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Threshold Serum Concentrations of Bupivacaine Associated with Early CNS Toxicity and Pharmacokinetics of Bupivacaine in Young versus Old Rhesus Monkeys
  1. Bernadette T. Veering, M.D.*,
  2. Constance S. Sehlhorst, B.S.**,
  3. Donald D. Denson, PH.D.**,
  4. Johan Spierdijk, M.D., PH.D., F.F.A.R.C.S.(HON.)* and
  5. Anton G.L. Burm, PH.D.*
  1. *Department of Anesthesiology, University Hospital Leiden, Leiden, The Netherlands
  2. **Department of Anesthesia, University of Cincinnati College of Medicine, Cincinnati, Ohio


Effects of aging on the onset of early signs of central nervous system (CNS) toxicity, associated total and free arterial threshold serum concentration, and the disposition of bupivacaine were studied in eight younger (11-15 years) and eight older (16-28 years) rhesus monkeys. Bupivacaine was infused at a rate of 0.15 mg/kg minute until unceasing movements of the eye, oscillating from side to side and up and down (nonpositional nystagmus). This was regarded as an objective sign of early CNS toxicity. Most animals showed drowsiness and sedation by the end of the infusion. CNS toxicity occurred significantly faster (p < 0.025) in the younger (13.7 ± 2.5 minutes) than in the older (17.1 ± 2.6 minutes) animal group. A significant correlation was found between the onset time of CNS toxicity and age. The coefficient of determination (R2 ) for this correlation was 0.48. Also, the dose associated with the onset of CNS toxicity was significantly smaller in the younger (2.06 ± 0.38 mg/kg) than in the older (2.60 ± 0.39 mg/kg) animals. However, the total and free arterial thresh-old serum concentration of bupivacaine was similar in both groups. Age did not influence the disposition of bupivacaine.

  • local anesthetic
  • bupivacaine
  • CNS toxicity
  • bupivacaine
  • pharmacokinetics
  • bupivacaine
  • effect of age

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