Influence Of Cerebrospinal Fluid Drainage And Other Variables On The Plasma Vancomycin Trough Levels In Postoperative Neurosurgical Patients

Background:Therapeutic drug monitoring (TDM) aims to minimise the clinical impact of vancomycin (VCM) pharmacokinetic variability. However, TDM data are limited among specific patient populations, including postoperative neurosurgical populations. The objective of this study was to retrospectively investigate the influence of cerebrospinal fluid (CSF) drainage and other factors on the serum trough concentrations of VCM. Methods:We analysed 154 patients who had been hospitalised in the neurosurgical ward and received intravenous infusions of VCM. We compared the daily doses of VCM, serum VCM concentrations, and serum concentration/dose ratio (C/D ratio) between patients who underwent CSF drainage (drainage group) and controls (nondrainage group). In addition, we also elucidated other factors affecting the attainment of target concentrations. Results:The patients in the drainage group showed a significantly lower trough concentration of VCM (6.2 +/- 4.2 mu g/mL) than that shown by the nondrainage group (8.5 +/- 6.6 mu g/mL,p = 0.03). Furthermore, the patients in the drainage group showed a significantly different trough C/D ratio (3.1 +/- 2.1) than that shown by the nondrainage group (4.3 +/- 3.4,p = 0.014). The Mann-WhitneyUtest demonstrated significantly lower VCM trough levels with concomitant use of diuretic than without (p = 0.004). Multivariable logistic regression demonstrated that coadministered diuretic independently predicted subtherapeutic trough levels of <10 mu g/mL (p = 0.04). The concomitant use of albumin and other variables exerted no effects on VCM trough levels. Conclusions:These data suggest that CSF drainage and diuretics have different effects, but it seems that both lower the VCM concentration in postoperative neurosurgical patients. Our findings strongly suggest that a high dose of VCM is required to maintain optimal serum concentrations of VCM in patients managed with CSF drainage or concomitant use of diuretic.