Is synergy the rule? A review of anesthetic interactions producing hypnosis and immobility.
BACKGROUND
Drug interactions may reveal mechanisms of drug action: additive interactions suggest a common site of action, and synergistic interactions suggest different sites of action. We applied this reasoning in a review of published data on anesthetic drug interactions for the end-points of hypnosis and immobility.


METHODS
We searched Medline for all manuscripts listing propofol, etomidate, methohexital, thiopental, midazolam, diazepam, ketamine, dexmedetomidine, clonidine, morphine, fentanyl, sufentanil, alfentanil, remifentanil, droperidol, metoclopramide, lidocaine, halothane, enflurane, isoflurane, sevoflurane, desflurane, N2O, and Xe that contained terms suggesting interaction: interaction, additive, additivity, synergy, synergism, synergistic, antagonism, antagonistic, isobologram, or isobolographic. When available, data were reanalyzed using fraction analysis or response surface analysis.


RESULTS
Between drug classes, most interactions were synergistic. The major exception was ketamine, which typically interacted in either an additive or infra-additive (antagonistic) manner. Inhaled anesthetics typically showed synergy with IV anesthetics, but were additive or, in the case of nitrous oxide and isoflurane, possibly infra-additive, with each other.


CONCLUSIONS
Except for ketamine, IV anesthetics acting at different sites usually demonstrated synergy. Inhaled anesthetics usually demonstrated synergy with IV anesthetics, but no pair of inhaled anesthetics interacted synergistically.
Hendrickx
Jan F A
JF
Department of Anesthesia, Onze Lieve Vrouw Hospital, Moorselbaan 164, 9300 Aalst, Belgium. jcnwahendrickx@yahoo.com
Eger
Edmond I
EI
Sonner
James M
JM
Shafer
Steven L
SL
D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D006801:Humans
D000777:Anesthetics; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous