ABSTRACT
Objective:
To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD)
parameters of
antibacterial agents in
children with
sepsis treated by
extracorporeal membrane oxygenation (ECMO).
Methods:
In this prospective
cohort study, 20
children with
sepsis (confirmed or suspected)
who were treated with ECMO and antimicrobial in the Department of Critical
Medicine of Hunan
Children's
Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through
therapeutic drug monitoring (TDM), the PK-PD
parameters of
antibacterial agents were analyzed. Twenty five
children with
sepsis in the same department
who were treated with
vancomycin but no ECMO at the same
time were enrolled as the
control group. The individual PK
parameters of
vancomycin were calculated by Bayesian
feedback method. The PK
parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (
AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison.
Results:
Twenty
patients in the ECMO group, included 6
males and 14
females, with an
onset age of 47 (9, 76) months. In the ECMO group, 12
children (60%) were treated with
vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases;
AUC/
minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11
children (55%)
who were treated with β-
lactam antibiotics, there were 10 cases with
drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of
cefoperazone reached the target. Among the 25 cases of
control group, 16 were
males and 9
females, with an
onset age of 12 (8, 32) months. There was a positive correlation between
vancomycin trough concentration and
AUC (r2=0.36, P<0.001). The
half-life of
vancomycin and the 24-hour
AUC (AUC0-24 h) in the ECMO group were higher than those in the
control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the
control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05).
Conclusion:
The PK-PD
parameters in septic
children treated by ECMO varied with a longer
half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.