Population pharmacokinetics of piperacillin and tazobactam in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

2021 ◽  
Author(s):  
Vesa Cheng ◽  
Mohd H. Abdul-Aziz ◽  
Fay Burrows ◽  
Hergen Buscher ◽  
Young-Jae Cho ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Plasma Concentrations ◽  
Membrane Oxygenation ◽  
Optimal Dosing ◽  
Patient Groups ◽  
Dosing Strategy ◽  
Toxic Concentrations ◽  
Staged Testing

Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analysed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (% f T >MIC ) and toxic exposures of greater than 360 mg/L. Tazobactam target of percentage time free concentrations >2 mg/L was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models with body mass index, creatinine clearance and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5 g 6-hourly regimen administered over 4-hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/L while exposing patients to a <3% probability of toxic concentrations. In patients receiving ECMO and RRT a frequency reduction to 12-hourly dosing reduces the probability of toxic concentrations, although this remains at 7 – 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.

Population pharmacokinetics of vancomycin in critically ill adult patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

2021 ◽  
Author(s):  
Vesa Cheng ◽  
Mohd H. Abdul-Aziz ◽  
Fay Burrows ◽  
Hergen Buscher ◽  
Young-Jae Cho ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Plasma Concentrations ◽  
Total Body Weight ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Membrane Oxygenation ◽  
Dosing Regimens ◽  
The Mean

Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analysed using a population PK approach on Pmetrics ®. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC 0-24 ) of 400 – 700 mg·h/L at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 mL/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT and total body weight found as significant predictors of clearance and central volume of distribution (V c ). The mean vancomycin renal clearance and V c were 3.20 L/h and 29.7 L respectively, while the clearance for patients on RRT was 0.15 L/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5 – 20 mg/kg 12-hourly are associated with a 97 – 98% probability of efficacy and 11 – 12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT.

scholarly journals Plasma Concentrations of Oseltamivir and Oseltamivir Carboxylate in Critically Ill Children on Extracorporeal Membrane Oxygenation Support

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10938 ◽  
Author(s):  
Enno D. Wildschut ◽  
Matthijs de Hoog ◽  
Maurice J. Ahsman ◽  
Dick Tibboel ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Plasma Concentrations ◽  
Critically Ill Children ◽  
Oseltamivir Carboxylate ◽  
Membrane Oxygenation

scholarly journals The Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in a Critically Ill Pediatric Patient Receiving Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemodialysis

2012 ◽  
Vol 17 (2) ◽  
pp. 173-176 ◽  
Author(s):  
Rachel F. Eyler ◽  
Kristin C. Klein ◽  
Bruce A. Mueller
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Standard Dose ◽  
Plasma Concentrations ◽  
Pediatric Intensive Care ◽  
Drug Clearance ◽  
High Dose ◽  
Oseltamivir Carboxylate ◽  
Membrane Oxygenation ◽  
Continuous Venovenous Hemodialysis

This report details the pharmacokinetics of oseltamivir and oseltamivir carboxylate following administration of high-dose oseltamivir in a critically ill child receiving extracorporeal membrane oxygenation (ECMO) and continuous venovenous hemodialysis (CVVHD). A 6-year-old critically ill male patient suffering from a presumed viral illness was transferred to our institution's pediatric intensive care unit from an outside hospital after developing respiratory failure and cardiomegaly. ECMO and oseltamivir therapy were initiated upon admission, and CVVHD was started on hospital day 3. Pharmacokinetic sampling occurred at an oseltamivir dose of approximately 4 mg/kg on hospital day 6. The patient's oseltamivir and oseltamivir carboxylate area under the plasma concentration time curves for the 12-hour dosing interval (AUC0–12) were 30.5 and 905 ng/mLhr, respectively. Drug clearance by CVVHD was 31.6 mL/min for oseltamivir and 26.9 mL/min for oseltamivir carboxylate. Pre- and postoxygenator oseltamivir and oseltamivir carboxylate plasma concentrations did not differ substantially. The patient's oseltamivir carboxylate plasma concentrations remained well above the reported mean 50% inhibitory concentration for 2009 pandemic H1N1 virus. However, despite receiving twice the standard dose of oseltamivir, the oseltamivir carboxylate AUC0–12 in our patient was less than that reported in noncritically ill pediatric subjects. The reduced oseltamivir carboxylate AUC0–12 found in our patient was most likely due to decreased drug absorption.

Sign in / Sign up

Export Citation Format

Share Document