Effect of cardiopulmonary bypass on plasma concentrations of diltiazem and its two active metabolites

Abstract

Diltiazem is often used to prevent myocardial ischaemia during the perioperative period of coronary artery bypass surgery. The purpose of this study was to investigate the effect of cardiopulmonary bypass (CPB) on plasma concentrations of diltiazem and of its two main and active metabolites (N-monodemethyldiltiazem (N-desmethyldiltiazem) and desacetyldiltiazem). The patients were administered their usual treatment during the preoperative days. The last dose was administered immediately before anaesthesia. At the onset of CPB, a significant decrease in the plasma concentrations of diltiazem and its metabolites was observed, whereas the variation was slight and not significant when the plasma concentrations were corrected for haemodilution. These results confirm that the decrease observed at the initiation of the bypass procedure can be ascribed to the haemodilution induced by the CPB. During CPB, the concentrations of diltiazem and its metabolites remained constant suggesting that the rate of metabolism and excretion of the drug was altered during the bypass procedure. At the end of CPB, there was no increase of drug plasma concentrations suggesting that no redistribution of diltiazem from tissues to plasma occurred. Furthermore, this study shows that only 33% of subjects have therapeutic levels of diltiazem before anaesthesia, and that all subjects have subtherapeutic levels during and after the CPB. These results suggest that a higher chronic oral dose of the drug should be given in patients undergoing cardiac surgery with CPB.

The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass

“…The plasma unbound fraction value increased sharply at onset of CPB and returned to baseline level 24 h after dosing ( 99). The study of Boulieu et al ( 100) confirmed these findings and demonstrated that only 33% of the subjects had therapeutic levels of diltiazem before anesthesia and that all subjects had subtherapeutic levels during and after the CPB. The authors suggest that a higher chronic oral dose of the drug should be given to patients undergoing cardiac surgery with CPB ( 100).…”

Massive diltiazem overdose treated with extracorporeal membrane oxygenation

“…A 17% increase in the plasma concentration of DTZ occurred after discontinuation of ECMO. This may represent a loss of the hemodiluting effect of cardiopulmonary bypass, because cardiopulmonary bypass itself has not been shown to decrease DTZ levels (16). Signs of recovery from clinical toxicity also paralleled the decrease in plasma drug concentrations.…”