Clearance of vancomycin during high-volume haemofiltration: impact of pre-dilution

Objective: To measure the sieving coefficient (SC) and clearance of vancomycin during high-volume haemofiltration (HVHF) and to evaluate the impact of different pre-dilution regimens on these variables. Design and setting: Prospective interventional study in the intensive care unit in a tertiary university hospital. Patients: Seven patients with septic shock and multi-organ dysfunction. Interventions: HVHF (6 l/h fluid exchange) was performed in septic shock patients using variable proportions of their replacement fluid in pre- and post-dilution mode. Measurements and results: Pre-filter, post-filter and ultrafiltrate vancomycin concentrations were measured simultaneously, and SC and clearance calculated. The measurements were repeated following each change in the proportion of pre-dilution fluid. SC steadily decreased as the proportion of pre-dilution decreased, changing from 0.76 in pure pre-dilution to 0.57 in pure post-dilution (p=0.0004). Clearance, however, increased with decreasing pre-dilution fluid rate, from 53.9 ml/min at pure pre-dilution to 67.2 ml/min at 2 l/h pre-dilution with 4 l/h post-dilution. Conclusions: HVHF achieves high vancomycin clearances, which despite some deterioration in SC increase with the proportion of replacement fluid given post-filter. Clinicians applying HVHF need to be aware of such clearances to avoid inadequate vancomycin dosing and to adjust therapy according to variations in HVHF technique.