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ANESTHETIC PHARMACOLOGY

The Central Nervous System and Cardiovascular Effects of Levobupivacaine and Ropivacaine in Healthy Volunteers

Jonathan Stewart, MBChB^*, Norma Kellett, MBChB^*, and Dan Castro, MD

*Inveresk Research, Edinburgh, Scotland, United Kingdom; and Abbott Laboratories, Abbott Park, Illinois

Address correspondence and reprint requests to Dr. Jonathan Stewart, Chugai Pharma Europe Ltd., Mulliner House, Flanders Rd., Turnham Green, London, W4 1NN. Address e-mail to jgs{at}doctors.org.uk

We compared the central nervous system (CNS) and cardiovascular effects of levobupivacaine and ropivacaine when given IV to healthy male volunteers (n = 14) in a double-blinded, randomized, crossover trial. Subjects received levobupivacaine 0.5% or ropivacaine 0.5% after a test infusion with lidocaine to become familiar with the early signs of CNS effects (e.g., tinnitus, circumoral paresthesia, hypesthesia). The development of CNS symptoms was assessed at 1-min intervals and study drug administration was terminated when the first CNS symptoms were recognized. Thereafter, symptoms were recorded at 1-min intervals until symptom resolution. Hemodynamic variables were assessed by transthoracic electrical bioimpedance. Continuous 12-lead electrocardiogram monitoring was also performed. There was no significant difference between levobupivacaine and ropivacaine for: the mean time to the first onset of CNS symptoms (P = 0.870), mean total volume of study drug administered at the onset of the first CNS symptom (P = 0.595), stroke index (P = 0.678), cardiac index (P = 0.488), acceleration index (P = 0.697), PR interval (P = 0.213), QRS duration (P = 0.637), QT interval (P = 0.724), QTc interval (P = 0.737), and heart rate (P = 0.267). Overall, fewer CNS symptoms were reported for levobupivacaine than ropivacaine (218 versus 277). This study found that levobupivacaine and ropivacaine produce similar CNS and cardiovascular effects when infused IV at equal concentrations, milligram doses, and infusion rates.

IMPLICATIONS: This study compared directly, for the first time, the toxicity of levobupivacaine and ropivacaine in healthy volunteers. Levobupivacaine and ropivacaine produced similar central nervous system and cardiovascular effects when infused IV at equal concentrations, milligram doses, and infusion rates.

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