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ANESTHETIC PHARMACOLOGY

The Relative Toxicity of Amitriptyline, Bupivacaine, and Levobupivacaine Administered as Rapid Infusions in Rats

Venkatesh Srinivasa, MD^*, Peter Gerner, MD^*, Anna Haderer, MD^*, Salahadin Abdi, MD PhD, Petr Jarolim, MD PhD, and Ging Kuo Wang, PhD^*

Departments of *Anesthesiology, Perioperative and Pain Medicine and Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and Department of Anesthesia and Intensive Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Peter Gerner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115. Address e-mail to gerner{at}zeus.bwh.harvard.edu

Intravascular injection of local anesthetics carries the risk of cardiovascular (CV) and central nervous system (CNS) toxicity. Amitriptyline, a tricyclic antidepressant, has local anesthetic potency that is more than that of bupivacaine. In this study, we compared the CV and CNS toxicity of the local anesthetics bupivacaine and levobupivacaine with that of amitriptyline. Twenty-nine Sprague-Dawley rats had their right external jugular vein and carotid artery cannulated under general anesthesia. On Day 2, rats were sedated with midazolam (0.375 mg/kg intraperitoneally) and received rapid infusions of either 1) bupivacaine, levobupivacaine, or amitriptyline at 2 mg · kg^-1 · min^-1 (5 mg/mL concentration) or 2) normal saline (400 µL · kg^-1 · min^-1) through an external jugular vein cannula. Electrocardiogram and arterial blood pressure were measured until the dose to cause impending death was reached (heart rate 50 bpm/asystole or apnea for >30 s). The mean dose required to cause apnea and impending death was significantly larger for amitriptyline (74.0 ± 21 mg/kg and 74.5 ± 21 mg/kg, respectively) than for levobupivacaine (32.2 ± 20 mg/kg and 33.9 ± 22 mg/kg, respectively) or bupivacaine (21.5 ± 7 mg/kg and 22.7 ± 7 mg/kg, respectively) (P < 0.05). A significantly larger dose of amitriptyline, given by rapid infusion, is required to cause CV and CNS toxicity in rats, when compared with bupivacaine and levobupivacaine.

IMPLICATIONS:Amitriptyline, a tricyclic antidepressant, has local anesthetic properties and is more potent than bupivacaine. Significantly larger doses of amitriptyline, given by rapid infusion, are required to cause cardiovascular and central nervous system toxicity in rats, when compared with bupivacaine and levobupivacaine.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999