Vancomycin Dosing Nomogram for Haemodialysis Patients

Infection is the second leading cause of mortality in haemodialysis patients. Vancomycin is commonly prescribed when Gram-positive bacterial sepsis is suspected; however, few data are available to guide dosing. At our institution, haemodialysis patients receiving vancomycin were administered 1 g when pre-dialysis levels were <15 mg/L. A 2011 audit of haemodialysis patients receiving >2 vancomycin doses demonstrated trough targets of 15–20 mg/L in 14/38 (36.8%). In 2012 we introduced a vancomycin dosing nomogram aiming to improve pharmacokinetic parameters (Table 1). After the initial vancomycin dose, the nomogram was prescribed by the treating physician. At subsequent haemodialysis sessions, blood was taken for an urgent vancomycin level to ensure availability for nursing staff to calculate and administer doses according to the nomogram. Doses were administered to ensure simultaneous infusion and haemodialysis completion. After implementation, an audit of the nomogram was performed. Local Human Research Ethics Committee approval was granted. Twenty-five patients received 28 vancomycin courses (median duration 17.5 days). Common indications included skin and soft tissue infection (32%) and bone/joint infection (18%). Mean duration to haemodialysis immediately after initial vancomycin dosing was 1.8 days. The mean subsequent inter-dialysis period was 2.4 days. A 25 mg/kg vancomycin load was administered in 6/25 courses. In all others the initial dose was 1 g. A loading dose resulted in a greater mean trough concentration prior to the next haemodialysis session (16.9 vs 9.8 mg/L; P = 0.01 by t-test). A vancomycin level was available to guide subsequent dosing in 239/247 (96.8%) instances. The mean maintenance vancomycin dose was 935 mg, and followed the nomogram in 223/230 (97.0%) instances. Trough concentrations of 15–20 mg/L were achieved in 116/213 (54.5%). In 32 (15%) and 9 (4.2%) instances trough levels were <15 mg/L and >25 mg/L respectively. Compared with historical controls, there was a trend towards higher target trough attainment using the nomogram (54.5% and 37%, P = 0.053 by Fisher’s exact). A vancomycin AUC/MIC of >400 has been correlated with improved outcomes when treating staphylococcal infections, with trough levels of 15–20 mg/L representing the recommended surrogate marker. In haemodialysis patients these levels are infrequently obtained. Complicated dosing calculators have been proposed to improve vancomycin dosing parameters. Here we have identified a simple dosing nomogram, which likely results in improved pharmacokinetics compared with traditional dosing regimens. Protocol strengths include high vancomycin level availability for dose calculations, ability for nurse facilitated administration to prevent delayed or missed doses, independence of dose calculation from subsequent inter-dialysis periods (an often unknown variable) and the avoidance of peripheral intravenous cannulas by administration during haemodialysis. Low patient numbers likely resulted in the study being underpowered to detect a statistically significant improvement in vancomycin pharmacokinetics. Due to low use of weight based loading doses, assessment of the best loading dose strategy was compromised. Given these findings, ongoing use of the policy is recommended, with further staff education to increase uptake, and monitoring of loading dose strategies and their influence on subsequent nomogram performance. Assessment of the nomogram in other haemodialysis settings should be performed to establish applicability elsewhere.