#5254 COMPARISON OF EFFICACY OF DIFFERENT VANCOMYCIN ADMINISTRATION REGIMENS IN ACUTE KIDNEY INJURY ON HEMODIALYSIS PATIENTS: A RANDOMIZED CLINICAL TRIAL

Abstract

Abstract Background and Aims 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. Methods 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 15 mg/kg after HD session), G intervention (I) 2 hours (dose of 7.5 mg/kg in the second hour of HD and 7.5 mg/kg after the session) and IG continuous infusion (dose of 30 mg/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<.0001), higher clearance dialysis (p = .04) and lower AUC/MIC (p<.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 = .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 = .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.