Interaction of propofol and sevoflurane on loss of consciousness and movement to skin incision during general anesthesia.
BACKGROUND
Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.


METHODS
Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.


RESULTS
The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 microg/ml (95% confidence interval, 1.1-1.3 microg/ml). It was not significantly different from that predicted (1.5 microg/ml; 95% confidence interval, 1.2-1.7 microg/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 microg/ml (95% confidence interval, 4.8-6.0 microg/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 microg/ml; 95% confidence interval, 4.8-5.9 microg/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.


CONCLUSIONS
Propofol and sevoflurane interact in a simple additive manner to produce LOC and immobility to surgical incision, suggesting a common mechanism or a single site of action. These clinical observations are consistent with a single site of interaction at the gamma-aminobutyric acid type A receptor.
Harris
Robert S
RS
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30303, USA. jay.johansen@emoryhealthcare.org
Lazar
Olga
O
Johansen
Jay W
JW
Sebel
Peter S
PS
D000328:Adult; D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D003243:Consciousness / Q000187:drug effects; D018592:Cross-Over Studies; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D009068:Movement; D015742:Propofol / Q000494:pharmacology*; D000077149:Sevoflurane
D000777:Anesthetics; D008738:Methyl Ethers; D000077149:Sevoflurane; D015742:Propofol