Eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto en triglicéridos de cadena media en pacientes pediátricos con quilotorax / Efficacy and safety of nutritional formula with low lipid content and high medium chain triglycerides in pediatric patients with chylothorax

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto en triglicéridos de cadena media (TCM) en pacientes pediátricos con quilotórax. Así, el médico Marco Morales Acosta, especialista en pediatría, del Servicio de Pediatría Clínica del Hospital Nacional Edgardo Rebagliati Martins, perteneciente a la Red Prestacional Rebagliati, siguiendo la Directiva N.° 003-IETSIESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso, por fuera del petitorio del producto: fórmula nutricional con bajo contenido lipídico y alto en TCM. ASPECTOS GENERALES: El quilotórax es la acumulación de líquido linfático en la cavidad pleural, que resulta de fugas provenientes de los vasos linfáticos (Tutor, 2014). El quilotórax se diagnostica tras la detección de concentración de triglicéridos en el líquido pleural mayor a 110 mg/dl (Rocha et al., 2006). En la población pediátrica, el quilotórax es causado, principalmente, por defectos congénitos o por daños al conducto torácico como resultado de complicaciones posquirúrgicas (Soto-Martinez & Massie, 2009). La incidencia aproximada del quilotórax congénito es de 1 por cada 10,000 nacidos vivos (Zheng et al., 2020); mientas que, la incidencia del quilotórax post-cirugía cardíaca en población pediátrica varía de 0.85 % a 9.2 % (Rocha et al., 2006). A pesar de no tener alta incidencia, los pacientes menores de 18 años con quilotórax tienen riesgo de mortalidad de hasta el 50 % cuando no reciben tratamiento, mayor morbilidad y tienen mayor tiempo de estancia hospitalaria (mediana = 38.8 días; rango intercuartil [R1Q) = 27.8 - 52.3, frente a mediana = 27.0 días, RIQ = 18.9 - 39.1 días; p < 0.001), comparado con los que no desarrollaron quilotórax luego de una cirugía cardiaca (Bai et al., 2021; Yeh et al., 2013). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de la fórmula con bajo contenido lipídico y alto contenido de TCM. La búsqueda bibliográfica se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo la World Health Organization (WHO), la National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish Intercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de Incorporção de Tecnologias no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica, no se encontró alguna GPC, ETS o ECA fase III que cumpla con los primeros criterios de inclusión. Tras la ampliación de los criterios de elegibilidad, se incluyeron tres estudios observacionales (Bellini et al., 2012; Cormack et al., 2004; Zheng et al., 2020). Dos de estos estudios (Cormack 2004 & Zheng 2020), usaron el diseño de cohortes de tipo retrospectivo, y compararon el tiempo hasta la resolución del quilotórax (solo en Zheng et al 2020), duración de drenaje pleural (solo en Cormack et al 2004), tiempo de hospitalización y mortalidad en los pacientes con quilotórax posquirúrgico que usaron la fórmula con bajo contenido lipídico alto en TCM versus los que usaron la NPT. El último estudio (Bellini et al 2012), se trata de una serie de casos de neonatos con quilotórax congénito, donde se reporta la experiencia de tratamiento de estos pacientes usando la fórmula nutricional con bajo contenido lipídico y alto en TCM con o sin la octreotida. Los desenlaces de interés evaluados fueron la resolución del quilotórax y la mortalidad. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de la fórmula con bajo contenido lipídico y alto en TCM, con o sin octreotida, en pacientes menores de 18 años con diagnóstico de quilotórax debido a cualquier etiología (congénito o adquirido) que pueden recibir nutrición enteral, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 μg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

MCT oil-based diet reverses hypertrophic cardiomyopathy in a patient with very long chain acyl-coA dehydrogenase deficiency.

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the genetic defects of mitochondrial fatty acid beta-oxidation presenting in early infancy or childhood. If undiagnosed and untreated, VLCAD deficiency may be fatal, secondary to cardiac involvement. We assessed the effect of replacing part of the fat in the diet of a 2 ½-month-old male infant, who was diagnosed with VLCAD deficiency,with medium-chain triglyceride (MCT) oil and essential fats. The patient presented with vomiting, dehydration, and was found to have persistent elevation of liver function tests, hepatomegaly, pericardial and pleural effusion, right bundle branch block, and biventricular hypertrophy. Because of the cardiomyopathy, hepatomegaly, and an abnormal acylcarnitine profile and urine organic acids, he was suspected of having VLCAD deficiency. This was confirmed on acyl-coA dehydrogenase, very long chain (ACADVL) gene analysis. He was begun on an MCT oil-based formula with added essential fatty acids, uncooked cornstarch (around 1 year of age), and frequent feeds. By 7 months of age, cardiomyopathy had reversed and by 18 months of age, all cardiac medications were discontinued and hypotonia had improved such that physical therapy was no longer required. At 5 years of age, he is at the 50th percentile for height and weight along with normal development. Pediatricians need to be aware about the basic pathophysiology of the disease and the rationale behind its treatment as more patients are being diagnosed because of expansion of newborn screen. The use of MCT oil as a medical intervention for treatment of VLCAD deficiency remains controversial mostly because of lack of clear phenotype-genotype correlations, secondary to the genetic heterogeneity of the mutations. Our case demonstrated the medical necessity of MCT oil-based nutritional intervention and the need for the further research for the development of specific guidelines to improve the care of these patients.

Transferência de lípides para a lipoproteína de alta densidade (HDl) em mulheres com diabetes melito tipo 1 / Lipid transfer to HDl in women with type 1 diabetes

INTRODUÇÃO: Os portadores de diabetes melito tipo 1 (DM1) possuem aumentado risco de doença cardiovascular e, ainda assim, podem apresentar perfil lipídico normal. Para esclarecer se os níveis normais de HDL podem ocultar defeitos na função, foram estudados a transferência de lípides para a HDL em DM1. MÉTODOS: Vinte e uma mulheres jovens portadoras de DM1 foram comparadas com 21 mulheres não-diabéticas. Nanoemulsões foram usadas como doadoras de lípides para HDL: uma marcada com ³H-triglicérides e 14C-colesterol livre e outra com ³H-éster de colesterol e 14C-fosfolípides. Após 1 hora de incubação com amostras de plasma, seguida por precipitação química, o sobrenadante, contendo HDL, teve a radioatividade contada. RESULTADOS: Nenhuma diferença foi encontrada nas transferências dos ésteres de colesterol, triglicérides, colesterol livre e fosfolípides para as HDL. CONCLUSÃO: A transferência de lípides para a HDL não está afetada em portadoras de DM1. Isso sugere que a doença não altera a composição de lipoproteínas e a ação de proteínas de transferência.

INTRODUCTION: People with type 1 diabetes mellitus (T1DM) have an increased risk of cardiovascular disease and may still have a normal lipid profile. In order to clarify whether normal HDL cholesterol levels may conceal defects in HDL function, we have studied the transfer of lipids to HDL in T1DM. METHODS: Twenty-one young women with T1DM were compared with 21 non-diabetic women. Nanoemulsion preparations were used as lipid donor to HDL: one labeled with ³H-triglycerides and 14C-free cholesterol and the other with ³H-cholesteryl esters and 14C-phospholipids. These preparations were incubated with plasma samples for 1h. After chemical precipitation, the supernatant containing HDL was counted for radioactivity. RESULTS: No difference in transfer was observed to nanoemulsion HDL from cholesteryl esters, triglycerides, free cholesterol and phospholipids. CONCLUSION: Simultaneous lipid transfer to HDL was not affected in T1DM patients. This suggests that the disease does not alter lipoprotein composition and transfer protein action in such way as to disturb HDL metabolism.

Efeito hepatoprotetor do consumo crônico de dieptanoína e trieptanoína contra a esteatose em ratos / Hepatoprotective effect of diheptanoin and tritreptanoin chronic consumption against steatosis in rats

OBJETIVO: Avaliar o efeito do consumo crônico de di e trieptanoínas sobre a esteatose hepática (EH) em ratos. METODOLOGIA: Ratos Wistar submetidos à dieta AIN-93 com 0 por cento, 30 por cento ou 50 por cento de substituição do óleo por óleo rico em di e trieptanoína, grupos TAGC(7)0, TAGC(7)30 e TAGC(7)50, respectivamente, por nove meses. O grupo-controle recebeu ração Labina®. Analisaram-se histologia e provas de função e lesão hepática, glicemia e perfil lipídico sérico. Realizaram-se análise de variância, teste F, teste de Dunnet e análises de regressão uni e multivariadas (p < 0,05). RESULTADOS: TAGC(7)0, TAGC(7)30 e TAGC(7)50 desenvolveram EH; 80 por cento de casos graves no TAGC(7)0 contra 40 por cento no TAGC(7)50. Os pesos absoluto (PAF) e relativo do fígado (PRF) foram maiores em TAGC(7)0 e TAGC(7)30 e a glicemia foi maior em TAGC(7)30 e TAGC(7)50, que no grupo-controle. Colesterol total, LDL-c, LDL-c/HDL-c e proteínas totais foram maiores no grupo-controle. O óleo experimental reduziu o PRF e determinou tendência de redução do peso corporal, PAF, percentual de lipídios hepáticos e graus de EH (GHE). As variáveis explicativas para GHE foram peso final, glicemia, albumina, HDL-c, LDL-c, LDL-c/HDL-c, VLDL-c e fosfatase alcalina. CONCLUSÕES: Sugere-se que di e trieptanoínas exerçam efeito hepatoprotetor contra a EH, em ratos, em uma feição dose-dependente.

OBJECTIVE: to evaluate the effect of chronic consumption of di- and triheptanoin on hepatic steatosis (HS) in rats. METHODOLOGY: Wistar rats were submitted to a diet AIN-93 with 0, 30 or 50 percent of its oil substituted with an oil rich in di- and triheptanoin, groups TAGC(7)0, TAGC(7)30 and TAGC(7)50 respectively, for nine months. The control group received Labina®. Liver histology, hepatic lesion and function proofs, glycemia and lipid profile, were performed. Variance analyses, F-test, Dunnet´s test and uni- and multivariate regression analyses were performed (p<0.05). RESULTS: TAGC(7)0, TAGC(7)30 and TAGC(7)50 developed HS; 80 percent of severe cases in TAGC(7)0, as against 40 percent in TAGC(7)50. The absolute (ALW) and relative (RLW) liver weights were higher in TAGC(7)0 and TAGC(7)30, and glycemia was greater in TAGC(7)30 and TAGC(7)50, than in the Control. Total cholesterol, LDL-c, LDL-c/HDL-c and total proteins were higher in the Control. The experimental oil reduced RLW and showed a tendency in the reduction of body weight, ALW, percentage of hepatic lipids and the severity of HS. The explanatory variables in relation to HS were final weight, glycemia, albumin, HDL-c, LDL-c, LDL-c/HDL-c, VLDL-c and alkaline phosphatase. CONCLUSIONS: It is suggested that di- and triheptanoin have a hepatoprotector effect against HS, in rats, in a dose-dependant manner.

Does addition of lidocaine to medium- and long-chain triglyceride propofol emulsions significantly reduce pain on injection?

BACKGROUND: Propofol formulated with medium- and long-chain triglycerides (MCT/LCT) causes less pain on injection than standard Propofol, but the incidence of pain persists between 28 and 67 percent. Such a broad range begs the question so the authors wanted to clarify whether the addition of lidocaine to medium- and long-chain triglyceride emulsion propofol results in any clinically significant lessening of pain on injection. The authors conducted a randomized, prospective, double-blinded study to compare the injection pain felt following the administration of propofol-MCT/LCT (Propofol-Lipuro) to propofol-MCT/LCT plus 20 mg lidocaine for the induction of anesthesia. MATERIAL AND METHOD: The present study included 270 non-premedicated ASA I-II adult patients scheduledfor elective surgery under general anesthesia. Patients were allocated randomly into two groups to receive either propofol-MCT/LCT alone or propofol-MCT/LCT plus 20 mg lidocaine. The study solution was injected at 1 mL/second by one anesthesiologist and patients graded any associated pain using a four-point scale. RESULTS: The overall incidence of pain on injection was 31/133 (23%) in the propofol-MCT/LCT plus lidocaine group vs. 45/135 (33%) in the propofol-MCT/LCT alone group. The difference in the incidence of pain on injection between groups failed to achieve statistical significance (p = 0.23) and no significant difference in intensity of pain between the two study groups occurred CONCLUSIONS: The authors concluded that the addition of lidocaine (20 mg) to the propofol-MCT/LCT does not significantly reduce the incidence or severity of the pain on injection.

A comparison of propofol-LCT with propofol-LCT/MCT on pain of injection.

BACKGROUND: Propofol-Lipuro 1% is consisting of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) that have been reported to reduce injection pain. OBJECTIVE: To compare the incidence and intensity of injection pain with 1% Propofol-LCT with 1% Propofol-LCT/MCT in female populations for minor surgery under total intravenous anesthesia (TIVA). MATERIAL AND METHOD: One hundred and ten female patients were double-blind randomized into two groups. Group long-chain triglycerdes (L) received 1% propofol-LCT while group long-chain triglycerides/medium-chain triglycerides (L/M) received 1% propofol-LCT/MCT. All patients received no benzodiazepine premedication and fentanyl 1 microg/kg was given 3 minutes before propofol injection. The propofol 1 mg/kg was manually injected at 0.5 mL/sec. The verbal rating score (VRS 0-10) was recorded on pain of injection. VRS > 4 indicates a significant response to pain. RESULTS: There was a significantly greater incidence and intensity of injection pain in group L compared with group L/M (p < 0.001 and p = 0.013 respectively). CONCLUSIONS: Propofol-LCT/MCT is superior to propofol-LCT on reducing pain of injection.

Níveis lipídicos em uma série de casos do Rio de Janeiro / Lipid levels in a series of cases od Rio de Janeiro city

Fundamentos: Encontra-se bem definida na literatura a relação entre alterações lipídicas e eventos coronarianos, sendo escassos os dados sobre a distribuição lipídica na população do Rio de Janeiro.Objetivo: Analisar a distribuição dos níveis lipídicos e a prevalência de alterações lipídicas numa série de casos da cidade do Rio de Janeiro.Métodos: A população estudada foi proviniente de um banco de dados com 2535 indivíduos do Serviço Disciplina de Cardiologia da UERJ. Foram incluídos os 2057 indivíduos (1163 mulheres; idade entre 4-93 anos) que não estavam em uso de hipolipemiantes e que apresentavam dados relativos ás variáveis lipidicas: colesterol total (CT), HDL colesterol (HDL) e triglicerídeos (TG).O LDL colesterol (LDL) foi calculado pela fórmula de Friedwald nos 2029 indivíduos com TG <400mg/dl.O colesterol não HDL (CNDL) foi calculado pela subtração do HDL dos valores do CT. Os valores lipídicos considerados como referência foram os da III diretrizes Brasileiras de dislipidemias...

A influência da suplementação de triglicerídeos de cadeia média no desempenho em exercícios de ultra-resistência / The influence of medium-chain triglycerides supplementation in ultra-endurance exercise performance

As competições de ultra-resistência representam um grande desafio no mundo esportivo. O gasto energético de uma prova de ultra-resistência pode variar de 5.000 a 18.000kcal por dia. Por causa dessa grande demanda, várias estratégias para melhora do desempenho têm sido desenvolvidas nos últimos anos, como a suplementação de triglicerídeos de cadeia média (TCM) em combinação com carboidratos (CBO). A suplementação de TCM visa aumentar a utilização dos ácidos graxos livres (AGL) como fonte de energia, poupando os estoques corporais de glicogênio para o final da competição. Quando comparados com os triglicerídeos de cadeia longa (TCL), os TCM são rapidamente absorvidos e transportados pelo organismo. Além disso, os TCM possuem velocidade de oxidação comparável à dos CBO, mas, por serem lipídios, fornecem uma quantidade de energia maior quando são oxidados. Dessa forma, os TCM parecem ser o combustível ideal para provas de longa duração. Portanto, esta revisão possui como objetivo esclarecer como os TCM podem influenciar o desempenho em provas de ultra-resistência.

Triglicerídios de cadeia média (TCM) no tratamento do quilotórax traumático / Medium chain triglycerides in the treatment of traumatic chylothorax

Procedeu-se a tratamento conservador nutriçäo enteral com triglicerídios de cadeia média (TCM)-em paciente com quilotórax secundário a lesäo por arma de fogo. Os autores fazem uma revisäo dos fatores etiológicos, da freqüência da doença e seus métodos diagnósticos. Discutem-se aspectos do tratamento do quilotórax enfatizando a conduta conservadora e nesta o uso dos TCM com suas vantagens sobre a nutriçäo parenteral total. Comentam-se também a fisiologia do TCM e suas implicaçöes clínicas