ABSTRACT
BACKGROUND: To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations. METHODS: Prospective observational study. Patients receiving CVVHDF and amikacin treatment were included. Pharmacokinetic parameters were calculated using Bayesian analysis. Spearman correlation test was used in order to assess the influence of CVVHDF flux on amikacin minimum concentration (Cmin) and plasma clearance. RESULTS: Thirty patients undergoing CVVHDF procedures were included. The treatment with amikacin started at an initial mean dose of 12.4 (4.1) mg/kg/day. An association between the flow rate and Cmin value (r = 0.261; p = 0.161) and plasma clearance was found (r = 0.268; p = 0.152). Four patients (13.3%) were not able to achieve peak concentration over MIC value higher than 8. In 4 patients, amikacin had to be discontinued due to a high Cmin value. CONCLUSIONS: Amikacin clearance in patients with CVVHDF is affected by the flow rate used. Therefore, CVVHDF dose should be taken into account when dosing amikacin.
Subject(s)
Amikacin/administration & dosage , Amikacin/pharmacokinetics , Hemodiafiltration , Aged , Critical Illness , Female , Humans , Male , Middle AgedABSTRACT
In this study, we evaluate the effect of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (Levitronix) on the pharmacokinetic of amikacin in critically ill patients. Twelve patients with ECMO and three with Levitronix devices who started treatment with amikacin were included. Amikacin pre (Cmax) and post (Cmin) dose serum concentrations were measured during the first 72-96 hours of treatment initiation. Pharmacokinetic parameters were performed by Bayesian adjustment. The median initial dose was 1,000 mg (range: 600-1,400 mg). Mean plasma concentrations were Cmax 58.6 mg/L (17.0 mg/L); Cmin 9.58 mg/L (7.8 mg/L). Patients with an ECMO device had a higher volume of distribution (0.346 [0.033] vs. 0.288 [0.110] L/kg) and a lower plasma clearance (1.58 [0.21] vs. 3.73 [1.03] L/h) than the control group. This phenomenon was also observed in those patients with simultaneous use of ECMO and hemodilafiltration. For patients with Levitronix system, no significant alterations in the volume of distribution were observed, although a lower plasma clearance was noticed. Placement of ECMO devices alters the pharmacokinetic parameters of amikacin in the critically ill patients and should be considered when selecting the initial dose.
Subject(s)
Amikacin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Extracorporeal Membrane Oxygenation , Heart-Assist Devices , Prosthesis-Related Infections/prevention & control , Bayes Theorem , Critical Care , Critical Illness , Extracorporeal Membrane Oxygenation/adverse effects , Female , Heart-Assist Devices/adverse effects , Humans , Male , Middle AgedABSTRACT
OBJECTIVES: This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients. METHODS: An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (Cmax) and minimum (Cmin) plasma concentration samples were taken during the first 48-96h after the beginning of treatment. The impact of Cmax/MIC ratio and area under the concentration-time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model. RESULTS: A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65. Clinical response at the end of treatment was significantly greater in patients with Cmax/MIC >6 [OR=5.48 (95% CI 1.28-11.40)], Cmax/MIC >8 [OR=6.01 (2.41-12.2)] and Cmax/MIC >10 [OR=8.02 (2.21-14.2)]. Cmax/MIC >10 was associated with a non-significant increase in microbiological eradication [OR=2.84 (0.76-10.61)]. Achieving Cmax/MIC >6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC curve 0.77 (0.66-0.87)]. CONCLUSIONS: The Cmax/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains.