Propranolol kinetics in patients submitted to cardiac surgery with cardiopulmonary bypass

Introduction

Propranolol plasma levels and pharmacokinetics (PK) may be altered by cardiopulmonary bypass (CPB). Propranolol kinetic disposition was investigated in patients submitted to myocardial revascularization with mild hypothermic cardiopulmonary bypass (HCPB).

Methods

Fifteen patients receiving propranolol pre-(30-120 mg/day) and postoperatively (5-10 mg/day) were evaluated. Propranolol plasma levels were measured before, during and after surgery using high-performance liquid chromatography. PK modelling based on one compartment open model was applied to data obtained after drug administration (propranolol, tablets) 1 day before surgery and at the first postoperative day.

Results

Plasma curve decay represents logarithmic transformation of plasma concentrations before, during and after surgery, presented in the Figure. Pre- and postoperative PK modelling showed a prolongation of biological half-life (t_1/2β) from 3.2 to 10.2 h (P < 0.01), increases of volume of distribution (Vd/F) from 3.5 to 7.7 l/kg (P ≤ 0.05) and reduction of plasma clearance from 15.8 to 9.1 ml/min.kg (P ≤ 0.05).

Discussion

Plasma levels indicate propranolol mobilization, probably due to stress and surgical trauma, since the beginning up to the end of hypothermic cardiopulmonary bypass. The influence of HCPB on pharmacokinetics of propranolol was demonstrated by the three times prolongation of t_1/2β and Vd/F increased by two times. Additionally, plasma levels increase could be justified by plasma clearance reduction.

Conclusion

An accumulation of propranolol might be expected in patients submitted to cardiac surgery with hypothermic cardiopul-monary bypass and lower doses of this drug could be required during the postoperative period.