Comparative Methods to Predict Redosing of Bupivacaine and Ropivacaine in Truncal Catheters.

Background: Despite the frequent use of ropivacaine and bupivacaine, there is limited guidance on redosing of these medications after an initial bolus. Intermittent redosing is a clinical practice in the setting of nerve catheters, often utilizing large doses. Comparatively, theoretical elimination rates are available from pharmacokinetic studies, providing estimates on total body content of these drugs. The authors hypothesized that published redosing of bupivacaine and ropivacaine in clinical literature comported with safe elimination of the drugs based on pharmacokinetic studies.

Methods: Clinical redosing of bupivacaine and ropivacaine were identified from previously published articles that used intermittent bolus dosing into the transversus abdominis plane and paravertebral space. The dosing data were fit to an exponential curve using least squares regression and 1/Y 2 weighting with the equation: Y = Y M - (Y M - Y 0 ) * e -k * x , where YM is the maximal dose (175 mg for bupivacaine, 210 mg for ropivacaine), Y0 is the dose at time zero, k is the elimination constant, and x is time. Both minimal ( i.e. , slowest) and average pharmacokinetic elimination constants for ropivacaine and bupivacaine were identified in the published literature. Clinical redosing was compared with pharmacokinetic elimination.

Results: The maximal pharmacokinetic half-lives of bupivacaine and ropivacaine were 603 min (range, 154 to 2,970 min; N = 49) and 528 min (range, 204 to 3,276 min; N = 39), respectively. Clinically reported redosing of bupivacaine fit to an exponential curve with k bupi(clinical) = 0.077 h -1 , representing the 53.5th percentile of extracted pharmacokinetic minimal elimination constants. Clinically reported redosing of ropivacaine fit to a curve with k ropi(clinical) = 0.083 h -1 consistent with the 52nd percentile of minimal pharmacokinetic elimination constants.

Conclusions: Clinically reported redosing of bupivacaine and ropivacaine in the published literature reflect the slowest pharmacokinetic elimination based on human studies. The combined data without evidence of toxicity permit the authors to make practical recommendations about safe redosing of these agents.