A sepse após a injúria térmica é a maior causa de morbidade e mortalidade em pacientes queimados, uma vez que profundas alterações ocorrem na farmacocinética de agentes antimicrobianos. Investigaram-se trinta e um pacientes, portadores de sepse documentada e apresentando lesões ativas; utilizou-se o tratamento empírico conforme seguem os regimes de dose: 1 g, 12/12 h para a vancomicina, 1 g, 6/6 h para o imipenem e 2 g, 8/8 h para o cefepime. Sete coletas seriadas de sangue foram realizadas através de cateter venoso (2 mL/cada); o plasma foi obtido pela centrifugação e armazenado no congelador (-80o C) até o ensaio. A concentração plasmática dos antimicrobianos foi determinada simultaneamente pela aplicação do método bioanalítico desenvolvido no estudo. O método de cromatografia líquida de alta eficiência demonstrou boa linearidade, precisão e exatidão para a determinação simultânea da vancomicina, cefepime e imipenem plasmáticos; a plicação desse método bioanalítico permitiu o monitoramento plasmático terapêutico e o estudo farmacocinético. Com base nos resultados obtidos de concentração plasmática versus tempo, aplicou-se a modelagem para investigar a farmacocinética desses agentes antimicrobianos nos pacientes queimados. Os parâmetros cinéticos foram estimados com base no modelo aberto de um compartimento pela aplicação do programa PK Solutions v. 2.0; a estatística foi realizada pela utilização do programa GraphPad Prism v. 4.0. Com base na farmacocinética alterada, as concentrações obtidas para a vancomicina e imipenem se mostraram abaixo dos valores recomendados para atingir eficácia; por outro lado, as concentrações obtidas para o cefepime se mostraram dentro da faixa recomendada para atingir eficácia, uma vez que não se registrou alteração da farmacocinética deste antimicrobiano nos pacientes queimados. Desta forma, o monitoramento plasmático terapeutico se mostrou importante, permitindo o ajuste de dose para a vancomicina e para o imipenem, uma vez que a concentração minima efetiva (CME) não foi atingida para ambos pela utilização do regime de dose empírica nos pacientes queimados. Por outro lado, o monitoramento do cefepime plasmático também se mostrou de relevância, uma vez que os pacientes queimados com longa permanência na terapia intensiva podem apresentar disfunção renal em alguma fase da internação; consequentemente, a individualização de dose será recomendada para esses pacientes. Adicionalmente, investigou-se a disposição cinética da vancomicina em nove pacientes queimados após duas diferentes intervenções cirúrgicas. Comparou-se a farmacocinética da vancomicina pós-desbridamento versus pos-enxerto com base no monitoramento plasmático após o regime de dose empírica (1 g, 12/12 h). Após multiplas infusões, o vale da vancomicina plasmática foi obtido pela coleta de sangue imediatamente antes da infusão subsequente e está relacionado ao acúmulo no estado de equilíbrio. Em conseqüência da depuração aumentada e meia-vida biológica reduzida pós-desbridamento comparado ao pós-enxerto, registrou-se para a vancomicina vale abaixo da concentração efetiva mínima nos pacientes queimados. Finalmente, os resultados obtidos no presente estudo permitem concluir que a farmacocinética da vancomicina e do imipenem está alterada nos pacientes queimados com sepse, e recomenda-se o monitoramento das concentrações plasmáticas para garantir a eficácia de forma a previnir a emergência bacteriana. / Sepsis after thermal injury is the major cause of morbidity and mortality in burn patients, once deep changes on the pharmacokinetics of antimicrobials agents are expected. Thirty one burn patients were investigated, all of them had documented sepsis and presented active lesions; they were treated with empirical dose regimen as follows: 1 g, 12/12 h for vancomycin, 1 g, 6/6 h for imipenem and 2 g, 8/8 h for cefepime. A serial of seven blood samples were collected from the venous catheter (2 mL/each); plasma was obtained by centrifugation and storaged in an ultra-low freezer (-80o C) until assay. Drug plasma concentration was determined simultaneously by application of a bioanalytical method described previously. High performance liquid chromatographic method showed good linearity, precision and accuracy for vancomycin, cefepime and imipenem plasma measurements; its application permitted therapeutic drug monitoring and pharmacokinetic studies. Pharmacokinetic modeling was applied to data obtained based on drug plasma concentrations versus time, to investigate those antimicrobial agents in burn patients. Estimated kinetic parameters were based on the one compartment open model by application the software PK Solutions v. 2.0; statistics was performed by using the software GraphPad Prism v. 4.0. Based on altered pharmacokinetics, obtained plasma concentrations to reach drug efficacy were below the recommended values for vancomycin and imipenem; on the other hand, cefepime plasma concentrations to reach drug efficacy were in the recommended range, once its pharmacokinetics didnt change in burn patients. Then, therapeutic plasma monitoring was cost-effective permitting dose adjustment for vancomycin and imipenem, once the minimum effective concentration (MEC) wasnt reached for both antimicrobial agents by using the empirical dose regimen for burn patients. On the other hand, cefepime plasma monitoring was also cost-effective, since burn patients long term therapy can present renal dysfunction at the minimum one period in the intensive care unit; consequently, dose adjustment could be required for them. Additionally, vancomycin kinetic disposition was investigated in nine burn patients after two different surgical interventions. Vancomycin pharmacokinetics post-debridement versus post-skin grafting procedure was compared based on drug plasma monitoring by using the empirical dose regimen (1 g, 12/12 h). Trough vancomycin plasma level after multiple infusions, obtained by blood collection before de next dose, is related to drug accumulation at the steady state level; then, trough below the minimum effective concentration (MEC) were obtained after both surgical procedures performed in burn patients. Meanwhile, increased plasma clearance and reduced biological half-life were obtained after debridement compared skin grafting procedure. Finally, data obtained in the present study permit to conclude that the pharmacokinetics is altered for vancomycin and imipenem in burn patients with sepsis, and drug plasma monitoring is recommended to guarantee drug efficacy and to prevent the bacterial emergency.

Les centres hospitaliers universitaires détenant une expertise pour les grands brûlés pédiatriques ont la responsabilité d’avoir du personnel infirmier compétent pour donner ces soins spécialisés. Cependant, il est constaté que les infirmières débutantes ne possèdent pas les connaissances suffisantes sur les soins de plaie de brûlures pour bien intervenir auprès de cette clientèle. Il y a donc un besoin urgent de formation pour préparer les infirmières débutantes à la prise en charge de ces patients. Cette étude pilote pragmatique avait pour buts : (i) de développer et de mettre à l’essai une formation en ligne sur les soins aux grands brûlés pédiatriques destinée aux infirmières débutantes; (ii) et d’évaluer la faisabilité et l’acceptabilité de la formation en ligne en plus d’estimer les effets de la formation sur l’amélioration des connaissances de ces infirmières débutantes en soins aux grands brûlés pédiatriques. Les cadres de référence utilisés pour soutenir cette étude incluaient le « Référentiel de compétences de l’infirmière en soins aux grands brûlés » de l’American Burn Association (2017b) pour développer le contenu théorique de l’intervention ainsi que les « Principes de l’apprentissage en ligne » de Clark et Mayer (2016) afin de guider la conception de la formation en ligne. Un devis préexpérimental prétest-posttest à un groupe d’infirmières débutantes (n=16) a été employé à l’unité de soins médico- chirurgicaux du Centre hospitalier universitaire Sainte-Justine entre mars à juillet 2020. La faisabilité, l’acceptabilité et les effets préliminaires de la formation en ligne ont été évalués par un questionnaire de connaissances sur les soins infirmiers aux grands brûlés pédiatriques et de satisfaction. Les analyses statistiques utilisées incluent des statistiques descriptives et des tests- t pour échantillons appariés. En ce qui concerne la faisabilité, toutes les participantes ont complété la totalité de l’étude via la plateforme en ligne. Les résultats préliminaires ont révélé une différence significative entre la moyenne des scores de connaissances des 16 infirmières débutantes pré-formation en ligne (58,6%±14,5) et post-formation en ligne (87,7%±8,7) (p<0,001). Pour l’acceptabilité, la moyenne des scores était satisfaisante avec 95,5% (3,8±0,2) post-intervention. Ainsi, cette nouvelle formation en ligne, basée sur des données probantes, semble faisable et acceptable, en plus d’indiquer un effet préliminaire sur l’amélioration des connaissances d’infirmières débutantes sur les soins aux grands brûlés pédiatriques. / Nurses working with pediatric burn care patients require to be properly trained to provide optimal burn care. However, it was found that novice nurses from this service do not have sufficient knowledge regarding burn wound care to provide efficient care for this specialized clientele. Therefore, an urgent need exists to train novice nurses to care for pediatric burn patients. This pilot study aimed to: (i) develop and pilot a pediatric nursing burn care e-learning training for novice nurses; and (ii) assess the feasibility and acceptability of this educational intervention as well as evaluate the intervention’s preliminary effects on novice nurses’ knowledge on pediatric nursing burn care. The frameworks that supported this study included the “Burn Nurse Competencies” from the American Burn Association (2017b) to develop the theoretical content of the intervention as well as the “Multimedia Principles ” from Clark and Mayer (2016) to design the e-learning training. A pragmatic quasi experimental one-group (n=16) pretest-posttest design was conducted from March to July 2020 at a pediatric burn care unit at the CHU Sainte-Justine Pediatric University Hospital. Feasibility, acceptability and preliminary effects of the e-learning training were assessed by a pediatric nursing burn care knowledge level questionnaire and a satisfaction survey. Statistical analyzes included descriptive statistics and tests-t for paired samples. In regards to feasibility, all participants completed the entire study with the e-learning platform. A significant difference was observed between the knowledge level mean score of novice nurses pre-training (58.6% ± 14.5) compared to post-training (87.7% ± 8.7) (p<0.001). Results showed that novice nurses’ mean score on satisfaction was 95.5% (3.8 ± 0.2) post-intervention, indicating a high satisfaction level. This new evidence-based pediatric nursing burn care e-learning training appeared feasible and satisfactory by novice nurses as well as indicating a preliminary effect on knowledge improvement regarding pediatric burn care.