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 following 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. We 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 manuscripts 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/Y² weighting with the equation : Y = Y_M – (Y_M – Y₀)* e^-k*x where Y_M 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 minutes (range 154 – 2970 minutes, N=49) and 528 minutes (range 204 – 3276 minutes, N=39) respectively. Clinically reported redosing of bupivacaine fit to an exponential curve with k_{bupi(clinical)} = 0.077 hrs^-1 , representing the 53.5 ^th percentile of extracted pharmacokinetic minimal elimination constants. Clinically reported redosing of ropivacaine fit to a curve with k_{ropi(clinical)} = 0.083 hrs^-1 consistent with the 52^nd 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 us to make practical recommendations about safe redosing of these agents.