The main findings of this study are that there was no significant difference in Vd, but a longer t1/2 and a lower CL were observed in ECMO patients compared with non-ECMO patients. Similar results were obtained after controlling for SCr: a prolonged t1/2 and a lower CL without a significant difference in Vd were found in the ECMO group based on a subgroup analysis using neonates with SCr <0.5 mg/dL.

Similar previous studies have reported inconsistent results, and no study has been conducted on Asian infants. The first study on this topic was conducted on six neonates and reported that there were no significant differences in the pharmacokinetic parameters of vancomycin in neonates undergoing ECMO. In that study, a historical control was employed as the comparison group and neonates whose SCr exceeded 1.5 mg/dL were excluded. Amaker et al. obtained pharmacokinetic parameters from 12 infants undergoing ECMO, and the results were also compared with previously published data. They reported increased Vd and t1/2 and decreased CL in infants undergoing ECMO. Another study showed that, among the vancomycin pharmacokinetic parameters measured, only t1/2 increased significantly in neonates undergoing ECMO relative to those not receiving ECMO. Unlike the first two studies, this study had an appropriate control group. However, the sample size was still small (n=30). Our study has the strengths of a relatively large sample size (n=50) and the use of an appropriate control group. Moreover, this is the first study of vancomycin pharmacokinetics in Asian neonates receiving ECMO.

Studies using gentamicin have shown that the Vd of hydrophilic drugs can be increased during ECMO. This finding can be explained by the increased circulating volume caused by the dilution of blood during ECMO. Although vancomycin is a hydrophilic compound, our results did not show a significant difference in the Vd between the two groups. One possible reason could be that vancomycin is less hydrophilic than gentamicin. However, further research should be conducted for more clarification.

The CL values for the neonates in our study were comparable to previously reported values. In our study, the CL of vancomycin in neonates receiving ECMO was 0.03±0.02 L/kg/hr, compared with 0.04 to 0.05 L/kg/hr in previous studies. In the non-ECMO group, the CL values (0.08±0.05 L/kg/hr) were also similar to those from other studies (0.07~0.10 L/hr/kg) using the Nonlinear Mixed Effects Modelling (NONMEM) program. Consistent with previous studies, our study showed that vancomycin CL was strongly associated with SCr, which is a measure of renal function. To achieve the target therapeutic range of vancomycin, an extended dosing interval is suggested for patients undergoing ECMO.

Because SCr was significantly higher in the ECMO group than in the non-ECMO group, and vancomycin CL showed a negative correlation with SCr, an additional subgroup analysis was conducted in patients with SCr <0.5 mg/dL. The pharmacokinetic differences between the ECMO and non-ECMO groups in patients with SCr <0.5 mg/dL were similar to those analysed in all study patients.

Unlike our results, a study using adult patients with normal SCr showed similar Vd and CL for vancomycin in patients with ECMO compared with those without ECMO. This was explained that the decreased vancomycin CL in neonates with ECMO was attributable to immature hepatic and renal antibiotic pathways rather than the ECMO circuitry itself.
To the best of our knowledge, this is the first evaluation of vancomycin pharmacokinetics in Asian neonates undergoing ECMO. In particular, this is the first instance in which vancomycin pharmacokinetic parameters from a subpopulation with SCr <0.5 mg/dL were compared between patients with and without ECMO. However, while some studies have reported that the pulsatility of pumps could affect the alteration of renal function, information about ECMO circuits could not be gathered in this study due to its retrospective nature. Given the limitations of this study, our study requires further independent validation using more robust prospective designs.
