The influence of cardiopulmonary bypass on pediatric pharmacokinetics

Figures & data

Figure 1. Schematic diagram of a CPB system.

Table 1. Summary of current evidence for the mechanisms behind the influence of cardiopulmonary bypass on pharmacokinetic parameters.

Pathophysiology	Present evidence
Adsorption of drugs to components of the CPB system	Depends on: physicochemical characteristics of the drug: most evidence for logP and plasma protein binding characteristics of the plastic: polyurethane > silicone > PVC presence of an arterial filter? coating of CPB system components? drug concentration in the CPB system interactions between drugs
Retention of drug in cell saver blood	Unknown clinical consequences
Hemodilution	Especially important for drugs with a small Vd?May be confounded by adsorption of drugs to the CPB system components May be confounded by adsorption of drugs to the CPB system components
Protein binding	Depends on: composition of the prime fluid heparin administration temperature management, especially DHCAExtensive studies have not been performed in children
Hypothermia	Often associated with changes in physiology such as cardiac output and organ blood flowDecreased P-glycoprotein transport only established in vitroNo influence on the PK of both renally and hepatically cleared drugs have been confirmed during pediatric CPBNo head-to-head comparisons of the influence of normothermic or hypothermic CPB on PK has been performed Decreased P-glycoprotein transport only established in vitro No influence on the PK of both renally and hepatically cleared drugs have been confirmed during pediatric CPB No head-to-head comparisons of the influence of normothermic or hypothermic CPB on PK has been performed
Blood flow and organ perfusion	Decreased pump flow during hypothermic CPBContinuous vs pulsatile blood flow?Redistribution of blood flow due to hypothermiaDecreased liver blood flow by 67% measured with indocyanine green clearance in childrenVolumetric renal blood flow directly correlated with CPB pump flow rate and linearly correlated with mean arterial pressure in childrenNo head-to-head comparison of high and low CPB flow rate Continuous vs pulsatile blood flow? Redistribution of blood flow due to hypothermia Decreased liver blood flow by 67% measured with indocyanine green clearance in children Volumetric renal blood flow directly correlated with CPB pump flow rate and linearly correlated with mean arterial pressure in children No head-to-head comparison of high and low CPB flow rate
Inflammation and capillary leak	Capillary leak with loss of fluid and protein from the central circulation to the tissuesChanges in organ blood flow due to vasodilation and hypovolemiaDecreased hepatic expression and/or activity of CYP450 mediated drug PK in pediatric ICUNo studies have been performed in pediatric CPB. Changes in organ blood flow due to vasodilation and hypovolemia Decreased hepatic expression and/or activity of CYP450 mediated drug PK in pediatric ICU No studies have been performed in pediatric CPB.
Ultrafiltration	No influence of the use of conventional or modified ultrafiltration on PK has been confirmed in pediatric CPB
Duration of CPB	Longer duration of CPB is often associated with lower temperatures, decreased flow rates, increased inflammation and use of ultrafiltrationConflicting results have been reported in pediatric CPB Conflicting results have been reported in pediatric CPB

Note: CPB cardiopulmonary bypass; DHCA deep hypothermic circulatory arrest; ICU intensive care unit; PK pharmacokinetics; PVC polyvinyl chloride; V_d volume of distribution.