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Correspondence  |   March 2005
In Clinical Practice, Coadministration of Sevoflurane or Propofol Could Antagonize Remifentanil Stimulation of N  -methyl-d-aspartate Receptors
Author Affiliations & Notes
  • Vincenzo Fodale, M.D.
    *
  • * University of Messina, Policlinico Universitario “G. Martino,” Messina, Italy.
Article Information
Correspondence
Correspondence   |   March 2005
In Clinical Practice, Coadministration of Sevoflurane or Propofol Could Antagonize Remifentanil Stimulation of N  -methyl-d-aspartate Receptors
Anesthesiology 3 2005, Vol.102, 695-696. doi:
Anesthesiology 3 2005, Vol.102, 695-696. doi:
To the Editor:—
In an important, exhaustive study, Hahnenkamp et al.  1 found that remifentanil, in clinically relevant concentrations, directly activates recombinantly expressed human N  -methyl-d-aspartate (NMDA) receptors. As evidenced by Hahnenkamp et al.  ,1 NMDA receptors are thought to play a critical role in the development of opioid tolerance and secondary hyperalgesia and also in neuroprotection, because antagonists of NMDA glutamate receptors can protect the brain against some injuries (such as stroke and trauma).2 The NR1/2B subunit is the focus of increasing interest as a therapeutic target in a wide range of central nervous system pathologies, including acute and chronic pain, ischemic brain injury, and head trauma.3,4 It could be concluded that administration of remifentanil is disadvantageous.
Nevertheless, it should be considered that in modern clinical practice, remifentanil-based anesthesia is performed administering either propofol or sevoflurane as adjuvants. Propofol inhibits the NMDA glutamate receptor subtype, possibly through an allosteric modulation of channel gating.5 Nagels et al.  4 could not demonstrate that ketamine, an NMDA antagonist, resulted in greater neuroprotective effects compared with remifentanil during cardiopulmonary bypass procedures when both were combined with propofol, and Luginbuhl et al.  6 reported that adding a small dose of ketamine to opioids may prevent acute tolerance to opioids. It is thought that the NR1/2A complex in particular displays a higher affinity for competitive NMDA antagonists than for agonists. Sevoflurane also exerts an NMDA receptor antagonism effect in a dose-dependent manner, producing an inhibition of NMDA-gated currents and partially inhibiting NMDA-induced mitochondrial membrane depolarization.7,8 
These data, taken together, support the hypothesis that propofol or sevoflurane, coadministered with remifentanil during anesthesia, produced an inhibiting effect at NMDA receptors antagonizing remifentanil-related stimulation.
It is also in accord with a number of recent clinical studies suggesting that administration of remifentanil is also safe in neurosurgery, neuro–intensive care unit sedation, and postoperative analgesia after craniotomy.9–11 Based on the cerebral effects of remifentanil and the evidence currently available, Hancock and Nathanson2 argue that remifentanil should replace nitrous oxide in the “at-risk” brain. As stated by Hahnenkamp et al.  ,1 the clinical use of remifentanil has gained wide clinical acceptance by anesthesiologists.1 
The clinical relevance is that during anesthesia, the coadministered anesthetics, especially the NMDA antagonists propofol and sevoflurane, should antagonize the remifentanil stimulation of NMDA receptors. We would like to ask for the authors’ thoughts on this possibility.
* University of Messina, Policlinico Universitario “G. Martino,” Messina, Italy.
References
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