Comparação quanto à eficácia e segurança de diferentes esquemas de administração de vancomicina em pacientes com injúria renal aguda em hemodiálise: um ensaio clínico randomizado
Data
2023-03-10
Autores
Zamoner, Welder
Título da Revista
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Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Introdução: Sepse é a principal causa de Injúria Renal Aguda (IRA) com necessidade dialítica em pacientes críticos, sendo a vancomicina amplamente utilizada. Sua farmacocinética e farmacodinâmica (PK/PD) sofrem alterações durante a hemodiálise (HD), aumentando o risco de concentrações subterapêuticas. Objetivo: Comparar diferentes protocolos de administração de vancomicina a fim de avaliar as concentrações séricas e razão área sob a curva/concentração inibitória mínima (ASC/CIM) a partir da PK/PD. Metodologia: Ensaio clínico randomizado, não-cego, incluindo pacientes críticos adultos, com diagnóstico de IRA séptica em HD convencional (4 horas) e prolongada (6 e 10 horas) e em uso de vancomicina há pelo menos 72horas de maio/2019 a maio/2021. Foram analisadas sessões de pacientes randomizados em 3 grupos (G): G controle (C, dose de 15mg/kg após a sessão de HD), G intervenção (I) 2 horas (dose de 7,5mg/kg na segunda hora da HD e 7,5mg/kg após a sessão) e GI infusão contínua (dose de 30mg/kg em bomba de infusão contínua, em 24 horas). Foram excluídos pacientes em diálise crônica, gestantes e com sessão interrompida por razões clínicas ou técnicas. Resultados: Dos 316 pacientes recrutados, 87 foram randomizados e 174 sessões de HD monitorizadas. Houve predomínio do sexo masculino (69,5%), idade 61±11anos, APACHE II 31±6, ATN-ISS 0,79±0,14. Para a análise, 28 sessões pertenciam ao GC, 47 sessões ao GI 2 horas e 31 sessões ao GI infusão contínua. Os grupos foram semelhantes quanto à idade, peso, comorbidades, escores de gravidade, uso de diurético e drogas nefrotóxicas, diurese, albumina, PCR, hematócrito, modalidade de HD, recuperação de função renal e óbito. Ao serem analisadas as sessões de HD, não houve diferença entre os grupos quanto a Kt/V, ultrafiltração, coagulação de sistema ou hipotensão. O GC apresentou maior frequência de concentração sérica subterapêutica ao término da HD em comparação com o GI 2 horas e infusão contínua (86,7% vs. 42,2% vs. 3,2%, p<0,0001), maior clearance dialítico (p=0,04) e menor ASC/CIM (p<0,0001). O GI infusão contínua apresentou maior frequência de concentrações supraterapêuticas (71%). Regressão logística identificou a variável concentração inicial (OR 1,16, p=0,001) como fator de risco para uma concentração não terapêutica (ASC/CIM menor que 400 mg·h/L ou maior que 600 mg·h/L) de vancomicina, enquanto que o grupo intervenção 2 horas foi identificado como fator de proteção (OR 0,24, p=0,04). Conclusão: Nossos resultados sugerem que administrar vancomicina durante a diálise resultou em menor proporção de concentrações supraterapêuticas ou subterapêuticas quando comparada à administração em infusão contínua ou após o término da sessão, respectivamente. Novos estudos são necessários para sugerir doses mais adequadas e avaliar o impacto desses achados nos desfechos clínicos.
Sepsis is the main cause of Acute Kidney Injury (AKI), requiring dialysis in critically ill patients, with vancomycin being widely used. Its pharmacokinetics and pharmacodynamics (PK/PD) change during hemodialysis (HD), increasing the risk of subtherapeutic concentrations. Objective: To compare different vancomycin administration protocols to assess serum concentrations and area under the curve/minimum inhibitory concentration (AUC/MIC) ratio from PK/PD. Methodology: Randomized, non-blind clinical trial, including critically ill adults diagnosed with septic AKI on conventional (4 hours) and prolonged HD (6 and 10 hours) and using vancomycin for at least 72 hours from May/2019 to May /2021. Sessions of patients were analyzed and randomized into three groups (G): G control (C, dose of 15mg/kg after HD session), G intervention (I) 2 hours (dose of 7.5mg/kg in the second hour of HD and 7.5mg/kg after the session) and IG continuous infusion (dose of 30mg/kg in continuous infusion pump, in 24 hours). Patients on chronic dialysis, pregnant women, and those whose session was interrupted for clinical or technical reasons were excluded. Results: Of the 316 patients recruited, 87 were randomized, and 174 HD sessions were monitored. There was a predominance of males (69.5%), age 61±11 years, APACHE II 31±6, ATN-ISS 0.79±0.14. For the analysis, 28 sessions belonged to the CG, 47 sessions to the 2-hour IG, and 31 to the continuous infusion IG. The groups were similar in age, weight, comorbidities, severity scores, use of diuretics and nephrotoxic drugs, urine output, albumin, CRP, hematocrit, HD modality, recovery of renal function, and death. When HD sessions were analyzed, there was no difference between the groups regarding Kt/V, ultrafiltration, system coagulation, or hypotension. The CG had a higher frequency of subtherapeutic serum levels at the end of HD compared to the 2-hour IG and continuous infusion (86.7% vs. 42.2% vs. 3.2%, p<0.0001), higher clearance dialysis (p=0.04) and lower AUC/MIC (p<0.0001). The IG continuous infusion had a higher frequency of supratherapeutic concentrations (71%). Logistic regression identified the initial concentration variable as a risk factor (OR 1.16, p=0.001) for a non-therapeutic concentration (AUC/MIC less than 400 mg·h/L or greater than 600 mg·h/L) of vancomycin. In contrast, the 2-hour intervention group was identified as a protective factor (OR 0.24, p=0.04). Conclusion: Our results suggest that administering vancomycin during dialysis resulted in a lower proportion of supratherapeutic or subtherapeutic concentrations compared to administration in continuous infusion or after the end of the session, respectively. New studies are needed to suggest more appropriate doses and assess these findings' impact on clinical outcomes.
Sepsis is the main cause of Acute Kidney Injury (AKI), requiring dialysis in critically ill patients, with vancomycin being widely used. Its pharmacokinetics and pharmacodynamics (PK/PD) change during hemodialysis (HD), increasing the risk of subtherapeutic concentrations. Objective: To compare different vancomycin administration protocols to assess serum concentrations and area under the curve/minimum inhibitory concentration (AUC/MIC) ratio from PK/PD. Methodology: Randomized, non-blind clinical trial, including critically ill adults diagnosed with septic AKI on conventional (4 hours) and prolonged HD (6 and 10 hours) and using vancomycin for at least 72 hours from May/2019 to May /2021. Sessions of patients were analyzed and randomized into three groups (G): G control (C, dose of 15mg/kg after HD session), G intervention (I) 2 hours (dose of 7.5mg/kg in the second hour of HD and 7.5mg/kg after the session) and IG continuous infusion (dose of 30mg/kg in continuous infusion pump, in 24 hours). Patients on chronic dialysis, pregnant women, and those whose session was interrupted for clinical or technical reasons were excluded. Results: Of the 316 patients recruited, 87 were randomized, and 174 HD sessions were monitored. There was a predominance of males (69.5%), age 61±11 years, APACHE II 31±6, ATN-ISS 0.79±0.14. For the analysis, 28 sessions belonged to the CG, 47 sessions to the 2-hour IG, and 31 to the continuous infusion IG. The groups were similar in age, weight, comorbidities, severity scores, use of diuretics and nephrotoxic drugs, urine output, albumin, CRP, hematocrit, HD modality, recovery of renal function, and death. When HD sessions were analyzed, there was no difference between the groups regarding Kt/V, ultrafiltration, system coagulation, or hypotension. The CG had a higher frequency of subtherapeutic serum levels at the end of HD compared to the 2-hour IG and continuous infusion (86.7% vs. 42.2% vs. 3.2%, p<0.0001), higher clearance dialysis (p=0.04) and lower AUC/MIC (p<0.0001). The IG continuous infusion had a higher frequency of supratherapeutic concentrations (71%). Logistic regression identified the initial concentration variable as a risk factor (OR 1.16, p=0.001) for a non-therapeutic concentration (AUC/MIC less than 400 mg·h/L or greater than 600 mg·h/L) of vancomycin. In contrast, the 2-hour intervention group was identified as a protective factor (OR 0.24, p=0.04). Conclusion: Our results suggest that administering vancomycin during dialysis resulted in a lower proportion of supratherapeutic or subtherapeutic concentrations compared to administration in continuous infusion or after the end of the session, respectively. New studies are needed to suggest more appropriate doses and assess these findings' impact on clinical outcomes.
Descrição
Palavras-chave
Sepse, Injúria renal aguda, IRA, Diálise, Vancomicina, Farmacocinética, Farmacodinâmica, Septicemia, Diálise, Hemodiálise