,”answers”:{“tnceh”:{“id”:”tnceh”,”image”:””,”imageId”:””,”title”:”A.\t10%”,”isCorrect”:”1″},”o15kt”:{“id”:”o15kt”,”image”:””,”imageId”:””,”title”:”B.\t20%”},”8iuw9″:{“id”:”8iuw9″,”image”:””,”imageId”:””,”title”:”C.\t30%”}}}}}

{“questions”:{“odfaq”:{“id”:”odfaq”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Bryce Ferry, DO and Destiny F. Chau, MD – Arkansas Children\u2019s Hospital\/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nA 3-month-old infant presenting with jaundice and pruritus undergoes liver biopsy which demonstrates multiple branches of the hepatic artery and vein and sparsity of bile ducts suggesting Alagille syndrome. What cardiac defect is MOST commonly associated with this syndrome? “,”desc”:”EXPLANATION \r\nAlagille syndrome is a rare inherited autosomal dominant disorder commonly associated with bile duct paucity, congenital cardiac defects and anomalies of other organs. It is associated with mutations in the JAG1 gene located on chromosome 20 (95%) or NOTCH2 gene located on chromosome 1 (5%). These mutations affect the notch signaling pathway leading to defective organogenesis and resulting in multiple systemic manifestations with a highly variable phenotype. This rare syndrome has an estimated prevalence of 1 in 70,000 newborns. De novo mutations account for half of the cases, with genetic inheritance accounting for the remainder. \r\nThe diagnostic criteria and major multi-system clinical manifestations are summarized in the table below, from Menon et al. (used under Creative Commons License). \r\n\r\n\r\nDiagnostic criteria for Alagille syndrome. From Menon et al. Multidisciplinary management of Alagille syndrome. J Multidiscip Healthc. 2022; 15:353-364. Used under Open Access Creative Commons License from Dove Press. (AS -Alagille Syndrome) \r\n\r\nCongenital cardiac disease remains one of the primary causes of death. Emerick et al. studied 92 patients with Alagille syndrome and found the following causes of mortality: 15% from complex congenital heart disease, 25% from intracranial hemorrhage, and 25% from hepatic disease or transplantation. Patients with structural intracardiac lesions had a 40% predicted probability of being alive at 20 years old as compared to 80% for those without intracardiac defects. As hepatic involvement can worsen over time, interventions to correct and manage cardiac lesions must be promptly addressed to minimize morbidity and mortality due to other systemic diseases. \r\n\r\nPulmonary hemorrhage is common in patients with Alagille syndrome undergoing cardiac catherization procedures. In a retrospective, single-institution study, Adamson et al. reported the outcomes of 87 cardiac catheterizations in 30 children with Alagille syndrome. A total of 37% had interventions on the branch pulmonary arteries and 73% were diagnostic cardiac catheterizations. The study demonstrated that 44% (14 of 32) of interventional and 22% (12 of 55) of diagnostic catheterizations were complicated by pulmonary hemorrhage; the coagulation profiles and liver function tests were similar in those with and without pulmonary hemorrhage. The etiology of pulmonary hemorrhage was unclear. Notably, the JAG1 gene mutation, which is present in the majority of patients with Alagille syndrome, is expressed in both the arterial endothelium and in megakaryocytes. The JAG 1 gene plays an important role in vascular development and normal hemostasis. Therefore, mutation of the JAG1 gene may be a major contributing factor to pulmonary hemorrhage. Other factors associated with pulmonary hemorrhage included diagnosis of Tetralogy of Fallot, greater right ventricular systolic pressure to aortic systolic pressure ratio, and procedural\/surgical interventions on the branch pulmonary arteries. Sixty five percent of pulmonary hemorrhages were mild, 15% were moderate, 19% were severe. The authors recommended a high degree of vigilance for this complication. \r\n\r\nPatients with Alagille syndrome present for a variety of diagnostic and surgical procedures including the Kasai operation, liver biopsy and liver transplantation. Therefore, a thorough preoperative evaluation, with particular attention to the hepatic and cardiovascular systems, is essential for perioperative management. Hepatic disease varies from intractable pruritus to advanced liver dysfunction requiring liver transplantation. Patients may present with hepatomegaly and splenomegaly secondary to portal hypertension. Liver function tests usually show elevated gamma glutamyl transpeptidase, bilirubin and prolonged PT\/PTT. The associated splenomegaly can result in thrombocytopenia, which may increase the risk of bleeding. Anesthetic drugs and neuromuscular blocking agents with minimal hepatic metabolism or excretion should be considered for patients with hepatic dysfunction. As chronic cholestasis can lead to osteopenia and fractures of long bones in this patient population, additional patient positioning precautions during general anesthesia are important. The presence of facial dysmorphism and vertebral anomalies are indicators of potential difficulty with mask ventilation and airway management. Associated cardiac lesions warrant appropriate anesthetic considerations tailored to the specific cardiac defect.\r\n\r\nPeripheral pulmonary artery stenosis is the most common cardiac defect found in patients with Alagille syndrome. Hypoplastic left heart syndrome and common atrioventricular canal are not typically associated with this syndrome. \r\n\r\nREFERENCES \r\nMenon J, Shanmugam N, Vij M, Rammohan A, Rela M. Multidisciplinary management of Alagille syndrome. J Multidiscip Healthc <\/em>. 2022;(15):353-364. doi:10.2147\/JMDH.S295441 \r\nYildiz T, Yumuk N, Baykal D, Solak M, Toker K. Alagille syndrome and anesthesia management. Pediatr Anesth <\/em>. 2007; 87-97 doi:10.1111\/j.1460-9592.2006.02022.x \r\nEmerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology<\/em>. 1999;29(3):822-829. doi:10.1002\/hep.510290331 \r\n\r\nMitchell E, Gilbert M, Loomes KM. Alagille Syndrome. Clin Liver Dis<\/em> .2018;22(4):625-641. doi:10.1016\/j.cld.2018.06.001 \r\n \r\nAdamson GT, Peng LF, Feinstein JA, et al. Pulmonary hemorrhage in children with Alagille syndrome undergoing cardiac catheterization. Catheter Cardiovasc Interv<\/em>. 2020;95(2):262-269. doi:10.1002\/ccd.28508\r\n\r\n”,”hint”:””,”answers”:{“i8wc4”:{“id”:”i8wc4″,”image”:””,”imageId”:””,”title”:”A. Peripheral pulmonary artery stenosis “,”isCorrect”:”1″},”oqr76″:{“id”:”oqr76″,”image”:””,”imageId”:””,”title”:”B. Common atrioventricular canal”},”i0lnh”:{“id”:”i0lnh”,”image”:””,”imageId”:””,”title”:”C. Hypoplastic left heart syndrome “}}}}}

{“questions”:{“q9ozc”:{“id”:”q9ozc”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Arturo Marrero MD, Georgetown Public Hospital Corporation, Georgetown, Guyana and \r\nDestiny F. Chau MD, Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR, USA \r\n\r\nPaciente femenina de 21 a\u00f1os se presenta para la reducci\u00f3n abierta y fijaci\u00f3n interna de una fractura de h\u00famero sufrida durante un episodio sincopal. En el examen f\u00edsico, se observa severa acropaquia (dedos en palillos de tambor) en los dedos de los pies. Los signos vitales son los siguientes: SpO2 97% (dedo de la mano derecha), SpO2 83% (dedo del pie derecho), pulso 118, presi\u00f3n arterial 100\/62. \u00bfCu\u00e1l de los siguientes hallazgos es M\u00c1S probable que se demuestre en una ecocardiograf\u00eda transtor\u00e1cica? \r\nA 21-year-old woman presents for open reduction and internal fixation of a humeral fracture sustained during a syncopal episode. On physical examination, severe clubbing of the toes is noted. The vital signs are as follows: SpO2 97% (right finger), SpO2 83% (right toe), HR 118 bpm, BP 100\/62. Which of the following findings is the MOST likely to be demonstrated on transthoracic echocardiography? “,”desc”:”Explicaci\u00f3n\/ Explanation \r\n\r\nLa acropaquia (dedos en palillos de tambor, hipocratismo digital, o clubbing) diferencial es un hallazgo f\u00edsico en pacientes con s\u00edndrome de Eisenmenger como consequencia del conducto arterioso persistente (CAP). \r\n\r\nLa evoluci\u00f3n natural del CAP es el empeoramiento de la hipertensi\u00f3n arterial pulmonar secundaria a la derivaci\u00f3n de izquierda a derecha de larga duraci\u00f3n, con la eventual reversi\u00f3n de la derivaci\u00f3n cuando la presi\u00f3n arterial pulmonar aumenta hasta alcanzar el nivel de la presi\u00f3n arterial sist\u00e9mica. La inversi\u00f3n de la derivaci\u00f3n da como resultado la perfusi\u00f3n de la parte inferior del cuerpo con sangre relativamente desaturada a trav\u00e9s del CAP y hacia la aorta descendente. En este caso, la oximetr\u00eda de pulso de las extremidades inferiores registrar\u00e1 una SpO2 m\u00e1s baja que la de las extremidades superiores. Esto es en contraste con las arterias car\u00f3tida y subclavia que reciben sangre completamente saturada del ventr\u00edculo izquierdo, lo que da como resultado una oximetr\u00eda de pulso normal en las extremidades superiores. La hipoxia cr\u00f3nica en las extremidades inferiores resulta en la acropaquia de los dedos de los pies, mientras que las extremidades superiores se salvan, dando como resultado la acropaquia diferencial. \r\nEl desarrollo de hipertensi\u00f3n arterial pulmonar con el s\u00edndrome de Eisenmenger resultante impide el cierre del conducto. La terapia m\u00e9dica con vasodilatadores pulmonares puede ser beneficiosa para reducir la presi\u00f3n de la arteria pulmonar y brindar alivio sintom\u00e1tico. El trasplante de coraz\u00f3n y pulm\u00f3n puede ser una opci\u00f3n en pacientes adecuadamente seleccionados. \r\n\r\nLa acropaquia es una manifestaci\u00f3n de numerosas condiciones y no es exclusiva de la hipoxia cr\u00f3nica. Aproximadamente el 75 % de las condiciones asociadas con la acropaquia implican enfermedades pulmonares en ausencia de hipoxia, como tumores pulmonares malignos y bronquiectasias, mientras que el 15 % son enfermedades card\u00edacas, como endocarditis infecciosa y cardiopat\u00edas cong\u00e9nitas cian\u00f3ticas. Otro 10% son enfermedades gastrointestinales como la enfermedad de Crohn y la cirrosis, y el resto incluye condiciones como la osteoartropat\u00eda hipertr\u00f3fica y el hipertiroidismo. El mecanismo para el desarrollo de la acropaquia no est\u00e1 completamente dilucidado. Los factores contribuyentes incluyen la hipoxia local, la activaci\u00f3n plaquetaria, la estimulaci\u00f3n de la angiog\u00e9nesis y la liberaci\u00f3n de prote\u00ednas se\u00f1alizadoras como el factor de crecimiento del endotelio vascular. \r\n\r\nEn el escenario de este caso, los hallazgos ecocardiogr\u00e1ficos mostrar\u00edan un CAP grande con derivaci\u00f3n de derecha a izquierda, presiones sist\u00f3licas ventriculares derechas elevadas, hipertrofia y dilataci\u00f3n ventricular derecha y aplanamiento sist\u00f3lico del tabique intraventricular. Los hallazgos de una presi\u00f3n sist\u00f3lica del ventr\u00edculo derecho normal y derivaci\u00f3n de izquierda a derecha no son consistentes con el s\u00edndrome de Eisenmenger debido al CAP en una persona adulta. \r\n\r\n————————————————— \r\n\r\nDifferential clubbing is a physical finding in patients with Eisenmenger syndrome resulting from a persistent patent ductus arteriosus (PDA). The natural history of a persistent PDA is worsening pulmonary arterial hypertension secondary to long-standing left to right shunt with eventual reversal of shunting as pulmonary arterial pressure increases to systemic pressure. The reversal of shunting results in the lower body being perfused with relatively desaturated blood through the PDA and into the descending aorta. In this setting, pulse oximetry of the lower extremities will register a lower SpO2 than the upper extremities. In contrast, the carotid and subclavian arteries receive fully saturated blood from the left ventricle resulting in normal pulse oximetry in the upper extremities. Chronic hypoxia in the lower extremities leads to clubbing of the toes, whereas the upper extremities would be spared which results in differential clubbing. The development of pulmonary arterial hypertension with resultant Eisenmenger syndrome precludes ductal closure. Medical therapy with pulmonary vasodilators may be beneficial in reducing pulmonary artery pressure and providing symptomatic relief. Heart-and-lung transplantation may be an option in appropriately selected patients. \r\n\r\nClubbing is a manifestation of numerous conditions and is not unique to chronic hypoxia. Approximately 75% of conditions associated with clubbing involve pulmonary diseases in the absence of hypoxia, such as lung malignancies and bronchiectasis while 15% are cardiac diseases such as infective endocarditis and cyanotic congenital heart disease. Another 10% are gastrointestinal diseases such as Crohn\u2019s disease and cirrhosis, and the rest include conditions such as hypertrophic osteoarthropathy and hyperthyroidism. The mechanism for the development of digital clubbing is not fully understood. Contributing factors include local hypoxia, platelet activation, stimulation of angiogenesis, and release of signal proteins such as vascular endothelial growth factor. \r\n\r\nIn this case scenario, echocardiographic findings would show a large PDA with right-to-left shunting, elevated right ventricular systolic pressures (RVSP), right ventricular hypertrophy and dilation, and systolic flattening of the intraventricular septum. A normal RVSP and left-to-right shunting are not consistent with Eisenmenger syndrome due to a persistent PDA in an adult. \r\n\r\nReferencias\/ References \r\n\r\n\r\nSrinivas SK, Manjunath CN. Differential clubbing and cyanosis: classic signs of patent ductus arteriosus with Eisenmenger syndrome. Mayo Clin Proc<\/em>. 2013;88(9): e105-e106. doi:10.1016\/j.mayocp.2013.02.016 \r\n\r\nUribe-Valencia MA, Ocampo Chaparro JM, Parra-Camarillo M. Hipocratismo digital: conociendo sus causas. Reporte de caso. Rev Fac Med <\/em>. 2019;6: 543-546. https:\/\/doi.org\/10.15446\/revfacmed.v67n3.69592 \r\n\r\n\r\nWald R, Crean A. Differential clubbing and cyanosis in a patient with pulmonary hypertension. CMAJ<\/em>. 2010;182(9):E380. doi:10.1503\/cmaj.091003 \r\n\r\nDimopoulos K. Eisenmenger syndrome in an adult patient with a large patent ductus arteriosus. Eur Respir Rev <\/em>. 2013;22(130):558-564. doi:10.1183\/09059180.00007013\r\n\r\nRutherford JD. Digital clubbing. Circulation <\/em>. 2013;127(19): 1997-1999. doi:10.1161\/CIRCULATIONAHA.112.000163\r\n\r\n\r\n”,”hint”:””,”answers”:{“iouxi”:{“id”:”iouxi”,”image”:””,”imageId”:””,”title”:”A.\tConducto arterioso persistente\/Patent ductus arteriosus”,”isCorrect”:”1″},”yg5fh”:{“id”:”yg5fh”,”image”:””,”imageId”:””,”title”:”B.\tPresi\u00f3n sist\u00f3lica del ventr\u00edculo derecho normal\/Normal right ventricular systolic pressure”},”wlkt2″:{“id”:”wlkt2″,”image”:””,”imageId”:””,”title”:”C.\tPresencia de derivaci\u00f3n de izquierda a derecha\/Presence of left-to-right shunting”}}}}}

{“questions”:{“bmvzk”:{“id”:”bmvzk”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Gokul Thimmarayan, MD and Destiny F. Chau, MD – Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nAn 18-month-old toddler with a history of Trisomy 21 is undergoing a full repair of a partial atrioventricular canal with cardiopulmonary bypass. Ten times the intended dose of tranexamic acid is administered during the procedure in error. In the early post-operative period, generalized tonic-clonic seizures are noted. Tranexamic acid induces seizures by the competitive antagonism of which of the following receptors?\r\n”,”desc”:”EXPLANATION \r\nTranexamic acid (TXA) is an analog of lysine, which binds to plasminogen and prevents its conversion to plasmin, thereby inhibiting fibrinolysis and improving hemostasis. TXA use decreases the risk of bleeding after cardiac surgery with cardiopulmonary bypass in both the adult and pediatric populations. Epsilon aminocaproic acid (EACA), another lysine derivative, and aprotinin, a serine protease inhibitor, are other antifibrinolytic agents. \r\n \r\nThe reported dosing ranges and protocols for TXA differ greatly from a 10 to 100 mg\/kg bolus prior to cardiopulmonary bypass (CPB) followed by an infusion at variable rates and\/or an additional bolus in the pump prime. TXA use has been associated with an increased risk of thromboembolism, seizure, and renal dysfunction. Seizure frequency is correlated positively with higher doses of TXA (total TXA dose of >100 mg\/kg), which was demonstrated in study of adult cardiac surgical patients by Kalavrouziotis et al. TXA-related seizures are most frequently reported in the early postoperative period after cardiac surgery and are associated with increased morbidity and mortality. In a propensity-score matched study of 3,739 pairs of pediatric patients undergoing cardiac surgery, Maeda et al. demonstrated an incidence of seizures of 1.6% in the patients treated with TXA versus 0.2% in those not treated with TXA.\r\n\r\n \r\nA 2012 study by Lecker et al. used the mouse neuron as a model to investigate the mechanism of seizure due to TXA. The study demonstrated that TXA, which is a structural analog of the inhibitory neurotransmitter glycine, competitively binds to and inhibits the activity of glycine receptors. Thus, the authors postulated that blockade of inhibitory glycine receptors by TXA leads to neuronal hyperexcitability and lowers seizure threshold. The authors temporally measured the TXA concentration in serum and cerebrospinal fluid (CSF) in patients undergoing vascular surgery or cardiac surgery with cardiopulmonary bypass. The authors found that the peak TXA concentration in CSF occurs after<\/em> the peak TXA concentration in serum. The peak concentration of TXA in CSF correlated with the reported observation that seizures occur more frequently in the early postoperative period. This time frame also coincides with the waning anti-convulsant effects of general anesthetic agents after surgery. The authors also postulated that enhancing glycine inhibitory potential could suppress seizures associated with TXA. Therefore, agents such as isoflurane, sevoflurane, and propofol, which are known to stimulate glycine receptor activity, could potentially be used to prevent or treat seizures induced by TXA. \r\n\r\nEACA, which is also an analogue of lysine, is associated with a much lower incidence of seizures because it is a much weaker inhibitor at glycine receptors than TXA. In a study comparing the incidence of seizures in adult cardiac surgical patients treated with TXA or EACA, Martin et al. reported an incidence of 7.6% in the TXA group versus 3.3% in the EACA group. \r\n\r\nAspartate, and acetylcholine are excitatory neurotransmitters in the central nervous system. Thus far, they have not been associated with seizures caused by TXA. \r\n\r\nThe most effective way to prevent TXA-induced seizures is by utilizing doses at the lower end of the range known to be effective in reducing blood loss after surgery and by lowering the dose administered to patients with renal dysfunction, as it is primarily eliminated in the urine. Currently, there is not a clearly defined safe, yet effective dose of TXA. \r\n \r\nREFERENCES \r\n\r\nMaeda T, Sasabuchi Y, Matsui H, Ohnishi Y, Miyata S, Yasunaga H. Safety of tranexamic acid in pediatric cardiac surgery: a nationwide database study. J Cardiothorac Vasc Anesth <\/em>. 2017;31(2):549-553. doi:10.1053\/j.jvca.2016.10.001 \r\n\r\nLecker I, Wang DS, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors.J Clin Invest<\/em>. 2012;122(12):4654-4666. doi:10.1172\/JCI63375 \r\n\r\nKalavrouziotis D, Voisine P, Mohammadi S, Dionne S, Dagenais F. High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. Ann Thorac Surg <\/em>. 2012;93(1):148-155. doi: 10.1016\/j.athoracsur.2011.07.085 \r\n\r\nLecker I, Wang D, Whissell P, Avramescu S, Mazer C, Orser B. Tranexamic acid-associated seizures: causes and treatment. Ann Neurol <\/em>. 2016;79(1):18-26. Doi:10.1002\/ama.24558 \r\n\r\nMartin K, Knorr J, Breur T et al. Seizures after open heart surgery: a comparison of E-aminocaproic acid versus tranexamic acid. J Cardiothorac Vasc Anesth<\/em>. 2011;25:20-5. doi: 10.1053\/j.jvca.2010.10.007.\r\n\r\n”,”hint”:””,”answers”:{“zzf35”:{“id”:”zzf35″,”image”:””,”imageId”:””,”title”:”A.\tAspartate”},”4o24p”:{“id”:”4o24p”,”image”:””,”imageId”:””,”title”:”B.\tGlycine”,”isCorrect”:”1″},”2ngc9″:{“id”:”2ngc9″,”image”:””,”imageId”:””,”title”:”C.\tAcetylcholine”}}}}}

{“questions”:{“8td7c”:{“id”:”8td7c”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Destiny F. Chau, MD and Jorge Guerrero, MD – Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nA 9 y\/o female child with a history of an extracardiac fenestrated Fontan presents for tonsillectomy and adenoidectomy. A recent cardiac catheterization demonstrated a Fontan pressure of 19 mmHg. Home medications include aspirin and sacubitril\/valsartan. Which class of medication does sacubitril belong to? \r\n”,”desc”:”EXPLANATION \r\nSacubitril is a neprilysin inhibitor, which is a naturally occurring endopeptidase enzyme that degrades neuropeptides that are known to contribute to the pathophysiology of heart failure. Chronic heart failure is associated with elevated neprilysin levels and faster clearance of neuropeptides. \r\n\r\nHeart failure results in the activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system leading to increased levels of renin, angiotensin II, aldosterone, and anti-diuretic hormone. The end result is increased vascular tone and blood pressure, which are compensatory mechanisms to increase organ perfusion. However, this activation impairs the function of endogenous neuropeptides such as atrial natriuretic peptide and B-type natriuretic peptide, bradykinin, and adrenomedullin. These peptides cause vasodilation, natriuresis, diuresis, and counteract the abnormal sympathetic response implicated in maladaptive vascular and cardiac remodeling. \r\n\r\nThe inhibition of neprilysin prevents the degradation of endogenous neuropeptides leading to an increased concentration of bradykinin, natriuretic peptides, adrenomedullin and angiotensin II. Therefore, a neprilysin inhibitor is paired with an angiotensin receptor blocker (ARB) to mitigate the effects of elevated angiotensin II levels. This class of drug, termed an ARNI (angiotensin receptor neprilysin inhibitor), received FDA approval in 2015 for the treatment of symptomatic heart failure with reduced ejection fraction. Patients must demonstrate tolerability to an angiotensin-converting enzyme inhibitor (ACEI) or ARB before starting sacubitril\/valsartan. \r\n\r\nAngiotensin II effects can reduced by using an ACEI. However, the combination of both a neprilysin inhibitor and an ACEI was found to cause significant angioedema due to the fact that both drugs increase bradykinin levels thus worsening angioedema. Therefore, the combination of an ACEI and ARNI should be avoided. Coadministration of a neprilysin inhibitor within 36 hours of an ACEI is contraindicated.\r\nIn a prospective, randomized trial by McMurray et al. (widely known as PARADIGM-HF – Prospective Comparison of ARNI [Angiotensin Receptor\u2013Neprilysin Inhibitor] with ACEI [Angiotensin-Converting\u2013Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) of adult patients with symptomatic heart failure and reduced ejection fraction, the use of sacubitril\/valsartan demonstrated increased efficacy in reducing morbidity and mortality versus standard treatment with enalapril. Adverse effects of sacubitril\/valsartan included hypotension, hyperkalemia, renal failure, cough, and angioedema. Compared to enalapril, treatment with sacubitril\/valsartan resulted in a higher incidence of hypotension and symptomatic hypotension but a lower risk of increased serum potassium and creatinine and lower risk of cough. Although not statistically significant, angioedema in the sacubitril\/valsartan group was higher than in the enalapril group, with no reported cases of angioedema causing airway compromise. \r\n\r\nAccording to the most recent 2022 AHA\/ACC\/HFSA guidelines (Heidenreich et al.), treatment with sacubitril\/valsartan is a Class I recommendation for the management of symptomatic heart failure with reduced ejection fraction. Additionally, treatment with sacubitril\/valsartan is a Class 2b recommendation for the management of heart failure with preserved ejection fraction. This drug is also known to enhance right sided ejection fraction and reduce pulmonary artery pressures independent of an improvement in left ventricular function. Sacubitril\/valsartan use in pediatric patients is based upon data from the adult population. However, there are current ongoing studies in the pediatric population. \r\n\r\nThe effect of general anesthesia on the blood pressure of patients taking an ARNI is currently unknown. Given the presence of an ARB in this combination drug and the reports of a higher risk of hypotension with ARNI use as compared to enalapril, it is reasonable to deduce that ARNI use may also be associated with severe refractory hypotension under general anesthesia. Therefore, vigilance and preparation for severe hypotension in patients taking an ARNI whilst undergoing general anesthesia is warranted. As of yet, there are no guidelines on how to best manage perioperative ARNI use. \r\n\r\n \r\nREERENCES \r\nMcMurray JJV, Packer M, Desai AS et al. Angiotensin-Neprolysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371:993-1004. DOI: 10.1056\/NEJMoa1409077 \r\n\r\nHeidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA\/ACC\/HFSA Guideline for the management of heart failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033] [published correction appears in Circulation. 2022 Sep 27;146(13):e185] [published correction appears in Circulation. 2023 Apr 4;147(14):e674]. Circulation<\/em>. 2022;145(18):e895-e1032. doi:10.1161\/CIR.0000000000001063\r\n\r\nDas BB, Scholl F, Vandale B, Chrisant M. Sacubitril\/Valsartan: potential treatment for paediatric heart failure. Cardiol Young<\/em>. 2018;28(9):1077-1081. doi:10.1017\/S1047951118001014 \r\n\t\r\nNicolas D, Kerndt CC, Reed M. Sacubitril\/Valsartan. [Updated 2022 May 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK507904\/ \r\n\r\nZhang J, Du L, Qin X, Guo X. Effect of sacubitril\/valsartan on the right ventricular function and pulmonary hypertension in patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis of observational studies. J Am Heart Assoc<\/em>. 2022;11(9):e024449doi:10.1161\/JAHA.121.024449\r\n”,”hint”:””,”answers”:{“xzyl1”:{“id”:”xzyl1″,”image”:””,”imageId”:””,”title”:”A.\tNeprilysin inhibitor”,”isCorrect”:”1″},”pxwle”:{“id”:”pxwle”,”image”:””,”imageId”:””,”title”:”B.\tAngiotensin converting enzyme inhibitor”},”anjbt”:{“id”:”anjbt”,”image”:””,”imageId”:””,”title”:”C.\tPhosphodiesterase inhibitor”},”r5utx”:{“id”:”r5utx”,”image”:””,”imageId”:””,”title”:”D.\tCalcium channel blocker”}}}}}