Cardiopulmonary bypass is accompanied by profound changes in the organism that may alter the pharmacokinetics of drugs. Drug distribution can be altered, for example, by changes in blood flow and by haemodilution, with a decrease in protein binding; a decrease in the elimination of some drugs can be caused by impairment of renal or hepatic clearance, due, for example, to lowered perfusion and hypothermia. The subject was reviewed in the Journal in 1982, and the emphasis of the present review is on new data related to specific drugs. The following substances are dealt with: benzodiazepines, cephalosporins, digitalis glycosides, general anaesthetics, glyceryl trinitrate (nitroglycerin), lignocaine (lidocaine), muscle relaxants, nitroprusside, opiates, papaverine and propranolol. For many of these substances an abrupt decrease has been observed in serum concentration upon initiation of bypass, which is explained by haemodilution and an increase in distribution due to decreased protein binding. For nitrates and some opiates, adsorption to the bypass apparatus was shown to be important. The gradual increase in serum concentrations seen during cardiopulmonary bypass with some drugs after the initial fall is usually explained by redistribution of the drug and/or decrease in its elimination. The same phenomena are thought to explain why in the post-bypass period a concentration increase occurs, or at least a slower decrease than expected. However, drug elimination has been directly measured in only a few studies. The short duration of the bypass procedure and the continuous changes during the process hamper a rigorous pharmacokinetic evaluation. Studies allowing more precise understanding of the mechanisms underlying the observed concentration changes are needed, but are difficult to design. Similarly, more data are awaited on the pharmacodynamic and clinical consequences of the concentration changes.
In vitro, local anesthetics containing Lidocaine are significantly more toxic to mature human articular chondrocytes than a saline 0.9% control group. The effect of Lidocaine on the viability of human chondrocytes in vivo needs further investigation. However, based on our in vitro results, cautious use of intra-articular Lidocaine in clinical practice is recommended.
This multi-centre, parallel group, randomized, double-blind study compared the efficacy and safety of high-dose remifentanil administered by continuous infusion with an intermittent bolus fentanyl regimen, when given in combination with propofol for general anaesthesia in 321 patients undergoing elective coronary artery bypass graft surgery. A significantly lower proportion of the patients who received remifentanil had responses to maximal sternal spread (the primary efficacy endpoint) compared with those who received fentanyl (11% vs 52%; P<0.001). More patients who received remifentanil responded to tracheal intubation compared with those who received fentanyl (24% vs 9%; P<0.001). However, fewer patients who received remifentanil responded to sternal skin incision (11% vs 36%; P<0.001) and sternotomy (14% vs 60%; P <0.001). Median time to extubation was longer in the subjects who received remifentanil than for those who received fentanyl (5.1 vs 4.2 h; P=0.006). There were no statistically significant differences between the two groups in the times for transfer from intensive care unit or hospital discharge but time to extubation was significantly longer in the remifentanil group. Overall, the incidence of adverse events was similar but greater in the remifentanil group with respect to shivering (P<0.049) and hypertension (P<0.001). Significantly more drug-related adverse events were reported in the remifentanil group (P=0.016). There were no drug-related adverse cardiac outcomes and no deaths from cardiac causes before hospital discharge in either treatment group.
Remifentanil proved efficient in reducing pain during colonoscopy. Emergence times were shorter and the recovery of cognitive function was faster with remifentanil compared with propofol. Remifentanil provided a smoother haemodynamic profile than propofol; however, the frequent occurrence of remifentanil-induced hypoventilation requires the cautious administration of this agent.
SummarySynthetic colloids have been implicated as a cause of coagulopathy when administered in large quantities. The effect of profound haemodilution (50%) on coagulation profile was measured in vitro by thromboelastography. Blood samples were taken from 11 ASA grade 1 patients prior to induction of anaesthesia for elective surgery. Each sample was simultaneously tested in four different preparations: undiluted blood (control sample); blood diluted with hydroxyethyl starch 6%; blood diluted with modified fluid gelatin 4%; blood diluted with dextran 40 10%. There was a significant decrease in reaction time in the preparations treated with hydroxyethyl starch 6% and modified fluid gelatin 4%, reflecting activation of initial fibrin formation. A significant increase in clot formation time was noted in the hydroxyethyl starch 6%-treated preparations. There was also a significant decrease in clot formation rate and maximum amplitude in the hydroxyethyl starch 6% group. Clot formation time, clot formation rate and maximum amplitude did not change in the modified fluid gelatin 4% group. Profound haemodilution with dextran 40 10% exerted extreme effects on the measured variables, very often resulting in a straight line on the thromboelastography profile. To avoid the risks associated with transfusion of homologous blood products and to limit the high cost of albumin solutions, artificial colloid solutions represent an alternative for intra-operative blood loss replacement [1]. However, synthetic colloids have been implicated as a cause of coagulopathy when administered in large quantities [1]. Although profound normovolaemic haemodilution (50% of circulating blood volume or haematocrit less than 20%) is not part of most blood-sparing strategies, clinical interest in maximising peri-operative blood conservation may involve normovolaemic haemodilution beyond currently accepted end points [2]. However, what effect this might have on coagulation is unclear as most studies examine only the effects of moderate quantities of artificial colloids [3,4].In this study, we measured the degree of impairment of the coagulation process when whole blood is diluted in vitro with large quantities (50% dilution) of hydroxyethyl starch 6%, modified fluid gelatin 4% and dextran 40 10%. Thromboelastography (TEG) records the dynamics of whole blood coagulation, including the interaction of cellular elements (red blood cells, platelets), coagulation factors and calcium [5,6] and was used to give overall evaluation of the clotting process. Methods
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