Influence of cardiac output on the pseudo‐steady state remifentanil and propofol concentrations in swine

Abstract

The propofol concentration during constant infusion is affected by a change in cardiac output, but the effect of this change on remifentanil, which is frequently used in combination with propofol, is unclear. Ten swine were anaesthetised through inhalation of isoflurane and maintained with 1.5% isoflurane. After infusion of remifentanil (0.5 μg/kg/min) and propofol (6 mg/kg/h after 2 mg/kg bolus infusion) for 60 min (baseline 1), cardiac output was increased by continuous infusion of dobutamine and termination of isoflurane (high cardiac output state). Dobutamine infusion was then stopped, 1.5% isoflurane was restarted, and cardiac output was allowed to return to baseline (baseline 2). Finally, cardiac output was decreased by administration of 3% isoflurane (low cardiac output state). Blood samples were collected from the femoral artery at 10, 30, and 60 min after the change to each haemodynamic state. An inverse relationship was found between cardiac output and the plasma remifentanil and propofol concentrations. The plasma drug concentrations were given by the following equations: [remifentanil] (ng/ml) = 17.5/cardiac output (l/min) + 4.52; and [propofol] (μg/ml) = 3.34/cardiac output + 1.17. The influence of changes in cardiac output on remifentanil were similar to those for coadministered propofol and the influence on the concentration of each drug was greater with decreasing cardiac output. The plasma remifentanil concentration is influenced by cardiac output in a similar manner to that of propofol during remifentanil and propofol anaesthesia, although the metabolic sites are different.