Effects of CPB on drug pharmacokinetics

The institution of CPB has profound effects on the plasma concentration, distribution and elimination of drugs. The major factors responsible for this are hemodilution, altered plasma protein binding, altered regional blood flow, hypothermia, isolation of the lungs from the circulation and sequestration of drugs into components of the extracorporeal circuit. These changes, which are influenced by physicochemical and pharmacokinetic characteristics, result in an alteration in free drug and effector-site concentration. Hemodilution and plasma protein binding. The CPB circuit is primed with 1500–2000 ml of crystalloid solution corresponding to a potential 30% increase in circulating blood volume with associated hemodilution occurring when CPB is instituted. The immediate effect of this hemodilution is a decrease in circulating drug concentration. The eventual plasma concentration of a drug is dependent on its plasma protein binding, its original volume of distribution and the extent of equilibration between tissue and plasma at the time of institution of CPB. An important consideration is the distinction between the total plasma concentration and the “free” or unbound fraction. The free concentration of the drug is that which moves to the effector site and can be eliminated. The impact of hemodilution on the unbound fraction of drugs tends to be greater for drugs that have high plasma protein binding (PPB). This may result in greater transfer of drug from the blood-prime mixture to the tissues, and thus a lower eventual circulating drug concentration. The volume of distribution (VD) is another factor determining the circulating concentration of drugs during CPB. Drugs with a large inherent VD tend to be less affected by hemodilution, as there is a large tissue reservoir from which the drug can diffuse back into the circulation to plasma.