High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures

The aim of this study was to evaluate retrospectively the importance of a B ayesian pharmacokinetic approach for predicting vancomycin concentrations t o individualize its dosing regimen in 18 critically ill patients admitted t o intensive care units following cardiothoracic surgery. The possible influ ence of some coadministered drugs with important haemodynamic effects (dopa mine, dobutamine, frusemide) on vancomycin pharmacokinetics was assessed. V ancomycin serum concentrations were measured by fluorescence polarization i mmunoassay. Vancomycin dosage regimens predicted by the Bayesian method (D- a) were compared retrospectively with Moellering's nomogram-based dosages ( D-M) to assess possible major differences in vancomycin dosing. D-a values were similar to D-M in 10 patients (D-a approximate to D-M group) (20.52 +/ - 8.40 mg/kg/day versus 18.81 +/- 7.24 mg/kg; P = 0.15), whereas much highe r dosages were required in the other eight patients (D-a much greater than D-M group) (26.78+/- 3.01 mg/kg/day versus 18.95 +/- 3.41 mg/kg/day; P < 0. 0001) despite no major difference in attained vancomycin steady-state troug h concentration (C-min (ss)) (9.22 +/- 1.33 mg/L versus 8.99 +/- 1.26 mg/L; = 0.75) or estimated creatinine clearance (1.23 +/- 0.49 mL/min/kg versus 1.21 +/- 0.24 mL/min/kg; P = 0.95) being found between the two groups. The ratio between D-a and D-M was significantly higher in the D-a much greater than D-M group than in the D-a approximate to D-M group (1.44 +/- 0.18 vers us 1.10 +/- 0.21; P < 0.01). In four D-a much greater than D-M patients the withdrawal of cotreatment with haemodynamically active drugs was followed by a sudden substantial increase in the vancomycin C-min ss (13.30 +/- 1.13 mg/L versus 8.79 +/- 0.87 mg/L; P < 0.01), despite no major change in body weight or estimated creatinine clearance being observed. We postulate that these drugs with important haemodynamic effects may enhance vancomycin clea rance by inducing an improvement in cardiac output and/or renal blood flow, and/or by interacting with the renal anion transport system, and thus by c ausing an increased glomerular filtration rate end renal tubular secretion. Given the wide simultaneous use of vancomycin and dopamine and/or dobutami ne and/or frusemide in patients admitted to intensive care units, clinician s must be aware of possible subtherapeutic serum vancomycin concentrations when these drugs are coadministered. Therefore, therapeutic drug monitoring (TDM) for the pharmacokinetic optimization of vancomycin therapy is strong ly recommended in these situations.