Effect of cardiopulmonary bypass on the pharmacokinetics of intravenous paracetamol [Propacetmol hydrochloride]

Recently, intravenous paracetamol [propacetamol] is commonly in use as analgesic and antipyretic after surgery. To our knowledge, the pharmacokinetic of intravenous paracetamol in patients undergoing cardiac surgery with cardiopulmonary bypass were not previously described. This study was designed to investigate the effect of cardiopulmonary bypass on the pharmacokinetics of single intravenous dose of paracetamol in adult patients undergoing coronary artery bypass surgery with hypothermic cardiopulmonary bypass. Nine patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass using mild hypothermia 30°C were selected. Intravenous paracetamol [2g single dose of Propacetamol hydrochloride [Pro-Daflgan UPSA, Fr]] 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. The pharmacokinetics of paracetamol was calculated assuming a linear one compartment model with instantaneous input and first order output. The pharmacokinetic data were reported as mean [SD]. ANOVA was used to compare between the pharmacokinetic parameters before and after CPB. C[max] 10.19 [0.9545] mg.litre[-1] appeared 20 min after the end 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 43% after CPB compared to pre-bypass values. However, the elimination half-life [t[1/2]] was significantly increased from 1.380 h before bypass to 2.431h in post bypass period. It appears from this study that hypotuermic cardiopulmonary bypass can affect the kinetic profile of IV paracetamol in patients undergoing coronary artery bypass graft surgery, and these changes should be considered while using this drug in such situations

Predictors of cerebral blood flow velocity in children undergoing open heart surgery for congenital heart diseases

Background: The use of TCD during paediatric cardiac surgery can help in early detection of cerebral blood flow velocity. The aim of this study was to describe the changes in cerebral blood flow velocity and to explore the relationship of such changes with different haemdynamic and cardiopulmonary bypass parameters in children undergoing open heart surgery

Methods: Sixteen patients from 1-12 years undergoing correction for congenital heart defects were included in this study. Two-channel transcranial Doppler system [Multi-Dop T[2] / DWL, Elektronische System GmbHGermany] were used for measuring mean cerebral blood flow velocity in middle cerebral artery after induction [basal], after sternotomy, during aortic cannulation, during stable CPB [10 min. after start of bypass], during rewarming, after weaning from CPB and after skin closure. Concomitant measurements of mean arterial blood pressure, arterial CO[2], haematorcrite, temperature and arterial oxygen tension were recorded with cerebral blood flow velocity. One way analysis of variance was used to study the changes in cerebral blood flow velocity and multiple regression analysis to predict different factors that can affect cerebral blood flow velocity

Results: A significant reduction in mean cerebral blood flow velocity was detected during stable CPB, during rewarming and after CPB compared with base line value. Before CPB, cerebral blood flow was directly dependent on the age and PaCO[2], while during rewarming it was only directly dependent on mean arterial blood pressure [P = 0.036]. However, an inverse association was found between PaO[2] and CBFV after CPB

Conclusion: These results suggest that cerebral blood flow velocity was reduced during hypothermic CPB, and it was only affected by mean arterial blood pressure during rewarming