INTRODUÇÃO: O controle de qualidade em Terapia Nutricional Parenteral permite a identificação de processos inadequados em nutrição parenteral. O objetivo deste estudo foi avaliar a qualidade da prática de Terapia Nutricional Parenteral em um hospital geral brasileiro de grande porte com uma Equipe Multidisciplinar de Terapia Nutricional estabelecida. MÉTODOS: O presente estudo observacional, longitudinal, analítico e prospectivo analisou 100 pacientes adultos internados sob terapia nutricional parenteral e os cuidados de uma equipe multidisciplinar de terapia nutricional, durante 21 dias ou até a alta hospitalar/óbito. Durante esse período, a qualidade da terapia nutricional parenteral praticada foi avaliada em relação à conformidade de sua indicação com diretrizes internacionais (ASPEN 2007), à conformidade do volume de solução de nutrição parenteral prescrito com aquele efetivamente infundido, à conformidade com metas de indicadores de qualidade em terapia nutricional (IQTN; ILSI-Brasil) e à incidência de complicações mecânicas, metabólicas e infecciosas. A associação entre as diferentes variáveis estudadas foi testada por análise univariada, aplicando-se o teste exato de Fisher. A correlação com desfechos clínicos (alta / óbito) incluiu a análise de variância Anova (para grupos de doenças) e o teste Mann-Whitney (para adequação entre volume prescrito e volume recebido de solução parenteral). Para todas as análises adotou-se nível de significância de 5% (p < 0,05) e o programa SPSS 18,0 para Windows (SPSS, Chicago, IL, EUA) para sua condução. RESULTADOS: As indicações de terapia nutricional parenteral não estavam em conformidade com as orientações da ASPEN 2007 em 15 pacientes. Entre os 85 pacientes restantes, 48 (56,5%) não receberam terapia nutricional parenteral adequadamente (> 80% do volume total prescrita). Fatores significativamente associados com inadequação do volume de nutrição parenteral infundido (p < 0,005) foram: ordem médica independente da equipe multidisciplinar de terapia nutricional, progressão da terapia nutricional parenteral, mudanças no cateter venoso central, causas desconhecidas e desajustes operacionais (por exemplo, perda de prescrição médica, não entrega da solução de NP por atraso na farmácia, temperaturas inadequadas para infusão da solução de NP). Observou-se correlação inversa significativa entre o tempo de administração de volume adequado de nutrição parenteral com a ocorrência de óbitos; e correlação direta dessa variável com a ocorrência de alta hospitalar (p = 0,047). Os indicadores de qualidade em terapia nutricional relacionados a cálculo de necessidades energéticas e proteicas e níveis de glicemia atingiram as metas estipuladas pelos indicadores; no entanto, a taxa de sepse e infecção de cateter venoso central foi maior do que a meta por eles preconizada. As complicações associadas à terapia nutricional parenteral encontradas foram de natureza infecciosa, principalmente relacionadas a infecções do cateter venoso central (28,23%). CONCLUSÕES: Em um hospital geral brasileiro de grande porte, apesar da presença de uma equipe de suporte nutricional estabelecida, observou-se um nível moderado de inadequação na indicação, administração e monitoramento da terapia nutricional parenteral nele praticada. Alguns fatores externos ao controle da equipe multidisciplinar de terapia nutricional parecem ser responsáveis por essas inadequações. Essas observações reforçam a necessidade de rever a eficiência da equipe de suporte nutricional, principalmente quanto à sua inter-relação com os demais membros da equipe assistencial hospitalar / INTRODUCTION: Quality control in parenteral nutrition therapy allows the identification of inadequate processes in parenteral nutrition. The objective of this study was to assess the quality of parenteral nutrition therapy at a large Brazilian general hospital with an established nutrition support team. METHODS: This observational, longitudinal, analytical, and prospective study examined 100 hospitalized adult patients under parenteral nutrition therapy and the care of a nutritional support team for 21 days or until hospital discharge / death. During this period, the quality of practiced parenteral nutrition therapy was evaluated for compliance of its indication with international guidelines (ASPEN 2007), for compliance of the total volume of parenteral nutrition solution prescribed with that effectively infused, for compliance with the goals of quality nutritional therapy indicators (IQTN; ILSI-Brazil), and for the incidence of mechanical, metabolic and infectious complications. The association between the different variables was tested by univariate analysis, applying the Fisher\'s exact test. The correlation with clinical outcomes (discharge / death) included the analysis of variance ANOVA (for groups of diseases) and the Mann-Whitney test (for compliance between prescribed volume and received volume of parenteral solution). For all analyzes we adopted a significance level of 5% (p < 0.05) and applied the SPSS 18,0 for Windows (SPSS, Chicago, IL, EUA) for statistical comparisons. RESULTS: parenteral nutrition therapy indications were not in accordance with the ASPEN 2007 guidelines in 15 patients. Among the remaining 85 patients, 48 (56.5%) did not receive parenteral nutrition therapy properly (> 80% of the total volume prescribed). Non-nutritional support team medical orders, progression to and from enteral nutrition, changes in the central venous catheter, unknown causes and operational errors (e.g., medical prescription loss, parenteral nutrition non-delivery, pharmacy delays, inadequate parenteral nutrition bag temperature) were associated with parenteral nutrition therapy inadequacy (p < 0.005). There was a significant inverse correlation between the administration time of appropriate amount of parenteral nutrition with the occurrence of deaths; and a direct correlation of this variable with the occurrence of hospital discharge (p = 0.047). The Quality Indicators for Nutrition Therapy related to estimated energy expenditure and protein requirements and glycemia levels reached the expected targets; however, the central venous catheter rate was higher than 6 per 1000 catheters/day and did not meet the expected targets. Complications associated with parenteral nutrition were infectious in nature, mainly related to the central venous catheter infection (28.23%). CONCLUSIONs: In a large Brazilian general hospital, despite the presence of an established nutritional support team, there was a moderate level of inadequacy in the indication, administration and monitoring of the practiced parenteral nutrition therapy. Some factors external to the control of the multidisciplinary team of nutrition therapy appear to account for these inadequacies. These observations emphasize the need to review the effectiveness of nutritional support team, mainly regarding its interrelation with the other hospital care team members

1) Introdução: A subnutrição em pacientes hospitalizados é comum, independente das condições econômicas do país. Os pacientes gravemente doentes são altamente predispostos a desenvolver subnutrição. E a descontinuidade da administração da terapia nutricional (TN) em unidade de terapia intensiva pediátrica (UTIP) está associada a vários fatores como: distúrbios digestórios, interrupções para procedimentos diagnósticos/terapêuticos, bem como pausa para administração de medicamentos. Objetivo: Identificar as possíveis causas da infusão incompleta da terapia nutricional no paciente gravemente doente. Métodos: Estudo prospectivo, realizado entre abril de 2015 a abril de 2017, foi avaliado sequencialmente a oferta de terapia nutricional enteral e/ou terapia nutricional parenteral com ênfase no volume efetivamente não administrado e as possíveis causas de oferta incompleta da TN. Resultados: Foram avaliados 120 pacientes com média de Z-escore para peso/estatura (-0,5) e desvio padrão (4.12) que apresentaram perdas significativas de terapia nutricional enteral (TNE) e/ou parenteral (TNP) no primeiro e terceiro dias de administração. A principal causa de perda foi a interrupção por procedimentos ou complicações do paciente na unidade de terapia intensiva pediátrica (UTIP). Conclusões: 1) Ocorreu administração incompleta de TN no primeiro e terceiro dias de avaliação em crianças gravemente doentes. 2) Procedimentos e complicações digestivas foram causas importantes de administração incompleta de TNE. 3) Pausa para administração de medicamentos repercutiu na administração incompleta da TNP. 4) O estudo enfatizou a necessidade de envolvimento de todos os profissionais no processo para garantir o aporte de macro e micronutrientes durante a administração da TN / Introduction: Undernutrition is common among hospitalized patients regardless of the economic conditions of a given country. Severely ill patients are predisposed to experience undernutrition. And the discontinuity of nutrition therapy (NT) in the pediatric intensive care setting is associated with several factors, such as gastrointestinal disorders, interruptions for diagnostic/therapeutic procedures, and pauses for the administration of medications. Aim: To identify possible causes of incomplete infusion of nutritional therapy (NT) for severely ill patients. Methods: A prospective study, conducted between April 2015 and April 2017, was sequentially evaluated the offer of enteral nutrition therapy (ENT) and/or parenteral nutrition therapy (PNT) with emphasis on the volume not effectively administered and the possible causes of incomplete offer of (TN). Results: One hundred twenty patients with a mean Z-score for weight/height of 0.5 (standard deviation, 4.12) who presented significant losses of ENT and PNT nutrition on the first and third days of administration. The main cause of losses was interruptions due to procedures or complications of the patient in the pediatric intensive care unit (PICU). Conclusion: 1) Incomplete TN administration occurred on the first and third day of evaluation in critically ill children. 2) Digestive procedures and complications were important causes of incomplete administration of TNE. 3) Pause for administration of drugs has repercussions on incomplete administration of NPT. 4) The study emphasized the need to involve all professionals in the process to ensure macro and micronutrient inputs during TN administration

Introduction : Les enfants prématurés ont la particularité de naître alors que leur développement est souvent incomplet et nécessite la mise en œuvre de soins intensifs visant à poursuivre leur croissance en dehors de l’environnement utérin. Souvent cependant, le stade développemental de l’enfant ne lui permet pas d’assimiler une alimentation entérale du fait de l’immaturité de son système digestif. Le recours à une voie centrale délivrant les nutriments assurant le développement devient alors une nécessité. Ce type de nutrition, appelée nutrition parentérale (NP, ou total parenteral nutrition TPN), permet l’administration de molécules simples, directement dans le sang du prématuré. Il n’est toutefois pas exempt de risques puisqu’exposée à la lumière, la NP peut s’oxyder et générer des molécules oxydantes telles que des hydroperoxydes lipidiques susceptibles de se fragmenter par la suite en hydroxy-alkénals. Ceci devient problématique au vu de l’immaturité des systèmes de défenses antioxydants du nouveau-né prématuré. L’utilisation prolongée de la NP est d’ailleurs à l’origine de maladie hépatiques dans lesquelles le stress oxydant et la nécro-inflammation sont des composantes majeures. Nous avons émis l’hypothèse que l’infusion chez les enfants prématurés, d’aldéhydes d’origine lipidique est en relation avec le développement du stress oxydant et de l’inflammation hépatique. Objectif : Notre étude a consisté à évaluer la relation entre les quantités d’hydroxy-alkénals dans la NP et les effets hépatiques engendrés sur les marqueurs de stress oxydant et les voies de signalisation responsables d’une induction de processus inflammatoire. Dans ce but, nous avons cherché à mesurer la peroxydation lipidique dans l’émulsion lipidique de la NP et la conséquence de l’infusion en continue d’hydroxy-alkénals sur les marqueurs de stress oxydant, sur la voie de signalisation médiée par le Nuclear Factor κB et sur le déclenchement du processus inflammatoire hépatique. A la suite de ce travail, nous avons également travaillé sur des alternatives à la photoprotection, qui est la seule méthode réellement optimale pour réduire la peroxydation des lipides de la NP, mais cliniquement difficilement praticable. Résultats : Nos résultats ont mis en évidence la génération de 4-hydroxynonenal in vitro dans la NP, ce phénomène est augmenté par une exposition lumineuse. Dans ce cadre, nous avons montré l’inefficacité de l’ajout de multivitamines dans l’émulsion lipidique comme alternative à la photoprotection. Dans la validation biologique qui a suivi sur un modèle animal, nos résultats ont permis de démontrer que l’augmentation des adduits glutathion-hydroxynonenal était imputable à l’augmentation de 4-hydroxynonenal (4-HNE) dans la NP, et non à une peroxydation endogène. Nos données indiquent que la probable augmentation hépatique des niveaux de 4-HNE a conduit à une activation du NFκB responsable de l’activation de la transcription des gènes pro-inflammatoires du Tumour Necrosis Factor-α (TNF-α) et de l’interleukine-1 (IL-1). Nous avons alors évalué la capacité d’une émulsion lipidique enrichie en acides gras polyinsaturés (AGPI) n-3 à baisser les concentrations de 4-HNE dans la NP, mais également à moduler le stress oxydant et les marqueurs pro-inflammatoires. Enfin, nous avons démontré, en collaboration avec l’équipe du Dr Friel, que certains peptides isolés du lait humain (par un processus mimant la digestion) permettent également une modulation du stress oxydant et du processus inflammatoire. Conclusion : Le stress oxydant exogène issu de la NP a conduit par activation de facteurs de transcription intra-hépatiques au déclenchement d’un processus inflammatoire potentiellement responsable du développement de maladies hépatiques reliées à la NP telle que la cholestase. Dans ce sens, les AGPI n-3 et les peptides antioxydants peuvent se poser en tant qu’alternatives crédibles à la photoprotection. / Introduction: Premature infants usually born before full term require intensive care to continue to grow up outside the uterine environment. Premature newborns are born with gastrointestinal systems that are too immature to absorb nutrients safely. Therefore they receive their initial nutrients through intravenous feeding, called total parenteral nutrition which delivers simple nutrients directly into bloodstream. However, light exposed-TPN can generate oxidant molecules such as lipid hydroperoxides, which can potently break up into hydroxy-alkenals. Prolonged use of TPN is also a cause of liver disease in which oxidative stress and necro-inflammation are major components. Thus, we hypothesize that lipid aldehydes contained in TPN are associated with oxidative stress and hepatic inflammation developments. Objectives: The aim of our study is to assess the relationship between quantities of hydroxyl-alkenals generated in TPN and effects on oxidative stress biomarkers and cell-signalling pathways molecules implicated in hepatic inflammation induction. To this end, we measure lipid peroxidation in the TPN lipid emulsion in and the consequence of continuous infusion of hydroxy-alkenals on markers of oxidative stress, on cell-signaling pathway mediated by the NFkB, and on liver inflammation induction. Following these data, we also worked on alternatives of photoprotection, which is the only optimal method for preventing lipid peroxidation, but unfortunately clinically impractical. Results: In vitro studies have highlighted the generation of 4-HNE in the TPN, increased under light exposure. In this context, we have demonstrated that the addition of multivitamins in the lipid emulsion cannot be a valuable alternative to photoprotection. Concerning the biological validation in our guinea pig animal model, our results demonstrated that the increase of GS-HNE adducts was due to increased 4-HNE in the TPN, and does not provide from endogenous peroxidation. Our data also indicate that the increase of hepatic 4-HNE led to an activation of NFkB, responsible for the activation of the transcription of proinflammatory genes TNF-α, IL-1. In the next study, we have evaluated the ability of a lipid emulsion enriched with n-3 polyunsaturated fatty acids (PUFA) to reduce 4-HNE concentrations generated in TPN, and to modulate oxidative stress markers and pro-inflammatory process on the same animal model. We also have demonstrated, in collaboration with Dr Friel’s team, that two antioxidant peptides (derived from a process mimicking digestion process of human milk) allow also a modulation of oxidative stress and inflammatory process in the liver. Conclusion: This form of exogenous oxidative stress from the TPN led to an inflammatory process resulting from the activation of intrahepatic transcription, which is potentially responsible of liver disease development such as cholestasis. In this sense, the n-3 PUFA and antioxidant peptides may arise as a valuable alternative of photoprotection.

Problématique : Le glutathion est une molécule clé de la défense antioxydante. Chez les enfants sous nutrition parentérale (NP), particulièrement les nouveau-nés, sa concentration tissulaire est anormalement basse. Puisque la capacité de synthèse de glutathion est adéquate, un déficit en cystéine, le substrat limitant, est soupçonnée. À cause de son instabilité en solution, la cystéine est peu présente en NP; la méthionine étant le précurseur endogène de cet acide aminé. L’activité de la méthionine adénosyltransférase (MAT), une enzyme essentielle à la transformation de la méthionine en cystéine, est facilement inhibée par l’oxydation. L’hypothèse : Le faible taux de glutathion chez les enfants sous NP est causé par l’inhibition de la MAT par les peroxydes contaminant ces solutions nutritives. Objectif: Mesurer l’impact d’une infusion de NP et de H2O2 sur l’activité hépatique de MAT en relation avec le niveau de glutathion. Méthode : Un cathéter est placé dans la jugulaire droite de cobayes de trois jours de vie. Quatre groupes sont comparés:1- Témoin (animaux aucune manipulation, sans cathéter) 2)-(animaux nourris normalement et le cathéter (noué)); 3) NP (animaux nourris exclusivement par voie intraveineuse (acides aminés + dextrose + lipides + vitamines + électrolytes), cette solution génère environ 400 µM de peroxyde. 4) H2O2 (animaux nourris normalement et recevant via le cathéter 400 µM de H2O2). Après quatre jours, le foie et le sang sont prélevés pour la détermination du glutathion, potentiel redox et l’activité de MAT, glutathion peroxydase et glutathion reductase. Résultats : L’activité de MAT est plus faible dans les groupes NP et H2O2. Le potentiel redox du foie et dans le sang est plus oxydé dans le groupe NP. Tandis que la concentration de GSSG du foie est plus élevée dans le groupe NP. Ainsi la concentration de GSH dans le sang et foie est plus faible dans les NP et H2O2 Discussion: La relation entre l’inhibition de MAT et le stress oxydant observée dans le groupe NP pourrait bien expliquer la perturbation du système glutathion observée chez les nouveau-nés prématurés. / Introduction: The low glutathione level in premature newborns can partly explain the high incidence of complications associated with oxidative stress in this population. Since the synthetic activity of glutathione is mature, a lack of substrate, especially cysteine, is suspected. Methionine provided by their parenteral nutrition (PN) is the in vivo precursor of cysteine. Since, methionine adenosyltransferase (MAT), the first enzyme in methionine transformation, has redox sensitive cysteines, we hypothesize that peroxides contaminating PN inhibit the activity of MAT, leading to a lower availability of cysteine for glutathione synthesis. Methods: At 3 days of life, guinea pigs a catheter fixed in jugular vein, the animals were separated in 4 groups: 1) Control: animals without any treatment and no catheter 2) sham: animals fed regular chow, a node closed their catheter; 3) PN: animals fed exclusively with parenteral nutrition (dextrose, amino acids, fat, vitamins) containing about 400 µM peroxides; 4) H2O2: animals fed regular chow and received continuously 400 µM H2O2 through the catheter. Four days later, liver and blood were sampling for determination of reduced glutathione (GSH), oxidized glutathione (GSSG), redox potential and activities of MAT, glutathione peroxidase, and glutathione reductase. Results: MAT activity was lower in groups receiving PN or H2O2. Liver redox was more oxidized in PN group whereas blood redox was more oxidized in PN and H2O2. Liver and blood GSH is lower in PN and H2O2. Liver GSSG was higher in PN. Conclusion: The inhibition of MAT in the PN group could explain the disruption of the glutathione system observed in premature infants. Furthermore the impact of a lower activity of MAT on GSH level is observed in liver and blood. Suggesting that the hepatic synthesis of GSH is insufficient to maintain its own level of glutathione and sustain the rate of export.

Introduction: Le supplément d’oxygène et la nutrition parentérale (NP) sont les deux sources majeures de stress oxydant chez le nouveau-né. Lors de la détoxification des oxydants, le potentiel redox du glutathion s’oxyde. Notre hypothèse est que le supplément d’oxygène et la durée de la NP sont associés à un potentiel redox plus oxydé et à une augmentation de la sévérité de la dysplasie bronchopulmonaire (DBP). Patients et Méthodes: Une étude observationnelle prospective incluant des enfants de moins de 29 semaines d’âge gestationnel. Les concentrations sanguines de GSH et GSSG à jour 6-7 et à 36 semaines d’âge corrigé étaient mesurées par électrophorèse capillaire et le potentiel redox était calculé selon l’équation de Nernst. La sévérité de la DBP correspondait à la définition du NICHD. Résultats: Une FiO2≥ 25% au 7ième jour de vie ainsi que plus de 14 jours de NP sont significativement associés à un potentiel redox plus oxydé et à une DBP plus sévère. Ces relations sont indépendantes de l’âge de gestation et de la gravité de la maladie initiale. La corrélation entre le potentiel redox et la sévérité de la DBP n’est pas significative. La durée de la NP était responsable de 15% de la variation du potentiel redox ainsi que de 42% de la variation de la sévérité de la DPB. Conclusion: Ces résultats suggèrent que l’oxygène et la NP induisent un stress oxydant et que les stratégies visant une utilisation plus judicieuse de l’oxygène et de la NP devraient diminuer la sévérité de la DBP. / Introduction: oxygen supplementation and total parenteral solution (TPN) are two main clinical practices that sustain oxidative stress. Glutathione is a key molecule that detoxifies peroxides resulting in a more oxidized redox potential. We hypothesize that O2 supplementation and longer TPN duration are associated with both more oxidized redox potential and more severe bronchopulmonary dysplasia (BPD). Patients and methods: A prospective observational study including infants of less than 29 weeks gestational age. GSH and GSSG from whole blood sampled on day 6-7 and at 36 weeks of corrected age (CA) were measured by capillary electrophoresis and redox potential was calculated using Nernst equation. BPD was classified according to NICHD guidelines. Results: There was a significant association between FiO2 ≥ 25% on day 7 of life and TPN duration longer than 14 days and both more oxidized redox potential and more severe BPD. TPN duration explained both 15 % of total variation observed in redox potential and 42 % of total variation in BPD severity. These associations remained significant after adjustment for gestational age and illness severity. The relation between the severity of BPD and the redox potential in blood was not significant. The statistic power (1-β) to show an effect of redox potential on severity of BPD was 52%. Conclusion: Both redox potential of glutathione and BPD severity are both associated with early O2 supplement and TPN. Strategies targeting judicious use of O2 supplement and either decreasing the duration or using safer formulation of TPN are expected to help reducing BPD.

Al is a ubiquitous element on the earth crust and is considered a non-essential element for humans since it is not involved in any biochemical process. Aluminum may act as a toxic species when it is introduced directly into the circulatory system. The most exposed patients are those receiving parenteral nutrition, mainly pre-term infants with less than 37 gestational weeks, under total parenteral nutrition. Due to organs immaturity, pre-term infants are vulnerable to the toxic effects of aluminum. The intoxication is related to symptoms such as anemia, bone disease and neurological disturbances. During the period that the patients are under intensive care, they receive nutrients and medication through the parenteral via. Infusion solutions and solutions for parenteral nutrition may be contaminated by aluminum and therefore be a source of this element to babies. This study aimed to evaluate the extent of the contamination of parenteral solutions and medications administered to patients as well as to establish a balance between the aluminum administered together with the parenteral infusion and eliminated by the babies through the urine. For this evaluation, 10 new-born babies, presenting normal renal function and aging from 32 to 36 gestational weeks were selected, independent of sex. All medication, infusion and nutritional solutions, administered to these babies were collected. Daily urine samples of each baby were also collected, as well as the blood at the first and last day in the intensive care unit. The commercial solutions that were used to 12 compound the nutritional solution administered to the patients were also analyzed. The determination of aluminum was carried out by atomic absorption spectrometry. Results showed that all components of solutions for parenteral nutrition were contaminated by aluminum. While infusion solutions (glucose, NaCl 0.9% and Ringer Lactate) presented a mean of 20 μg/L Al, in bags containing nutritional components the Al level was 500 μg/L. Infusion sets (burette and tubing system) increased in 20% the aluminum in the fluid being administered to the patient. The same was observed for the medication, dilution and administration by means of syringes increased the aluminum present in these samples. The balance between the Al administered and excreted by the new-born babies showed that approximately 58% of the Al is not eliminated in the urine. Moreover, 50% of the patients ingested more than 5 μg Al/kg/day, which is the limit recommended by the US Food and Drug Administration (FDA) for patients under total parenteral nutrition. Since the Al in the patient s blood practically did not change between the first and the last day of internment, the noneliminated Al must have been deposited in any part of the patient s body. / O alumínio é um metal onipresente na crosta terrestre, é considerado não essencial, porque não participa de nenhum processo bioquímico. Devido a imaturidade dos órgãos e principalmente do sistema renal, o alumínio poderá ser tóxico aos recém-nascidos pré-termos. Recém-nascidos prematuros ou pré-termos são aqueles que nascem com menos de 37 semanas de idade gestacional. Os principais problemas toxicológicos do alumínio estão relacionados a neurotoxicidade, hepatoxicidade, doença do metabolismo ósseo, além de distúrbios hematológicos, como a anemia microcítica hipocrômica. Durante o período de internação, pacientes prematuros recebem nutrientes e medicações através da via parenteral. Soluções para infusão e para nutrição parenteral podem se apresentar contaminadas por alumínio e desta forma ser uma fonte deste elemento para os prematuros. Este estudo teve por finalidade avaliar as soluções parenterais, medicações injetáveis, fluidos biológicos e estabelecer um balanço do alumínio que é administrado e excretado por via renal pelos recém-nascidos. Para esta avaliação foram selecionados dez recém-nascidos pré-termo com 32 a 36 semanas e 6 dias de idade gestacional, independentes do sexo e com função renal normal. Foram coletadas amostras de medicamentos, seringas de administração e bolsas de infusão parenteral. Amostras de urina foram coletadas diariamente. Amostras de soro foram coletadas no primeiro e último dia de internação. Foram analisados além das bolsas de infusão parenteral os componentes que fazem parte de sua composição. Toda a medicação injetável utilizada pelos recém-nascidos foi analisada e também os diluentes que fazem parte de sua preparação. A concentração de alumínio em todas as amostras foi determinada pela técnica de espectrometria de absorção atômica (AAS). Os resultados mostraram que as soluções de nutrição parenteral são as mais contaminadas por alumínio, sendo que a presença do dispositivo de administração, conhecido como bureta, aumenta consideravelmente o teor deste metal no fluido que está sendo administrado ao paciente. As amostras de medicamentos apresentam elevada contaminação por alumínio, no entanto, o fato da administração ser feita através de seringas, o nível de Al nestas amostras aumentou significativamente. O balanço do alumínio administrado e excretado aos recémnascidos pré-termos mostrou que em média 58% do alumínio administrado não é eliminado na urina, e que 50% dos recém-nascidos pré-termos ingerem mais do que 5 μg Al/kg/dia, este valor encontra-se acima do limite estabelecido pela Food and Drug Administration (FDA) para pacientes pediátricos. Como o nível de Al no sangue dos pacientes praticamente não se alterou entre o primeiro e o último dia de internação, o Al não eliminado deve ter se depositado em alguma parte do corpo do paciente.

This diploma thesis deals with the issue of life quality of patients taking home parenteral nutrition. Its intention is to present the achieved life quality scores in the individual domains of physical and mental health in comparison with general population and to point out the differences in what dimensions the life quality of these patients is particularly affected. The theoretical section describes the present situation of the issue of home parenteral nutrition in the CR and the system of the care about the patients. The chapter about indications and contraindications to HPN is elaborated in more detail. The possibilities of the long-term vascular accesses, the care about them are also mentioned here, and particularly the role of a nurse in patient education in transferring parenteral nutrition to the domestic environment. The problems with long-term parenteral nutrition resulting from mechanic, metabolic and septic complications are also outlined. Parenteral nutrition failure is the most serious problem, which is why a chapter on small intestine transplantation as the last resort to save a patient with combined failure of intestine and nutrition is included. The second part of the theoretical section describes the life quality. I wanted to define the nature of this unambiguously graspable a term, determinants affecting life quality are also mentioned here. The possibilities of life quality measurement and assessment and particularly the follow-up use of the obtained data are mostly summarized here. Goals and hypotheses: Two goals were set to meet the main purpose of the thesis: Goal 1: To find whether the life quality of patients on HPN differs from that of the general public. Goal 2: To find the spheres in which the life quality of patients on HPN is mostly affected. A zero hypothesis was set to achieve the goals: Life quality of patients on HPN does not differ from that of the general public. There is no statistically significant difference between men and women. Eight alternative hypotheses to each life quality domain followed: H1: Patients on HPN show lower life quality score compared to the general public in the sphere of physical functions. H2: Patients on HPN show lower life quality score compared to the general public in the sphere of physical roles' limitation. H3: Patients on HPN show lower life quality score compared to the general public in the sphere of emotional roles' limitation. H4: Patients on HPN show lower life quality score compared to the general public in the sphere of emotional limitation of social functions. H5: Patients on HPN show lower life quality score compared to the general public in the sphere of pain. H6: Patients on HPN show lower life quality score compared to the general public in the sphere of general mental health. H7: Patients on HPN show lower life quality score compared to the general public in the sphere of vitality. H8: Patients on HPN show lower life quality score compared to the general public in the sphere of general health perception. A quantitative method of collected data analysis was applied to the research implementation. The research was based on the standardized questionnaire SF-36 supplemented with questions dealing with identification of respondents, time consumption of their treatment and their consequent satisfaction at the beginning. The questionnaire was distributed to patients using home parenteral nutrition in specialized nutrition centres of the Thomayer Faculty Hospital in Prague, Faculty hospitals in Brno and Hradec Králové and also by electronic means through the website of the citizen association Life without Intestine. The obtained data were statistically evaluated and processed into illustrative tables and graphs.Detailed mapping of the problems of life quality and highlighting of the neglected spheres of life quality of patients using HPN are the outputs of the thesis. The results will be presented to the members of the workgroup for HPN within their.

Introdução: A infusão parenteral de emulsão lipídica (EL) de óleo de peixe (OP), rica em ácidos graxos ômega-3 (AG n-3), está associada à diminuição do perfil de mediadores pró-inflamatórios em estudos experimentais e clínicos. AG n-3 se incorporam em poucas horas em membranas celulares e geralmente são administrados após a agressão inflamatória. A pancreatite aguda (PA) experimental é modelo de inflamação, local e sistêmico, bem estabelecido. Objetivo: O presente estudo avaliou o efeito da infusão parenteral de EL de OP por curto período, antes da indução de PA, sobre a modulação da resposta inflamatória sistêmica e sobrevida. Métodos: Após cateterização do sistema venoso central, ratos isogênicos Lewis receberam infusão parenteral de EL de óleo de peixe ou solução salina durante 48 horas, quando então foram submetidos à pancreatite aguda, pela injeção retrógrada de 0,5 mL de solução de taurocolato de sódio a 3% no duto pancreático. Após indução de PA, nos períodos de 2, 12 e 24 horas, os animais foram sacrificados para coleta de amostras de sangue e de tecidos para dosagem de marcadores inflamatórios e histopatológicos. Paralelamente, 20 animais de cada grupo foram observados até sete dias após indução de PA, para avaliação de sobrevida. Resultados: O tratamento com EL de óleo de peixe foi associado com diminuição de citocinas pró-inflamatórias IL-1beta (p=0,0006) e IL-6 (p=0,05), diminuição de IL-4 (p= 0,0019) e tendência no aumento de anti-inflamatória IL-10 (p= 0,06), após 24 horas de PA; e com aumento da expressão pulmonar e hepática de proteínas de choque térmico HSP 90, 2 e 12 horas após PA, respectivamente. Após infusão de EL de óleo de peixe, não foram encontrados efeitos sobre os níveis de malonaldeído no fígado e na histopatologia do pâncreas, no período de 2 e 12 horas pós pancreatite aguda; e na taxa de sobrevida, em relação aos demais grupos (p > 0,05). Conclusão: Nossos resultados sugerem que a infusão parenteral de EL de OP 48 horas antes da indução de pancreatite aguda experimental parece influenciar favoravelmente a produção de citocinas inflamatórias e HSP90 hepática e pulmonar, sem impactar sobre a histopatologia da lesão pancreática e a taxa de sobrevida / The parenteral infusion of fish oil (FO) lipid emulsion (LE), rich in omega-3 fatty acids (n-3 FA), is associated with the decrease of pro-inflammatory mediators profile in experimental and clinical studies. N-3 FA are incorporated in a few hours in cell membranes and are generally administered after the inflammatory injury. The experimental acute pancreatitis (AP) is an inflammation, local and systemic well-established model. This study evaluated the effect of parenteral infusion of fish oil LE for a short period before AP induction, on the modulation of systemic inflammatory response and survival. For this, after the central venous catheterization Lewis rats received parenteral infusion of fish oil LE or saline solution for 48 hours, when they were induced to acute pancreatitis by retrograde injection of 0.5 mL of sodium taurocholate at 3% in pancreatic duct. After AP induction, in periods of two, 12 and 24 hours, the animals were sacrificed to collect blood samples and tissues for measurement of inflammatory markers and histopathological. In parallel, 20 animals in each group were observed up to 7 days after induction of AP, for survival analysis. The treatment with fish oil LE was associated with decreased of pro-inflammatory cytokines IL-1beta (p = 0.0006) and IL-6 (p = 0.05), reduction of IL-4 (p = 0.0019) and upward trend of anti-inflammatory IL-10 (p = 0.06) after 24 hours of AP; and increased pulmonary and hepatic expression of heat shock proteins HSP 90 two and 12 hours after AP, respectively. After infusion of fish oil LE, there were no effects on malondialdehyde levels in the liver and the pancreas histopathology in the periods of 2 and 12 hours after acute pancreatitis; and survival rate, compared to the other groups (p > 0.05). Our results suggest that parenteral infusion of FOLE 48 hours before the induction of experimental acute pancreatitis appears to favorably influence the production of inflammatory cytokines; hepatic and pulmonary HSP90, without impacting on the histopathology of pancreatic injury and the survival rate

INTRODUÇÃO: Emulsões lipídicas parenterais (EL) contendo óleo de peixe podem modular favoravelmente a resposta inflamatória e manter ou promover a resposta imunológica, mas há dados insuficientes sobre seu impacto em funções de células da imunidade inata. OBJETIVO: Verificar o efeito da administração endovenosa de EL composta por mistura de triglicérides de cadeia média e óleos de soja, oliva e peixe sobre a migração e fagocitose de leucócitos de ratos, em comparação à EL composta por mistura física de triglicérides de cadeia média e cadeia longa - TCM/TCL, suplementada ou não com óleo de peixe (OP). MÉTODOS: Ratos (Lewis) isogênicos (n=40) foram submetidos à cateterização da veia jugular externa para acesso parenteral. Os animais foram randomizados em quatro grupos, de acordo com sua infusão endovenosa: grupo SMOF: EL contendo 30% de óleo de soja (TCL), 30% de TCM, 25% de óleo de oliva e 15% de OP; grupo TCM/TCL: EL contendo TCM e TCL (1:1 v/v); grupo TCM/TCL/OP: EL composta por TCM/TCL com adição de OP (8:2 v/v); grupo SF: solução fisiológica. Um grupo de animais sem cateterismo venoso também foi desenvolvido (CO-NC). No quinto dia de experimento e após injeção de carvão coloidal pela veia caudal, amostras de sangue e tecido (fígado, pulmão e baço) foram coletadas para análise quimiotática de neutrófilos (câmara de Boyden adaptada) e quantificação do número de macrófagos fagocitantes do carvão coloidal (imunohistoquímica). Os dados foram analisados por ANOVA e pós-teste de Tukey. RESULTADOS: SMOF não alterou a quimiotaxia e fagocitose nos leucócitos estudados. TCM/TCL e TCM/TCL/OP aumentaram o número de macrófagos fagocitantes do fígado e pulmão e somente TCM/TCL/OP apresentou aumento no número de macrófagos fagocitantes no baço (p<0,05). CONCLUSÕES: 1) Emulsões lipídicas, independente de sua composição, não influenciaram a quimiotaxia de neutrófilos; 2) Emulsão lipídica composta por mistura de triglicérides de cadeia média e óleos de soja, oliva e peixe apresentou efeito neutro sobre a quimiotaxia, migração espontânea de neutrófilos e recrutamento de monócitos no fígado, pulmão e baço; 3) Emulsão lipídica de mistura física de triglicérides de cadeia média e cadeia longa estimulou o recrutamento de monócitos, com aumento do número de macrófagos fagocitantes no fígado e pulmão; 4) Emulsão lipídica de mistura física de triglicérides de cadeia média e cadeia longa enriquecida com emulsão lipídica de óleo de peixe, estimulou o recrutamento de monócitos, com aumento do número de macrófagos fagocitantes no fígado, pulmão e baço. / RATIONALE: Parenteral lipid emulsions (LE) with fish oil could modulate inflammatory response and promote or maintain immunologic response, but there are insufficient data about the impact on innate immunity cells functions. AIM: To evaluate the effects of endovenous infusion of LE containing mixture of medium-chain triglycerides and soybean, olive and fish oils on leukocytes migration and phagocytosis in rats, compared to a physical mixture of medium and long-chain triglycerides - MCT/LCT LE supplemented or not with fish oil (FO). METHOD: Isogenic Lewis rats (n=40) were submitted to jugular vein catheterization for parenteral access. The animals were randomized in four groups, according to their infusion: group SMOF: LE containing 30% of soybean oil (LCT), 30% MCT, 25% olive oil and 15% fish oil; group MCT/LCT: LE containing MCT and LCT (1:1 v/v); group MCT/LCT/FO: MCT/LCT LE enriched with fish oil based LE (8:2 v/v); group SS: saline. A non-surgical control (CO-NS) was also performed. In the 5th experimental day and after colloidal carbon injection in tail vein, blood and tissue (liver, lung and spleen) samples were collected for chemotaxis assay (adapted Boyden chamber) and colloidal carbon phagocyting-macrophages quantification (immunohistochemistry). ANOVA and Tukey post test were performed. RESULTS: SMOF LE didn?t influence leukocytes chemotaxis and phagocytosis. MCT/LCT and MCT/LCT/FO LE increased liver and lung resident phagocyting-macrophages number (p<0.05) and only in MCT/LCT/FO group, spleen resident phagocyting-macrophages number was increased (p<0.05). CONCLUSION: 1) Lipid emulsion, independently of composition, has no influence on neutrophils chemotaxis; 2) Lipid emulsion with a mixture of medium-chain triglycerides, soybean, olive and fish oils has neutral effect on neutrophil chemotaxis, random migration and monocyte recruitment to the liver, lung and spleen; 3) Lipid emulsion with a physical mixture of medium and long-chain triglycerides has stimulatory effect on monocyte recruitment, with increase of phagocyting-macrophages number in liver and lung; 4) Lipid emulsion with a physical mixture of medium and longchain triglycerides supplemented with fish oil, has stimulatory effect on monocyte recruitment, with increase of phagocyting-macrophages number in liver, lung and spleen.

Carbon black, which has polycyclic aromatic hydrocarbons (PAHs) adsorbed on its surface, is used in the composition of rubber for pharmaceutical used in injectable drugs and parenteral formulations such as amino acid solutions and lipid emulsions. In this study, the contamination of parenteral preparations administered to newborn infants (NB) by PAHs was evaluated. Commercial solutions used in the composition of parenteral nutrition bags (NP) and the content of the bags administered to a group of ten RN during their period in the neonatal intensive care unit was analyzed. It was also analyzed the metabolite 1-hydroxypyrene in the urine of these infants, as well as in the urine of a group of infants who were not receiving NP (control group). Methods for determination of PAHs and 1-hydroxypyrene by high performance liquid chromatography using detection with DAD and fluorecence, respectively, were developed and validated for the samples of the study. PAHs were extracted from the samples using a polyethylene column. In the urine samples, extraction of metabolite was performed on a C-18 cartridge after its enzymatic hydrolysis. The results showed PAHs contamination in 56 out of 59 samples. Total PAHs concentration ranged from 0.013 mg/L to 10.562 mg/L. Pyrene was present in 50 out of 59 samples. The analysis revealed the presence of the metabolite 1- hydroxypyrene in the urine of babies who received NP, with concentration ranging from 0.039 mg/L to 0.544 mg/L (0.03 and 0.877 mmol/mol creatinine). In the urine of the control group the metabolite was not detected. Considering the toxicity of PAHs and the large volume usually administered in the NP, the results found in this study are worrying. The presence of PAHs in NP administered to newborns is even more important because they are the most vulnerable to adverse effects. / O negro de fumo, que possui hidrocarbonetos policíclicos aromáticos (HPAs) adsorvidos em sua superfície, é utilizado na composição de borrachas de uso farmacêutico usadas em medicamentos injetáveis e formulações parenterais como soluções de aminoácidos e emulsões lipídicas. Neste estudo avaliou-se a contaminação por HPAs em preparações parenterais administradas a recémnascidos (RN). Soluções comerciais usadas na composição das bolsas de nutrição parenteral (NP) bem como o conteúdo das próprias bolsas administradas a um grupo de dez RN durante o período de internação na UTI neonatal foram analisados. Foi também analisado o metabólito 1-hidroxipireno na urina desses RN, bem como de um grupo de RN que não estava recebendo NP (grupo controle). Os métodos para determinação dos HPAs e do 1-hidroxipireno por cromatografia líquida de alta eficiência usando detecção por arranjo de fotodiodos e fluorescência, respectivamente, foram desenvolvidos e validados para as amostras do estudo. Os HPAs foram extraídos das amostras utilizando uma coluna de polietileno. Nas amostras de urina, a extração do metabólito foi realizada em um cartucho C-18 após hidrólise enzimática do mesmo. Os resultados mostraram contaminação por HPAs em 56 das 59 amostras analisadas. O total de HPAs variou de 0,013 mg/L a 10,562 mg/L. O pireno esteve presente em 50 das 59 amostras. A análise das urinas revelou a presença do metabólito 1-hidróxipireno para os bebes que receberam NP, com concentração média entre 0,039 μg/L e 0,544 μg/L (0,03 e 0,877 μmol/mol de creatinina). Na urina dos bebes controle o metabólito não foi detectado. Considerando a toxicidade dos HPAs e o grande volume usualmente administrado na NP, os resultados encontrados nesse estudo são preocupantes. A presença de HPAs na NP administrada a recém-nascidos é ainda mais relevante, dado que são os mais vulneráveis a efeitos adversos.