Continuous perineural infusion of bupivacaine for prolonged analgesia: pharmacokinetic considerations

The pharmacokinetic parameters for 50 patients undergoing continuous extravascular perineural bupivacaine infusions for the treatment of their chronic pain were studied. The total plasma clearance (CL), volume of distribution (Vz), and elimination rate (lambda z) were estimated from two blood samples. These parameters were compared to values obtained from the actual mono-exponential decay curve at the termination of infusion. Estimated and actual pharmacokinetic parameters were found to be in excellent agreement. No evidence of accumulation was seen even after 5 days of continuous infusion. Steady states (Css) were found to be independent of the infusion site. This study demonstrates a wide margin of safety during continuous perineural bupivacaine infusions at dosages used in our study, e.g., up to 30 mg/h in normal patients. Such patients do not require determination of serum bupivacaine concentration to monitor the changes in dosages necessary for adequate clinical effect. On the other hand, in patients with renal or hepatic dysfunction, altered clearance rates are expected. In such patients, monitoring of serum bupivacaine concentrations is necessary to determine the range of dosages available for adjustment to provide adequate clinical effect and prevent systemic toxicity. This study demonstrates that two blood samples drawn at 3-5 h after the start of infusion and at steady state are sufficient to accurately determine the clearance rate for a patient. Safe management is then possible using this clearance to calculate the range of dosages permissible for that patient during continuous perineural infusion. Steady-state concentrations estimated from clearances were found to be in excellent agreement with the steady-state concentrations actually measured for a given infusion rate.