High Single-dose Vancomycin Loading Is Not Associated With Increased Nephrotoxicity in Emergency Department Sepsis Patients

Abstract

Objective: Vancomycin loading doses are recommended; however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (>20 mg/kg) versus lower doses (≤20 mg/kg).Methods: A retrospective cohort study was performed in three academic EDs. Inclusion criteria were age ≥ 18 years, intravenous vancomycin order, and hospital admission. Exclusion criteria were no documented weight, hemodialysis-dependent, and inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (>20 mg/kg) versus low dose (≤20 mg/kg).Results: A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High-dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs. 11.1%). After age, sex, and initial SCr were adjusted for, the risk of high-dose vancomycin compared to low-dose was decreased for the development of nephrotoxicity (relative risk = 0.60; 95% confidence interval = 0.44 to 0.82).Conclusion: Initial dosing of vancomycin > 20 mg/kg was not associated with an increased rate of nephrotoxicity compared with lower doses. Findings from this study support compliance with initial weight-based vancomycin loading doses.ACADEMIC EMERGENCY MEDICINE 2016;23:744-746

Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients

“…This reduces mortality and the length of hospitalization in patients with bacteremia by S. aureus (2,25). Moreover, the use of an LD represents a safe strategy, which does not increase the incidence of nephrotoxicity (26).…”

Vancomycin dosing, monitoring and toxicity: Critical review of the clinical practice

“…Especially in septic patients admitted to the ICU, the presence of other factors concomitantly with the use of vancomycin makes it difficult to assess nephrotoxicity as the aetiology of AKI, since they act as confounding factors and make these patients more susceptible to kidney damage due to the severity of the underlying disease, and not due to the treatment. Then, some authors question whether high serum levels of vancomycin are the cause (due to higher serum concentration) or a consequence of AKI (drug build‐up due to impaired kidney function as a consequence of other factors) …”

“…Among patients with stage 5 chronic kidney disease receiving some renal replacement therapy or critically ill patients on acute renal support therapy and concomitant administration of vancomycin, the drug elimination during therapy should be based on dose adjustment . Vancomycin clearance by dialysis depends on the type of dialysis membrane, dialysis fluxes and duration, ultrafiltration rate, and Kt/V .…”

“…A retrospective study conducted by Rosini et al evaluated 2131 patients at three academic centres and compared the vancomycin dose of >20 to ≤20 mg/kg, and found a lower incidence of nephrotoxicity in the higher dose group (5.8% vs 11.1%, P < 0.001). After adjustment for age, sex and baseline creatinine, exposure to high dose of vancomycin was not initially associated with nephrotoxicity (RR = 0.60).…”

“…Vancomycin clearance by dialysis depends on the type of dialysis membrane, dialysis fluxes and duration, ultrafiltration rate, and Kt/V . There are no data confirming that levels between 15 and 20 mg/L related to AUC in haemodialysis patients …”