Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation.

BACKGROUND: Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia. METHODS: Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured. RESULTS: Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values. CONCLUSIONS: Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.

Repeated episodes of myocardial ischaemia during combined thoracic epidural-isoflurane anaesthesia.

A patient with a history of coronary artery diseases developed new ST segment depressions in the ECG registration during a low dose (0.7%) isoflurane anaesthesia that was combined with a continuous thoracic epidural analgesia. Simultaneously a small decrease in mean arterial blood pressure (MAP) was noted. During the next 5 min these changes were followed by a severe drop in MAP (from 88 to 60 mmHg) and in cardiac output from 5.5 to 3.2 L/min. When isoflurane was discontinued both the ECG and the cardiovascular changes returned to the previous condition. Later, when 0.5% isoflurane was restarted, the ECG changes reappeared within ten min, but disappeared once again when isoflurane administration was discontinued. Thus, this patient had repeated episodes of myocardial ischaemia which were associated with the use of low dose isoflurane. Although isoflurane-induced "coronary steal" may appear as a likely cause of these ischaemic episodes, it is possible that the thoracic epidural had synergistic action and rendered the patient exceptionally sensitive to minor changes in perfusion pressure.