Abstract
Adrenaline is known to prolong the duration of local anesthesia but its effects on the pharmacokinetic processes of local anesthetic drugs are not fully understood. Our objective was to develop a compartmental model for quantification of adrenaline’s impact on the pharmacokinetics of perineurally-injected lidocaine in the dog. Dogs were subjected to paravertebral brachial plexus block using lidocaine alone or adrenalinated lidocaine. Data was collected through a prospective, randomised, blinded crossover protocol performed over three periods. Blood samples were collected during 180 minutes following block execution. Compartmental pharmacokinetic models were developed and their goodness-of-fit were compared. The lowering effects of adrenaline on the absorption of lidocaine were statistically determined with one-sided tests. A one-compartment disposition model with two successive zero-order absorption processes best fitted our experimental data. Adrenaline decreased the peak plasma lidocaine concentration by approximately 60% (P < 0.001), decreased this local anesthetic’s fast and slow zero-order absorption rates respectively by 50% and 90% (P = 0.046, and P < 0.001), which respective durations were prolonged by 90% and 1300% (P < 0.020 and P < 0.001). Lidocaine demonstrated a previously unreported atypical absorption profile following its paravertebral injection in dogs. Adrenaline decreased the absorption rate of lidocaine and prolonged the duration of its absorption.
Highlights
2 to 5 years old, and weighing 11 (1.3) [mean (SD)] kg were used. They belong to our institutional Teaching & Research dog colony, where they are housed together in facilities that are approved by the Canadian Council on Animal Care, and accustomed to human interaction and manipulation by the veterinary students of the Comited’Ethique et Bien-Etre des Animaux (CEBA)
The results reported support our hypothesis regarding the ability of our alternative compartmental model at accurately measuring the lowering effect of adrenaline on the doi:10.1371/journal.pone.0169745.g003
In the case of plain lidocaine, both absorption rates were faster than the elimination rate of lidocaine, which induced a shoulder in the absorption phase of the kinetic profile
Summary
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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