Impactos da covid-19 sobre a gestaçãono desenvolvimento da pré-eclâmpsia: revisão integrativa / Impacts of COVID-19 during pregnancy on the development of pre-eclampsia: an integrative review

Objetivo: Identificar as evidências cientificas acerca da associação da covid-19 e o desenvolvimento de pré-eclâmpsia. Método: Trata-se de uma revisão integrativa, realizada em abril de 2022, mediante acesso às bases de dados: Medical Literature Analysis and Retrieval System Online (MEDLINE) e Portal Regional da Biblioteca Virtual em Saúde (BVS). A partir da utilização dos descritores em saúde: Gestantes, Pré-eclâmpsia e COVID-19. Resultados: Foram incluídos 15 estudos na síntese avaliativa, onde 13 foram provenientes da PubMed (86,6%) e 02 da BVS (13,3%). Quanto ao desenho, seis (40%) estudos foram do tipo relato ou estudo de caso, cinco (33,3%) do tipo revisão sistemática, com destaque para três revisões com meta-análise, dois (13,3%) se tratou estudos observacionais, um (6,6%) estudo descritivo e um (6,6%) estudo de coorte. Conclusão: Foram identificados estudos que associaram o desenvolvimento da pré-eclâmpsia à infecção causada pelo Covid-19, no entanto, outros estudos destacam a detecção de uma síndrome semelhante a pré-eclâmpsia, destacando a necessidade da realização de um diagnóstico diferencial.(AU)

Objective: To identify the scientific evidence on the association between covid-19 and the development of pre-eclampsia. Method: This is an integrative review, carried out in April 2022, through access to the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) and Regional Portal of the Virtual Health Library (VHL). Using the health descriptors: Pregnant women, Pre-eclampsia and COVID-19. Results: 15 studies were included in the evaluation synthesis, of which 13 came from PubMed (86.6%) and 02 from the VHL (13.3%). In terms of design, six (40%) studies were of the case report or study type, five (33.3%) were of the systematic review type, with emphasis on three reviews with meta-analysis, two (13.3%) were observational studies, one (6.6%) was a descriptive study and one (6.6%) was a cohort study. Conclusion: Studies were identified that associated the development of pre-eclampsia with infection caused by Covid-19, however, other studies highlight the detection of a syndrome similar to pre-eclampsia, highlighting the need for a differential diagnosis.(AU)

Objetivo: Identificar las evidencias científicas sobre la asociación entre el covid-19 y el desarrollo de preeclampsia. Método: Se trata de una revisión integradora, realizada en abril de 2022, a través del acceso a las bases de datos: Medical Literature Analysis and Retrieval System Online (MEDLINE) y Portal Regional de la Biblioteca Virtual en Salud (BVS). Utilizando los descriptores de salud: Embarazadas, Preeclampsia y COVID-19. Resultados: 15 estudios fueron incluidos en la síntesis de evaluación, de los cuales 13 procedían de PubMed (86,6%) y 2 de la BVS (13,3%). En cuanto al diseño, seis (40%) estudios fueron del tipo informe o estudio de caso, cinco (33,3%) fueron revisiones sistemáticas, especialmente tres revisiones con meta-análisis, dos (13,3%) fueron estudios observacionales, uno (6,6%) fue un estudio descriptivo y uno (6,6%) fue un estudio de cohortes. Conclusión: Fueron identificados estudios que asocian el desarrollo de preeclampsia con infección causada por Covid-19, sin embargo, otros estudios destacan la detección de un síndrome semejante a la preeclampsia, enfatizando la necesidad de realizar un diagnóstico diferencial.(AU)

Pharmacokinetics and therapeutic target attainment of vancomycin in pediatric post-liver transplant patients

Abstract Introduction Vancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. Materials and methods Patients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. Results Sixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2= 0.5). Conclusions Pediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment.

Monitoramento orientado pela área sob a curva da vancomicina em pacientes pediátricos / Vancomycin area under the curve-guided monitoring in pediatric patients

RESUMO Objetivo: Avaliar a probabilidade de atingir o alvo pela razão entre a área sob a curva e a concentração inibitória mínima de vancomicina em pacientes pediátricos após o esquema de dose empírica e demonstrar a aplicabilidade desse método para o monitoramento da vancomicina. Metódos: Foi realizado um estudo de coorte retrospectivo que incluiu pacientes pediátricos com função renal normal internados entre janeiro e dezembro de 2020. O modelo de um compartimento com cinética de primeira ordem foi utilizado para estimar os parâmetros farmacocinéticos, e a área sob a curva foi calculada pela regra do trapézio. O alvo terapêutico foi definido como a razão entre a área sob a curva e a concentração inibitória mínima ≥ 400 e < 600. O teste do qui-quadrado foi aplicado para comparar a probabilidade de atingir o alvo nos grupos etários, enquanto os parâmetros farmacocinéticos foram comparados pelo teste de Kruskal-Wallis com o teste de Dunn para análises post hoc. Consideraram-se significativos os valores de p < 0,05. Resultados: Foram analisados, no total, 42 pares de níveis de vancomicina de 17 pacientes inscritos neste estudo. Após a dose diária empírica de vancomicina, o alvo terapêutico foi atingido em cinco (29%) pacientes; quatro pacientes (24%) apresentavam razão entre a área sob a curva inicial supraterapêutica e o valor de concentração inibitória mínima (> 600mg.h/L) e oito (47%) tinham valores subterapêuticos (< 400mg.h/L). Os patógenos mais identificados foram Staphylococcus spp. (n = 7). Os níveis de vale e as áreas sob a curva mostraram valores moderados de correlação (R2 = 0,73). Um (6%) paciente apresentou lesão renal aguda. Conclusão: A maioria dos pacientes não atingiu o alvo terapêutico com esquema de dose empírica de vancomicina, e a implementação de dosagem baseada na área sob a curva usando duas medições de amostra permitiu ajustes de dose em tempo real com base nos parâmetros farmacocinéticos dos indivíduos.

ABSTRACT Objective: To assess the percentage of vancomycin area under the curve/minimum inhibitory concentration target attainment in pediatric patients after the empirical dose regimen and to demonstrate the applicability of this method for vancomycin monitoring. Methods: A retrospective cohort study was performed including pediatric patients with normal renal function admitted between January 2020 and December 2020. The one-compartment model with first-order kinetics was used to estimate the pharmacokinetic parameters, and the area under the curve was calculated by the trapezoidal rule. The therapeutic target was defined as area under the curve/minimum inhibitory concentration ≥ 400 and < 600. The Chi-squared test was applied to compare the percentage of target attainment over age groups, while the pharmacokinetic parameters were compared by the Kruskal-Wallis test with Dunn's test for post hoc analyses. We considered significant p-values < 0.05. Results: In total, 42 pairs of vancomycin levels were analyzed from 17 patients enrolled in this study. After empirical vancomycin daily dosing, the therapeutic target was achieved in five (29%) patients; four patients (24%) had a supratherapeutic initial area under the curve/minimum inhibitory concentration value (> 600mg.h/L), and eight (47%) patients had subtherapeutic values (< 400mg.h/L). The most identified pathogens were Staphylococcus spp. (n = 7). Trough levels and areas under the curve showed moderate correlation values (R2 = 0.73). Acute kidney injury occurred in one (6%) patient. Conclusion: Most patients did not reach the therapeutic target with a vancomycin empirical dose regimen, and the implementation of area under the curve-based dosing using two sample measurements allowed for real-time dose adjustments based on individuals' pharmacokinetic parameters.

Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

OBJECTIVES: The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure. METHODS: Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10) or the equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol target-controlled infusion (2 μg/mL) during surgery. The propofol concentration was then reduced to 1 μg/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed. RESULTS: Significant increases (two- to five-fold) in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048). CONCLUSIONS: The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.

Análise de impacto orçamentário de tecnologia de tecnologias de banho no leito em pacientes adultos em unidades cardiointensivas / Analysis of the budget impact of technology of bathing technologies in the bed in adult patients in cardiointensive units

Os estudos de Avaliações Econômicas em Saúde (AES) compreendem um grande número de métodos usados na Avaliação de Tecnologias em Saúde (ATS). As ATS são uma prioridade na agenda de pesquisas e fomentos do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Esses estudos geram impactos diretos na instituição e para a assistência de enfermagem e, no sentido mais lato, à população de uma maneira geral, na medida em que pode otimizar a alocação de recursos aumentando a sua base de abrangência populacional, sobretudo aquela coberta pelo Sistema Único de Saúde (SUS). Este estudo teve o como Objetivo Geral: Construir uma calculadora de custos baseada na Planilha Brasileira de Impacto Orçamentário do banho no leito tradicional a 42,5ºC; banho no leito com frasco de água destilada aquecida e; banho no leito com lenços umedecidos em pacientes cardíacos graves internados em unidades cardiointensivas. Os objetivos específicos do estudo foram: Elencar os itens de custo das tecnologias de banho no leito em pacientes cardíacos graves em uma unidade cardiointensiva. Mensurar o tempo médio da assistência de enfermagem despendido e requerido para a realização cada uma das tecnologias de banho no leito; Registrar as possíveis intercorrências clínicas associadas às tecnologias de banho no leito; e Elaborar uma calculadora de custos das tecnologias de banho no leito, através da adaptação da PBio com a inclusão do custo do capital humano, baseado no tempo requerido e necessário para a realização de cada um dos banhos no leito nas diferentes composições de equipe de enfermagem. O estudo foi desenvolvido entre os dias 01 fevereiro a 30 de agosto de 2017. A amostra de conveniência correspondeu a 18 pacientes em pós-operatório imediato de cirurgia cardíaca. A coleta de dados deu-se nas primeiras 72 h após a cirurgia cardíaca. Trata-se de um segmento do Projeto Integrado "Análise do padrão hemodinâmico e o impacto dos tipos de banho no leito em uma unidade cardiointensiva: estudo descritivo", que foi desenvolvido simultaneamente a este estudo. A análise dos dados foi baseada na Planilha Brasileira de Impacto Orçamentário (PBIO) do Ministério da Saúde (MS) do Brasil. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa (CEP) do Hospital Universitário Pedro Ernesto (HUPE) em conformidade com a Resolução 466/2012 do Conselho Nacional de Saúde (CNS) através do parecer Nº 1.823.316. O cálculo de custo das tecnologias de banho no leito estudadas, levando em consideração exclusivamente a Planilha Brasileira de Impacto Orçamentária foi respectivamente de R$ 18.73 (US $ 5.73) para o banho no leito tradicional, R$ 20.71 (US $ 6.33) para o banho no leito com água destilada e de R$ 31.73 (US $ 9.70) para o banho no leito com lenços para banho. Já os custos médios totais identificados dos banhos tradicionais, com água destilada e lenços para banho considerando também o custo com o capital humano foram respectivamente de R$ 75,15 (US $23.00), R$ 60,91 (US $18,62) e R$ 63,23 (US $19.34). A calculadora de custos auxiliará os gestores da instituição onde o estudo foi realizado na indicação da tecnologia de banho no leito que deverá ser padronizada, além de demonstrar o real custo do capital humano de enfermagem na realização deste procedimento. O estudo teve caráter inovador, na medida em que com este produto é possível calcular o custo não só das tecnologias de banho no leito, mas também de outras tecnologias de enfermagem. Isto permitirá o conhecimento do real custo das atividades de enfermagem levando-se em consideração as características regionais e institucionais onde elas são realizadas

The studies of Economic Assessments in Health (AES) comprise a large number of methods used in the Assessment of Health Technologies (ATS). The ATS are a priority in the research and promotion agenda of the National Council for Scientific and Technological Development (CNPq). These studies generate direct impacts on the institution and nursing care and, in the broadest sense, on the population in general, insofar as it can optimize the allocation of resources by increasing its population coverage base, especially that covered by the System Unified Health System (SUS). This study aimed to: Construct a cost calculator based on the Brazilian Budget Impact Spreadsheet of the bath in the traditional bed at 42.5ºC; bed bath with heated distilled water bottle; bath in the bed with wipes moistened in severe cardiac patients hospitalized in cardiointensive units. The specific objectives of the study were: To list the cost items of bathing technologies in the bed in severe cardiac patients in a cardiointensive unit; Measure the average time of nursing care spent and required to perform each of the bath technologies in the bed; To record the possible clinical complications associated with bathing technologies in the bed; and Elaborating a cost calculator for bathing technologies in the bed, through the adaptation of PBio with the inclusion of the cost of human capital, based on the time required and necessary for the realization of each of the baths in the bed in the different compositions of nursing team. The study was carried out from 01 February to 30 August 2017. The convenience sample corresponded to 18 patients in the immediate postoperative period of cardiac surgery. Data collection occurred within the first 72 hours after cardiac surgery. This is a segment of the Integrated Project "Analysis of the hemodynamic pattern and the impact of bath types on the bed in a cardiointensive unit: a descriptive study", which was developed simultaneously with this study. Data analysis was based on the Brazilian Budgetary Impact Sheet (PBIO) of the Brazilian Ministry of Health (MS). This study was approved by the Research Ethics Committee (CEP) of the Pedro Ernesto University Hospital (HUPE) in accordance with Resolution 466/2012 of the National Health Council (CNS) through opinion Nº 1,823,316. The calculation of the budget impact of bathing technologies in the bed studied was respectively R $ 18.73 (US $ 5.73) for bathing in the traditional bed, R $ 20.71 (US $ 6.33) for bathing in the bed with distilled water and R $ 31.73 (US $ 9.70) for bathing in bed with bath towels. Meanwhile, the total average costs of traditional baths, with distilled water and bath towels, also considering the cost of human capital were R $ 75.15 (US $ 23.00), R $ 60.91 (US $ 18.62), and R $ 63.23 (US $ 19.34). The cost calculator will help the managers of the institution where the study was carried out in the indication of bath technology in the bed that should be standardized, in addition to demonstrating the real cost of nursing human capital in performing this procedure. The study had an innovative character, since with this product it is possible to calculate the cost not only of bathing technologies in the bed, but also of other nursing technologies. This will allow the knowledge of the real cost of nursing activities taking into account the regional and institutional characteristics in which they are performed

Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method / Correlação farmacocinética-farmacodinâmica de imipenem em pacientes queimados pediátricos utilizando um método bioanalítico de cromatografia líquida

A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r²=0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients...

Desenvolveu-se e aplicou-se método bioanalítico para quantificar concentrações de imipenem livre para estudos de farmacocinética (PK) e de correlação PK/PD dos ajustes de dose requeridos para manter a efetividade antimicrobiana em pacientes pediátricos queimados. Utilizou-se coluna Supelcosil LC18 (250 x 4,6 mm 5 micra), fase móvel binária, consistindo de tampão fosfato 0,01M pH 7,0 e acetonitrila (99:1, v/v) e fluxo de 0,8 mL/min. O método mostrou boa recuperação absoluta (acima de 90%), boa linearidade (0,25-100,0 µg/mL, r²=0.999), boa sensibilidade (LLOQ: 0,25 µg/mL; LLOD: 0,12 µg/mL) e estabilidade aceitável. Os valores de precisão inter/intradia foram 7,3/5,9% e a exatidão média foi de 92,9%. O método bioanalítico foi aplicado para quantificar concentrações de fármaco livre em crianças com queimaduras, Seis pacientes pediátricos queimados (idade média de 7,0 anos, 27,5 kg), com função renal normal e 33% da superfície total queimada foram investigados prospectivamente. Lesões por inalação estavam presentes em 4/6 (67%) dos pacientes. O monitoramento plasmático e a as avaliações de PK foram efetuadas utilizando coleção de amostras seriais de sangue para cada série, totalizando 10 conjuntos. O alvo PK/PD alcançado (40%T>MIC) para cada concentração inibitória mínima (MIC: 0,5, 1,0, 2,0, 4,0 mg/L) ocorreu em porcentagem maior do que 80% dos conjuntos investigados e 100% após o ajuste de dose. Em conclusão, a purificação das amostras do plasma usando técnica de ultrafiltração seguida de quantificação das medidas do imipenem no plasma usando método de cromatografia líquida é bastante simples, útil e necessita de pequenos volumes para as amostras de sangue. Além disso, pequena quantidade de plasma (0,25 mL) é necessário para garantir a efetividade do fármaco nos pacientes pediátricos queimados. Há, ainda, baixo risco de neurotoxicidade, o que é importante, visto que as farmacocinéticas são imprevisíveis nesses pacientes...

Susceptibility oo antibiotics in urinary tract nfections in a secondary care ssetting from 2005-2006 and 2010-2011, in são paulo, Brazil: data from 11,943 urine cultures / Suscetibilidade a antibióticos em infecções de trato urinário em um hospital secundário, 2005-2006 e 2010-2011, em São Paulo, Brasil: dados de 11.943 uroculturas

Introduction: Urinary tract infection (UTI) has a high incidence and recurrence, therefore, treatment is empirical in the majority of cases. Objectives: The aim of this study was to analyze the urine cultures performed at a secondary hospital, during two periods, 2005-2006 and 2010-2011, and to estimate the microbial resistance. Patients and methods: We analyzed 11,943 aerobic urine cultures according to basic demographic data and susceptibility to antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) for Vitek 1 and 2. Results: Most of our cohort consisted of young adult females that were seen at the Emergency Department. E. coli was the most frequent (70.2%) among the 75 species isolated. Resistance of all isolates was ≥ 20% for trimethoprim/sulfamethoxazole (TMP/SMX), norfloxacin, nitrofurantoin, cefazolin and nalidixic acid. Although E. coli was more susceptible (resistance ≥ 20% for TMP/SMX and nalidixic acid) among all of the isolates, when classified by the number and percentage of antibiotic resistance. Global resistance to fluoroquinolones was approximately 12%. Risk factors for E. coli were female gender and an age less than 65 years. Men and patients older than 65 years of age, presented more resistant isolates. Extended spectrum beta-lactamases (ESBL) were identified in 173 out of 5,722 Gram-negative isolates (3.0%) between 2010 and 2011. Conclusion: E. coli was the most frequent microbe isolated in the urine cultures analyzed in this study. There was a significant evolution of bacterial resistance between the two periods studied. In particular, the rise of bacterial resistance to fluoroquinolones was concerning.

Introdução: A infecção do trato urinário (ITU) tem alta incidência e recorrência, e o tratamento é empírico na maioria dos casos. Objetivos: O objetivo deste estudo foi analisar as culturas de urina realizadas em um hospital secundário, durante dois períodos: 2005-2006 e 2010-2011, para estimar a resistência microbiana. Pacientes e métodos: Foram analisadas 11.943 culturas aeróbicas de urina de acordo com um conjunto de dados demográficos básicos e susceptibilidade aos antibióticos, obedecendo às normas do Clinical and Laboratory Standards Institute (CLSI) para Vitek 1 e 2. Resultados: A maioria dos participantes era adulta e jovem atendida no Serviço de Emergência. E. coli foi a mais freqüente (70,2%) entre as 75 espécies isoladas. Resistência de todos os isolados foi ≥ 20% para sulfametoxazol/trimetoprim (SMX/TMP), norfloxacina, nitrofurantoína, cefazolina e ácido nalidíxico, apesar de E. coli ter sido mais suscetível (resistência ≥ 20% apenas para SMX/TMP e ácido nalidíxico) entre todos os isolados, levando em conta a porcentagem de resistência e o número de antibióticos testados. Resistência às fluoroquinolonas foi de 12%. Fatores de risco para E. coli: sexo feminino e idade < 65 anos. Homens e pacientes com mais de 65 anos apresentaram isolados mais resistentes. Beta-lactamases de espectro estendido (ESBL) foram identificadas em 173 de 5.722 isolados Gram-negativos (3,0%), 2010-2011. Conclusões: E. coli foi o isolado mais sensível a antibióticos. Houve uma evolução significativa da resistência antimicrobiana entre os dois períodos. Foi preocupante o aumento da resistência às fluoroquinolonas.

Inclusão digital e conselheiros de saúde: uma política para a redução da desigualdade social no Brasil / Digital inclusion and health counselors: a policy for the reduction of social inequalities in Brazil

Inequalities in health conditions remain even twenty years after the implementation of Unified Health System (SUS). This condition burdens social movements exerting social control on the health care area with a continuous fight. In this struggle, the accumulation of political power is related to an increase in the capacity to acquire knowledge and information. This study aims at fathoming the inequality surrounding the digital inclusion of Health Counselors (HC) of different regions within the country. We have adopted the qualitative survey method, which employs the Focal Groups technique, with HC representing managers, services providers, workers and users, all from national, state and municipal levels. Four aspects were examined, comprising reading and writing habits; Internet utilization; the use of health indicators; and the role of information in the Council-State-Society relation. Results have evidenced the need to broaden the foundations of digital inclusion initiatives in the health care area, and to overcome the cross-sector challenge of linking them to politics and education. By using benchmarks of educational philosophy, we were able to outline a theoretical-analytical matrix as a contribution to understanding the complexity involved in fostering digital inclusion in the health care area.

Após vinte anos do SUS, a desigualdade nas condições de saúde da população permanece como uma realidade, impondo aos movimentos sociais que exercem o controle social sobre a saúde uma contínua luta. Nesse embate, o acúmulo de força política está relacionado ao aumento da capacidade de apropriação de conhecimento e informação. Conhecer dimensões da desigualdade na inclusão digital de conselheiros de saúde (CS) de diferentes regiões do país é o objetivo desse trabalho. O método adotado foi a pesquisa qualitativa, por meio da técnica de grupos focais com CS representantes dos gestores, dos prestadores, dos trabalhadores e dos usuários, atuantes na esfera nacional, estadual ou municipal. Foram trabalhadas quatro dimensões, abrangendo: o hábito de leitura e de redigir textos; o uso da Internet; o uso de indicadores de saúde e o papel da informação na relação Conselho-Estado-Sociedade. Os resultados indicaram a necessidade de se ampliar a fundamentação das ações de inclusão digital em saúde, articulando-a, então, à política e à educação, enquanto desafio intersetorial. Utilizando referenciais da filosofia da educação, delineia-se matriz teórico-analítica como contribuição ao entendimento da complexidade que envolve promover a inclusão digital na Saúde.

Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration

OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 µg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1 (p=0.085), FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL-1 and morphine group= 4.08 ng.mL-1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not ...

Effects of cardiopulmonary bypass on propofol pharmacokinetics and bispectral index during coronary surgery

PURPOSE: Cardiopulmonary bypass is known to alter propofol pharmacokinetics in patients undergoing cardiac surgery. However, few studies have evaluated the impact of these alterations on postoperative pharmacodynamics. This study was designed to test the hypothesis that changes in propofol pharmacokinetics increase hypnotic effects after cardiopulmonary bypass. METHODS: Twenty patients scheduled for on-pump coronary artery bypass graft (group, n=10) or off-pump coronary artery bypass graft (group, n=10) coronary artery bypass grafts were anesthetized with sufentanil and a propofol target controlled infusion (2.0 µg/mL). Depth of hypnosis was monitored using the bispectral index. Blood samples were collected from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma propofol concentrations were measured using high-performance liquid chromatography, followed by a non-compartmental propofol pharmacokinetic analysis. Data were analyzed using ANOVA, considering p<0.05 as significant. RESULTS: After cardiopulmonary bypass, despite similar plasma propofol concentrations in both groups, bispectral index values were lower in the on-pump coronary artery bypass graft group. Time to extubation after the end of propofol infusion was greater in the on-pump coronary artery bypass graft group (334 ± 117 vs. 216 ± 85 min, p = 0.04). Patients undergoing cardiopulmonary bypass had shorter biological (1.82 ± 0.5 vs. 3.67 ± 1.15h, p < 0.01) and terminal elimination (6.27 ± 1.29 vs. 10.5h ± 2.18, p < 0.01) half-life values, as well as higher total plasma clearance (28.36 ± 11.40 vs.18.29 ± 7.67 mL/kg/min, p = 0.03), compared to patients in the off-pump coronary artery bypass graft group. CONCLUSION: Aside from the increased sensitivity of the brain to anesthetics after cardiopulmonary bypass, changes in propofol pharmacokinetics may contribute to its central nervous system effects.

Monitoramento das concentrações plasmáticas de vancomicina em paciente grande queimado / Monitoring plasma vancomycin concentrations in a burned patient

É apresentado um caso de monitoramento de vancomicina  por meio  de cromatografia líquida de alta eficiência (CLAE-UV) e também modelagem farmacocinética em paciente grande queimado. Dados obtidos do pico e do vale indicam que o regime posológico e tipo de infusão endovenosa devem ser revistos, utilizando a farmacocinética como ferramenta importante.

Determining plasma morphine levels using GC-MS after solid phase extraction to monitor drug levels in the postoperative period

OBJECTIVE: To implement a selective and sensitive analytical method to quantify morphine in small volumes of plasma by gas-liquid chromatography-mass spectrometry (GC-MS), aimed at post-operatively monitoring the drug. METHOD: A gas-liquid chromatographic method with mass detection has been developed to determine morphine concentration in plasma after solid phase extraction. Morphine-d3 was used as an internal standard. Only 0.5 mL of plasma is required for the drug solid-phase extraction in the Bond Elut-Certify®, followed by the quantification of morphine derivative by GC-MS using a linear temperature program, a capillary fused silica column, and helium as the carrier and make-up gas. The method was applied to determine morphine content in plasma samples of four patients during the postoperative period of cardiac surgery. Patient-controlled analgesia with morphine was performed by a venous catheter, and a series of venous blood samples were collected. After the oro-After the orotracheal extubation, morphine plasma levels were monitored for up to 36 hours. RESULTS: The run time was 16 minutes because morphine and the internal standard were eluted after 8.8 minutes. The GC-MS method had 0.5 -1000 ng/mL linearity range (r²=0.9995), 0.1 ng/mL limit of detection, intraday and interday precision equivalent to 1.9 percent and 6.8 percent, and 0.1 percent and 0.8 percent systematic error (intraday and interday, respectively). The analytical method showed optimal absolute (98 percent) and relative (100.7 percent) recoveries. Morphine dose requirements and plasma levels are discussed. CONCLUSION: The analytical gas-liquid chromatography-mass spectrometry method is selective and adequate for morphine measurements in plasma for applications in clinical studies.

Influência da circulação extracorpórea sobre as concentrações plasmáticas de atenolol / Influence of cardiopulmonary bypass on the plasma concentrations of atenolol

FUNDAMENTO: Os betabloqueadores são usados no tratamento da angina pectoris e outras doenças coronarianas isquêmicas, reduzindo mortalidade e eventos cardiovasculares. O atenolol é um betabloqueador hidrofílico, de absorção gastrointestinal, extensão de distribuição pequena e eliminação função renal-dependente. OBJETIVO: O objetivo deste estudo é o de determinar a variabilidade inter-individual do atenolol em pacientes coronarianos. MÉTODOS: Quantificou-se o atenolol plasmático em 6 amostras sangüíneas coletadas no pré-operatório de sete indivíduos portadores de insuficiência coronariana e indicação cirúrgica de revascularização do miocárdio, tratados cronicamente com atenolol, com doses diárias variando entre 25 a 100 mg PO. Todos os pacientes apresentavam função renal dentro da normalidade ou levemente reduzida. RESULTADOS: As concentrações plasmáticas obtidas evidenciaram decaimento monoexponencial, confirmando que o atenolol apresenta farmacocinética de primeira ordem nas doses empregadas para o controle da insuficiência coronariana grave (médias ± DP): 123 ± 56, 329 ± 96, 288 ± 898, 258 ± 85, 228 ± 79 e 182 ± 73 ng/mL, nos tempos zero, 2, 4, 6, 8 e 12 horas após a administração da dose. Registrou-se pequena variabilidade inter-pacientes nas concentrações plasmáticas de atenolol no grupo investigado tratado em regime de doses múltiplas, devido à característica hidrofílica do fármaco. Registrou-se ainda, maior persistência do atenolol nos pacientes coronarianos investigados, comparado a indivíduos saudáveis. CONCLUSÃO: Em virtude da sua cardioseletividade e baixa variabilidade, sugere-se que o atenolol deve ser empregado como fármaco de primeira escolha para o tratamento da síndrome coronariana aguda e outras doenças cardiovasculares.

BACKGROUND: Betablockers are used in the treatment of angina pectoris and others ischemic coronary diseases, reducing mortality and cardiovascular events. Atenolol is a hydrophilic betablocker which is characterized by gastrointestinal absorption, small extent of distribution and renal function-dependent elimination. OBJECTIVE: The study objective was to determine the inter-individual variability of atenolol in coronary patients. METHODS: Plasma atenolol was quantified in six blood samples collected during the preoperative period from seven patients with coronary insufficiency and surgical indication, chronically treated with atenolol PO 25 to 100 mg/day. All patients presented a normal or slightly reduced renal function. RESULTS: All enrolled patients presented normal or slightly reduced renal function as a result of age and underlying disease. Atenolol plasma concentrations showed a monoexponential decline, confirming the first-order pharmacokinetics at the doses employed for the control of coronary insufficiency (mean ± SD): 123 ± 56, 329 ± 96, 288 ± 898, 258 ± 85, 228 ± 79 and 182 ± 73 ng/ml at times zero, 2, 4, 6, 8 and 12h after dose administration. The investigated group showed a small inter-patient variability of atenolol administrated at multiple regimens due to the hydrophilic characteristic of the drug. Furthermore, accumulation of atenolol administered chronically was greater in coronary patients, compared to healthy subjects. CONCLUSION: In view of its cardio-selectivity and low-variability, atenolol should be used as the first-choice drug for the treatment of acute coronary syndrome and other cardiovascular diseases.

Propranolol plasma monitoring in children submitted to surgery of tetralogy of Fallot by a micromethod using high performance liquid chromatography

OBJECTIVE: To evaluate the analytical micromethod using liquid chromatography for the quantification of propranolol in children submitted to surgery of tetralogy of Fallot (TLF). Methods: Only 0.2 mL of plasma is required for the assay. Peaks eluted at 8.4 (Propranolol) and 17.5 min (verapamil, internal standard) from a C18 column, with a mobile phase 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v/v) at flow rate 0.7 mL/min, detected at 290 nm (excitation) and 358 nm (emission). Surgery was started 776 min of drug administration (8.7mg, mean); seven blood samples were collected from six patients (4M/2F; 2.1yrs;11.5kg; 0.80m; 18.9kg/m²). RESULTS: Confidence limits of the method showed high selectivity and recovery, sensitivity of 0.02ng/mL, good linearity (0.05-1000ng/mL), precision of 8.6 percent and accuracy of 3.1 percent. The mean duration of surgery was 283.2min, with the patients remaining under cardiopulmonary bypass (CPB) for 114min. A declining curve of propranolol plasma concentration was obtained after the last dose in the night that preceded the day of surgery. Plasma concentration also was normalized with hematocrit due to the hemodilution caused by the CPB procedure. On the other hand a decrease on drug plasma concentration was obtained between periods, the beginning of surgery to the postoperative day 2 (7.09 ng/mL and 0.05 ng/mL, p<0.05 respectively) and from the end of CPB to the postoperative day 2 (2.79ng/mL e 0.05ng/mL, p<0.05). CONCLUSION: Propranolol monitoring of plasma concentrations of children (TLF) normalized after the last preoperative dose revealed a decline from the beginning of surgery to the second postoperative day, suggesting that, once redistribution was restored, propranolol washout was complete.

OBJETIVO: Avaliar o micrométodo analítico empregando a cromatografia líquida para quantificação de propranolol em crianças operadas de tetralogia de Fallot (TLF). MÉTODO: Requereu-se apenas volumes de 0,2mL de plasma para a realização do ensaio. Os picos foram eluídos em 8.4 (Propranolol) e 17.5 min (verapamil, padrão interno) de uma coluna C18, com fase móvel (tampão acetato 0,1 M pH 5,0 e acetonitrila, 60:40, v/v) em fluxo de 0,7 mL/min, sendo detectados em 290 nm (excitação) e em 358 nm (emissão). A cirurgia iniciou-se 776 min depois da dose administrada (8,7mg, média) e sete amostras de sangue foram coletadas de seis pacientes (4M/2F; 2,1 anos;11,5kg; 0,80m;18,9kg/m²). RESULTADOS: Os limites de confiança do método analítico evidenciaram alta seletividade e recuperação, sensibilidade (0,02ng/mL), boa linearidade (0,05-1000ng/mL), precisão de 8,6 por cento e exatidão de 3,1 por cento. A duração média da cirurgia foi de 283,2min, com os pacientes em circulação extracorpórea (CEC) durante 114min. Uma curva de declínio do propranolol no plasma foi obtida após a última dose na noite que precedeu o dia da intervenção. A concentração plasmática foi normalizada com o hematócrito devido à hemodiluição causada pela CEC. Por outro lado obteve-se decréscimo nas concentrações plasmáticas entre os períodos início da cirurgia para o 2° dia de pós-operatório (7,09 ng/mL e0,05 ng/mL, p<0,05 respectivamente) e do final da CEC para o 2° dia de pós-operatório (2,79ng/mL e 0,05ng/mL, p<0,05). CONCLUSÃO: O monitoramento das concentrações plasmáticas normalizadas do propranolol, em crianças com TLF, após a última dose pré-operatória revelou decaimento do início da cirurgia para o segundo pós-operatório, sugerindo que após a correção cirúrgica, uma vez restaurada a distribuição, a eliminação do fármaco foi completa.

Perioperative cefuroxime pharmacokinetics in cardiac surgery

OBJECTIVE: The objective was to investigate the plasma levels and to compare the pharmacokinetics of cefuroxime during and after surgery in adult patients with elective indication for coronary artery bypass grafting. METHODS: Seventeen patients received three 1.5-g bolus IV doses of cefuroxime, one every 12 hrs. Serial blood samples (3 mL) were collected 1, 3, 6, 9, and 12 hrs after the first dose (given during the intervention) and after the second and third doses (postsurgery). Blood samples were centrifuged and stored frozen until being assayed. For assessment of the cefuroxime plasma levels by liquid chromatography, only 200 æL of plasma were required. Determination of cefuroxime plasma levels was followed by a pharmacokinetic (PK)-modeling using PK Solutions 2.0 software. RESULTS: The kinetic parameters obtained remained unchanged after the first, second, and the third dose as follows: elimination half-life: 1.8 h, 1.9 h, and 1.8 h; clearance: 1.4, 1.5, and 1.5 mL/min/kg, respectively. Additionally, the apparent volume of distribution did not change during and after the intervention: 0.19, 0.25, and 0.22 L/kg, after the first, second, and the third dose, respectively. Since the drug has a low volume of distribution, plasma levels obtained after a 1.5-g IV bolus injection of cefuroxime decreased rapidly due to the high plasma clearance, with a consequent short half-life. CONCLUSIONS: The kinetic disposition of cefuroxime remains unaltered in patients undergoing coronary artery bypass grafting; to reduce the fluctuation in plasma concentrations so that the antibiotic prophylaxis in the peri-operative period is guaranteed, the dose regimen should be reviewed.

OBJETIVO: Investigar os níveis plasmáticos e comparar a farmacocinética da cefuroxima durante e após cirurgia de revascularização do miocárdio. MÉTODOS: Dezessete pacientes receberam três doses intravenosas de 1,5 g de cefuroxima, a cada 12 horas. Foram coletadas amostras de sangue nos tempos de 1, 3, 6, 9 e 12 horas após a primeira dose (durante a cirurgia) e após a segunda e terceira dose (administradas após a cirurgia). As amostras de sangue foram centrifugadas e armazenadas congeladas até o momento da análise. Os níveis plasmáticos da cefuroxima foram determinados através de cromatografia líquida, utilizando-se apenas 200 mL de plasma. A determinação da farmacocinética da cefuroxima foi realizada utilizando o software PK-solutions 2.0. RESULTADOS: Todos os parâmetros cinéticos obtidos permaneceram inalterados após a adminstração da 1ª, 2ª e 3ª doses: meia vida de eliminação 1,8h, 1,9h and 1,8h, depuração 1,4, 1,5 and 1,5 mL/min/kg respectivamente. Adicionalmente, o volume aparente de distribuição, não se alterou durante ou após a intervenção: 0,19, 0,25 and 0,22 L/kg, após 1ª, 2ª e 3ª dose, respectivamente. Os níveis plasmáticos obtidos após administração da cefuroxima reduziram rapidamente devido à alta depuração plasmática com conseqüente curta meia-vida plasmática, atingindo valores abaixo da concentração inibitória mínima a partir da 9ª hora da administração. CONCLUSÕES: A disposição cinética da cefuroxima permanece inalterada em pacientes submetidos à cirurgia de revascularização do miocárdio, e com vistas à redução da flutuação no período perioperatório, o regime de dose para a antibioticoprofilaxia poderia ser revisto.

Vancomycin pharmacokinetics in preterm infants

OBJETIVE: The objective of the present study was to evaluate the kinetic disposition of vancomycin in preterm infants with emphasis on the apparent volume of distribution, biological half-life, and total body clearance as well as whether their variations cause significant modification of the trough plasma concentration of the drug, depending on the postconceptional age (PCA) and the postnatal age (PNA). MATERIAL AND METHOD: Twenty-five selected patients were distributed into 2 groups which differed significantly in terms of mean PCA (31.2-32.3 weeks in group 1, n = 13; 33.5-34.1 weeks in group 2, n = 12: CI95 percent, P < .001) and PNA (group 1, 12.0-18.5 days; group 2, 18.0-34.0 days, CI95 percent, P < .05). The parents were informed and signed a written consent for participation of the infants in the protocol that had been previously approved by the Ethics Committee of the hospital. RESULTS: Apparent volume of distribution was significantly increased in group 1 compared with patients of group 2 (0.85 vs. 0.56 L/kg, respectively; P = .01,). Additionally multiple linear regression revealed a good linear correlation (r = 0.85) of trough plasma concentration of vancomycin with the apparent volume of distribution and also with the biological half-life in patients of group 1, while a good correlation (r = 0.91) was obtained for the trough plasma concentration with total body clearance in infants of group 2. The influence of these kinetic parameters on the trough concentration of vancomycin in preterm infants seems to vary according to PCA and PNA. CONCLUSION: In conclusion, the trough plasma concentration of vancomycin depends on the pharmacokinetics, and multiple linear correlation indicates that it varies according to the postconceptional and postnatal age of preterm infants.

OBJETIVO: O objetivo do presente estudo foi investigar a farmacocinética da vancomicina em neonatos pretermo, considerando a idade pós-conceptual e também a idade pós-natal para determinar se as alterações no volume aparente de distribuição, meia-vida biológica e depuração plasmática causam variação significativa no vale plasmático da vancomicina. MATERIAL E MÉTODO: Os vinte e cinco pacientes selecionados foram distribuídos em dois grupos, que diferiram significativamente em termos de idade pós-conceptualgrupo 1, n=13: 31,2-32,3 semanas; grupo 2, n=12: 33,5-34,1 semanas, IC95 por cento, p<0,0001) e idade pós-natalgrupo 1: 12,0-18,5 dias; grupo 2: 18,0-34,0 dias, p<0,05). Todos os responsáveis foram informados sobre os detalhes do estudo e assinaram o termo de consentimento livre e esclarecido. O protocolo foi submetido e aprovado previamente pelo Comitê de Ética em Pesquisa do hospital. RESULTADO: O volume aparente de distribuição se mostrou significativamente aumentado no grupo 1 comparado aos pacientes do grupo 2 0,85 vs 0,56 L/kg, p=0,01). Adicionalmente, o teste de regressão linear múltipla mostrou boa correlação linear: 0,85) da concentração plasmática de vale com o volume aparente de distribuição, e também com a meia-vida biológica nos pacientes do grupo 1. Nas crianças do grupo 2 evidenciou-se boa correlação(r: 0,91) entre o vale e a depuração plasmática. A influência desses parâmetros farmacocinéticos sobre o vale nos prematuros parece variar de acordo com a idade pós-conceptual e a idade pós-natal. CONCLUSÃO: Concluindo, a concentração de vale para a vancomicina depende da farmacocinética e a correlação múltipla varia de acordo com a idade pós-conceptual e a idade pós-natal dos recém-nascidos pré-termos.

Disposição cinética do atenolol em pacientes coronarianos submetidos a revascularização do miocárdio / Kinetic disposition of atenolol in coronary patients submitted to the CABG surgery

A isquemia miocárdica é um importante fator de risco para a mortalidade e eventos cardiovasculares no perioperatório de cirurgias cardíacas e não-cardíacas, sendo que a administração profilática de 'beta'-bloqueadores nesse período, reduz estes riscos. Sabe-se que alterações fisiológicas ocorridas durante a cirurgia de revascularização do miocárdio (RM) com circulação extracorpórea (CEC) podem afetar as concentrações plasmáticas e a cinética de muitos fármacos. Neste estudo, investigou-se a farmacocinética do atenolol em pacientes com angina instável e sem prejuízo renal, submetidos à revascularização com CEC e em terapia crônica com atenolol peroral. O estudo farmacocinético exigiu coleta de amostras sangüíneas seriadas após as doses pré- e pós-operatória. Comparado ao pré-operatório, registrou-se redução não significativa no volume de distribuição e na depuração plasmática após a cirurgia, permanecendo inalterada a meia-vida biológica (p>0,05). Uma correlação linear negativa entre meia-vida e depuração pode ser estabelecida nos dois períodos do estudo (r: -0,77, p= 0,06 no pré-operatório e r: -0,89, p= 0,06 no pós-operatório), enquanto que se estimou correlação linear direta entre volume de distribuição e meia-vida biológica apenas no pré-cirúrgico (r: 0,54, p= 0,03 no pré-operatório e r: 0,09, p= 0,03 no pós-operatório). Conclui-se que a cirurgia de revascularização auxilia no restabelecimento da extensão da distribuição do atenolol

Myocardium ischemia is an important factor of risk for mortality and cardiovascular events in the perioperative period of cardiac and non cardiac surgeries. However, the prophylactic administration of b-blocker agents could reduce these risks. Physiologic changes, occurred during the coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB), could alter plasma concentration and pharmacokinetics of many drugs. This study investigated the pharmacokinetics of atenolol in patients with unstable angina and without renal dysfunction, submitted to CABG surgery and treated chronically with atenolol PO. For pharmacokinetic analysis, 13 blood samples were collected after doses administrated pre- and post-operatively. Compared to the pre-operative period, it was verified a non-significant reduction in the apparent volume of distribution and plasma clearance after the surgery, remaining unchanged the biological half-life, p>0.05 (NS). A negative linear correlation between plasma clearance and elimination half-life was demonstrated in both periods of the study (r: -0.77 p=0.06, pre-surgery and r: -0.89, p=0.06, post-surgery), while a correlation between volume of distribution and biological half-life was established only before revascularization (r: 0,54 p= 0,03 , pre-surgery and r: 0,09, p=0,03, post-surgery). We suggest that the CABG surgery leads to the normalization of the extension of distribution of atenolol

Obesity influences propranolol pharmacokinetics in patients undergoing coronary artery bypass grafting employing cardiopulmonary bypass

Propranolol plasma levels and kinetic disposition may be altered by hypoyhermic cardiopulmonary bypass (CPB-H). We investigated the potential influence of obesity on propranolol pharmacokinetics in patients undergoing coronary artery bypass grafting employing CPB-H. Fifteen patients, receiving propranolol perorally pre-(10-40 mg, 2-3 times a day) and post-operatively (10 mg, once a day) were distributed in two groups, based on body mass index (BMI), in obese (n=9, BMI: mean 29,4 kg/m²) and non-obese (n=6 BMI: mean 24.8 kg/m²). A serial of blood samples was collected at the pre- and post-operative periods at time dosing interval (`tau´) propranolol plasma levels were measured one day before and after surgery using a high performance liquid chromatographic procedure described previously...