We thank Drs. Fodale and Santamaria for their kind comments and thoughts on our study.1They note that possible disadvantages of the use of remifentanil-based analgesia resulting from N -methyl-d-aspartate receptor activation might be prevented clinically, when given in combination with sevoflurane or propofol. These substances have indeed been shown to produce an inhibiting effect on glutamate-evoked (N -methyl-d-aspartate) receptor currents in electrophysiologic experiments,2,3and volatile anesthetics in addition have been shown to reduce cell damage in cultured neurons.4 

This is certainly a potentially valid train of thought. In no way did we intend to imply that remifentanil would not be an appropriate compound to be used in the clinical setting. The suggestion by Drs. Fodale and Santamaria provides additional reassurance that clinical use of the drugs should not necessarily be associated with detrimental N -methyl-d-aspartate–related effects. Also, their observation might explain some of the disagreements in the literature regarding the increased analgesic required observed postoperatively after remifentanil-based anesthesia.

At the same time, this provides a testable hypothesis that could be explored in a clinical setting (although it seems there are not many clinically applicable anesthetics left that do not induce N -methyl-d-aspartate receptor antagonism).

We thank the authors for this insightful suggestion.

* University of Virginia Health System, Charlottesville, Virginia. durieux@virginia.edu

1.
Hahnenkamp K, Nollet J, Van Aken HK, Buerkle H, Halene T, Schauerte S, Hahnenkamp A, Hollmann MW, Strumper D, Durieux ME, Hoenemann CW: Remifentanil directly activates human N -methyl-d-aspartate receptors expressed in Xenopus laevis  oocytes. Anesthesiology 2004; 100:1531–7
2.
Criswell HE, Ming Z, Pleasant N, Griffith BL, Mueller RA, Breese GR: Macrokinetic analysis of blockade of NMDA-gated currents by substituted alcohols, alkanes and ethers. Brain Res 2004; 1015:107–13
3.
Orser BA, Bertlik M, Wang LY, MacDonald JF: Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones. Br J Pharmacol 1995; 116:1761–8
4.
Kudo M, Aono M, Lee Y, Massey G, Pearlstein RD, Warner DS: Effects of volatile anesthetics on N -methyl-d-aspartate excitotoxicity in primary rat neuronal–glial cultures. Anesthesiology 2001; 95:756–65