ABSTRACT
OBJECTIVE: Local anesthetics (LA) are often administered in combination for regional anesthesia in order to obtain the specific advantages (onset and duration of effect) of each drug. However, few data on the safety of such combinations are available and consequently plasma concentrations possibly associated with toxicity and interactions between the specific anesthetics are not sufficiently established. We measured pharmacokinetics and toxicity parameters of prilocaine and ropivacaine after combined use as single doses in brachial plexus blockade. METHODS: In an open clinical study using a combined dose regime (300 mg prilocaine followed immediately by 75 mg ropivacaine) total plasma concentrations of prilocaine and ropivacaine were measured serially in 60 patients using a gas-chromatographic method. The data were analyzed regarding a relationship with central nervous and cardiovascular toxicity. RESULTS: Following the administration in combination prilocaine and ropivacaine were rapidly absorbed. Mean prilocaine peak plasma concentrations (mean Cmax = 1.51 microg/ml) were measured between 15 and 30 min after injection. Highest ropivacaine plasma concentrations (mean Cmax = 1.12 microg/ml) were seen between 30 min and 1 hour after injection (calculated mean tmax = 44 min). One of 59 patients showed signs of myoclonus which were suspected of being due to intravascular injection. There was no relevant cardiovascular toxicity observed in terms of changes in the QRS complex, PQ interval prolongation, AV dissociation, occurrence of extrasystoles or sinus arrest. The pharmacokinetics of combined administration did not differ from those of prilocaine and ropivacaine given alone. CONCLUSION: The use of a combined prilocaine/ ropivacaine (300 mg/75 mg) dose regimen in patients given single dose for brachial plexus blockade can generally be regarded as safe with regard to peak plasma concentrations and cardiovascular toxicity and this holds true for patients with a higher perioperative risk profile (ASA III grading, American Society of Anesthesiologists). The considerable inter-individual variation in LA peak plasma concentrations observed in our patients and the one case of suspected accidental intravascular injection, highlight the necessity of adequate monitoring of the patients undergoing LA injections.
