Effect of Cardiopulmonary Bypass on the Pharmacokinetics of Drugs

Abstract

The cardiopulmonary bypass apparatus must temporarily substitute for the cardiac and pulmonary function of the patient undergoing heart surgery. In order to meet the metabolic needs of the patient and the technical demands of the surgeon, within the limits of engineering technology, a number of major alterations are made in normal physiology. The patient is typically cooled to 27 degrees C and perfused with a non-pulsatile flow of blood which has been diluted with saline to a haematocrit in the mid-20s. Blood flow and pressure are often considerably less than normal. Blood coagulation is prevented by administration of a massive dose of heparin. Central redistribution of blood flow, elaboration of stress-reactant hormones, and fluid and electrolyte shifts occur in response to these changes. In the postoperative period, these alterations are reversed, and normal physiology is restored. Effects upon the pharmacokinetics of drugs are anticipated. The clearance of many drugs may be reduced. Protein binding is diminished by haemodilution, but may rise above normal in the postoperative period for basic drugs which bind to alpha 1-acid glycoprotein. Changes in volume of distribution depend upon the opposing influences of protein binding and reduced peripheral perfusion. Previous studies on the pharmacokinetics of drugs during and after cardiopulmonary bypass illustrate many of these effects. The clearance of digoxin, fentanyl, and the cephalosporins is reduced after cardiopulmonary bypass, and the volume of distribution of cefazolin is increased during cardiopulmonary bypass. Studies of digitoxin and propranolol are also reviewed. Many of the investigations in this area of study have been limited by logistical and methodological factors. Thus, the effects of cardiopulmonary bypass on the pharmacokinetics of drugs are incompletely understood, and the subject merits further attention.

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

“…Total body clearance remained unchanged Plasma diclofenac levels (ng/ml) for both groups of patients in spite of a 30% reduction in hepatic blood flow as reported previously (4,5). The present data showed wide interindividual variation for both groups when expressed as median: 3.50 CPB vs 5.03 ml min -1 kg -1 control, P = 0.13 (Table 1), or as range of variation IC95%: 2.91-4.43 ml min -1 kg -1 (CPB) and 3.32-6.03 ml min -1 kg -1 (control) (P>0.05).…”

“…During the postoperative period of cardiac surgery with cardiopulmonary bypass, there is a 30% reduction of hepatic blood flow accompanied by changes in the metabolism of diclofenac (4,5). The aim of the present study was to measure the pharmacokinetics and pharmacodynamics of diclofenac on the basis of plasma protein binding, during the postoperative period in surgical patients submitted or not to cardiopulmonary bypass.…”

“…In cardiac surgery, loss of blood, high mobilization of liquids and cardiopulmonary bypass (CPB) with hemodynamic consequences such as hypothermia and hemodilution occur (4). During the postoperative period of cardiac surgery with cardiopulmonary bypass, there is a 30% reduction of hepatic blood flow accompanied by changes in the metabolism of diclofenac (4,5).…”

Pharmacokinetics and cardiovascular dynamics of pipecuronium bromide during coronary artery surgery

“…The first sample was taken before administration of pipecuronium, the others were collected 2, 4,6,8,10,15,20,30,45,60,90,120,180,240,360 and 480 min after the end of injection. Additional blood samples were taken five minutes after the start of extracorporeal circulation and immediately at the end of cardiopulmonary bypass.…”

Alfentanil pharmacokinetics in patients undergoing abdominal aortic surgery

“…Haemodilution decreases drug binding to plasma proteins, and the resulting increase of the unbound drug fraction tends to increase the Vdss. 24 The large volumes of fluids infused could have contributed to the large Vd.,..,. of alfentanil in our patients.…”