Efeitos da administração contínua versus intermitente da nutrição enteral em pacientes críticos

PURPOSE: Enteral alimentation is the preferred modality of support in critical patients who have acceptable digestive function and are unable to eat orally, but the advantages of continuous versus intermittent administration are surrounded by controversy. With the purpose of identifying the benefits and complications of each technique, a prospective controlled study with matched subjects was conducted. PATIENTS AND METHODS: Twenty-eight consecutive candidates for enteral feeding were divided into 2 groups (n = 14 each) that were matched for diagnosis and APACHE II score. A commercial immune-stimulating polymeric diet was administered via nasogastric tube by electronic pump in the proportion of 25 kcal/kg/day, either as a 1-hour bolus every 3 hours (Group I), or continuously for 24 hours (Group II), over a 3-day period. Anthropometrics, biochemical measurements, recording of administered drugs and other therapies, thorax X-ray, measurement of abdominal circumference, monitoring of gastric residue, and clinical and nutritional assessments were performed at least once daily. The principal measured outcomes of this protocol were frequency of abdominal distention and pulmonary aspiration, and efficacy in supplying the desired amount of nutrients. RESULTS: Nearly half of the total population (46.4%) exhibited high gastric residues on at least 1 occasion, but only 1 confirmed episode of pulmonary aspiration occurred (3.6%). Both groups displayed a moderate number of complications, without differences. Food input during the first day was greater in Group II (approximately 20% difference), but by the third day, both groups displayed similarly small deficits in total furnished volume of about 10%, when compared with the prescribed diet. CONCLUSIONS: Both administration modalities permitted practical and effective administration of the diet with frequent registered abnormalities but few clinically significant problems. The two groups were similar in this regard, without statistical differences, probably because of meticulous technique, careful monitoring, strict patient matching, and conservative amounts of diet employed in both situations. Further studies with additional populations, diagnostic groups, and dietetic prescriptions should be performed in order to elucidate the differences between these commonly used feeding modalities.ANTECEDENTES: A alimentação enteral é a modalidade preferida de suporte em pacientes graves com função digestiva aceitável porém incapazes de se alimentar por via oral, entretanto as vantagens da oferta contínua em contraste com a intermitente são rodeadas de controvérsias. Tendo como objetivo identificar os benefícios e as complicações destas técnicas, realizou-se um estudo prospectivo e controlado com casos pareados. PACIENTES E MÉTODOS: Vinte e oito pacientes consecutivos candidatos a alimentação enteral foram divididos em dois Grupos (n= 14), pareados segundo diagnóstico e índice APACHE II.Uma dieta polimérica comercial imuno-estimulante foi administrada por sonda nasogástrica e bomba de infusão na proporção de 25 kcal/kg/dia, em forma de bolo por uma hora a cada três horas (Grupo I), ou continuamente nas 24 horas (Grupo II), durante três dias. Os métodos incluiram antropometria, dosagens bioquímicas, registro de uso de drogas e outras terapêuticas, RX de tórax, circunferência abdominal, resíduo gástrico, e avaliação clínica e nutricional, efetuada no mínimo uma vez por dia. Os principais desfechos colimados neste estudo foram frequência de distensão abdominal e aspiração pulmonar, e capacidade de atingir a meta calórica pretendida. RESULTADOS: Quase metade da população total (46,4%) apresentou resíduos gástricos elevados em pelo menos uma ocasião, porém somente foi registrado um episódio confirmado de aspiração pulmonar (3,6%). Ambos os grupos padeceram de um número moderado de complicações, sem diferenças. O ganho de dieta no Grupo II foi maior no primeiro dia, porém no terceiro dia ambos os grupos exibiam déficits pequenos e semelhantes no ganho dietético, quando comparados com o volume prescrito. CONCLUSÕES: Ambas as modalidades de oferta permitiram a administração prática e eficiente da dieta, com freqüentes anormalidades registradas porém escassas complicações clinicamente significativas. Os dois grupos se comportaram analogamente, com poucas diferenças nos resultados, provavelmente devido à técnica meticulosa, monitorização cuidadosa, rígido pareamento dos pacientes, e volumes modestos da dieta empregados nas duas circunstâncias. Investigações subseqüentes deveriam ser elaboradas com populações, grupos diagnósticos e prescrições dietéticas adicionais, a fim de elucidar as diferenças entre estas modalidades de alimentação comumente usadas

Custo de medicamentos produzidos pelo Hospital Universitário, papel da Farmácia Central

The hospital pharmacy in large and advanced institutions has evolved from a simple storage and distribution unit into a highly specialized manipulation and dispensation center, responsible for the handling of hundreds of clinical requests, many of them unique and not obtainable from commercial companies. It was therefore quite natural that in many environments, a manufacturing service was gradually established, to cater to both conventional and extraordinary demands of the medical staff. That was the case of Hospital das Clinicas, where multiple categories of drugs are routinely produced inside the pharmacy. However, cost-containment imperatives dictate that such activities be reassessed in the light of their efficiency and essentiality. METHODS: In a prospective study, the output of the Manufacturing Service of the Central Pharmacy during a 12-month period was documented and classified into three types. Group I comprised drugs similar to commercially distributed products, Group II included exclusive formulations for routine consumption, and Group III dealt with special demands related to clinical investigations. RESULTS: Findings for the three categories indicated that these groups represented 34.4%, 45.3%, and 20.3% of total manufacture orders, respectively. Costs of production were assessed and compared with market prices for Group 1 preparations, indicating savings of 63.5%. When applied to the other groups, for which direct equivalent in market value did not exist, these results would suggest total yearly savings of over 5 100 000 US dollars. Even considering that these calculations leave out many components of cost, notably those concerning marketing and distribution, it might still be concluded that at least part of the savings achieved were real. CONCLUSIONS: The observed savings, allied with the convenience and reliability with which the Central Pharmacy performed its obligations, support the contention that internal manufacture of pharmaceutical formulations was a cost-effective alternative in the described setting.A Farmácia Hospitalar em instituições avançadas e de grande porte evoluiu de uma simples unidade de armazenamento e distribuição, para um centro de manipulação altamente especializado, responsável pelo processamento de centenas de requisições clínicas, muitas delas únicas e não disponíveis de fontes comerciais. Foi perfeitamente natural portanto que em muitos ambientes, um Serviço Industrial fosse gradualmente estabelecido, visando responder a demandas tanto convencionais como extraordinárias da equipe médica. Tal foi o caso do Hospital das Clínicas, onde múltiplas categorias de fármacos são rotineiramente elaboradas nas dependências da Farmácia. Entretanto, imperativos de contenção de gastos determinam que tais atividades sejam reajuizadas sob o prisma de sua eficiência e essencialidade. MÉTODOS: Num estudo prospectivo, a produção do Serviço Industrial da Farmácia Central durante um período de 12 meses foi documentada, e classificada em três modalidades. O Grupo I abrangia medicamentos similares a outros fornecidos comercialmente, no Grupo II foram listadas formulações de composição exclusiva, e finalmente o Grupo III espelhava pedidos especiais voltados para investigações clínicas. RESULTADOS: Os achados das diversas categorias assinalaram que 34,4%, 45,3% e 20,3% dos medicamentos elaborados correspondiam a estes três grupos, respectivamente.Os custos industriais foram calculados para os fármacos do Grupo I e comparados com valores de mercado, chegando-se a uma economia de 63,5%.Quando extrapolada para os outros dois grupos, relativamente aos quais não se contava com preços comerciais diretamente equivalentes, atingiu-se uma estimativa superior a 5 100 000 dólares de economia durante um ano de operação. Mesmo levando-se em conta que tais contas deixaram de lado muitos custos, notavelmente aqueles subordinados à comercialização e distribuição, foi lícito concluir que pelo menos parte da economia citada era verdadeira. CONCLUSÕES: A economia observada, em combinação com a eficiência e confiabilidade com que a Farmácia desempenhou suas obrigações, vieram ao encontro do ponto de vista de que a manufatura interna de drogas foi uma alternativa vantajosa sob o prisma de custos, no contexto descrito

Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>;95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications

A Higher Meal Frequency May be Associated with Diminished Weight Loss after Bariatric Surgery

OBJECTIVE: This study aimed to investigate the relationship between meal frequency, the occurrence of vomiting and weight loss among patients submitted to Roux-en-Y gastric bypass up to 9 months after surgery. METHODS: Female patients (n = 80) were followed at 3-month intervals for 9 months. Weight, BMI, 24-hour dietary recall, drug consumption and vomiting episodes were recorded and compared with nutritional outcome. RESULTS: The BMI values at 3, 6 and 9 months were 45.1 ± 9.7, 39.9 ± 7.6 and 35.4 ± 8.2 kg/m², respectively. The corresponding choleric intakes were 535.6 ± 295.7, 677.1 ± 314.7 and 828.6 ± 398.2 kcal/day, and the numbers of daily meals were 5.0 ± 2.5, 4.7 ± 1.8 and 4.9 ± 1.0, respectively. The peak of vomiting episodes occurred within 6 months; however, patients tolerated this complication despite its high prevalence. A significant negative correlation between weight loss and diet fractioning, but not vomiting, was observed throughout the entire postoperative period (P = 0.001). CONCLUSIONS: 1) Frequent small meals were associated with a reduction in weight loss after gastric bypass and a decrease in vomiting episodes at 6 months, and 2) vomiting did not interfere with nutritional outcome. Unless required because of vomiting or other reasons, multiple small meals may not be advantageous after such intervention

Uso de múltiplos antimicrobianos por pacientes clínicos: um índice prognóstico de mortalidade hospitalar

PURPOSE: To quantify the use of multiple and prolonged antibiotics and anti-infective drug therapy in clinical patients in a 144-bed hospital. METHODS: Adult patients (2,790 patients with 3,706 admissions over a period of 19 months) were investigated prospectively regarding treatment with anti-infective agents. The mean age was 57.4 (range, 18.8 - 97 years), and 54.3% were females (2012). RESULTS: Hospital stay was 5.5 (6.7 days (range, 2 - 226 days), with duration up to 10 days for 91.9% of the subjects. Antibiotics or other agents were administered to 1,166 subjects (31.5%), 325 (8.8%) required assistance in the ICU, and a total of 141 (3.8%) died. The association between anti-infective drug therapy and hospital mortality was statistically significant (P < .01) with a strong linear correlation (r = 0.902, P = .014). The quantity of prescribed antimicrobial drugs, age, and need for ICU assistance were independent variables for death by logistic regression analysis. The odds ratio for anti-infective drug therapy was 1.341 (1.043 to 1.725); for age, 1.042 ( 1.026 to 1.058); and for stay in the ICU, 11.226 ( 6.648 to 18.957). CONCLUSIONS: 1) The use of large amounts of anti-infective drug therapy was associated with higher hospital mortality according to both univariate and logistic regression analysis; 2) The adverse influence was less marked than that of hospitalization in ICU but of a similar order of magnitude as age; 3) Further studies should elucidate whether infectious foci, noninfectious morbidity, or drug effects underlie this undesirable concurrence.OBJETIVOS: Tendo como propósito quantificar o uso múltiplo ou prolongado de antibióticos e quimioterápicos antimicrobianos em pacientes clínicos, um estudo prospective foi executado em um hospital de 144 leitos. MÉTODOS: Enfermos adultos tratados com antibióticos e quimioterrápicos anti-infecciosos (2.790 pacientes com 3.706 internações) foram investigados. A duração da hospitalização foi de 5,5 &plusmn; 6,7 dias (2 -226), sendo o prazo de até 10 dias em 91,0% da população. A idade era de 57.4 &plusmn;18.8 anos (20 -97), e 54.3% eram mulheres (2.012). Antibióticos e outros agentes foram administrados a 1.166 indivíduos (31,5%); 325 (8,8%) necessitaram de assistência na unidade de terapia intensiva, e no total 141 (3,8%) faleceram. RESULTADOS: A associação entre medicação antiinfecciosa e mortalidade hospitalar foi estatisticamente significativa (p< 0,01) com forte correlação linear (r= 0,902, p=0,014). A quantidade de antimicrobianos prescritos, a idade e o requerimento de cuidados intensivos foram variáveis independentes para óbito na regressão logística. O cálculo do "odds ratio" para a medicação analisada assinalava probabilidade de desfecho negativo de 1,341 (1,043 a 1,725) para múltiplos antimicrobianos, para a idade de 1,042 (1,026 a 1,058), e para admissão na UTI de 11,226 (6,648 a 18,957). CONCLUSÕES: 1) O uso de grandes quantidades de agentes antimicrobianos associou-se com mortalidade hospitalar aumentada tanto pela análise univariada como na regressão logística; 2) Seu efeito adverso foi menos marcado que o associado à internação na unidade de cuidados intensivos, porém de magnitude semelhante ao da idade; 3) Estudos adicionais são necessários para elucidar se este resultado indesejável se prende à ação de focos infecciosos subjacentes, à morbidade não infecciosa ou aos efeitos colaterais das drogas utilizadas

Pulmonary function and aerobic capacity in asymptomatic bariatric candidates with very severe morbid obesity

PURPOSE: Aerobic capacity and respiratory function may be compromised in obesity, but few studies have been done in highly obese bariatric candidates. In a prospective study, these variables were documented in the preoperative period, aiming to define possible physiologic limitations in a apparently healthy and asymptomatic population. METHOD: Forty-six consecutively enrolled adults (age 39.6 &plusmn; 8.4 years, 87.0% females, body mass index /BMI 49.6 &plusmn; 6.3 kg/m² ) were analyzed. Ventilatory variables were investigated by automated spirometry, aerobic capacity was estimated by a modified Bruce test in an ergometric treadmill, and body composition was determined by bioimpedance analysis. RESULTS: Total fat was greatly increased (46.4 &plusmn; 4.6% of body weight) and body water reduced (47.3 &plusmn; 4.6 % body weight), as expected for such obese group. Spirometric findings including forced vital capacity of 3.3 &plusmn; 0.8 L and forced expiratory volume-1 second of 2.6 &plusmn; 0.6 L were usually acceptable for age and gender, but mild restrictive pulmonary insufficiency was diagnosed in 20.9%. Aerobic capacity was more markedly diminished, as reflected by very modest maximal time (4.5 &plusmn; 1.1 min) and distance (322 &plusmn;142 m) along with proportionally elevated maximal oxygen consumption (23.4 &plusmn; 9.5 mL/kg/min) achieved by these subjects during test exercise. CONCLUSIONS: 1) Cardiopulmonary evaluation was feasible and well-tolerated in this severely obese population; 2) Mean spirometric variables were not diminished in this study, but part of the population displayed mild restrictive changes; 3) Exercise tolerance was very negatively influenced by obesity, resulting in reduced endurance and excessive metabolic cost for the treadmill run; 4) More attention to fitness and aerobic capacity is recommended for seriously obese bariatric candidates;OBJETIVOS: A capacidade aeróbica e a função respiratória podem estar comprometidas na obesidade mórbida, todavia poucos estudos são disponíveis em candidatos à cirurgia bariátrica com massa corporal muito elevada.Num protocolo prospectivo, estas variáveis foram documentadas no pré-operatório, visando despistar possíveis limitações fisiológicas numa população nominalmente sadia e sem queixas. MÉTODO: Foram analisados 46 casos consecutivos (idade 39.6 &plusmn; 8.4 anos, 87.0% mulheres, índice de massa corporal /IMC 49.6 &plusmn; 6.3 kg/m2 )). As variáveis ventilatórias foram investigadas por espirometria automatizada e a capacidade aeróbica mediante um teste de Bruce modificado em esteira ergométrica, sendo que a composição corpórea foi fornecida pela bioimpedância. RESULTADOS: A gordural total estava fortemente aumentada (46.4 &plusmn; 4.6% do peso) e a água corporal diminuída (47.3 &plusmn; 4.6 % do peso) nesta série, tal como esperado para o grau de obesidade descrito. Os achados espirométricos médios incluindo-se capacidade vital forçada de 3.3 &plusmn; 0.8 L e volume expiratório forçado de 1 segundo de 2.6 &plusmn; 0.6 L não fugiram do aceitável para idade e sexo. Entretanto em 20,9% insuficiência respiratória restritiva leve foi diagnosticada. A capacidade aeróbica estava mais nitidamente prejudicada, seja pelo baixo tempo e distância máxima atingidos (respectivamente 4.5 &plusmn; 1.1 min e 322 &plusmn;142 m), seja pelo custo proporcionalmente alto do esforço, refletido pelo consumo máximo de oxigênio (23.4 &plusmn; 9.5 ml/kg/min); CONCLUSÕES: 1) A avaliação cárdio-respiratória foi factível e bem tolerada; 2) As variáveis espirométricas méias não estavam alteradas, porém parte da população exibiu transformações restritivas leves; 3) A obesidade interferiu negativamente sobre a tolerância ao exercício, reduzindo o desempenho e aumentando o custo metabólico da corrida em esteira ergométrica; 4) Recomenda-se maior atenção à capacidade aeróbica de candidatos bariátricos seriamente obesos

Alterações nos compartimentos hídricos e energéticos do organismo durante a greve de fome

Prolonged total food deprivation in non-obese adults is rare, and few studies have documented body composition changes in this setting. In a group of eight hunger strikers who refused alimentation for 43 days, water and energy compartments were estimated, aiming to assess the impact of progressive starvation. Measurements included body mass index (BMI), triceps skinfold (TSF), arm muscle circumference (AMC), and bioimpedance (BIA) determinations of water, fat, lean body mass (LBM), and total resistance. Indirect calorimetry was also performed in one occasion. The age of the group was 43.3±6.2 years (seven males, one female). Only water, intermittent vitamins and electrolytes were ingested, and average weight loss reached 17.9%. On the last two days of the fast (43rd-44th day) rapid intravenous fluid, electrolyte, and vitamin replenishment were provided before proceeding with realimentation. Body fat decreased approximately 60% (BIA and TSF), whereas BMI reduced only 18%. Initial fat was estimated by BIA as 52.2±5.4% of body weight, and even on the 43rd day it was still measured as 19.7±3.8% of weight. TSF findings were much lower and commensurate with other anthropometric results. Water was comparatively low with high total resistance, and these findings rapidly reversed upon the intravenous rapid hydration. At the end of the starvation period, BMI (21.5±2.6 kg/m²) and most anthropometric determinations were still acceptable, suggesting efficient energy and muscle conservation. Conclusions: 1) All compartments diminished during fasting, but body fat was by far the most affected; 2) Total water was low and total body resistance comparatively elevated, but these findings rapidly reversed upon rehydration; 3) Exaggerated fat percentage estimates from BIA tests and simultaneous increase in lean body mass estimates suggested that this method was inappropriate for assessing energy compartments in the studied population; 4) Patients were not morphologically malnourished after 43 days of fasting; however, the prognostic impact of other impairments was not considered in this analysis.A privação total e prolongada de alimentos em adultos não-obesos é raramente vista, e poucos estudos documentaram as modificações da composição corpórea neste contexto.Num grupo de oito casos de greve de fome durante 43 dias, procedeu-se à estimativa dos compartimentos hídricos e energéticos, visando averiguar a influência sobre os mesmos da desnutrição progressiva.Os métodos incluiram índice de massa corporal (IMC), prega cutânea do tríceps (PCT), circunferência muscular do braço, e determinação através da bioimpedância (BIA) da água, massa gorda, massa magra e resistência corpórea total..A calorimetria indireta foi realizada em uma ocasião apenas.A idade do grupo era de 43,3± 6,2 anos (sete homens, uma mulher), somente água e ocasionais eletrólitos e vitaminas foram ingeridos no jejum, e a perda de peso média foi de 17,9%. Por volta do 43º dia da greve iniciou-se a reposição venosa rápida de fluidos, vitaminas e eletrólitos,antes de se prosseguir com a realimentação.A gordura corporal diminuiu em aproximadamente 60% (BIA e PCT), ao passo que o IMC caiu apenas 18%.A estimativa da gordura total inicial por BIA foi de 52,2± 5,4% do peso corporal, e mesmo no 43º dia do evento o valor calculado era de 19,7± 3,8% do peso.Os valores correspondentes deduzidos da PCT mostraram-se substancialmente inferiores, e mais compatíveis com os demais índices antropométricos. A água corporal revelou-se inicialmente contraída, com resistência elevada,sendo que estes achados se reverteram rapidamente por ocasião da hidratação venosa rápida.Quando do término da greve de fome o IMC (21,5± 2,6 kg/m²) e outras variáveis antropométricas revelavam-se numericamente aceitáveis, sugerindo eficiente conservação de musculatura e energia na fase de dieta zero.Conclui-se que: 1) Todos os compartimentos orgânicos se contrairam na greve de fome, porém o tecido adiposo foi de longe o mais afetado; 2) A água corporal mostrou-se reduzida com elevada resistência total, mas estes achados inverteram-se prontamente mediante hidratação parenteral; 3) O encontro de gordura total excessiva e de aumento da massa magra com o avançar do jejum sugerem que as leituras de BIA são inapropriadas para esta população e fornecem resultados incoerentes; 4) Com base nos parâmetros expostos os doentes não estavam morfologicamente desnutridos ao cabo de 43 dias, todavia não foram aqui avaliados outros transtornos de considerável importância prognóstica

Oseltamivir compounding in the hospital pharmacy during the (H1N1) influenza pandemic

AIMS: Pandemics impose large demands on the health care system. The supply of appropriate chemotherapeutic agents, namely oseltamivir solution, presented a serious challenge in the recent influenza pandemic. This study reports on the rational series of pharmacotechnical steps that were followed to appropriately handle bulk oseltamivir powder to meet the increased demand. METHODS: During a six-week period in August and September of 2009, a task force was created in the Central Pharmacy of Hospital das Clínicas to convert imported oseltamivir phosphate into ready-to-use solution for utilization by physicians and public health authorities. The protocol included dissolution, physico-chemical tests and the bottling of a liquid microdose formulation for emergency room and outpatient dispensing with adequate quality control during all phases. RESULTS: The successful production routine was based on a specially designed flowchart according to which a batch of 33210 g of oseltamivir powder was converted into 32175 solution units during the aforementioned period with a net loss of only 2.6%. The end products were bottles containing 50 ml of 15 mg/mL oseltamivir solution. The measured concentration was stable and accurate (97.5% - 102.0% of the nominal value). The drug was prescribed as both a prophylactic and therapeutic agent. DISCUSSION: Hospital pharmacies are conventionally engaged in the manipulation of medical prescriptions and specialty drugs. They are generally responsible for only small-scale equipment used for manufacturing and quality-control procedures. The compounding of oseltamivir was a unique effort dictated by exceptional circumstances. CONCLUSION: The shortage of oseltamivir solution for clinical use was solved by emergency operationalization of a semi-industrial process in which bulk powder was converted into practical vials for prompt delivery