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Intravenous ropivacaine bolus is a reliable marker of intravascular injection in premedicated healthy volunteers

[L’administration intraveineuse d’un bolus de ropivacaïne est un marqueur fiable de l’injection intravasculaire chez des volontaires sains prétraités]

Colin J.L. McCartney, MBCHB FFARCSI FRCA^*, Damian B. Murphy, MD FFARCSI, Anna Iagounova, MD^* and Vincent W.S. Chan, MD FRCPC^*

^* From the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network; Toronto, Ontario, Canada;
and the Department of Anaesthesia, Intensive Care Medicine and Pain Management, Cork University Hospital, Wilton, Cork, Ireland.

Address correspondence to: Dr. Vincent W.S. Chan, Department of Anesthesia and Pain Management, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. Phone: 416-603-5118; Fax: 416-603-6494; E-mail: vincent.chan{at}uhn.on.ca

Purpose: We 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.

Methods: After 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.

Results: In 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.

Conclusion: An intravascular bolus of ropivacaine 60 mg reliably produces mild CNS toxic symptoms in premedicated volunteers.

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