Avaliação da remoção do antimicrobiano Vancomicina pelos diferentes métodos de diálise em pacientes com lesão renal aguda associada à sepse.
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Data
2018-11-20
Autores
Freitas, Fernanda Moreira de
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Universidade Estadual Paulista (Unesp)
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Introdução: O controle da infecção no ambiente de terapia intensiva por patógenos hospitalares, frequentemente, inclui a utilização de vancomicina. Ressalta-se que profundas alterações ocorrem na farmacocinética dos antimicrobianos prescritos aos pacientes criticamente doentes e que os diferentes métodos dialíticos podem removê-los parcial ou totalmente. Objetivo: Avaliar a redução do antimicrobiano vancomicina por diferentes métodos de diálise em pacientes com lesão renal aguda (LRA) associada à sepse e identificar as variáveis associadas a concentrações terapêuticas. Metodologia: Estudo transversal que avaliou pacientes sépticos com LRA em hemodiálise convencional intermitente (HDI) ou hemodiálise prolongada (HDP) e em tratamento com vancomicina internados em Unidade de Terapia Intensivas (UTI) do Hospital das Clínicas da Faculdade de Medicina de Botucatu-UNESP. Foram colhidas amostras seriadas de sangue no início da terapia dialítica, após 2 e 4 horas do tratamento e ao final da terapia. A concentração sérica de vancomicina foi aferida por cromatografia líquida de alta eficiência (CLAE) ou por Imunoensaio enzimático homogêneo (Enzyme Multiplied Immunoassay Technique - EMIT). A partir desses dados foi realizado avaliação farmacocinética e Modelagem PK/PD. Resultados: De março de 2015 a agosto de 2017 foram incluídos 27 pacientes tratados por HDI, 17 por HDP 6h e 11 por HDP 10h. O volume de distribuição, assim como o tempo de meia vida e clearence dialítico da vancomicina foram maiores nos grupos HDP 6h e HDP 10h (p<0,001). A redução da vancomicina após 2 horas de terapia foi de 26,65% (±12,64) e ao fim da diálise foi de 45,78 (±12,79), maior no grupo HDP 10h, 57,70% (40,48-64,30), p=0,037. A razão da área sob a curva pela concentração inibitória mínima (ASC/CIM) em 24h no grupo HDP 10h apresentou menores valores, com diferença significativa (p=0,047). Na regressão logística, as variáveis Clearence dialítico da vancomicina (OR=0,0184, p=0,027), hemodiálise prolongada (OR=0,00386, p=0,025) e vancocinemia no início da terapia (T0) (OR=1,96, p=0,006) foram associadas a concentração terapêutica no fim da diálise. A ASC/CIM 24h, melhor parâmetro de eficácia da vancomicina, foi analisado em 41 pacientes, e na regressão logística a hemodiálise prolongada foi fator de risco para ASC/CIM menor que 400 (OR=11,59, p=0,033), enquanto que maior concentração sérica de vancomicina no T0 foi fator protetor para ASC/CIM menor que 400 (OR=0,791, p=0,009). Na análise dos pacientes em relação a concentrações de vancomicina consideradas nefrotóxicas, no fim da terapia apenas 14 (25,45%) pacientes apresentavam vancocinemia maior que 20mg/dl, o único fator de risco identificado na regressão logística foi a maior concentração sérica de vancomicina no início da diálise (OR=1,725, p=0,027). Conclusão: Estes resultados mostram alta prevalência de pacientes com concentração subterapêutica de vancomicina durante e no final da diálise, o que pode estar relacionado a um maior risco de resistência bacteriana e mortalidade, além de apontar para a necessidade de doses adicionais de vancomicina durante a terapia dialítica, principalmente em pacientes em hemodiálise prolongada.
Introduction: Infection control in the intensive care environment by hospital pathogens often includes the use of vancomycin. It is noteworthy that profound changes occur in the pharmacokinetics of antimicrobials prescribed to critical patients and that different dialytic methods may partially or totally remove them. Objective: To evaluate the reduction of antimicrobial vancomycin by different dialysis methods in patients with AKI associated with sepsis and to identify the variables associated with its therapeutic level. Methodology: A cross-sectional study evaluating septic patients with AKI on intermittent conventional hemodialysis (IHD) and prolonged hemodialysis (PHD) and vancomycin treatment in intensive care unit (ICU) of Clinics Hospital of the Faculty of Medicine of Botucatu - UNESP. Serial blood samples were collected at the start of dialysis therapy after 2 and 4 hours of treatment and at the end of therapy. The serum level of vancomycin was measured by high performance liquid chromatography (HPLC) or by Enzyme Multiplied Immunoassay Technique (EMIT). From these data, pharmacokinetic evaluation and PK / PD modeling were performed. Results: From March 2015 to August 2017, 27 patients treated for IHD, 17 for PHD 6h and 11 for PHD 10h were included. The volume of distribution was higher in the groups PHD 6h and PHD 10h (p <0.001), as well as half-life (p <0.001) and dialytic clearance of vancomycin (p <0.001). The reduction of vancomycin after 2 hours of therapy was 26.65% (± 12.64) and at the end of the dialysis was 45.78 (± 12.79), highest in the PHD 10h group, 57.70% (40,48-64.30), p=0.037. The ratio of the area under the curve by the minimum inhibitory concentration (AUC / MIC) in 24h in the PHD 10h group presented lower values, with a significant difference (p=0.047). In the logistic regression, the variables Clearence dialytic vancomycin (OR=0.0184, p=0.027), PHD (OR=0.00386, p=0.025) and concentration of vancomycin at the start of therapy (T0) (OR=1.96, p=0.006) were associated with the therapeutic concentration at the end of the dialysis. AUC/MIC 24h, the best vancomycin efficacy parameter, was analyzed in 41 patients. In logistic regression, prolonged hemodialysis was a risk factor for AUC/MIC 24h of less than 400 (OR=11.59, p=0.033), while that greater vancomycin concentration in T0 was a protective factor for AUC/MIC 24h of less than 400 (OR=0.791, p=0.009). In the analysis of patients with vancomycin concentrations considered nephrotoxic, at the end of therapy, only 14 (25.45%) patients had vancomycin concentration greater than 20mg/dl, the only risk factor identified in the logistic regression was the highest serum concentration of vancomycin at the beginning of the dialysis (OR=1.725, p=0.027). Conclusion: These results show a high prevalence of patients with vancomycin subtherapeutic concentration during and at the end of dialysis, which may be related to a higher risk of bacterial resistance and mortality, besides pointing to the need for additional doses of vancomycin during therapy dialysis, especially in patients on prolonged hemodialysis.
Introduction: Infection control in the intensive care environment by hospital pathogens often includes the use of vancomycin. It is noteworthy that profound changes occur in the pharmacokinetics of antimicrobials prescribed to critical patients and that different dialytic methods may partially or totally remove them. Objective: To evaluate the reduction of antimicrobial vancomycin by different dialysis methods in patients with AKI associated with sepsis and to identify the variables associated with its therapeutic level. Methodology: A cross-sectional study evaluating septic patients with AKI on intermittent conventional hemodialysis (IHD) and prolonged hemodialysis (PHD) and vancomycin treatment in intensive care unit (ICU) of Clinics Hospital of the Faculty of Medicine of Botucatu - UNESP. Serial blood samples were collected at the start of dialysis therapy after 2 and 4 hours of treatment and at the end of therapy. The serum level of vancomycin was measured by high performance liquid chromatography (HPLC) or by Enzyme Multiplied Immunoassay Technique (EMIT). From these data, pharmacokinetic evaluation and PK / PD modeling were performed. Results: From March 2015 to August 2017, 27 patients treated for IHD, 17 for PHD 6h and 11 for PHD 10h were included. The volume of distribution was higher in the groups PHD 6h and PHD 10h (p <0.001), as well as half-life (p <0.001) and dialytic clearance of vancomycin (p <0.001). The reduction of vancomycin after 2 hours of therapy was 26.65% (± 12.64) and at the end of the dialysis was 45.78 (± 12.79), highest in the PHD 10h group, 57.70% (40,48-64.30), p=0.037. The ratio of the area under the curve by the minimum inhibitory concentration (AUC / MIC) in 24h in the PHD 10h group presented lower values, with a significant difference (p=0.047). In the logistic regression, the variables Clearence dialytic vancomycin (OR=0.0184, p=0.027), PHD (OR=0.00386, p=0.025) and concentration of vancomycin at the start of therapy (T0) (OR=1.96, p=0.006) were associated with the therapeutic concentration at the end of the dialysis. AUC/MIC 24h, the best vancomycin efficacy parameter, was analyzed in 41 patients. In logistic regression, prolonged hemodialysis was a risk factor for AUC/MIC 24h of less than 400 (OR=11.59, p=0.033), while that greater vancomycin concentration in T0 was a protective factor for AUC/MIC 24h of less than 400 (OR=0.791, p=0.009). In the analysis of patients with vancomycin concentrations considered nephrotoxic, at the end of therapy, only 14 (25.45%) patients had vancomycin concentration greater than 20mg/dl, the only risk factor identified in the logistic regression was the highest serum concentration of vancomycin at the beginning of the dialysis (OR=1.725, p=0.027). Conclusion: These results show a high prevalence of patients with vancomycin subtherapeutic concentration during and at the end of dialysis, which may be related to a higher risk of bacterial resistance and mortality, besides pointing to the need for additional doses of vancomycin during therapy dialysis, especially in patients on prolonged hemodialysis.
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Palavras-chave
sepse, lesão renal aguda, diálise, vancomicina, farmacocinética, farmacodinâmica, sepsis, acute renal injury, dialysis, vancomycin, pharmacokinetics, pharmacodynamics