Pharmacokinetics of vancomycin in patients with continuous flow left-ventricular assist devices

Purpose:   To describe the pharmacokinetics of vancomycin in patients with continuous flow left-ventricular assist devices (CF-LVADs).

Methods:   This IRB-approved retrospective, descriptive analysis was conducted at an urban, tertiary hospital.  Eligible patients were ≥18yrs old, implanted with a HeartMateII CF-LVAD during January2008-April2012, and treated with vancomycin ≥48hrs for infection.  Key exclusion criteria include <2 vancomycin levels, ≥Stage1 AKIN acute kidney injury (change in Scr ≥0.3mg∙dL^-1 or ≥1.5∙baseline or urine output <0.5mL∙kg^-1∙hr^-1 for ≥6hrs), acute heart failure exacerbation, hemodynamic instability, and surgery ≤5d before initiating vancomycin.  Methods for estimating first-order elimination rate constant (K_e)(Table1) and volume of distribution (V_d)[using ideal (IBW), adjusted (AdjBW), and actual (ABW) body weights]  were compared with the actual K_e and V_d.  Actual pharmacokinetic parameters were calculated from steady-state peak and trough vancomycin levels using one-compartment model equations.  Paired t-test or signed-rank test was used. 

Results:   Twelve patients were included (age 44.9±15 years, 91.7% male, 58.3% obese, CLcr 79.2±27 mL∙min^-1).  Common reasons for exclusion were <2 vancomycin levels drawn (n=65) and unstable renal function or hemodynamics (n=4).  Common treatment indications (n≥2) were health-care associated pneumonia (41.7%), driveline infection (25%), and sepsis (16.7%). Methods CL_cr1 and CL_cr2 for estimating K_e were highly correlated with actual K_e (r=0.78 and 0.79, respectively; p<0.01).  CL_cr3a tended to overestimate actual K_e for obese patients [0.0254hr^-1 (-0.0001-0.051hr^-1; p=0.051)].  Obese patients had a lower-than-expected actual V_d, which was numerically less compared with non-obese patients (0.44L∙kg^-1ABW vs. 0.57L∙kg^-1ABW; p=0.17).  Therefore, EstV_d_ABW overestimated actual V_d for obese patients [23.2L (7.5-38.9L; p=0.028)].

Conclusion: General population methods may accurately estimate the pharmacokinetic parameters of vancomycin for stable non-obese patients with CF-LVADs.  Obese patients may require use of AdjBW or IBW for an accurate prediction of V_d.

Table1.  Methods for estimating K_e^*

Method	ABW∙IBW-1	Designated body weight for CLcr equation†,‡
CLcr1†	any	IBW
CLcr2†		72kg
CLcr3a‡	≥1.3 (obese)	ABW
CLcr3b†		AdjBW

^*K_e=0.00117∙CL_cr+0.03.  ^†Cockcroft-Gault.  ^‡Salazar-Corcoran.