Hussain Mulla, Suneel Pooboni, David Jenkins, Graham Lawson, Richard Firmin, David Upton
Glenfield Hospital, Leicester
Objectives: Extracorporeal membrane oxygenation (ECMO) is a life support system used in the treatment of severe respiratory or cardiorespiratory failure. Drug disposition is known to be altered during ECMO. Thus, the objective of this study was to determine population pharmacokinetics (POPPK) of vancomycin and their variability during ECMO. The study group included term neonates (0-1 month, n=15), older children (1 month-18 years, n=12) and adults (>18 years, n=18).
Methods: The study utilised both prospective rich and retrospective scant data. A POPPK model was developed using WinNonMix (Version 2.0.1) from a total of 366 plasma observations from 45 patients. Vancomycin doses were based on age and renal function, ranging 10-15mg.kg-1 8-24 hourly. Prospective samples were drawn at baseline and then 30, 60,90, 120, 180, 240, 300, 360 and 420 mins post infusion. Steady state, scant data were obtained retrospectively from an assay database, cross-referencing with the patients medical records.
Results: Mean (range) serum creatinine (SCr) levels were significantly higher amongst adults (125.1(48.3-224.5)), compared to neonates and older children (79.6(39-180) and 73.5 (26.5-158.9) μmol/L respectively), reflecting age and severity of illness. Data was examined using a two compartment model with an additive and proportional residual error. Exploration of covariates (following inclusion of weight) revealed correlations: SCr and age with CLC; age with VC. Significant improvement in model fit was observed when CLC was modelled as a non-linear function of SCr, and linearly associated with age up to 1000 days. The influence of age on VC was included into the model as a dichotomous variable (breakpoint 4000 days). The final population model was: CLC(age <1000 days) = 2.4 + 0.0018*Age (days) / Scr (μmol/L) L/kg/hr; CLC (age >1000 days) = 4.3 / Scr (μmol/L) L/kg/hr; CLi = 0.09L/kg/hr; VC (age < 4000 days) =0.45L/kg; VC(age > 4000 days) = 0.36L/kg; VT = 0.25L/kg. Interpatient coefficient of variation in CLC, CLi, VC and VT were 25.2%, 91%, 25.2% and 47.6% respectively, whilst residual error corresponded to a proportional error of 11.8% and additive error of 2.1mg/L. A validation data set showed the model to have a bias, –7.7% and precision, 26.7%.
Conclusions: The results show significantly reduced clearance and expanded volume (Vss) in ECMO compared to previous reports in non-ECMO patients of similar ages. The results reflect expansion of blood volume during ECMO.
Reference: PAGE 12 (2003) Abstr 377 [www.page-meeting.org/?abstract=377]
Poster: poster