Remifentanil and Pulmonary Extraction During and After Cardiac Anesthesia

Abstract

We measured the apparent blood clearance and pulmonary extraction ratio of remifentanil in 10 adult patients undergoing elective myocardial revascularization for the first time with hypothermic cardiopulmonary bypass (CPB). Patients received continuous infusions of remifentanil 1.0, 1.5 or 2.0 microg x kg(-1) x min(-1). After surgery, remifentanil was infused at 1.0 microg x kg(-1) x min(-1) in all patients. Remifentanil concentrations were measured in pulmonary and radial artery blood by gas chromatography with high resolution mass spectrometry before and after CPB and 165 min (60 SD) after surgery. Cardiac output was measured by thermodilution at the time of blood sampling. The mean pulmonary extraction ratio of remifentanil was 5.7% (13.1% SD), which was not significantly different from zero. However, pulmonary extraction ratio was related inversely to the pulmonary artery hydrogen ion concentration and directly to the percent of nonionized form of the base in the pulmonary artery. Remifentanil concentrations in pulmonary and radial artery blood were related directly to infusion rate, but not to duration of infusion. There was no evidence of accumulation or sequestration. Mean apparent blood remifentanil clearance was 2.03 L/min (0.35 SD) and, in contrast to remifentanil pulmonary extraction ratio, was related directly to cardiac index and oxygen delivery. Increased tissue perfusion increased blood remifentanil clearance. We found predictable blood remifentanil levels with no evidence of accumulation or pulmonary extraction.

Remifentanil and tramadol

“…39 The pharmacokinetics of remifentanil make blood concentrations predictable. Remifentanil blood concentrations obtained by infusions of 1.0-2.0 g kg 91 min 91 were related linearly to the rate of infusion and unrelated to the duration of infusion, 14 unlike those of fentanyl and alfentanil, which demonstrate accumulation. 17 31…”

“…The lung does not clear remifentanil from the circulation. 14 The esterase metabolism suffered by remifentanil is not related to pseudo-cholinesterase (butyrlcholinesterase), which terminates the action of suxamethonium. Remifentanil is not a substrate for pseudo-cholinesterase and patients who are deficient in pseudo-cholinesterase and therefore susceptible to suxamethonium apnoea, metabolize remifentanil normally.…”

Influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a swine model: a comparison with propofol and the effect of haemorrhagic shock stage

“…These findings suggest that hydrolysis in tissue, rather than in circulatory blood, is the main contributor to metabolism of remifentanil and that perfusion of these tissues linearly depends on CO. Several previous studies have also suggested that tissue metabolism is the major site for remifentanil hydrolysis, and that the blood component contributes less to remifentanil metabolism. 8 15 Duthie and colleagues 16 showed that pulmonary extraction of remifentanil did not occur in adult patients undergoing elective cardiac surgery, but that clearance was related directly to CO. Remifentanil has the attractive feature that the pharmacokinetics are unlikely to be affected significantly by hepatic 17 or renal impairment; 18 however, pathological conditions with accompanying tissue hypoperfusion, similarly to the effects of haemorrhage, might increase the remifentanil concentration.…”

Remifentanil Concentration during Target-controlled Infusion of Propofol

“…Our results are consistent with those of Matot et al 6 , who demonstrated that, in the case of alfentanil and fentanyl, first-pass pulmonary uptake is decreased due to competition with propofol. Duthie et al 10 reported that the lungs did not extract remifentanil, however their study was conducted in the presence of propofol. As with the other opioids it appears that remifentanil competes with propofol for hydrophobic binding in the lungs.…”