Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support

Abstract

To our knowledge, this is the first pharmacokinetic and pharmacodynamic study of neonates receiving vancomycin with a contemporary ¼-inch extracorporeal life support circuit including the Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC). The data suggest differences in vancomycin pharmacokinetics compared with previous extracorporeal life support data, notably a more rapid clearance, which could result in lower vancomycin concentrations. Considering this, a more aggressive initial dosing regimen may need to be employed in infants on extracorporeal life support.

Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series

“…These pharmacokinetic alterations are not unexpected as similar changes have previously been described in the PICU setting . As TDM becomes more common to the practice of caring for critically ill children, recognition of pharmacokinetic variations similar to those described here will most likely become customary.…”

“…Commonly anti‐infective drugs are not widely evaluated in the population in which they are intended to be used. This is especially true in the setting of critical illness even though critical illness is a known risk factor for alterations to drug pharmacokinetics and pharmacodynamics in adult and pediatric patients . As such, there is a lack of information regarding the pharmacokinetics and pharmacodynamics of PRV in a pediatric intensive care unit (PICU) population and the degree of these alterations in comparison to healthy volunteers.…”

Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

“…2,12,31,40 Of note, vancomycin was studied in 6 separate studies, only one of which included a non-ECMO comparator group 12 while the remaining 5 did not. 27,32,36,38,47 Although a trend was observed towards smaller V d of vancomycin relative to non-ECMO controls, the difference did not reach statistical significance in the study by Buck et al 12 However, when the V d values were compared against historical controls, increased V d was observed compared to pediatric patients not on ECMO. 27,32,36,38,47 In addition, we did not identify any significant correlation between lipophilicity (as measured by log P) of drugs and changes in V d attributable to ECMO (Supplementary Table 1).…”

“…In addition, 17 studies (41%) did not report the type of ECMO used. 8,9,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Of those that reported the type of ECMO used, 10 studies (24%) employed both veno-venous (VV) and venousarterial (VA) ECMO, [26][27][28][29][30][31][32]32,33 10 studies (24%) used VA ECMO only, 10,[34][35][36][37][38][39][40][41][42] and the remaining 4 studies (10%) used VV ECMO only. [43][44][45][46] Only 7 studies (17%) were conducted with intra-study comparisons to non-ECMO controls.…”

“…Of the 23 drugs studied, V d values were reported for 16 drugs (70%), 8,11,12,17,18,20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][38][39][40]42,43,[45][46][47][48] with the remaining 7 other drugs having only clearance values reported without V d values. 9,10,13,14,19,21,37,41,44 Relative to non-ECMO controls, significant alterations in V d were observed in pediatric patients supported on ECMO for 11 of 16 studied drugs ( increase relative to non-ECMO controls), suggesting the need for higher initial dosing.…”