Factors affecting serum concentration of vancomycin in critically ill oliguric pediatric patients receiving continuous venovenous hemodiafiltration

Abstract

Vancomycin is known to be unintentionally eliminated by continuous renal replacement therapy, and the protein bound fraction of vancomycin is also known to be different in adults and children. However, there are only a few studies investigating the relationship between the dose of continuous venovenous hemodiafiltration (CVVHDF) parameters and serum concentration of vancomycin in pediatric patients. The aim of this study was to determine clinical and demographic parameters that significantly affect serum vancomycin concentrations. This retrospective cohort study was conducted at a pediatric intensive care unit in a tertiary university children’s hospital. Data from oliguric patients who underwent CVVHDF and vancomycin therapeutic drug monitoring were collected. The correlation between factors affecting serum concentration of vancomycin was analyzed using mixed effect model. A total of 177 serum samples undergoing vancomycin therapeutic drug monitoring were analyzed. The median age of study participants was 2.23 (interquartile range, 0.3–11.84) years, and 126 (71.19%) were male patients. Serum concentration of vancomycin decreased significantly as the effluent flow rate (EFR; P < 0.001), dialysate flow rate (DFR; P = 0.009), replacement fluid flow rate (RFFR; P = 0.008), the proportion of RFFR in the sum of DFR and RFFR (P = 0.025), and residual urine output increased. The adjusted R2 of the multivariate regression model was 0.874 (P < 0.001) and the equation was as follows: Vancomycin trough level (mg/L) = (0.283 × daily dose of vancomycin [mg/kg/d]) + (365.139 / EFR [mL/h/kg])–(15.842 × residual urine output [mL/h/kg]). This study demonstrated that the serum concentration of vancomycin was associated with EFR, DFR, RFFR, the proportion of RFFR, and residual urine output in oliguric pediatric patients receiving CVVHDF.

Determinants of Vancomycin Trough Concentration in Patients Receiving Continuous Veno-Venous Hemodialysis

“…A major factor impacting vancomycin trough concentration in our analysis was the weight-based vancomycin dose (mg/kg) similar to previous literature. 10 The current evaluation found that for each 1 mg/kg increase in vancomycin dose, the trough concentration increased by approximately 1 mcg/mL. In our study, 83% of patients receiving ≤10mg/ kg dose of vancomycin daily achieved a target trough goal, compared to only 47% of patients in higher dosage groups, with a median trough of 25.5 mg/mL in the higher-dose groups.…”

“…This result is similar to prior literature; however, in pediatric CVVHDF populations. 10,25 These findings are in contrast to Petejova et al, 30 who found no significant relationship between clearance of vancomycin and residual renal function in their 17 CVVH patients. It might be necessary to consider vancomycin dosage adjustment if renal function begins to recover and urine output improves.…”

“…Previous studies have evaluated various vancomycin dosing strategies in CRRT but without consistent results regarding dosing or factors that may impact resultant vancomycin concentrations. [10][11][12] Furthermore, available literature is limited by small numbers of patients, evaluation of only a single vancomycin dose, inconsistent CRRT modalities, or evaluation in pediatric populations.…”

Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update

“…Vancomycin clearance in critically ill patients receiving CRRT is reliably predicted by effluent flow rate. 23,94 Variability in the published literature for vancomycin exists regarding dosing recommendations needed to achieve target trough or AUC goals. Increasingly, AUC-targeted regimens are utilized, although precise dosing targets have not been studied and validated in a population requiring RRT.…”

Optimizing the Use of Antibiotic Agents in the Pediatric Intensive Care Unit: A Narrative Review

“…CRRT-related clearance accounted for 63% of the total meropenem clearance in PICU patients [125]. For the frequently used antibiotics meropenem, piperacillin-tazobactam, and vancomycin, the effluent flow rate (net ultrafiltration + dialysate flow rate) appears to be the most reliable predictor of antibiotic clearance and should be taken into account when deciding on a dosing scheme [124,126]. In contrast with ECMO, most studies on antibiotic PK in CRRT have been performed in critically ill adults and some antibiotic dosing recommendations have been formulated for this population [124].…”