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LETTER TO THE EDITOR

Neurotoxicity of Anesthetic Agents in Children

Professor of Anesthesia; Stanford University; Acting Chair; FDA Anesthesia and Life Support Drugs Advisory Committee; Meeting to Discuss the Preclinical Neurotoxicity of Anesthetic Drugs

In Response:

Dr. Rowe (1) makes several useful suggestions regarding assessment of the risk of anesthetic neurotoxicity in children. Following publication of the recent report by Mellon et al. (2), the Food and Drug Administration (FDA) held an advisory meeting on March 29, 2007, where experts in the field summarized their findings.

The outcome of the FDA meeting (3) was recognition of exactly the issues summarized by Dr. Rowe:

1. It is important to monitor physiological status during animal studies, to preclude attributing neurotoxicity caused by metabolic derangement (e.g., hypoxia, acidosis) to the anesthetic itself.
   
2. Considerable thought must be given when calibrating expo-sure between animal and human studies. This is fairly easy for the inhaled anesthetics, where the partial pressure equilibrates among tissues, and the MAC of inhaled anesthetics is fairly consistent across species. However, it represents a considerable challenge for the IV drugs where differences in pharmacokinetics, blood–brain equilibration, and apparent potency complicate interpretation of animal data.
   
3. There is presently no "postanesthesia" syndrome in very young children suggesting acute neurologic injury from exposure to anesthesia. This does not rule out the possibility that sensitive testing could pick up postanesthesia cognitive deficits.
   

The "bottom line" of the FDA meeting was that there are insufficient data to infer that any anesthetic drug poses a unique neurological risk to children. Although such risk may exist, it likely pales in significance to the well-understood risks of loss of airway, hypoxia, aspiration, positioning injury, and cardiovascular collapse that are well known and significant risks of anesthesia in children.

REFERENCES

1. Rowe R. Neurotoxicity of anesthetic agents in children. Anesth Analg 2007;105:882[Free Full Text]
2. Mellon RD, Simone A, Rappaport B. Use of anesthetic agents in neonates and young children. Anesth Analg 2007;104: 509–20[Abstract/Free Full Text]
3. www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4285b1-01.pdf

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