Pharmacokinetics of ropivacaine in patients with chronic renal failure.

BACKGROUND: As ropivacaine and its metabolites are excreted by the kidneys, we studied their disposition in subjects with renal dysfunction. METHODS: Twenty patients with moderate or severe renal insufficiency and 10 healthy volunteers received ropivacaine 1 mg kg(-1) i.v. over 30 min. The concentrations of ropivacaine and its main metabolites, pipecoloxylidide (PPX) and 3-hydroxy-ropivacaine, were measured in plasma and urine for 16-48 h. The relationship between pharmacokinetic parameters and creatinine clearance (CL(CR)) was assessed. A model for estimating non-renal clearance of a metabolite of ropivacaine is described. RESULTS: Renal dysfunction had little or no influence on the pharmacokinetics of ropivacaine. The median plasma concentrations of unbound ropivacaine were similar in uraemic and non-uraemic subjects. Renal clearance of PPX correlated significantly with CL(CR) (R(2)=0.81). Lack of correlation between total PPX exposure, expressed as area under the total plasma concentration-time curve from zero to infinity, and CL(CR) suggests that the clearance of PPX also includes non-renal elimination. However, in two uraemic patients, there was increased exposure to PPX resulting from low non-renal elimination. CONCLUSIONS: The pharmacokinetics of ropivacaine is not affected by renal failure. Although the renal clearance of PPX correlates with CL(CR), non-renal elimination seems to compensate for reduced renal clearance in most patients. PPX may accumulate in plasma during long-term postoperative infusions, in particular in patients with co-existing low non-renal elimination. Systemic toxicity is still unlikely because PPX is markedly less toxic than ropivacaine.

Fentanyl-prilocaine mixture for intravenous regional anaesthesia in patients undergoing surgery.

The effect of the addition of 0.1 mg or 0.2 mg fentanyl to 40 ml 0.5% prilocaine in intravenous regional anaesthesia of the arm was investigated in 37 patients in a randomised, double-blind study. The characteristics of the sensory and motor block were studied. There was no difference in the speed of onset of analgesia in the groups (mean latency approximately 4 min in each group). However, significantly more patients in the fentanyl 0.2 mg group (7/12) had complete anaesthesia at 15 min than in the fentanyl 0.1 mg group (1/13) and the control group (2/12) (p less than 0.05). There were no differences in the incidence of tourniquet pain immediately before cuff deflation (tourniquet time 45-87 min). After cuff deflation, in those patients who complained of wound pain within 30 min, on average the pain appeared later in the fentanyl 0.2 mg group (six patients, mean 14.3 min) than in the control group (eight patients, mean 9.4 min) (ns). In the fentanyl groups, the incidence of central nervous system side effects was greater than in the control group (fentanyl 0.1 mg 7/13 patients, fentanyl 0.2 mg 6/12 patients, control 1/12 patients) (p less than 0.05). The plasma concentrations of prilocaine after cuff deflation were higher, in a dose-dependent fashion, in the fentanyl groups than in the control group, but the concentrations of prilocaine and fentanyl did not correlate with the symptoms. Postoperative nausea occurred only in the patients who had received fentanyl.