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Toxicity of Local Anesthetic Additives
  1. John C. Rowlingson, M.D.
  1. From the Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville, Virginia.
  1. Address correspondence to John C. Rowlingson, M.D., Professor of Anesthesiology, Box 238, Department of Anesthesiology, University of Virginia HSC, Charlottesville, VA 22908.


Background and Objectives. In a critical review of the possible agents that may cause or contribute to neurotoxicity of drugs given subarachnoid, the common and the new-age additives to local anesthetics must be considered.

Methods. A review of the literature disclosed a wide array of animal models in which the expected physiologic effects of the drugs given were documented.

Results. Research studies showed that epinephrine, phenylephrine, and clonidine produce vasoconstriction in the tissues around the spinal cord, but the clinical consequences of this response in humans was poorly defined. That the common additive dextrose, given alone, does not appear to be neurotoxic in spite of its hyperosmolar effect, but is suspect when combined with local anesthetics, indicated the need for dose-controlled studies to elucidate a synergistic interaction. The antioxidants have been the most studied of the additives, and the positive findings have resulted, appropriately, in changes in the formulations of local anesthetic preparations for clinical use. Evidence of neural tissue damage with short- and long-term opioid administration was inconclusive, as was that related to subarachnoid deposteroids.

Conclusions. It is necessary to repeat neurotoxicity studies using modern-day techniques, and to then gain more significant insight through clinical correlation.

  • Local anesthetics
  • additives
  • epinephrine
  • phenylephrine
  • methylparabens
  • dextrose
  • metabisulfite
  • EDTA
  • pH-adjustment drugs
  • clonidine
  • opioids
  • deposteroids
  • subarachnoid.

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  • Professor of Anesthesiology; Director, Pain Management Center.