Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers

• Published in: British journal of anaesthesia : BJA Vol. 78; no. 5; pp. 507 - 514
• Main Authors: Knudsen, K, Beckman Suurküla, M, Blomberg, S, Sjövall, J, Edvardsson, N
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.1997; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adult; Amides - adverse effects; Amides - blood; Amides - pharmacology; Anesthetics, Local - adverse effects; Anesthetics, Local - blood; Anesthetics, Local - pharmacology; Biological and medical sciences; Bupivacaine - adverse effects; Bupivacaine - blood; Bupivacaine - pharmacology; Central Nervous System Diseases - chemically induced; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug toxicity and drugs side effects treatment; Electrocardiography - drug effects; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Male; Medical sciences; Pharmacology. Drug treatments; Ropivacaine; Toxicity: nervous system and muscle; Ventricular Function, Left - drug effects; Human; Nervous system diseases; Echocardiography; Intravenous administration; Toxicity; Cardiovascular disease; Ropivacaine; Local anesthetic; Bupivacaine; Activity concentration relation; Central nervous system disease; Electrocardiography; Hemodynamics; Anilide; Comparative study
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/78.5.507

We have compared the incidence of CNS symptoms and changes in echocardiography and electrophysiology during i.v. infusions of ropivacaine, bupivacaine and placebo. Acute tolerance of i.v. infusion of 10 mg min-1 was studied in a crossover, randomized, double-blind study in 12 volunteers previously acquainted with the CNS effects of lignocaine. The maximum tolerated dose for CNS symptoms was higher after ropivacaine in nine of 12 subjects and higher after bupivacaine in three subjects. The 95% confidence limits for the difference in mean dose between ropivacaine and bupivacaine were -30 and 7 mg. The maximum tolerated unbound arterial plasma concentration was twice as high after ropivacaine (P < 0.001). Muscular twitching occurred more frequently after bupivacaine (P < 0.05). The time to disappearance of all symptoms was shorter after ropivacaine (P < 0.05). A threshold for CNS toxicity was apparent at a mean free plasma concentration of approximately 0.6 mg litre-1 for ropivacaine and 0.3 mg litre-1 for bupivacaine. Bupivacaine increased QRS width during sinus rhythm compared with placebo (P < 0.001) and ropivacaine (P < 0.01). Bupivacaine reduced both left ventricular systolic and diastolic function compared with placebo (P < 0.05 and P < 0.01, respectively), while ropivacaine reduced only systolic function (P < 0.01).