Comparison of Adverse Events With Vancomycin Diluted in Normal Saline vs Dextrose 5%
Background: IV vancomycin is widely used for infections caused by Gram-positive bacteria; however, nephrotoxicity is commonly associated with its use. Clinical trials have shown an increased incidence of acute kidney injury (AKI) using normal saline (NS) for fluid resuscitation. This study evaluated differences in AKI and other patient outcomes associated with vancomycin diluted in NS compared with dextrose 5% in water (D5W).
Methods: This retrospective cohort study conducted at a single US Department of Veterans Affairs hospital included veterans who received vancomycin for at least 48 hours between July 1, 2015 and June 30, 2020. This study compared adverse events (AEs) of patients receiving vancomycin diluted in either NS or D5W. The primary outcome was incidence of AKI. Secondary outcomes included incidence of hyperglycemia, hyperchloremia, hypernatremia, metabolic acidosis, in-hospital mortality, and 30-day posthospitalization mortality.
Results: The study included 123 patients in each group (N = 246). The percentage of AKI was 22.8% in the D5W group compared with 14.6% the NS group ( P = .14). There were no significant differences in the rates of hyperglycemia, hyperchloremia, hypernatremia, or metabolic acidosis between the 2 groups. In-hospital mortality and 30-day posthospitalization mortality were similar between the groups.
Conclusions: This study comparing the AEs of IV vancomycin diluted in NS and D5W found no significant differences in AKI or other patient outcomes. These study results do not suggest the crystalloid used to dilute IV vancomycin is associated with differences in nephrotoxicity or other relevant AEs.
The combination of piperacillin/tazobactam plus vancomycin has commonly been associated with an increased risk of nephrotoxicity. Previous studies have identified this nephrotoxic combination to have a significantly increased risk of AKI compared with vancomycin alone or when used in combination with alternative antibiotics such as cefepime or meropenem.15,16 In our study, there was a higher percentage of patients in the NS group with concomitant piperacillin/tazobactam, so this difference between the groups may have influenced the incidence of AKI. Nephrotoxic medications other than antibiotics were not assessed in this study; however, these also could have impacted our results significantly. While the vancomycin duration of therapy and highest trough levels were similar between groups, the NS group had a larger average daily dose and overall cumulative dose. Studies have identified the risk of nephrotoxicity increases with a vancomycin daily dose of 4 g, troughs > 15 mg/mL, and a duration of therapy > 7 days.15,16 In our study, the daily doses in both groups were < 4 g, so it is likely the average daily vancomycin dose had little impact on the incidence of AKI.
Another potential confounder identified was assessment of underlying conditions in the patients. Due to the limitations associated with the data extraction method, we could not assess for underlying conditions that may have impacted the results. Notably, the potential nephrotoxicity of NS has mostly been shown in critically ill patients. Therefore, the mixed acutely ill patient sample in this study may have been less likely to develop AKI from NS compared with an exclusively critically ill patient sample.
Selection bias and information bias are common with observational studies. In our study, selection bias may have been present since prospective randomization of patient samples was not possible. Since all data were extracted from the medical health record, information bias may have been present with the potential to impact the results. Due to the single-center nature of this study with a predominantly older, white male veteran patient sample, generalizability to other patient populations may be limited. We would expect the results of this study to be similar among other patient populations of a similar age and demographic; however, the external validity of this study may be weak among other populations. Although this study included enough patients based on sample size estimate, a larger sample size could have allowed for detection of smaller differences between groups and decreased the chance for type II error.
Conclusions
Overall, the results of this study do not suggest that the crystalloid used to dilute IV vancomycin is associated with differences in nephrotoxicity or other relevant AEs. Future studies evaluating the potential for AEs from medication diluent are warranted and would benefit from a prospective, randomized design. Further studies are both necessary and crucial for enhancing the quality of care to minimize the rates of AEs of commonly used medications.
Acknowledgment
This material is the result of work supported with resources and the use of facilities at the North Florida/South Georgia Veterans Health System in Gainesville, Florida.
