[The blood level and a pharmacokinetic model of prilocaine during a continuous brachial plexus blockade]

Continuous brachial plexus blockade achieved by repeated injections through an axillary catheter is used increasingly often for microsurgical procedures and for postoperative pain relief. Repetitive administration, especially of long-acting agents, can cause problems with local anesthetic toxicity. Based upon a pharmacokinetic analysis of prilocaine serum concentrations after single-dose axillary plexus blockade in 14 patients, a pharmacokinetic model was established from which to predict serum concentrations after successive doses. METHODS. Each of 14 patients (ASA I-II, age 42 +/- 20 years, height 171 +/- 10 cm, body weight 72 +/- 9 kg) undergoing minor hand surgery received a single dose of 600 mg (40 ml 1.5%) prilocaine for axillary plexus blockade. Serial samples were taken from the contralateral antecubital vein and serum local anesthetic concentrations were measured by gas chromatography. Least square, non-linear regression analysis was performed to fit a triexponential curve; standard formulas were applied to develop the corresponding open two-compartment model. Computer simulation was carried out to predict the accumulation of mean local anesthetic concentrations after repetitive dosages. The kinetic model was verified with another set of 5 patients receiving a repetitive dose of prilocaine. The initial dose was 400 mg (40 ml 1%), followed by insertion of a catheter which allowed repetition at 2 and 4 h. The repetition dose was 300 mg (20 ml 1.5%). RESULTS. Maximal prilocaine serum levels of 2.32 +/- 0.80 micrograms/ml were found after 34 +/- 13 min. Mean pharmacokinetic data of the open two-compartment model with first order absorption from extravascular sites were: t alpha 1/2 = 10 min; t beta 1/2 = 139 min; V1 = 661; V dss = 254 1; Cltot = 2310 ml/min; tabs 1/2 = 35 min. The comparison of predicted and observed serum concentrations after continuous anesthesia was excellent. DISCUSSION. Pharmacokinetic data after axillary plexus blockade are comparable to those found after i.v. injection. Low serum levels were found throughout the 8 h of investigation and accumulation in serum was minimal following repetitive doses. There was no loss of action on repetition. Predicted values after pharmacokinetic modeling showed good agreement with actual measured values. Prilocaine may be a reasonable choice for repetitive use, as is appears to be toxicologically safe. Methemoglobinemia resulting from metabolites of prilocaine did not lead to complications in our study. It may, however, be a problem with repetitive dosages. Further investigations concerning this question would be useful.