O papel da vancocinemia como preditora diagnóstica e prognóstica de lesão renal aguda associada ao uso da vancomicina
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Data
2018-08-08
Autores
Zamoner, Welder
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Universidade Estadual Paulista (Unesp)
Resumo
Introdução: A vancomicina é um antimicrobiano estratégico no tratamento de infecções graves por germes Gram positivos, que embora usado há mais de 60 anos ainda gera dúvidas quanto a sua eficácia e segurança. São escassos os estudos que avaliaram a monitorização de seu nível plasmático em pacientes sépticos e sua associação com desfechos clínicos, como desenvolvimento de lesão renal aguda (LRA) e óbito. Esse estudo tem por objetivo avaliar a prevalência de níveis séricos adequados, subterapêuticos e tóxicos de vancocinema em pacientes sépticos hospitalizados e associar a adequação da monitorização terapêutica com desfechos clínicos. Metodologia: Estudo de coorte unicêntrico que avaliou pacientes maiores de 18 anos em uso de vancomicina admitidos tanto em unidades de terapia intensiva (UTIs) quanto em enfermarias clínicas e cirúrgicas de um centro universitário brasileiro no período de 01 de agosto de 2016 a 31 de julho de 2017 de modo diário e ininterrupto. Foram excluídos pacientes com LRA prévia à introdução de vancomicina ou com desenvolvimento de LRA em menos de 48h após o seu uso, pacientes com LRA de outras etiologias, doentes renais crônicos estadio 5 e gestantes. Foram avaliados dois desfechos clínicos: desenvolvimento de LRA e óbito. Resultados: Foram avaliados 198 pacientes, sendo incluídos 63 pacientes críticos e 135 não críticos. Na população admitida em UTI, a dosagem de nível sérico de vancomicina foi realizada em 92% dos pacientes e destas, 58,7% estavam em nível tóxico. A prevalência de LRA foi de 44,4% e ocorreu, em média, no 6° dia de uso da vancomicina. Entre o 2° e o 4° dia, valor de vancocinemia acima de 17,53 mg/L mostrou-se preditor de LRA com área sob a curva de 0,806 (IC 95% 0,624-0,987, p=0,011) antecedendo o diagnóstico de LRA em pelo menos 2 dias. Desses pacientes, 46,03% evoluíram a óbito e as variáveis idade, níveis de vancocinemia entre os 2° e 4° dias de tratamento, taxa de filtração glomerular estimada e valor médio de PCR foram identificados como fatores de risco para óbito. Já na população admitida nas enfermarias clínicas e cirúrgicas, a dosagem de nível sérico de vancomicina foi realizada em 94,1% e destas, 59,3% apresentaram nível tóxico. A prevalência de LRA foi de 27,4% e ocorreu, em média, no 9º dia de uso da vancomicina. Entre o 4° e o 6° dia, valor de vancocinemia acima de 21,5 mg/L mostrou-se preditor de LRA com área sob a curva de 0,803 (IC 95% 0,625-0,98, p=0,005) antecedendo o diagnóstico de LRA em pelo menos 3 dias. Desses pacientes, 20,7% evoluíram a óbito e a presença de DM2, o uso de DVA e a níveis séricos de vancomicina entre o 4º e 6º dia de uso foram identificados como fatores de risco associados ao desfecho negativo. Conclusão: A vancocinemia é excelente preditora de LRA tanto em pacientes críiticos como em pacientes admitidos em enfermarias, antecedendo o diagnóstico da LRA em pelos menos 48h. Apesar de diretrizes recomendarem níveis terapêuticos entre 15 e 20mg/L, para pacientes em UTIs, os resultados desse estudo sugerem que o alvo da monitorização terapêutica deva ser entre 15 e 17,5mg/L. Ainda, os níveis séricos de vancomicina associaram-se ao óbito nas duas populações, porém após ajuste para as variáveis estatisticamente significantes pelo modelo de Cox, a única variável associada ao óbito foi a idade na população crítica e a vancocinemia acima de 21,5mg/dL na população não crítica.
Introduction: Vancomycin is a strategic antimicrobial for the treatment of severe Gram-positive infections, which raises doubts to its efficacy and safety although it used for more than 60 years. There are few studies evaluating the monitoring of its serum level in septic patients and its association with clinical outcomes, such as the development of acute kidney injury (AKI) and death. This study aims evaluate the prevalence of adequate, subtherapeutic and toxic serum levels of vancomycin in hospitalized septic patients and associate the adequacy of therapeutic monitoring with clinical outcomes. Methodology: A unicentric cohort study that evaluated patients older than 18 years with vancomycin use admitted in intensive care units (ICUs) and clinical and surgical wards of a Brazilian university center from August 1, 2016 to July 31, 2017 on a daily and uninterrupted basis. Patients with AKI prior to the introduction of vancomycin or with the development of AKI in less than 48 hours after their use were excluded, patients with AKI of other etiologies, end stage of kidney disease, and pregnant women were excluded. Two clinical outcomes were evaluated: AKI development and death. Results: 198 patients were evaluated, including 63 critical and 135 non-critical patients. In the population admitted to the ICU, the serum level of vancomycin was measured in 92% of the patients, of which 58.7% were in the toxic level. The prevalence of AKI was 44.4% and occurred on average at the 6th day of vancomycin use. Between day 2 and day 4, the value of serum level above 17.63 mg/L was a predictor of AKI with an area under the curve of 0.806 (CI 95% 0.624-0.987, p=0,011), preceding the diagnosis of AKI in at least 2 days. Of these patients, 46.03% died, and the variables age, number of adjustments, subtherapeutic levels and higher levels of vancocinemia between the 2nd and 4th days of treatment were identified as risk factors for death. In the population admitted to the clinical and surgical wards, the serum level of vancomycin was measured in 94.1% of the patients, and 59.3% were toxic. The prevalence of AKI was 27.4% and occurred on average at the 9th day of vancomycin use. Between the 4th and 6th day, the value of serum level above 21.5 mg/L was a predictor of AKI with an area under the curve of 0.803 (CI 95% 0.625-0.98, p=0,005), which preceded the diagnosis of AKI in at least 3 days. Of these patients, 20.7% died and the presence of diabetes, the use of VAD and higher levels of vancocinemia between the 4th and 6th days of treatment were identified as risk factors for death. Conclusion: Serum level of vancomycin is an excellent predictor of AKI in both critically ill patients and patients admitted to the ward, which precedes the diagnosis of AKI in at least 48 hours. Although guidelines recommend therapeutic levels between 15 and 20 mg/L for patients in ICUs, the results of this study suggest that the target of the therapeutic monitoring should be between 15 and 17.5 mg/L. In addition, serum levels of vancomycin were associeted with death in both populations, but after Cox model adjustment for statistically significant variables, the only variable associated with death was age in the critially ill patients and sérum level of vancomycin above 21,5mg/dL in population admitted to the clinical and surgical wards.
Introduction: Vancomycin is a strategic antimicrobial for the treatment of severe Gram-positive infections, which raises doubts to its efficacy and safety although it used for more than 60 years. There are few studies evaluating the monitoring of its serum level in septic patients and its association with clinical outcomes, such as the development of acute kidney injury (AKI) and death. This study aims evaluate the prevalence of adequate, subtherapeutic and toxic serum levels of vancomycin in hospitalized septic patients and associate the adequacy of therapeutic monitoring with clinical outcomes. Methodology: A unicentric cohort study that evaluated patients older than 18 years with vancomycin use admitted in intensive care units (ICUs) and clinical and surgical wards of a Brazilian university center from August 1, 2016 to July 31, 2017 on a daily and uninterrupted basis. Patients with AKI prior to the introduction of vancomycin or with the development of AKI in less than 48 hours after their use were excluded, patients with AKI of other etiologies, end stage of kidney disease, and pregnant women were excluded. Two clinical outcomes were evaluated: AKI development and death. Results: 198 patients were evaluated, including 63 critical and 135 non-critical patients. In the population admitted to the ICU, the serum level of vancomycin was measured in 92% of the patients, of which 58.7% were in the toxic level. The prevalence of AKI was 44.4% and occurred on average at the 6th day of vancomycin use. Between day 2 and day 4, the value of serum level above 17.63 mg/L was a predictor of AKI with an area under the curve of 0.806 (CI 95% 0.624-0.987, p=0,011), preceding the diagnosis of AKI in at least 2 days. Of these patients, 46.03% died, and the variables age, number of adjustments, subtherapeutic levels and higher levels of vancocinemia between the 2nd and 4th days of treatment were identified as risk factors for death. In the population admitted to the clinical and surgical wards, the serum level of vancomycin was measured in 94.1% of the patients, and 59.3% were toxic. The prevalence of AKI was 27.4% and occurred on average at the 9th day of vancomycin use. Between the 4th and 6th day, the value of serum level above 21.5 mg/L was a predictor of AKI with an area under the curve of 0.803 (CI 95% 0.625-0.98, p=0,005), which preceded the diagnosis of AKI in at least 3 days. Of these patients, 20.7% died and the presence of diabetes, the use of VAD and higher levels of vancocinemia between the 4th and 6th days of treatment were identified as risk factors for death. Conclusion: Serum level of vancomycin is an excellent predictor of AKI in both critically ill patients and patients admitted to the ward, which precedes the diagnosis of AKI in at least 48 hours. Although guidelines recommend therapeutic levels between 15 and 20 mg/L for patients in ICUs, the results of this study suggest that the target of the therapeutic monitoring should be between 15 and 17.5 mg/L. In addition, serum levels of vancomycin were associeted with death in both populations, but after Cox model adjustment for statistically significant variables, the only variable associated with death was age in the critially ill patients and sérum level of vancomycin above 21,5mg/dL in population admitted to the clinical and surgical wards.
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Palavras-chave
pacientes sépticos, lesão renal aguda, vancomicina, nefrotoxicidade