Pharmacokinetics of Vancomycin in Critically Ill Patients Undergoing Sustained Low‐Efficiency Dialysis

Abstract

INTRODUCTION Vancomycin pharmacokinetic data in critically ill patients receiving sustained low-efficiency dialysis (SLED) is limited. Published data using vancomycin with intermittent hemodialysis and continuous renal replacement therapy may not be applicable to hybrid dialysis modalities such as SLED. Current drug references lack recommendations for vancomycin dosing in patients receiving SLED. OBJECTIVE The objective of this study was to determine vancomycin pharmacokinetics during SLED. METHODS A total of 20 patients who were critically ill with oliguric or anuric renal failure who received vancomycin and SLED were included in the study. Surrounding one SLED session, serum vancomycin blood samples were drawn before the initiation of SLED, at the termination of SLED, and 4 hours after completion of SLED treatment. Following this, patients received vancomycin, dosed to target a goal peak of 20-30 mcg/ml. A vancomycin peak level was drawn 1 hour after the end of the infusion. SLED treatment duration was at least 7 hours. Continuous data are reported as median (interquartile range) and categorical data as percentage. RESULTS The vancomycin elimination rate and half-life were 0.051 hours (0.042-0.074 hours) and 13.6 hours (9.4-16.6 hours), respectively. SLED reduced vancomycin serum concentrations by 35.4% (31.5-43.8%), and vancomycin rebound was 9.8% (2.5-13.7%). The vancomycin dose administered post-SLED was 1000 mg (875-1125 mg). For 18 patients, the patient-specific volume of distribution was 0.88 L/kg (0.67-1.1 L/kg), vancomycin clearance was 3.5 L/hr (2.2-5.2 L/hr), and the area under the concentration-time curve during the study time period was 280.8 mgÁhr/L (254.7-297.3 mgÁhr/L). CONCLUSION Vancomycin is significantly removed during SLED with little rebound in serum concentrations 4 hours after completion of SLED. Based on study findings, patients who are critically ill require additional vancomycin dosing after each SLED session to maintain therapeutic post-SLED vancomycin concentrations. Therapeutic drug monitoring of vancomycin is recommended during SLED.

Antimicrobial dosing in prolonged intermittent renal replacement therapy: a systematic review

“…Dosing should be given at least 30-mins before a PIRRT treatment to allow a high Cmax to be achieved. 22 Vancomycin dosing and PK in PIRRT has been comparatively well investigated, including small prospective PK studies of critically ill patients with AKI 16,17,[23][24][25][26][27] ; three combined with a MCS population PK simulation. [28][29][30] Vancomycin clearance on-PIRRT is higher, although varies significantly (33-150%) 16,25,28,29 and depends on dialysis settings, including the filter membrane and PIRRT duration.…”

“…29,[33][34][35][36][37] A rebound phenomenon has been observed; in which vancomycin plasma concentrations increase over the first few hours following a PIRRT session compared with the measured concentration immediately at the end of a PIRRT session, caused by redistribution of vancomycin from tissues back into the blood stream. 16,25,26 Caution should be exercised when interpreting plasma concentrations drawn within 3 h of PIRRT concluding. 25 The recommended vancomycin PD target of AUC24/ MIC ratio of ≥ 400 can be achieved using a loading dose of vancomycin, followed by a different maintenance dose that is informed by TDM.…”

“…25 The recommended vancomycin PD target of AUC24/ MIC ratio of ≥ 400 can be achieved using a loading dose of vancomycin, followed by a different maintenance dose that is informed by TDM. 26 The suggested loading dose in the setting of PIRRT is variable, ranging between 15-25 mg/kg of actual body weight. 16,23,30 Maintenance vancomycin dose recommendations vary, likely due to the effect of different PIRRT settings, and may be fixed (between 500 mg-1600 mg once daily) or weight-based (15-20 mg/kg daily).…”

“…16,23,30 Maintenance vancomycin dose recommendations vary, likely due to the effect of different PIRRT settings, and may be fixed (between 500 mg-1600 mg once daily) or weight-based (15-20 mg/kg daily). 26 Doses should be given after PIRRT and supplemented by TDM to guide ongoing dosing. 16,17,27 PK variability is significant and dosing without TDM risks significant proportions of patients manifesting potentially toxic exposures (AUC24 > 700 mg h/L).…”

“…Vancomycin dosing and PK in PIRRT has been comparatively well investigated, including small prospective PK studies of critically ill patients with AKI 16,17,23–27 ; three combined with a MCS population PK simulation 28–30 …”