• Colin J L McCartney, Damian B Murphy, Anna Iagounova, and Vincent W S Chan.
• Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Ontario, Canada.
• Can J Anaesth. 2003 Oct 1;50(8):795-800.

PurposeWe designed the following volunteer study to determine if an intravascular bolus dose of ropivacaine could be found that would reliably produce mild symptoms of central nervous system (CNS) toxicity in sedated humans.MethodsAfter Ethics Committee approval and informed consent 15 volunteers were recruited. Cardiovascular (CVS) monitoring including pulse oximetry, electrocardiogram and non-invasive blood pressure monitoring was applied. In phase 1, volunteers received in sequence placebo, 30 mg, 45 mg and 60 mg of ropivacaine as a 10-mL iv bolus over 20 sec with a two-hour rest period between each injection to allow plasma clearance of drug. Volunteers were asked to report symptoms of local anesthetic toxicity on a verbal response scale. After any dose volunteers reporting greater than three symptoms with a severity of > 3/10 for greater than three minutes were excluded from further study doses. The dose that consistently produced mild CNS toxic effects was chosen for phase 2 of the study. In phase 2, volunteers were given iv midazolam 0.03 mg*kg(-1) prior to bolus ropivacaine or placebo in a randomized double-blind crossover fashion. Volunteers were asked to report toxic symptoms and venous blood samples were obtained for ropivacaine assay.ResultsIn phase 1, ropivacaine 60 mg was found to produce consistent mild symptoms of CNS toxicity. No volunteer experienced major CNS or CVS adverse effect during the study. After midazolam premedication all volunteers reported symptoms with bolus ropivacaine 60 mg. Mean peak ropivacaine venous concentration was 4.48 mg*L(-1).ConclusionAn intravascular bolus of ropivacaine 60 mg reliably produces mild CNS toxic symptoms in premedicated volunteers.

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