Effect of cardiopulmonary bypass on the pharmacokinetics of intravenous paracetamol

ABSTRACT

Recently, intravenous paracetamol [propacetamol] is commonly in use as analgesic and antipyretic after surgery. The pharmacokinetics of intravenous paracetamol in patients undergoing cardiac surgery with cardiopulmonary bypass [CPB] were not previously described. This study was designed to investigate the effect of CPB on the pharmacokinetics of single intravenous dose of paracetamol in adult patients. Experimentally, nine patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass using mild hypothermia were selected. Intravenous propacetamol [2 g] was infused over 10 min and arterial samples were taken starting from 20 min after infusion and afterwards over 8 hours from infusion. Plasma paracetamol concentrations were measured by high-pressure liquid chromatography. ANOVA was used to compare between the pharmacokinetic parameters before and after CPB. The results revealed a C of 10.19 +/- 0.9545 mg. litre[-1] which was appeared after 20 min of infusion [experimentally]. Mean clearance [CL] was significantly reduced by about 40% in post CPB [prebypass 0.589 +/- 0.1069 L.h[-1]. Kg[-1] vs. 0.357 +/- 0.0394 L.h[-1]. Kg[-1] after CPB, P < 0.05]. The elimination rate constant [Ke] was significantly reduced by about 55% after CPB compared to prebypass values. However, the elimination half-life [t1/2] was significantly increased from 1.380 h before bypass to 2.431 h in post bypass period. It appears from this study that hypothermic cardiopulmonary bypass can affect the kinetic profile of IV paracetamol in patients undergoing coronary artery bypass graft surgery by altering its elimination. However, the change in the pharmacokinetic parameters and blood level of paracetamol is not serious and its use in such situations as analgesic and antipyretic is safe